BOSTON PUBLIC LIBRARY / 3 9999 06317 757 8 2 • y ^' METABOLISM OF PESTICIDES UPDATE II UNITED STATES DEPARTMENT OE THE INTERIOR EISH AND WILDLIFE SERVICE Special Scientific Report- Wildlife No. 212 METABOLISM OF PESTICIDES UPDATE II By Calvin M. Menzie UNITED STATES DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE SERVICE Special Scientific Report— Wildlife No. 212 Washington, D.C. • 1978 ^D W.V.0^ TABLE OF CONTENTS Page Introduction xiii Acknowledgment xiv Abar 163 Acarol 51 Accothion 254 Acephate 193 Acephate-met 193 Alar 1 Aldicarb 2 Aldrin 4 Allyl alcohol 18 Ametryne 271,272 Ami nopyri dine 19 Aminotriazole 20 Aniline 21 Aniten 142 Aresin 297 Aroclor 206 Arsenate, sodium 23 Arsenicals 23 Arsenite, sodium 23 Asulam 24 Asulox 24 ATA 20 Atrazine 271,273 Azinphosmethyl 25 Banvel 112 Bas 392 26 Basalin 26 Bay 68138 195 Bay 94337 278 Benazolin 27 Benefin 28 Benlate 29 Benomyl 29 Bentazon 35 Benthiocarb 261,262 Benzoyl chloride trichlorophenyhydrazide 36 Benzoyl prop-ethyl 37 n Page Betanal 222 BHC 38 Bidrin 116 Bio-allethrin 236 Bioresmethrin 234 Bi phenyl 45 Blasticidin S 47 Botran 49 BPBSMC 50 BPMC 50 Bromacil 288 Bromopropylate 51 Bromosimazine 271 Bromoxynil 52 Busulfan 53 Buturon 290 Butyl dinitroaniline 119 Butylate 261 C 709 116 C 2307 54 C 6989 141 Cacodylic Acid 23 Calixin 284 Captan 55 Carbaryl 56 Carbendazim 29 Carbicron 116 Carbofuran 60 Carboxin 63 CCC 75 CDAA 65 Cela W524 287 CEPA 66 Chevron RE 5365 50 Chevron RE 11775 50 Chloral hydrate 67 Chlorbromuron 291 Chlordane 68 Chlordene 68 Chlordimeform 74 Chlormequat 75 Chlorodioxin 76 Chloronaphthalene 219 m Page Chloroneb 78 Chi orop ropy late 51 Chlorothalonil 79 Chlorpropham 80 CIPC 80 Clophen 206 Clopidol 83 Cobeko 121 Cobex 121 Counter 256 Credazine 84 Cyanazine 276 Cyanide 85 Cycloate 261 Cyolane 86 Cyprazine 276 2,4-D 88 Dasanit 139 DBNPA 94 DCB 95 DCNA 49 DD 114 DDD . 98 DDE 98 DDOD 96 DDT 98 DDVP 115 Demosan 78 Destun 105 Dexon 106 Dial late 261 Dianisylneopentane 107 Diazinon 109 Dibromo nitrilopropionamide 94 Dicamba 112 Dichlobenil 113 Dichloroanisic acid 112 Dichlorobenzene 95 Dichloropropene 114 Dichlorvos 115 Dichlozoline 96 Dicofol 98 Dicrotophos 116 Dicryl 117 IV Page Dieldrin 4 Diethamine 121 Diethion 136 Diflubenzuron 292 Dimecron 223 Dimethoate 118 Dimi Dim' Dim' Dim Dim' Dim' lin 292 tramine 121 tro compounds 119 troaniline, methyl -propyl -t-butyl 124 troaniline, sec, butyl -t-butyl 119 trodi propyl cumi dine 123 Dinobuton 120 Dinoseb 120 Diphenamid 125 Di phenyl 45 Diquat 126 Disugran 112 Disyston 127 Dithiocarbamate 128 DNBP 120 DS 15647 130 DuPont 1179 184 DuPont F 1991 29 Dyfonate 131 Dymid 125 EBC 29 EDB 132 Edifenphos 149 Ektafos 116 EMD-IT 3233 142 Endosulfan 133 Endothall 135 Endrin 4 Enide 125 ENT 27696 267 E0 137 EPTAM 261 EPTC 261 Ethion 136 Ethoprop 192 Ethoxychlor 185 Ethylene di bromide 132 Page Ethylene oxide 137 Ethyl propylphosphonate 197 ETO 137 ETU 128 Fenazaflor 138 Fenitrothion 254 Fensulfothion 139 Fentin 266 Flu 140 Fluchloralin 26 Fluenethyl 140 Fluometuron 294 Fluoroacetate 140 Fluorodifen 141 Fluorosimazine 271 Flurecol 142 Flurencol 142 Flurenol 142 FMC 1103 243 Folpet 55 Formetanate 143 Frescon 144 Fulvicin 147 Furadan 60 Furamethrin 237 Galecron 74 Gardona 145 Glyphosate 146 Gramoxone 126 Griseofulvin 147 GS 13005 182 HCB 148 HCE 4 HCH 38 HEOM 4 Heptachlor 68 Hinosan 149 Imidan 151 VI Page Iodoatrazine 271 Iodopropazine 271 Iodosimazine 271 Ioxynil 52 IPC 80 Irgasan DP 300 152 Isodrin 4 Isopropalin 123 Isopropyl carbanilate 80 Isopropyl chlorocarbanilate 80 Isopropyl dibromobenzilate 51 Isopropyl dichlorobenzilate 51 Isoxathion 153 IT 3233 142 Kanechlor 20b Karphos 153 KC 206 Kelevan 155 Kelthane 98 Kepone 155 Kerb 229 Kitazin 159 L 34314 125 Lambrol 140 Landrin 161 Lannate 184 Lauryl valine 162 Leptophos 163 Linuron 295 Lovozal 138 Luprosil 164 Mafu 115 Malathion 165 Maleic hydrazide 167 Maneb 128 Matacil 168 MBC 29 MBT 296 MCA 29 MCPA 92 VI l Page Meobal 169 Mercury compounds 170 Mesurol 178 Methamidophos 193 Methazole 179 Methbenzthiazuron 296 Methidathion 182 Me thorny 1 184 Methoxychlor 185 Methylchlor 188 Methyl enedioxy compounds 190 Methyl guthion 25 Methyl propyl butyl dinitroanil ine 124 Metribuzin 278 Mexacarbate 301 MH 167 Mi rex 155 Mobam 191 Mocap 192 Molinate 261 Monitor 193 Monolinuron 297 Monuron 298 NAA 194 NC 2983 138 NDA 196 Nemacur 195 Neodecanoic acid 196 Neo-Pyamin 243 Neoron 51 NF 48 29 NIA 9260 243 Niagara 10637 197 Nitrapyrin 198 Norflurazone 253 N-Serve 198 Nuvan 115 OMS 1804 292 Ordram 261 Orthene 193 Ortho 9006 193 Oryzemate 199 vm Page Oxadiazon 200 Oxydiazol 179 Oxycarboxin 63 Paraquat 126 Parathion 202 Parbendazole 29,32 PCB 206 PCN 219 PCNB 220 PCP 221 Pebulate 261,264 Perf luoridone 105 PH 6040 292 Phaltan 5b Phenisobromolate 51 Phenmedipham 222 Phenoclor 206 Phenothrin 238 Phosphamidon 223 Phosvel 163 Phthalthrin 243 Picloram 224 Piperonylic acid 190 Pirimiphos-methyl 226 Plantvax 63 Preforan 141 Probe 179 Prolan 227 Prometone 280 Prometryne 271 Pronamide 229 Propanil 230 Propazine 271,281 Propham 80 Propionic acid 165 Proximpham 231 Pyramin 232 Pyrazon 232 Pyrethrin 234 Ouintozene 220 IX Page R 7465 245 Racuza 112 Randox 65 Resmethrin 239 Rhothane 98 Robenidine 247 Robenz 247 Ro-Neet 261 Rotenone 249 S 1358 250 S 2539 238 Salithion 252 San 6706 253 San 9789 253 SD 3562 116 Saturn 261,262 Sencor 278 Sevin 56 Simazine 271,282 Simetryne 271 SP 1103 243 Suffix 37 Sumithion 254 Supracide 182 Sutan 261 2,4,5-T 93 Tamaron 193 TBZ 259 TDE 98 Tenn'k 2 Terbufos 256 Terraclor 220 Terracur 139 Tersan SP 78 Tetramethrin 243 TFM 257 TH 60-40 292 Thiabendazole 259 Thiodan 133 Thiofanox 130 Thiolcarbamates 260 Thiophanate 29 Page Thiophanate-methyl 29 TIBA 265 Till am 261,264 Tin compounds 266 Tirpate 267 Toluenesufenyl carbofuran 62 Toxaphene 268 TPE 29 TPM 29 Triallate 261 Triazine 270 Tribunil 296 Tn'demorph 264 Trifenmorph 144 Trifluralin 285 Triforine 287 Uracil 288 Urea 289 USB 3584 121 Vapona 115 VCS 438 179 VCS 506 163 Vernam 261 Vernolate 261 Vitavax 63 Warfarin 300 WL 8008 144 WL 9385 283 Zectran 301 Zineb 128 1080 140 Bibliography 303 Bibliography - Addendum 378 XI Page Appendix I Effect of Temperature on Carbamate Insecticides 379 Appendix II Jjn Vivo Inhibition of Live Arylamidase . . . 380 Appendix III Effect of Substitution in Parathion Analogs 381 XI 1 Metabolism of Pesticides Update II by Calvin M. Menzie U.S. Fish and Wildlife Service Division of Habitat Preservation-Research Washington, D.C. 20240 INTRODUCTION This publication supplements the preceding Metabolism of Pesticides (1969) and Metabolism of Pesticides -- An Update (1974). Readers are also advised that, during the period from preparation to printing of this volume, a considerable additional literature on this subject matter has been published. xm ACKNOWLEDGMENTS I should like to express my appreciation to the following people who have graciously given of their time to read this manuscript and who have offered helpful suggestions: R. Barron (NIEHS) P. Datta (EPA) C. Collier (EPA) D. Severn (EPA) H. Day (EPA) G. Zweig (EPA) and to Marge Bader and Larry Koehler for their diligence and patience in the preparation of the manuscript. xiv ALAR [Succinic acid 2,2-dimethylhydrazide] N-Methyl-ll4C- labeled alar was applied to four soils under greenhouse conditions. The data indicated that microbial degradation was the major route of alar dissipation from soil. The half-life of alar war 3 to 4 days on all soils and the major degradation product was 11+C02. In 14 days, about 84% of the label was recovered as 14C02 and most of the remainder of the lkC was associated with the soil organic matter (Dannals et al . , 1974). ALDICARB (Tenik) [2-Methyl -2- (methyl thio)propionaldehyde 0- (methyl carbamoyl )oxime] Five soil fungi were tested in culture media for their ability to degrade aldicarb. The results indicated the following order of effectiveness: Gliocladium catenulatum > Penicill ium multicolor = Cunninghamella elegans > Rhizoctonia sp. > Trichoderma harzianum. Metabolites found included aldicarb sulfoxide and sulfone, nitrile sulfoxide and sulfone, and oxime sulfoxide and sulfone. A considerable amount of water-soluble metabolites were also observed, including the alcohol and amide sulfones and sulfoxides. Small amounts of the acid sulfone and sulfoxide were also observed (Jones, 1976). In soil treated with aldicarb, the sulfoxide and sulfone were observed (Jamet et al . , 1974). After administration of a single dose (0.7 mg/kg) of Temik-S35 to hens, about 1% of the radioactivity was observed in eggs over a 10-day period. Analyses of tissues, eggs and feces showed the presence of the sulfoxide and sulfone metabolites (Hicks, 1970). Boll weevils (Anthonomus grandis Boheman) and houseflies (Musca domes tica L. ) were treated with carbonyl-^C-aldicarb. Following topical application of the insecticide, aldicarb disappeared rapidly. The sulfoxide was the major non-conjugated metabolite in boll weevils and houseflies. The sulfone formed subsequently in smaller amounts. 11+C02 detected was very small. Water soluble products that formed were suspected of being conjugated metabolites but were not identified (Andrawes and Dorough, 1970). ch -s-c-ch=noh £h3 Aldicarb oxime (VII) CH. CH3 J-CH=NOH Aldicarb oxime sulfoxide(VIII) Sulfoxide alcohol Conjugate CH3 0 CH_-S-C-CH=N-0-C-fd!, CH3 CH3-S-C-CH=N-0-C-N^„ Aldicarb sulfoxide(II) 0 CH -'^-C-CH=N-0-C,-NH. Aldicarb N-demethyl sulfoxide (XV) 0 ch=n-o-c-nC-u ^-M3 Aldicarb sulfone(III) CH ,4U- 1 » i 0 CH, =N-0-C-NH„ 0 it H °"C"NXH20H Aldicarb N-CH OH sulfone (IV) Aldicarb N-demethyl sulfone (XVI) I CH. -(?H=N0H QfH3 ^X* Aldicarb oxime Nitrile sulfoxide(X) \ 0 CH „ CH_ ""5"C-Cviliu 3 fcH^NH2 Sulfoxide amide / (XI) 0 CH. C-CN sulfone (V) CH, . * , 0 CH Nitrile sulfone(XIV) u CH cH3-!U-d* CH - it I 51 ■CHO H, \ *T A. -* Conj. I I 3 ffll&O / I fa ^6cH3^2]/CH3t^H20H Sulfone amide / Sulfone a13cohol " 0 CH, T CH3-s'-C-C^, &> Sulfoxide acid (XII) CHi1Hc3v°H Sulfone acid(XIII) cohol(VI) Conjugate -' :•-- 1,8,9,10,11 ,11 -Hexachloro-2,3-7, 6- endo-2.1-" . :-e«;o-tetracyc1o ~J.ir.":-z- ::";:::e;--.r-:--e I" =* --~~ ' .: .9,10,11 ,11 -Hexa:-" :-:--.:- = = :-;::=•-:. ':-' . f-endo-2, 1-7, 8-exo- :e: -=: . :" z'.z.l.' .' - •"' :; ■""::: = : -.:- =- = 1 ,8,9,10,11 ,11-Hexach1oro-2, 3-7, 6-endo-2, 1-7, 8-endo-tetracyclo If.:/ ." : :: ;:::e:-^.r-: ee ,8,9,10,11 ,ll-Hexachloro-4,5-ej»-epoxy-2,3-7 ,5-endo-2,l-7,8-endo- -":--- Dieldrin -■ . : '.' When labeled trans-4,5-aldrindiol was administered to rats, a small portion (6%) of the radioactivity was excreted as a polar metabolite which was identified as the hexachloro-tetrahydroindane-1 ,3- dicarboxylic acid (dihydrochlordene dicarboxylic acid) by TLC, GLC, IR and mass spectrometry (Oda and Muller. 1972). This compound was administered with labeling intravenously to rats. The radioactivity was rapidly excreted and almost half consisted of metabolites. Of the nine compounds isolated from feces and urine, three have been identified as: dihydrochlordene dicarboxylic acid dimethyl ester; and two isomers of the monodechlorinated dihydro- chlordene dicarboxylic acid. Two compounds were \iery polar and, after hydrolysis with methanol/HCl , could be methylated to form the dimethyl ester of dihydrochlordene dicarboxylic acid. The other four compounds have molecular weights ranging from 244 to 336 and four to six chlorines (Lay et al . , 1975). Dieldrin was administered intravenously to rhesus monkeys. Excreta was collected and four metabolites were isolated by TLC. Three were identified: 12-hydroxydieldrin; 4,5-aldrin-trans-dihydrodiol and a glucuronic acid conjugate of the diol (Muller et al . , 1975b). The same metabolites were found in urine of Swiss white mice, Sprague-Dawley rats, New Zealand white rabbits, and a female chimpanzee when they were fed dieldrin (Muller et al . , 1975a). In other studies, aldrin- trans- dihydrodiol and the di- acid were observed in treated rats and mice. The pentachloroketone was also excreted by rats but not the mice. Rhesus monkeys excreted 9- hydroxydieldrin but no pentachloroketone. Bile contained the glucuronide of 9-hydroxydieldrin (Baldwin, 1971). Using microsomal preparations, the conversion of aldrin to dieldrin was found to be much slower in trout liver microsomes than in male rat liver microsomes (Chan et al . , 1967). Mixed function oxidase (MFO) activity in liver of bluegill (Lepomis macrochirus) converted aldrin to dieldrin in the presence of NADPH. Optimal activity occurred at pH 8.2-8.4 and 22-26C. Bass (Micropterus dolomeiux) MFO was linear with aldrin for 4.6 min at pH 7.4 and 25C. Mouse MFO also epoxidized aldrin to dieldrin (Stanton and Khan, 1973). Hepatic mixed function oxidase with aldrin substrate Epoxidation Vmax Km Bluegill (adult) 0.62 8.58 Bluegull (fry) 1.72 6.98 Bass (fry) 1.72 5.97 Aldrin H .OH I Aldrin ketone Dihydrochlordene dicarboxylic acid cu-^rp trans-Diol N, Glucuronide Vmax Hepatix mixed- function oxidase Dieldrin Photodieldrin Endrin Bass (fry) 1.19 Bluegill (fry) 1.45 - 0.81 Mouse 3.35 2.15 1.17 (Stanton & Khan, 1973) Susceptible and resistant mosquitofish (Gambusia affinis) were treated with 14C-aldrin. Resistant fish converted aldrin to dieldrin and other unidentified materials at a greater rate than did susceptible fish (Wells et al . , 1973). When hepatopancreases from male lobsters (Homarus americanus) were incubated with aldrin, dieldrin was formed. The pH optimum was 8.0 and greatest activity was observed in the 105,000xg soluble fraction (Carlson, 1974). The freshwater ostracod [Chlamydotheca arcuata (Sars.)] metabolized aldrin to dieldrin. No metabolism of dieldrin was observed (Kawatski, 1970). Resistant and susceptible strains of the house fly (Hylemia antigua) metabolized aldrin to dieldrin at the same rate when aldrin was applied at the rate of 0.02 ug/fly. At 25 yg/fly, metabolism of aldrin by the resistant strain was ^ery low (Temizer, 1970). Radiolabeled dieldrin was observed in hemolymph of adult male Periplaneta americana and P_. brunnea after application of lhC- aldrin to the pronotum. There were indications that dieldrin was bould to a protein of about 18,900 MW and two groups of proteins of MW > 160,000 (Olson, 1973). Larvae of Hel iothis zea and He! iothis virescens metabolized aldrin to dieldrin. Larvae of the latter exhibited a greater rate of conversion. Most of the labeled material used was excreted as metabolites more polar than dieldrin. Treatment with HC1 indicated that these polar metabolites were primarily conjugated. None were identified. Within 24 h of treatment with labeled aldrin, H. zea excreted the radioactivity as aldrin (5%), dieldrin (12%), and polar metabolites (83%). With H. virescens, it was 3, 5 and 92%, respectively (Plapp, 1973). Pea and bean root preparations degraded aldrin to a series of related polar metabolites (in addition to dieldrin, aldrin ketone, cis- and trans-aldrin diols, and exo-aldrin alcohol). Exo-aldrin alcohol gave rise to traces of aldrin ketone. An unidentified major component was observed and thought to be 12-hydroxydieldrin from GC relative retention times. An isomer of dieldrin, possibly the endo-epoxide isomer, was also observed (McKinney and Mehendale, 1973). The aldrin epoxidase enzyme from peas is particulate and not soluble. Almost all activity was located in the pellet from centrifugation at 250,000xg. Epoxidation of aldrin was not stimulated by addition of NADPH to high centrifugation fractions. Addition of Mg++ inhibited the reaction but the addition of ~\0~k M p_- ami no ben zoic acid increased the activity of dwarf bean root homogenates. The results of the studies suggested the presence of two or more aldrin epoxidizing systems (Mehendale, 1973). In other studies cell-free pea root preparations metabolized aldrin to dieldrin. In 0.02 M phosphate buffer, the optimum pH was 6.5. The reaction increased up to 35C and decreased thereafter. In these studies, a need was not shown for the cofactors NADPH2 and Mg++ (Oloffs, 1970). In Japanese soils, on which organochlorine compounds has been sprayed for 2-20 years, photodieldrin was observed in 14 of 52 soil samples tested (Suzuki et al . , 1974). Ten years after a single application of aldrin to soil, dieldrin and photodieldrin were detected (Lichtenstein et al . , 1971). Maize and wheat were grown in soils treated with aldrin-^C at locations in Europe and the U.S. Aldrin-ll*C treated wheat seeds were also planted. When the grains were harvested, residues in the grain did not exceed 0.01 ppm. The main labeled products identified in soils and plants from all locations were dieldrin, dihydrochlordene dicarboxylic acid, photodieldrin, aldrin and some unidentified acidic and non-polar compounds (Weisgerber et al . , 1974). Sugar beets grown in soil treated with ll*C-aldrin, gave similar results. At harvest, dieldrin and a group of hydrophylic compounds comprised more than 95% of the luC-label recovered from soils. Besides dihydrochlordene dicarboxylic acid, photodieldrin and two minor acidic compounds not identified were observed (Kohli et al., 1973). In England and Germany, aldrin-ll+C was applied to soils outdoors and potatoes were sown. Traces of aldrin were found in potato hulm and peeled tubers. Small amounts of aldrin were detected in the peel. The main metabolite in potato samples and upper soil layers from Germany was dieldrin. In the potato hulm from England, but not from Germany, a compound was observed which behaved like photodieldrin. Small amounts of photoaldrin were also observed. In all samples, after aldrin and dieldrin, most of the radioactivity recovered was in the form of hydrophilic material. The main 8 compound was identified as dihydrochlordene-11+C-dicarboxylic acid (1 ,2,3,4,8,8-hexachloro-l ,4,4a,6,7,7a-hexahydro-l ,4-ejido-methylene- indene-5,7-dicarboxylic acid). Formation of this acid apparently does not take place via dieldrin (Klein et al . , 1973). Vapor phase ultraviolet irradiation of aldrin gave rise to photo- aldrin, dieldrin and photodieldrin. Irradiation of dieldrin produced photodieldrin (Crosby and Moilanen, 1974). Diquat inhibited microsomal aldrin epoxidation. I50 = 6.6xlO"6M (Krieger et al . , 1973). Fenton's reagent, modified by addition of bovine serum albumin, effected epoxidation of aldrin (Marshall, 1972) Rat liver preparations transformed dieldrin in vitro to the cis- and trans^ isomers of dihydroaldrindiol . An epimerase, also present in the same fraction of rat liver homogenate, rapidly epimerized the cis-isomer to the trans- isomer. The epimerase, located in the microsomes, required NADPH and cytochrome P-450 but not molecular oxygen (Matthews and McKinney, 1974). A major animal metabolite of dieldrin was identified as the syn-9- hydroxy derivative. When photolyzed, it rearranged to form an isomer analogous to that of the photosiomer of HEOD. The syn-9- hydroxydleldrin was oxidized to 9-keto-dieldrin by refluxing for 1 h at 100C in a saturated solution of chromium trioxide in dry pyridine. Reduction of the ketone with sodium borohydride gave a product identified as 9-anti-hydroxydieldrin. Neither by photolysis nor after oral administration to a male CFE rat was the 9-anti- hydroxydieldrin converted to the pentachloroketone metabolite of dieldrin (Baldwin et al . , 1973 and 1974). Dieldrin half-life in lake water was 4.7 days. When freshwater mussels were exposed to the lake water, dieldrin concentration in the mussels increased 1200-fold (Bedford, 1971). After injection of two female American cockroaches with dieldrin, extraction and analysis of an homogenate of the roaches indicated the presence of at least eight metabolites. The major metabolite was found to be cis-aldrindiol . Trans-aldrindiol, syn-hydroxy- dieldrin, 9-hydroxy analog of photodieldrin, 9-keto analog of photodieldrin and one unidentified compound were also observed. Metabolites from German cockroaches differed only quantitatively. Metabolites isolated from houseflies after exposure to dieldrin differed only in that cis-aldrindiol was not observed (Nelson and Matsumura, 1973). In houseflies, dieldrin metabolism was very slow. Six metabolites were observed and one was characterized in five to seven chromato- graphic systems as trans-aldrindiol . Another resembled one metabolite from rats (Sellers, 1971). Four weeks after application of 11+C-trans-aldrindiol to leaves of lettuce heads, the radioactivity was in the form of extractable and non-extractable residues. Less than 1% was in the soil. In addition to unchanged aldrindiol, analyses showed the presence of non-polar, methanol insoluble, and hydrophilic material. The latter consisted of at least 4 radioactive substances, the main product being about one-third of the mixture and identified by GLC/MS as aihydrochlor- denedicarboxyl ic acid (Kilzer et al . , 1974). ltfC- trans -aldrindiol was applied to soil. Seven weeks later, the soil analyses revealed the presence of 90.7% of the radioactivity as unchanged aldrindiol. In addition to non-polar material which could not be chromatographed, there was hydrophilic material. In this fraction, dihydrochlordenedicarboxylic acid was observed (Kilzer et al., 1974). Aldrin was stable in demineralized water irradiated with UV at A>300nm. When sensitizers (acetone and actaldehyde) were added, dieldrin formed (Ross and Crosby, 1975). When 14C-dieldrin-treated onion-seed was grown, residues found in skins, roots and soil consisted of photodieldrin, hydrophilic products and some non-extractable material (Kohli et al., 1972). 1LfC-Dieldrin was applied to soil in which kohlrabi was grown. Leach water contained a compound identified by GC and mass spec- trometry as dihydrochlordenedicarboxylic acid. Studies indicated that this compound was formed in the plants. Photodieldrin was also observed in soil and plant material. Similar results were obtained with carrots. Some radioactive material was not extract- able (Kohli et al., 1973). Studies on the effect of waste composting on dieldrin indicated little or no further degradation of dieldrin in a 3-week period (Muller and Korte, 1975). Various species of marine algae differed significantly in ability to take up dieldrin. Two hours after treatment, the percent removal of dieldrin from the medium was: Skeletonema costatum Tetraselmis chuii Isochrysis gallana (Chrysophyta) Olisthodiscus luteus (Xanthophyta) Cyclotella nana (Bacillariophyta) Amphidinium carteri (Pyrrophyta) 42.0 16.0 15.5 13.0 13.0 2.3 (Rice and Sikka, 1973) After 4-day exposure of Daphnia pulex or 30-day exposure of Ankistrodesmus spiralis to ll4C-die1drin and 11+C-photodieldrin at 4 ppb, both compounds were recovered unchanged (Neudorf and Khan, 1975). 10 Little or no degradation of dieldrin occurred in skim milk containing E. coli , B_. subtil is, P. fluorescens or S. aureus (Collins, 1969). The epoxide ring of dieldrin is unusually stable and does not react with Grignard compounds or LiAlH4 nor in molten K0H/KN03 at 230C. No reaction occurred in alkali at elevated pressure. With acid catalysis, in methanol/benzene at 13K bar and 140C, the epoxide ring of dieldrin reacted to form a series of compounds (Roemer- Mahler, 1973). In a model ecosystem, the accumulation, metabolism and degradation of dieldrin was studied. About 97% of the dieldrin was recovered unchanged. In addition to about seven unidentified metabolites, the 9-hydroxy and 9-keto derivatives were observed. Algae Clam Crab Daphnia Elodea Mosquito Fish Snail Dieldrin 9-keto 9-hydroxy Unknown 1 2 3 4 5 6 7 Polar 1 + + (In water only) + + + + + + + + + Dieldrin C.F. 7480 1015 247 2145 1280 6145 114,935 C.F, Concentration Factor (Sanborn and Yu, 1973) ll+C-Photodieldrin was administered orally and ip to make rabbits. Most of the radioactivity in urine and feces was in the form of water soluble and/or conjugated material. Two of the urinary metabolites were identified as trans-di hydro photodieldrin and photodieldrin ketone (Reddy and Khan, 1975a) or trans-photoaldrin diol and photodieldrin ketone (Reddy and Khan, 1975c) . The in vitro metabolism of photodieldrin was studied with microsomal mixed function oxidase (MFO) of mouse, rat and houseflies. Photo- dieldrin was converted at very low levels to three metabolites in preparations from male and female mice; two metabolites in male rat and none in the female; one metabolite in female houseflies. Piperonyl butoxide blocked formation of these metabolites. None were identified 11 (Reddy and Khan, 1974). Photoaldrin was oxidized by mouse MFO to photodieldrin (Stanton and Khan, 1973). In other studies with CFE rats and beagles, there was evidence of some metabolism of photo- dieldrin to pentachloroketone (Baldwin, 1971). Photodieldrin was applied to primary leaves of bush red kidney beans (Phaseolus vulgaris). Under laboratory light and sunlight, photo- dieldrin decreased by 17% during an 8-day period. No metabolites were detected. When freshwater algae (Ankistrodesmus spiralis) were exposed to dieldrin, no metabolites were detected. UV irradia- tion of photodieldrin on silica gel plates produced two metabolites not identified (Reddy and Khan, 1975b). Soil was treated with labeled photodieldrin at the rate of 5 ppm on a dry-weight basis. Fifteen months later, the treated soil was removed and analyzed. Most of the radioactivity was not extractable with organic solvents. Three metabolites were isolated and identified 1. Bridged isomer of dihydrochlordene dicarboxylic acid. 2. Bridged isomer of dihydrochlordene dicarboxylic acid, methoxylated. 3. Bridged isomer of aldrin-trans-diol . The latter compound, because of the bridged skeleton and the asymmetry from the diol group, should exist in a total of four isomeric forms (Weisgerber et al . , 1975). Endrin in arachis oil was administered by stomach tube to six male and six female rats. In a 6-day period, males excreted in feces 66% of the dose whereas females eliminated only 37%. Excretion in urine was small but females excreted three times that of males. Feces from rats fed endrin was collected and analyzed. Analysis revealed the presence of endrin (11%), anti-12-hydroxyendrin (83%), syn-1 2-hydroxyendrin (<0.01%), 3-hydroxyendrin (5%), 12-ketoendrin (1%) and A-ketoendrin (<0.01%). A polar metabolite was identified as trans-4,5-dihydroisodrin-4,5-diol . Another polar metabolite was not identified. Collected urine from male rats contained endrin, 12-ketoendrin, anti - 1 2- hydroxyendr i n and 3-hydroxyendrin (17:19:2:1, respectively). The extracts from female rats did not contain the 12-ketoendrin. The major metabolite in female rat urine was identical to 1 2-hydroxyendrin 0-sulfate by paper and thin-layer chromatography and paper electrophoresis (pH7). In tissues analyzed, 12-ketoendrin was the major compound in fat of males; endrin, in females, but 12-ketoendrin was also present. In liver of males no endrin was detected and the 12-ketoendrin was the major metabolite. Liver of females contained endrin and traces of 12-ketoendrin. Kidneys of males primarily contained 12-keto- endrin; those of females contained endrin. Much of the residue was not identified. Bile contained anti -1 2-hydroxyendrin, 12- 12 ketoendrin and 3-hydroxyendrin as glucuronides (Hutson et al . , 1975) After exposure of rats to endrin, analyses have also shown the presence of 9-ketoendrin in tissues and urine and the presence of 5- and 9-hydroxyendrin in feces (Baldwin, 1971). ^C-Labeled isodrin was applied to leaves of young white cabbage (Brassica oleracea var. capitata). After 4 weeks, only 2% was unchanged isodrin. After 10-weeks, there were only conversion products as residues. Endrin and A-keto-endrin were found (Klein et al., 1972). In other studies when isodrin-ll4C was applied to cabbage leaves, six metabolites were isolated and identified or characterized: I (27%) Endrin II (27%) A-keto-endrin III (14%) A monohydroxy acid IV (0.5%) A monohydroxy acid V (1%) A dicarboxylic acid VI (1.4%) A dicarboxylic acid (Weisgerber et al., 1975) After application of 11+C-isodrin to soil, carrots (Daucus carota ssp. sativus) grown in the soil contained 3.1% of the radioactivity after 4 weeks. The soil contained 48% unchanged isodrin after 4 weeks and 41% after 12 weeks. Endrin and A-keto-endrin were identified as conversion products of isodrin. Four water-soluble compounds were also found but not identified (Klein et al . , 1972). In vitro studies showed that MFO of bluegill and mouse converted isodrin to endrin (Stanton and Khan, 1973). After exposure of third instar larvae of tobacco budworm (He! iothis virescens) , 14C-labeled endrin was more readily extracted from nerve tissue of the susceptible strains. Susceptible budworms degraded endrin somewhat to the aldehyde and ketone. The same metabolites plus two unidentified decomposition products were recovered from resistant strains (Polles, 1971). Endrin in hexane was exposed to sunlight. The main photolysis product, identified as the ketone, was also obtained by UV irradia- tion of endrin in hexane (Fujita et al . , 1969). A dieldrin analog, HEOM, was incubated with enzyme preparations from pupae of blowfly (Calliphora erythrocephala) , larvae of the southern armyworm (Prodenia eridania) , and adult Madagascar cock- roaches (Gromphadorhina portentosa). HEOM was hydrated by the three enzyme systems to the corresponding diol . Maximum activity s associated with the 100,000xg pellet (Slade et al . , 1975). 13 wa Homogenates and microsomal preparations from livers of rabbits, rats, quail and pigeons were used to study the transformation of HCE, a dieldrin analog. The results are summarized in the following tables. % HCE Converted To Diol PERCENTAGE OF TOTAL METABOLITES % HCE % HCE Trans Di hydroxy Oxidized Metabolized Diol HHC HCE Ui U2 U3 Rabbit M 73 29 33 10 20 4 S 20 75 95 37 12b 18 3b Rat M 27 5 95 a S 13 39 48 55 b b Quail M 17 8 92 a S 2 31 67 57 b b Pigeon M 27 0 90 4 6 S 0 95 95 42 34b 11 a = formed from HCE where more than 70?4 of substrate had been converted. b = formed from HHC under oxide iti ve conditions . M = liver microsomal preparation. 5 = 11, ,000xg superno itant from 1 iver homogenate After rabbits were dosed with labeled HCE, only 35-40% of the radio- activity was extractable with ether. After refluxing with acid, most of the remainder became ether extractable. HHC and an unidentified polar compound were released by the acid hydrolysis. PERCENT OF DOSE HHC HCE Diol Di hydroxy HCE Ui U3 Others Rabbit Rat Pigeon Quail 42.0 29.0 5.7 20.0 2.2 1.9 <2.0 6.3 6.0 5.0 1.0 36.0 0.0 0.0 6.7 3.0 0.0 0.0 21.0 (Walker and El Zorgani , 1973 and 1974) The shag (Phalacrocorax aristotel is) has been found to contain rather high dieldrin levels. A study of shag enzymes indicated that the epoxide hydrase and the hydroxylating capacity of liver preparations was substantially lower in the shag than in the rat. Liver microsomes of the shag exhibited <8% of epoxide hydrase and <14% of the hydroxylating activity of a similar preparation from a rat (Walker et al . , 1975). 14 CI crW HEOM HO HEOM trans-diol CI ^Cl HCE trans-diol Other Compounds o + U, Oi hydroxy HCE 15 Dihydrochlordene dicarboxylic acid was irradiated by UV (a>300 nm). After treatment with diazomethane, the following compounds were observed: Compound 1 UV> CH3N2> Compounds 5 to 11 or 2 Acetone Compound 2 n-Hexane >• Compound 3 Compound 2 M^M^ Compound 4 (Gab et al., 1974) OOH OOH T-COOCHj COOCH, ■.COOCH3 OOCH, CI CI OOCH3 OOCH3 YCOOCH3 OOCH3 X.iCOOCH. rci/V Cl COOCH. ;ooch, '3 ...j^-COu^nj COOCH, OOCH OOCH OOCH, OOH 11 16 ^OOCHg ci^q COOCH3 H-. N H^l j Cl (CI) (H) 12 13 :oocH3 :ooch, ci ' — 7COOCH3 00CH3 (H)Cl4^(£l) 14 OOCH. COOCH, OOCH COOCH. OOCH 3 : cooch 3 15 16 17 OOCH COOCH OOCH: OOCH. OOCH. CI C 1 6 — ^V^~ -7-COOCH : XT T ' 18 19 20 ^ OOCH2C1 COOCH2CI 21 >- 12,13 ,14 15, 16 ,17 M9 uv 18 , 20. 21 CC14 ' ' (Gab et al., 1973) Incubation of compound 1 with rat liver homogenate produced two isomers of the monodechloro analog as the main metabolites (Lay et al., 1974). 17 Ally! alcohol When allyl alcohol was added to growing cultures and washed mycelium of Trichoderma viride, acetate and acrylate were produced. Additional studies with arsenite-inhibited mycelium indicated that allyl alcohol was metabolized by T. viride by a pathway that includes acrylate, lactate, or their acyl-CoA esters, and pyruvate (Jackson, 1973). Acrylic acid appeared to be an intermediate in metabolism of allyl alcohol by Pseudomonas fluorescens and Nocardia coral! ina (Jensen, 1961). 13 AMINOPYRIDINE [4-Aminopyridine] After application of 14C-labeled ami nopyri dine to corn and sorghum grown in nutrient cultures, studies showed that the ami nopyri dine was readily absorbed by the roots of both plants and translocated to foliar portions of the plants. There was a general distribution pattern throughout the plants. After one week, no acetone-soluble metabolites were found in corn. In sorghum, however, autoradiograms indicated some degradation within shoots and roots. The presence of acetone-soluble radioactivity suggested that some of the amino- pyridine was bound by cellular components (Starr, 1972; Starr and Cunningham, 1974). Adsorption to soil increased with pH. Soil metabolism studies indicated the need for aerobic conditions for degradation. After a one-week lag period, in soils having optimum temperature, moisture and oxygen requirements, 42 to 60% of the ll*C-labeled aminopyridine was degraded to 11+C02 within two months. The rate of breakdown decreased with increasing soil pH. Two metabolites were detected in trace amounts (Starr, 1972; Starr and Cunningham, 1975). 19 AMINOTRIAZOLE [3-Amino-l ,2,4-triazole] When couch grass triazole, two mai identically with thistle [Cirsium observed but none studies with Cana identified as B-( system from pea ( lized aminotriazo was metabolized v metabolic pathway (II) ■* lb (Smith [Agropyron repens (L.)] was treated with amino- n metabolites were observed. These chromatographed two metabolites previously observed in Canada arvense (L.)]. Several other metabolites were also were identified (Fiveland et al . , 1972). In other da thistle, three compounds were observed. One was 3-amino-l ,2.4-triazolyl-l )-a-alanine) . An enzyme Pisum sativum L. cv. Thompson Laxton) also metabo- le. The pea studies indicated that aminotriazole ia a pathway similar to tryptophan synthesis. The appeared to be: aminotriazole ■*■ alanine derivative and Chang, 1973). After a 39-year-old woman ingested 20 mg/kg of aminotriazole, urine taken some hours later contained unchanged aminotriazole (100 mg/ 100 ml). No metabolites were found (Geldmacher-v. Mallinckrodt and Schmidt, 1970). C02 + H2N- ■NH. H2N-CN N=CH^ / = N' N-CH2-CH2-NH2 / H,N N=CH ^N-CH2-C0OH C= \\y Ia N=C U I NH ^ M- NH N= I N ':M \ HN-CH ;n- N^C-NH '" ^C= Ho 2 Aminotriazole I H,N N=CH. ^=N y •N-CH- ■CH-C00H 2 1 II N=CH C=N ^-CH=CH=C00H H,N N=CH, C=N / 'N-CH; ■C00H M=CH \ C«N' OH N-CHo-CH-COOH HoN / lb 20 ANILINE When soil was treated with more than one substituted aniline, asym- metric azobenzenes were produced. Phenyl hydro xyl amine was identified as a key intermediate which condensed with excess aniline to form the corresponding hydrazobenzene. This was then oxidized to the azobenzene (Bordeleau, 1972). The fungus Geotrichum candidum produced two extracellular enzymes, an aniline oxidase and a peroxidase, capable of transforming anilines. The apparent Km (aniline) were 3.1 x 10"4M and 4.4 x 10_1+M for perox- idase and aniline oxidase, respectively. Susceptibility to transfor- mation was dependent on electron distribution in the molecule with increased susceptibility to enzymic transformation correlated to increased electron density at the amino group. Anilines substituted at both 2 and 6 positions by electron attracting groups were not transformed. Sequential transformation of propanil to 3,3' ,4,4' -tetrachloroazobenzene and other complex materials was affected by synergistic interaction of the two common fungi Penicillium piscarm and Geotrichum candidum (Bordeleau, 1972). Chloroanil ine residues of herbicides were immobilized in soil by formation of complexes with humus. In studies with labeled 3, 4-di chloro- anil ine (DCA), it was found that P. frequentans degraded DCA-humic complexes by creating humic oligomers with considerable radioactivity still attached. When the fungus A. versicolor was used, the aniline ring was mineralized (Hsu and Bartha, 1974). An aryl acylamidase, inducible in Bacillus sphaericus, was obtained and purified. Molecular weight was 75,000 and Km (1 inuron) was 2 x 10" 6. Substrate specificity of the enzyme was rather low. The enzyme was inducible by linuron, maloran, monalide, propanil, propham, 2- chlorobenzanilide, and 2,5-dimethylfuran-3-carboxanil ide (Engelhardt et al., 1973). A mixture of microorganisms was cultured on propham as the sole carbon source. The microorganisms grew rapidly on nonchlorinated anil ides. Ring chlori nation depressed respiration and inhibited growth. Acyl anil ides were hydrolyzed more rapidly than carbanilates and chlorinated rings were degraded more slowly than unchlorinated rings. Ring degradation was affected by chlorination in order: 0 > 2, 4 > 2,4,5 > 3 > 4 > 3,4. Compounds tested were isopropyl N-phenyl carbamate and the 3-, 4-, 3,4-, 2,4-, and 2,4,5-chlorinated analogs; karsil; propanil; swep; propionanilide; fenuron; and phenylurea. The mixture of organisms used was identified as Mycobacterium sp., Arthrobacter sp., Nocardia sp., Fusarium sp., Streptomyces sp., Aspergillus sp. , Penicillium sp., and possibly Corynebacterium sp. (McClure, 1974). 21 The soil fungus Fusarium oxysporum metabolized 4-chloroaniline via oxidation as well as acylation of the amine moiety. The oxidative route was the major metabolic pathway. Products isolated and iden- tified included: 4-chlorophenyl hydro xyl amine; 4-chloronitrosobenzene; 4-chloronitrobenzene; 4-chloroacetani 1 ide; 4,4' -dichloroazoxybenzene; and 4,4'-dichloroazobenzene. Chloride ion and three phenolic metabolites were also detected. One phenol has been identified tentatively as 2-chloro-4-nitrophenol . The latter implies chlorine migration and requires further identification (Kaufman et al., 1973). In the presence of a NADPH-generating system, heparinized rat blood, and a liver homogenate, a methemoglobin-forming metabolite was produced with 3,4-DCA (Chow and Murphy, 197b). Other studies have also shown the formation of N-hydroxylated derivatives of £-chloroaniline (Debackere and Uehleke, 1964, from Chow and Murphy, 1975). 22 ARSENICALS Sodium arsenate (Na3AsOi+) Sodium Arsenite (Na3As03) Cows and dogs were fed sodium arsenite and sodium arsenate daily for five days. Urine was collected and analyzed for methylarsenate and inorganic arsenate. In the cow, the levels rose to 0.1 to 0.5 and 1.0 to 4.0 ppm, respectively. When the cows were returned to normal diets, all values returned to control levels (0.02 to 0.10 ppm and 0.1 to 0.2 ppm). In dogs, arsenite feeding produced identical peak values 5.0 to 7.0 ppm for both methylarsenate and inorganic arsenate. Feeding of sodium arsenate to dogs produced a rise to 10 ppm methylarsenate and 5.0 ppm inorganic arsenate. Six days after withdrawal from the arsenic-containing diet, all values reached control levels (Peoples and Lakso, 1973). Cacodylic acid [Dimethyl arsinic acid] When applied to soil, cacodylic acid decreased by two routes. The observation of a pungent garlic odor suggested production of alkyl- arsine and a source of arsenic loss. Degradation to CO2 and arsenate by microbial action was another route for cacodylic loss (Wool son and Kearney, 1973). When exposed to DMA and MMA, the three fungi Candida humicola (Dazewska) Diddens and Kodder, Giocladium roseum Bain, and Penicillium sp. produced trimethylarsine. Of these three, Candida humicola only was able to metabolize arsenate and arsenite to trimethylarsine (Cox and Alexander, 1973). 23 ASULAM (Asulox) [Methyl 4-aminobenzenesul fonyl carbamate] Asulam exhibits rapid mobility in soil and would be expected to readily leach into subsurface water. Mobility of asulam in soil would be pH dependent, where the undissociated form would leach less rapidly than the associated form (Babiker and Duncan, 1975) 24 AZINPHOSMETHYL (Methyl guthion) [0,0- Dimethyl S-(4-OXO-l ,2,3- benzotriazin-3-(4H)-ylmethy1 )phosphorodithioate] The kinetics of azinphosmethyl persistence in soil was studied. Losses of insecticide followed first-order kinetics. [A]0 = initial concentration x = amount of A decomposed per unit volume at time t = rate constant -l log([A]0-x) ■i 2.303 t + log [A] plotting of log([A]0-x) vs t, y intercept = log[A]( and ki = -2.303 (slope) Tl/2 _ to + ti/2 where t0 = lag period '1/2 time for half of to t 1/2 azinphosmethyl to be lost experimentally determined 0.693k! Moisture and temperature affected the persistence of azinphosmethyl The half-life varied from 5 days (40C and wet) to 484 days (6C and wet or dry) (Yaron et al . , 1974). The degradation of azinphosmethyl in water was studied. The effect of pH and temperature was determined. Aqueous solution Temperature °C PH tl/2 Kl 25 40 8.6 9.6 10.7 8.6 9.6 10.7 8.6 9.6 10.7 36.4 1.9 x lO-2 4.95 1.4 x 10-1 3.9 1.8 x 10"1 27.9 2.5 x lO"2 2.4 2.46 x 10"1 2.0 3.4 x 10_1 7.2 9.5 x lO"2 0.65 1.06 0.41 4.1 x 10"1 (Heuer et al . , 1974) 25 BASAL IN (Fluchloralin, BAS-392) [N-(2-Chloroethyl )-N-propyl-2,6-dinitro- 4-trifluoromethylanil ine] Irradiation of basalin in methanol -water with a photoreactor yielded nine products. Identification was based mainly on mass spectral data. When basalin was irradiated in water-methanol in sunlight for 48 days, compounds 3,5,6,7,8 and 11 were observed (Nilles and Zabik, 1974). n-C3H7— N-CH2-CH2C1 02N«»^S-N02 Y Basalin 2 -CjH^Cl C H ON-r^VVM). V ' CF, -C^Cl C3H7 m 02"jr^p°2 CF. |^Muc2vh 10 11 26 BENAZOLIN [4-Chloro-2-oxobenzothiazol in-3-ylacetic acid] The breakdown of 11+C-benazolin was studied in wild mustard [Brassica kaber (DC L.C. Wheeler var. pinnatifida (Stokes) L.C. Wheeler], turnip rape (Brassica campestris L. 'Echo' ) , and rape (Brassica napus L. 'Target'). Negligible amounts of ^CC^ were released by the three species after treatment with benazolin. The Brassica species metabolized benazolin to four less toxic derivatives. None of the metabolites were identified but one was characterized as a conjugate of unchanged benazolin (Schafer and Stobbe, 1973). 27 BENEFIN [N-Butyl -N-ethyl -a ,a ,a-tri f 1 uoro-2 ,6-di ni tro-p_-to1 ui di ne] Roots of tobacco seedlings (Nicotiana tobacum L. Kentucky) accumulated benefin from nutrient solutions containing labeled benefin. Two compounds were detected but not identified (Long et al . , 1974). 28 BENOMYL (Benlate, Dupont F - 1991) [Methyl N-(N- butyl carbamoyl )- 2-benzimidazolyl carbamate] EBC [Ethyl N-(2-benzimidazolyl )carbamate] MBC (Carbendazim) [Methyl N-(2-benzimidazolyl )carbamate] PARBENDAZOLE [Methyl N-(5(or 6)-butyl-2-benzimidazolyl )carbamate] THIOPHANATE (TPE) [l ,2-Bis(ethoxycarbonyl thioureido)benzene] THIOPHANATE-METHYL (TPM) [l ,2-Bis(methoxycarbonyl thioureido)benzene] MCA (NF 48) [2-(3-methoxycarbonylthioureido)aniline] The fate of benomyl was studied in mice, rabbits, and sheep and with enzyme preparations made from mouse liver, kidney, heart, brain, intestine and blood. Preparations were also made from sheep blood, liver and rumen fluid and from rabbit liver and blood. A summary of the pattern of metabolites is given in Table 1. The pattern of metabolites with mouse kidney, heart and brain was similar to that with liver; but with the intestinal preparation, compounds III and IV were not observed. The butyl carbamoyl side chain was stable at pH 7.5 but became increasingly labile with increased acidity. Optimal pH for hydroxylation was between pH 7.0 and 8.0, and at about pH 8.0 for ester cleavage. After benomyl was administered per os to animals, urine and feces were collected at 24-h intervals for 96 h. Results are shown in Table 2 (Douch, 1973). TABLE 1 In Vitro prep. Mouse Rabbit Sheep Liver II - VI II - VI II - VI Blood II, III, V, VI II, III, V, VI II, III, V, VI Rumen Fluid ™ ™ II, III, V, VI After melon plants were treated with benomyl containing 3H-MBC, most of the label was recovered in the leaves after three weeks. In addi- tion to MBC, 2-AB, conjugates of MBC and 2-AB, benzimidazole, o-amino- benzonitrile, and aniline (Rouchaud et al . , 1974). In other studies, benomyl degradation occurred in non-sterilized soil. Cleavage of the benzimidazole ring and production of C02 was observed (Siege! , 1975). 29 Urinary Metabol ites (%) Fecal Metabol ites (%) Metabolite Free Cor ljugated Free Con jugated Mice VI 12.2 7.8 IV 1.6 3.9 1.5 3.8 II 29.2 15.0 III 3.0 5.1 3.3 5.6 Rabbit VI 11.1 6.5 IV 5.4 5.1 3.5 3.2 II 23.0 9.9 III 3.1 8.3 3.0 8.0 Sheep VI 23.5 12.1 IV 1 .1 1.9 1.6 2.6 II 18.6 4.4 III 4.1 6.5 3.0 4.7 [2-11+C]-Benomyl was applied to soil and turf. After 3 months, the parent compound was not detected in soil. Soil residues consisted of [2-11+C]-MBC and [2-li+C]-AB. The "half-life" of the total labeled residues was about 6-12 months on bare soil and 3-6 months on turf (Baude et al . , 1974). When benomyl was applied to plant foliage, only MBC was found (Baude et al., 1973). Some studies indicated that benomyl hydrolysis was not rapid in plant tissues nor in aqueous solution. The complete hydrolysis indicated by others may be the result of extraction procedures used (Jhotty and Singh, 1972). From air over moistened benomyl, a volatile compound was trapped in hexane and identified by GLC on two different columns and by infrared spectroscopy as butyl isocyanate (BIC) (Hammerschlag and Sisler, 1973), 2-ll+C-Benomyl was fed to a rat. After hydrolysis, the urine contained 5-hydroxy analog (III). Similar results were obtained with 2-11*C-MBC. Three conjugates were indicated. When administered to a beagle dog, benomyl was metabolized to 5-HBC. The dairy cow metabolized benomyl to 4- and 5-HBC. In the eggs of chickens fed benomyl, only 5-HBC was observed at the high (25 ppm) feeding level. No residues (<0.02 ppm) were observed in eggs from hens on the low (5 ppm) feeding level (Gardiner et al . , 1974). Dwarf pea plants were grown in nutrient solutions and root-treated with li+C-benomyl . MBC was present in large quantities. Hydrolysis of plant-bound residues with hot NaOH released half the bound label, part of which was 2-aminobenzimidazole (Siegel and Zabbia, 1972). 30 31 Cells of apple and cucumber leaves were exposed in nutrient media to MBC. Cytoplasmic uptake by apple cells was constant for 26 h, whereas uptake by cucumber cells was negligible. When applied to cucumber leaves, 1.56% of the [ring-14C]-MBC was metabolized to C02 (Solel et al . , 1973). Benomyl decomposes in many solvents to give MBC as a precipitate. Solvents included: benzene, ethyl ether, ethanol , acetone, ethyl acetate, methylene chloride, chloroform (Chiba and Doornbos, 1974). Benomyl was taken from sprays, waxes, and alkaline peeling solutions and brought to pH 6 with 0.1N HC1 . The precipitate was removed and analyzed. After characterization on the basis of evidence derived from infrared, nmr, and mass spectra, verification of the structure as that of STB was made by synthesis and comparison of the preceding physical evidence plus m.p. or decomposition point. Standing alkaline solutions also produced a second precipitate which was identified as BBU (White et al . , 1973). PARBENDAZOLE In cattle and sheep, one of the major parbendazole metabolites was identified as compound II by means of UV and mass spectra. The other major metabolite in sheep and cattle was identified as the glycol, compound III. Other metabolites obtained from sheep were the alcohols, compounds IV, V and VI. The phenol VII was obtained from cattle (Dunn et al . , 1973). In other studies with sheep, after an oral dose of 14C-parbendazole (labeled at C-2), urine was collected and analyzed. Structures of the metabolites were determined by means of UV, IR, proton magnetic resonance, mass spectrometry and chemical synthesis. Seven metabolites were identified as compounds II, III, IV, V, VI, VII and IX. Incubation of the metabolites with glucuronidase resulted in 38% hydrolysis of the total radioactivity and supported the fact that compounds II, III and IX were excreted primarily unconjugated, whereas compounds IV, V, VI and VII were excreted mainly as glucuronides. Other studies with glusulase indicated little excretion of the metabolites as sulfates (DiCuollo et al., 1974). The metabolites identified as compounds II and VI were obtained from Cunninghamella bainieri ; and the fungus Paecilomyces sp. , produced compound VIII (Dunn et al., 1973). Other studies with C. bainieri ATCC 9244 also gave compounds II and VI (Valenta et al . , 1974T 32 H 0 I ll ■N-C-OCH3 Parbendazole (I) R i. ch3-ch2-ch2-ch2 - ii. h00c-ch2-ch2-ch2- iii. ch3-ch2-ch ch - ~ 6h 6h iv. ch3-ch2-ch2— ch - v. ch3-ch2-ch— ch2- vi. ch2-ch2-ch2-ch2- OH VII. CH3-CH2-CH2- CH2- VIII. CH3-C — CH2- CH2- H- H- H- H- IX. H00C-CH2-CH -CH2- H- HO- H- H VI II / IX '4 ^ch3-£h-ch2-ch7J VIII VII IV III 33 THIOPHANATE When thiophanate or the methyl analog was irradiated with UV in the solid state, no reactions occurred. When exposed in aqueous solution to UV and sunlight, both fungicides were converted to their respective alkyl benzimidazol-2-yl carbamates (EBC and MBC). Residues of the fungicides on cotton plants, following spray appli- cation, were also converted by sunlight to EBC and MBC (Buchenauer et al., 1973). In soil, thiophanate underwent rapid conversion to MBC. Conversion was reduced by treating the soil with steam or increasing the alkalinity. At pH 7.4 the rate was more than 4 times that at pH 5.6. Very little (less than 1%) of ring-14C-labeled MBC was converted to lt+C02 even after 51 days incubation of soil. When 11+C-methyl label was used, about 15% of the label appeared as CO2 after 51 days (Fleeker et al . , 1974). Photoisomerization of benzimidazole gave rise to two compounds iden- tified as the dimers XII and XIII (see diagram on page 31) (Cole et al., 1973). 34 BENTAZON [3-Isopropyl -1H-2 ,1 ,3-benzothiadiazin-4(3H)-one-2,2-dioxide] After oral administration to rats, bentazon was rapidly absorbed. Excretion, primarily (84%) in urine, was rapid and largely unchanged bentazon. Two metabolites, one of which may be the N-glucuronide of bentazon, were detected. Traces of radioactivity were also found in the bile (BASF, 1973; Chasseaud et al . , 1972). When 11+C-bentazon was applied to spring wheat, Opal variety, the active ingredient was taken up via roots from a nutrient solution. At harvest, 173 days after test start, two-thirds of total activity could not be extracted from the straw. The remainder consisted of soluble complexes of the active ingredient and of free bentazon. Fifty days after foliar spraying of soya plants, more than 40% of the methanol extractable residues was in the form of complexes of mono- or ol igo-saccharides with hydroxylation of the aromatic ring (BASF, 1973). Bentazon does not persist in loamy sand soil. Within 15 weeks, bentazon broke down quantitatively at room temperature and 15% soil moisture. Anthranilic acid-isopropylamide was identified. This broke down quickly (BASF, 1973). 35 N-Benzoyl chloride-N/-(2,4,6-trichlorophenylhydrazide) The photolytic half-lives of this compound were 12 and 16 h, with and without a filter. Under the experimental conditions, using a combin- ation of TLC, GLC and MS, eight products were identified: I. Benzoyl 2-(2,4-dichlorophenyl )hydrazide II. 2,4,6-trichlorobenzophenone III . l^-(2,4,6-trichlorophenyl )benzamide IV. P[-(2,4-dichlorophenyl )benzamide V. N-(2,6-dichlorophenyl )benzamide VI. 2,4-dichlorobenzophenone VII. 1 ,2-dibenzoyl-l-(2,4,6-trichlorophenyl hydrazine VIII. 1 ,2-dibenzoyl-l-(2,4-dichlorophenyl )hydrazine (Koshy et al . , 1975) 36 BENZOYLPROP-ETHYL (Suffix) [Ethyl N-benzoyl N-(3,4-dichlorophenyl )- 2-aminopropionatel lltC-Benzoyl prop-ethyl was applied to foliage of wheat (Triticum aestivum), oat (Avena sativa), and barley (Hordeum vulgare) seedlings. Metabolism of herbicide was similar in all three plant species. Extracts of wheat seedlings sampled up to 15 days after treatment indicated the presence of as many as five metabolites: des-ethyl analog and its 3-glucoside, debenzoylated analog, g-hydroxybenzoic acid as a conjugate, and one unidentified compound (Beynon et al . , 1974d). In other studies with labeled herbicide and spring and winter wheat, the crop was sampled at harvest and the following compounds were observed: N-benzoyl 3,4- dichloroaniline; benzoyl prop; several sugar complexes. Other products present were not identified (Beynon et al . , 1974a and c). In soil, benzoyl prop-ethyl was de-ethylated. The acid, upon standing, became tightly bound to the soil before undergoing slow debenzoylation to N-(3,4-dichlorophenylalanine) and benzoic acid. 3,4-Dichloraniline which formed was present as humic acid complexes. Polar products observed were shown to arise from the dichloroaniline. No 3,31,4,41- TCAB was detected. The rate of degradation for various soils varied from 1 to 12 weeks (Beynon et al . , 1974a, b,c). After 14C-benzoyl prop-ethyl was applied to the leaves of cereal plants, only 7% of the total applied radioactivity moved from the treated leaf during a 3-day period. Movement of this herbicide occurred in the form of the acid and acid conjugates (Jeffcoat and Harries, 1973). 37 BHC (HCH) [1,2,3,4,5,6-Hexachlorocyclohexane] When a, 6, y and 6 isomers of BHC were orally administered to rats, some B isomer accumulated in the tissues, presumably from isomeriza- tion. The level of accumulation was B>>a>y>6 (Kamada, 1971). y-PCCH was metabolized by rats primarily to 2,4,5-TCP and a trace of 2,3,5-TCP; B-BHC was metabolized to 2,4,6-TCP. When a- and 6-BHC were administered to rats, 2,4,5- and 2,4,6-TCP formed. The y-isomer was metabolized to 2,4,6-, 2,3,5- and 2,4,5-TCP and 2,3,4,5- and 2,3,4,6-tetrachlorophenol (TTCP) in addition to a configurational isomer of 2,3,4,5,6-pentachlorocyclohex-2-en-l-ol (Freal and Chadwick, 1973). When rats were fed y-BHC plus DDT, there was significantly more excretion of 2,4,5-TCP and 2,3,4,6- and 2,3,4,5-TTCP than in the absence of DDT (Chadwick and Freal, 1972). Wistar rats were orally administered a-BHC. Controls and treated rats were sacrificed; the livers were removed, homogenated and then centrifuged for 10 min at 12,000g. The supernatant was centrifuged at an average 100,000g (140,000g maximum) for 90 min. Portions of these fractions were dialyzed or gel-filtered. When these prepara- tions were incubated with labeled (ll+C, 3H, or 36C1) a-BHC in the presence of air (2 h, 37C, and pH 7.4), 5 to 10% of the label was converted to water-soluble materials. Longer incubation, more alkaline pH, and preparations from treated rats increased the amount of water-soluble labeled materials. GSH was required for the reaction. These studies indicated that dechlorination was part of the overall reaction and that four atoms of chlorine per molecule HCH were elim- inated. Although the main product of the reaction was not established, there was evidence that it was a conjugate of glutathione with the BHC-moiety rendered aromatic, probably S-2,4-dichlorophenylglutathione. Alkaline hydrolysis produced a thiophenol or mixture of thiophenols (Kraus et al . , 1973; Noack and Portig, 1973; and Portig et al . , 1973). After adaptation of rats to lindane, 14C-lindane was orally admin- istered. Fat, kidney and musculature were the main sites of deposition. Pituitary and thyroid glands had highest activity. Differences between cortex, stem and cerebellum were marked. The metabolites y-PCCH, pentachlorobenzene and hexachlorobenzene were observed. Large amounts of conjugates and strongly polar, hexane-soluble metabolites were also present in feces, urine and organs. Glucuronides and other unidentified water-soluble conjugates were observed. Half of the administered lindane was excreted within 3 or 4 days (Seidler et al . , 1975). 38 Studies with mice indicated differences in excretion rates of a, 6 and y isomers. The data indicated that metabolism of the y-isomer was greater than the 3-isomer and that the a-isomer was intermediate. Most metabolites from the y- and B-BHC were conjugated as sulfates and glucuronides . After hydrolysis, chlorophenol s were obtained. About 25% of the total metabolites in urine was 2,4,6-trichlorophenol . 2,4-Dichlorophenol was also prominent. From 3-HCH, traces of 2,4,5- trichlorophenol were also identified. Free chlorophenols were also observed. One behaved like 2.4-dichlorophenol (Kurihara and Nakajima, 1974). Uniformly labeled lindane-14C was fed in gelatin capsules to rabbits for 26 weeks. About 54% of the label was excreted in urine and 13% in feces by the end of the feeding period. Of the urinary metabolites, 55% was ether-soluble, in which 14 chlorophenols were observed. Four were identified by infrared: 2,3,5-, 2,4,5- and 2,4,6-tri- chlorophenol and 2,3,4,6-tetrachlorophenol . Three were identified by gas chromatography and mass spectrometry: 2,3- and 2,4-dichloro- phenol and 2,3,4,5-tetrachlorophenol . Seven chlorophenols were tentatively identified by gas chromatography: 2,5-, 2,6- and 3,4-dichlorophenol ; 2,3,4-, 2,3,6- and 3,4,5-trichlorophenol ; and pentachlorophenol . Six chlorobenzenes were also observed: 1,2- dichlorobenzene; 1 ,2,4-trichlorobenzene; 1,2,3,4-, 1,2,4,5- and/or 1 ,2,3,5-tetrachlorobenzene; and pentachlorobenzene (Karapally et al . , 1973). After injection of uniformly ll+C-labeled a-BHC into adult rats, urine and feces were collected. In 4 weeks, 65% of the label was excreted in urine and 16% in feces. Most of the urinary metabolites apparently contained chlorine. Nearly all of the fecal lkC was unchanged a-BHC (Noack et al . , 1975). Urinary metabolites obtained in other studies indicated that the proportion of free chlorophenols was 5% or less of all urinary BHC metabolites. Both 2,4,5- and 2,4,6-trichlorophenol were identified by UV, IR and cocrystal lization with authentic compounds. There were indications that 2,3,5-tri- chlorophenol and 2,3,4,6-tetrachlorophenol were also present but this could not be confirmed. After alkaline and acid hydrolysis, 2,4,6-trichlorophenol was found. The presence of 2,3,4,6-tetra- chlorophenol, 2,4,5- or 2,3,5-trichlorophenol were indicated. The presence of dichlorothiophenols was also observed (Koransky et al., 1975). Incubation of lindane with rat liver homogenates produced hexa- chlorocyclohexene (HCCH). When rats were administered HCCH, previously observed lindane phenolic metabolites were observed: 2,4,6-, 2,3,5-, and 2,4,5-trichlorophenol ; 2,3,4,5- and 2,3,4,6- tetrachlorophenol. In addition to these, 2,3,4,5,6-pentachloro- 2-cyclohexen-l-ol was also found. Similar results were obtained with in vitro studies. The enzyme system involved in the initial 39 dehydrogenation of lindane to HCCH was characterized as a hepatic microsomal MFO and a cytochrome P-450 which requires molecular oxygen and NADPH (Chadwick et al . , 1975). When pentachlorobenzene was orally administered to rabbits, uniden- tified dechlorinated compounds appeared in feces and tissues. In urine, data indicated the presence of p_-chlorophenol , pentachloro- phenol and some less chlorinated benzenes. After administration of 1 ,3,5-trichlorobenzene to rabbits, monochlorobenzene was expired and found in feces and tissues. Urine contained 2,4,6-trichlorophenol , 4-chlorophenol , 4-chlorocatechol and perhaps other monochlorophenols (Parke and Williams, 1960). When the three tetrachlorobenzenes were orally administered to rabbits in arachis oil they were partly excreted unchanged in feces. The 1 ,2,3,4-tetrachlorobenzene was slowly metabolized to 2,3,4,5- tetrachlorophenol which was excreted in urine as such and conjugated. In 6 days, 43% of the 1 ,2,3,4-tetrachlorobenzene was oxidized. 1 ,2,3,5-tetrachlorobenzene was oxidized (5% in 6 days) to the 2,3,4,6-tetrachlorophenol . Approximately 2% of the administered 1 ,2,4,5-tetrachlorobenzene was oxidized to 2,3,5,6-tetrachlorophenol in 6 days. Some dechlorination products were also probably formed. The phenols were excreted as glucuronides and sulfates as well as unconjugated (Jondorf et al . , 1958). Percent of dose excreted Tetrachlorobenzene administered Glucuronide Sulfate Mercapturic Free 1,2,3,4- 1,2,3,5- 1,2,4,6- 30 6 4 3 2 1 A O O — ■ — ■ — ' 00 The mussel Mytil us edulis was ex posed to lkC- •labeled lindane. Analyses indicated the formation of two highly polar compounds amounting to about 3% of the lindane. Neither metabolite was identified (Ernst, 1975). 14C-Lindane was added to a nutrient solution in which lettuce plants were grown. Radioactivity extracted from the nutrient solution after 4 weeks amounted to 7.8% of the applied material. About 14.1% of the applied radioactivity was recovered from the plants and the remainder was lost, possibly by evaporation. Of the material recovered from the nutrient solution, 82% was unchanged lindane; 15%, polar material; and 3%, nonpolar. The polar material was identified with the aid of GLC/MS as 2,3,4,6-tetrachlorophenol (<1%), pentachlorophenol (ca. 5%) and conjugated pentachlorophenol (1%). An unidentified highly hydrophilic substance (8%) was also present. In the nonpolar fraction, there was 1 ,2,3-trichlorobenzene, 1 ,2,3,4-tetrachlorobenzene, pentachlorobenzene, hexachlorobenzene, 40 Y-pentachlorocyclohexene and an unidentified compound that is probably a hexachlorocyclohexene. From the lettuce plants, the extracted radioactivity consisted of unchanged lindane (77%), polar material (20%), and nonpolar material (about 3%). Again, the polar fraction contained free 2,3,4,6-tetrachlorophenol (ca. 1%), conjugated phenols including a tetrachlorophenol (ca. 3%), pentachlorophenol (ca. 4%) and a highly polar unidentified compound (11 to 12%). The nonpolar material consisted of 1 ,2,3-trichlorobenzene, 1,2,4-tri- chlorobenzene, pentachlorobenzene, y-pentachlorocyclohexene and a hexachlorocyclohexene. There were also indications of a tetra- chlorobenzene (Kohl i et al . , 1976). S-R 0H 41 Wheat plants were grown from seeds. From the roots, metabolites identified included 1 ,3,5-trichlorobenzene; 1 ,2,4-trichlorobenzene; 1 ,2,3-trichlorobenzene; 1 ,2,3,4-tetrachlorobenzene; 1,2,4,5- and/or 1 ,2,3,5-tetrachlorobenzene; y-PCCH; and pentachlorobenzene. The presence of m- and p_-dichlorobenzene were also indicated. Also observed, but lacking confirmation because they appeared in quanti- ties too small, were a number of chlorophenols: pentachlorophenol ; 2,3,5,6- and/or 2,3,4,6-tetrachlorophenol ; 2,3- and 2,4-dichlorophenol ; 2,3,4- and/or 2,4,5-trichlorophenol ; and 2,4,6-trichlorophenol (Balba and Saha, 1974). Use of lindane for protection of stored wheat grain against insects has been suggested. When the fate of lindane residues in wheat flour under normal conditions of bread making was studied with 14C-labeled compound, about 75 to 82% of the radioactivity was retained by the baked bread and 94% of this was present as lindane. Identified in the bread were: y-PCCH; 1 ,2,4-trichlorobenzene; 1 ,2,3,4-tetrachloro- benzene; 1,2,4,5- and/or 1 ,2,3,5-tetrachlorobenzene (Saha, 1974). After treatment with 11+C-labeled lindane, wheat grains were stored in closed containers at varying temperatures and times, with and without added water. Less than 3% of the lindane was degraded. Small amounts of y-PCCH were present as residues. No other products were detected (Saha and Lee, 1974). Houseflies were dosed topically with 14C-y-BHC. Homogenation and chromatography of the extract indicated the presence of S_-2,4- dichlorophenyl glutathione. Studies with grass grubs gave similar results. Houseflies and grass grubs also converted y-PCCH and 6-PCCH into metabolites that had chromatographic properties identical with S_-2,4-dichlorophenylglutathione. Inhibitors and colorimetric assays lead to the conclusion that a PCCH is not a major intermediate metabolite of y-BHC in these insects. These studies tend to support earlier assumptions that a pentachlorocyclohexylglutathione is the initial metabolite of y-BHC (Clark et al . , 1969). A mold capable of degrading lindane was isolated but not identified. The main metabolite, short-lived, was identified as y-pentachloro- cyclohexene. The following compounds were also found in varying amounts: hexachlorobenzene; pentachlorobenzene; 1,2,3,4-, 1,2,4,5- and 2,3,4,6-tetrachlorobenzene; 1,2,3-, 1,2,4- and 1 ,3,5-trichloro- benzene; 2,3,4- and 2,4,6-trichlorophenol; 1,2- and 1 ,4-dichloro- benzene; 2,3,4,5-tetrachlorophenol ; and pentachlorophenol (Engst et al., 1974). In laboratory studies, P_. putida normally produced y-PCCH from y-BHC. In the presence of NAD, a-HCH was also formed. y-Tetrachloro- cyclohex-1-ene was observed (Benezet and Matsumura, 1973). 42 In an aerobic artificial lake impoundment, 15% of y-BHC was converted in 2100 h to the a-isomer. Under anaerobic conditions, 90% of the y-isomer was converted to a- and 6-isomers in 2100 h (Newland, 1969). Two-thirds to three-fourths of the material lost from a calcareous soil treated with lindane was lost by volatilization as PCCH (Cliath and Spencer, 1972). Fifteen years after application of HCH to soil, samples were taken and analyzed. Isomeric composition of BHC in the soil samples was considerably different from that of technical BHC. Persistence was of the order 6>6>y>a (Stewart and Chisholm, 1971). A bacterium was isolated from rat feces and identified as Escherichia coli . When incubated in trypticase soy broth with lindane, 10% of the lindane was metabolized to y-PCCH. Structure was confirmed by synthesis, gas chromatography and mass spectra (Francis et al . , 1975). The relationship between concentrations of BHC in the medium and the concentration in bacteria (living and dead) is given by the relation- ship CB = KCM Cg = concentration in bacteria (ppm) C^ = concentration in media (ppm) a-BHC K = 4.2 x 101 n = 0.7 6-BHC K = 3.7 x 102 n = 0.7 Y-BHC K = 2.6 x 101 n = 1.0 The process is apparently not energy dependent (Sugiura et al . , 1975). An apparent half-life equal to 16 days was calculated for y-BHC degradation in an anaerobic artificial impoundment. Under aerobic conditions, degradation was considerably slower. Onset of degradation occurred at 264th and 840th hour anaerobically and aerobically, respectively. After 2100 h of incubation of lindane in anaerobic and aerobic sediments, 83.2 and 19.0% respectively, of the added 14C activity was volatilized. Chromatograohy of the hexane-acetone extract of the aerobic impoundment sediment showed only y- and a-BHC. With the anaerobic sediment, chromatography of the extract showed a-, y- and 6-BHC. These studies indicated that y-BHC could undergo isomerization in. natural systems. Thermodynamic stability of the isomers is of the order 3>6>a>y (Newland et al . , 1969). Lindane was added to a sandy loam soil and incubated for 6 weeks under flooded conditions. The soil and water was extracted and chromatographed. Five peaks were observed and the retention times 43 corresponded to 1 ,2,4-trichlorobenzene, 1,2,3,5- and/or 1,2,4,5- tetrachlorobenzene, 1 ,2,3,4-tetrachlorobenzene, y-PCCH and y-3,4,5,6- tetrachlorocyclohexene (y-BTC). GC/MS was used to confirm the identities of the compounds except 1,2,3,5- and/or 1 ,2,4,5-tetra- chlorobenzene whichwerenot present in sufficient quantity (Mathur and Saha, 1975). When pentachlorocyclohexene (PCCH) was synthesized by partial additive chlorination of chlorobenzene, combined gas chromatography- mass spectrometry revealed that at least five different Isomers of pentachlorocyclohexene had been formed. Dechlorination products of various isomers of BHC or PCCH in NaOH and in pyridine were compared. Results indicated that 3-PCCH was the monodechlorination product of a-BHC (Munster et al . , 1975). The isomerization of 1 ,3,4,5, 6-pentachlorocyclohexene-l (y-PCCH) was studied in dimethyl sulfoxide. After a long reaction time, starting with any isomer, y-PCCH became the most abundant component. Three new isomers were also isolated for the first time (Kurihara, et al., 1974b). Recent studies have also shown that lindane forms a colored complex with montmorillonite clay (Haque and Hansen, 1975). 44 Pi phenyl [Bi phenyl] Adult male Wistar rats were fed a diet containing biphenyl. Urine was collected and analyzed. Five metabolites were isolated and identified by means of melting point depression, chemical test, and infrared spectra as: IX. 4-hydroxydi phenyl X. 4,4-dihydroxydiphenyl XII. 3,4-dihydroxydi phenyl XV. p_-(e-D-glucuronosidodiphenyl ) XVI. N-acetyl-p_-(S_-di phenyl )-L-cysteine (West et al., 1956) Studies with rabbits fed biphenyl, showed that the 3-hydroxybi phenyl (XI) and a mixture of monomethylated analogs of 3, 4-dihydroxybi phenyl (XIII and XIV) were present in urine (Raig and Ammon, 1972). The ability of several phyla of marine organisms to metabolize biphenyl was investigated with in vitro studies: mature skate (Raja ocellata) , mussels (Mytilus edulisj, starfish (Asterias vulgaris), rock crab (Cancer irroratus), red crab (Gerydon quinquidens) , lobster (Homarus americanus), brook trout (Salve! inus fontinal is), and plankton that consisted mainly of large zooplankton. Tissue homogenates and intact plankton samples were used. Biphenyl was metabolized in vitro by all tissues primarily to 4-hydroxybi phenyl (IX) and to some extent to 2-hydroxybi phenyl (II). Rates of formation of the 4-hydroxy analog ranged from a high of 400 n moles/g skate tissue to a low of 2 n moles/g starfish tissue (Willis and Addison, 1974). Metabolism of biphenyl by Pseudomonas putida apparently proceeded by way of 2 , 3-di hydro-2 , 3-di hydro xybi phenyl (III), 2, 3-dihydroxybi phenyl (IV), and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (V) to benzoic acid (VI) (Catelani et al . , 1971 and 1974). The presence of either 2-hydroxypenta-2,4-dienoate (VII) or 4-hydroxy-2-oxovalerate (VIII) was also indicated (Catelani et al . , 1973). 45 3: o o * z: o o O II g / V 3 7> H>^ 46 BLASTICIDIN S After application to rice plants via culture solution, Blasticidin S(I) was degraded. A small amount of cytomycin(III) and the deamino- blasticidin S analog II were also observed. When incubated with micro- organisms, Blasticidin S was also degraded: soil bacterium (unident- ified) > Ps. aernginosa > Phytophythora parasitica > Fusarium oxysporum > soil fungus (unidentified) > Ps. oval is 1002 > Ps. marginal is. The main products after exposure to washed mycelia of a soil fungus were compounds II, III, and IV (Yamaguchi et al . , 1972). In other studies, a strain of Aspergillus fumigatus, isolated from soil, converted blasticidin S into four metabolites. One was identified as deaminohydroxyblasticidin S ( 1 1 ) . Another was identified as deamino- hydroxycytomycin(IV) (Seto et al . , 1966). When hydrolyzed with acid, compound III gave rise to uracinine(V) and pseudoblastidone(VII) ; XI gave uracinine(V) and blastidone(VIII); blasticidin S(I) gave cytosine(IX), cytosinine(VI) , blastidic acid(X); cytomycin(III) gave pseudoblastidone(VII) (Seto et al., 1966). Cytosinine acid hydrolysis gave cytosine, levulinic acid, NH3, and C02- Analysis of this data plus that derived from Pt02 reduction and ozonolysis of the N,j^- diacetyl methyl ester permitted assignment of the structure of cytosinine. Similarly, acid hydrolysis of uracinine gave uracil and permitted assignment of a structure (Otake et al . , 1966a). Acid hydrolysis of blasticidin S gave cytosinine and blastidic acid. Products of alkaline hydrolysis and Pt02 hydrogenolysis permitted structural assignments to blasticidin S and cytomycin (Otake et al . , 1966b). 47 I / \ m i- C / 2: *J : — \ z-t_> in c o o o ^ c o o ■o 0 II I 10 CO o 48 BOTRAN (DCNA) [2,6-Dichloro-4-nitroanil ine] Incubation of botran with cultures of bacteria indicated that metabolism proceeded via 2,6-dichloro-£-phenylenediamine (DCPD) to 4-amino-3,5-dichloroacetanil ide (ADCAA) (Van Al fen and Kosuge, 1974). Cl- ■Cl ■CI DCPD ADCAA 49 BPBSMC (Chevron RE 11775) [3- (2-Butyl phenyl )N-benezenesulfenyl N-methyl carbamate] BPMC (Chevron RE 5365) [3- (2-Butyl phenyl )N-methyl carbamate] Male albino rats (Sprague-Dawley strain) were orally administered lkC- carbonyl and ll+C-butyl-labeled BPBSMC and BPMC in dimethyl sulfoxide. Urine was collected for 48 h and then analyzed. Quantitatively the major urinary products were identified in the order 2-(3-hydroxyphenyl ) butan-2-ol (4), the butan-3-ol analog (5), and then the butan-1-ol analog ( 3 ). In addition to these, compounds 2 and 6 to 18, inclusive, were also observed and identified using syntheses and infrared, electron impact mass, chemical ionization and NMR spectra and TLC (Cheng and Casida, 1973). When BPBSMC was exposed to either UV, sunlamp, or sunlight irradiation for one hour, six compounds formed. BPMC degraded only under UV irradiation to form six or more products of which only compounds 2 and 18 were identified. BPBSMC yielded compounds 2, 10, 18, 19, and 22. Under more rigorous conditions, compounds 2, 4, 10, 12, 18, 19, 20 and 21 were observed (Cheng and Casida, 1973). 1 . BPBSMC 2. 3-(2-butyl)phenol 3. 2-(3-hydroxyphenyl )butan-l-ol 4. 2-(3-hydroxyphenyl )butan-2-ol 5. 2-(3-hydroxyphenyl )butan-3-ol 6. 2-(3-hydroxyphenyl )butan-4-ol 7. 2-(3-hydroxyphenyl )butan-3-one 8. 2-(3-hydroxyphenyl )butanoic acid 9. 3-(3-hydroxyphenyl jbutanoic acid 10. BPMC 11. 3-(2-butan-l-ol )N-methyl phenyl carbamate 12. 3-(2-butan-2-ol ) N-methyl phenyl carbamate 13. 3-(2-butan-3-ol )N-methyl phenyl carbamate 14. 3-(2-butan-4-ol ) N-methyl phenyl carbamate 15. 3- (2-butan-3-oneTN-methyl phenyl carbamate 16. 2- (3-N-methyl carbamoyl phenyl )butanoic acid 17. 3- (3-N-methyl carbamoyl phenyl jbutanoic acid 18. 3-butyl N-hydroxymethyl phenyl carbamate 19. 3-(2-butyl )phenyl carbamate 20. 3-(2-butyl )N-benzenesulfinyl N_-methyl phenyl carbamate 21. 3-(2-butyl )N-benzenesulfonyl N-methyl phenyl carbamate 50 BROMOPROPYLATE (Acarol , Phenisobromolate, Neoron, Isopropyl 4 .41- dibromobenzilate) [Isopropyl 2-(4,41-dichbromophenyl )-2- hydroxyacetate] CHLOROPROPYLATE (Isopropyl 4,41-dichlorobenzilate) [Isopropyl 2-(4, "X^dTchTorophenyl )-2-hydroxyacetate] When chloropropylate was fed to a cow, the major route of elimination was via urine (>80% of total dose). About 28% of the material was identified as 4,41-dichlorobenzil ic acid and 55% as conjugates, not further identified. Chloropropylate was stable (up to 7 h) in rumen fluid but decomposed in 10,000xg supernatant fraction of beef liver (St. John and Lisk, 1973). When exposed to bromopropylate, spider mites (Tetranychus urticae Kock) and house flies (Musca domestica L.) metabolized this material to the bromine analogs of benzilic acid, benzhydrol , benzophenone, and benzoic acid (Al-Rubae and Knowles, 1972). Spider mites and house flies also metabolized chloropropylate to the corresponding chlorine-containing analogs of benzilic acid, benzhydrol, benzophenone, and benzoic acid (Al-Rubae and Knowles, 1972). 51 BROMOXYNIL [3,5-Dibromo-4-hydroxybenzonitrile] IOXYNIL [3,5-Diiodo-4-hydroxybenzonitrile] Labeled bromoxynil was applied as the octanoate to wheat (Triticum vulgare var. Kloka). Under outdoor conditions, when ring-labeling was used, 88% of the radioactivity was gone in 28 days. Using 11+C-cyano labeling and 11+C-ring labeling, the studies indicated elimination of label occurred more rapidly with the former and that metabolic attack occurred on the cyano group (Buckland et al . , 1973a). After application to leaves of wheat seedlings, bromoxynil octanoate was initially hydrolyzed. This was followed by hydrolysis of the cyano group to the amide and acid and decarboxylation; replace- ment of bromine by hydroxy; and replacement of bromine by hydrogen (Buckland et al . , 1973b). When exposed to a flexibacterium, strain BR4, bromoxynil was rapidly degraded. After five weeks, only 5% of the herbicide remained. The benzamide and benzoic acid analogs were identified. A third metabolite was not identified (Smith and Cullimore, 1974). In other studies, when the octanoate ester of bromoxynil was applied to soils, 80% of lt+C-label in the cyano group and as much as 63% of luC-ring label were liberated as carbon dioxide. Small amounts of benzamide and benzoic acid analogs were detected (Collins, 1973). At 25C, 50% of bromoxynil applied to Regina heavy clay was degraded in 2 weeks. The amide and acid were detected (Smith, 1971). Ioxynil was degraded in a clay loam with high organic matter content. Most of the 14C-label, both cyano and ring, was recovered as lt+C02. Mercuric chloride (10_5M) and p-chloromercuribenzoate (5xlO"5M) inhibited production of ^C02. Ferricyanide was slightly inhibitory at lO'^M. The benzamide and benzoic acid analogs were identified as metabolites (Hsu and Camper, 1975). 52 BUSULFAN [1,4-Butanediol di (methylsulfonate)] The hydrolysis of busulfan (I) proceeded through the unstable 4- (methyl sulfonate)butanol (II) to the cyclic tetrahydrofuran (III). At pH 3 and 7.4 and 37C, the cyclization reaction was determined to be first order with a half-life of 12 min (Feit and Rastrup-Andersen, 1973). CH3S020-(CH2)l+-0S02CH3 >- CH3S020-(CH2)4-0H I II HtC CHo I I ■or III 53 C-2307 [0,0- Dimethyl 0-3-(N-methoxy-N-methyl-cis-crotonamide) phosphate] Rats were treated with 32P- and lt+C-labeled C-2307. With both labels, r[-dealkylation occurred to produce the unsubstituted amide derivative. An intermediate, thought to be the N-hydroxy-N-methyl analog, was detected (Bosik, 1971). 54 CAPTAN [N-Trichloromethyl thio)-cyclohex-4-ene-l ,2-dicarboximide] FOLPET (Phaltan) [N-(trichloromethylthio)phthal imide] 1LtC-Captan, orally administered to rats, was rapidly metabolized. Urinary metabolites four days after oral dosing consisted of thiazo- 1 idine-2-thione-4-carboxylic acid (18.6%), dithiobis (methane- sulfonic acid) (54%) and its disulfide monoxide (13.8%) . After ip administration, the latter two metabolites were not seen. T. viride and R^. solani degraded captan by a pathway different than in rats (DeBaun et al . , 1974a and b). Captan was degraded in wort. Tetrahydropthal imide was detected chromatographically and HC1 was inferred from the pH change. CS2 and H2S were not observed (Davidek et al . , 1973). Hydrolysis of captan in water was pH independent in the range 2-6 and exhibited a half-life of less than one day at 27C. Products of hydrolysis indentified were 4-cyclohexene-l ,2-dicarboximide, sulfur and chloride (Wolfe et al . , 1974). Folpet was degraded in wort with formation of phthalimide. detected but CS2 and H2S were not observed (Davidek et al . HC1 was 1973). H + RSSCCI3 0 H " I H2C CH-C-N-CHo-COOH I I * S\r/N"CsCH2-CH2-CH-C00H 1 Peptidases H,C \^/ CH-COOH NH Thiazol idine-2-thione 4-carboxyl ic acid H03S-CH2-S-S-CH2-S03H Dithiobis(methanesulfonic acid) monosulfoxide CO- 55 CARBARYL (Sevin) [1-Naphthyl N-methyl carbamate] Selected human tissues were incubated with carbaryl labeled in the ring or in the [[-methyl group. Five of the 11 metabolites were identified. Male Female Li K Lu Li P V U UL Dihydro-dihydroxycarbaryl glucuronide + + + + Hydroxycarbaryl glucuronide + + + Napthyl glucuronide + + + + + tr Hydroxycarbaryl sulfate + + + Naphthyl sulfate + + + + + tr tr Li = Liver P = Placenta K = Kidney V = Vaginal mucosa Lu = Lung U = Uterus UL = Uterine Leiomyoma (Chin et al . , 1974) Discrepancies between toxic level of carbaryl in various studies were the result of varying absorption associated with the mode of adminis- tration and vehicle (Pekas and Giles, 1974). Absorption from perfused swine intestinal loops % Absorption in 1 h Baygon Carbaryl Carbyne Mobam Zectran 55-56 67-69 66-71 64-70 66 (Pekas, 1974) Studies have shown that stomach of a fasted rat 1-naphthol by intestine When injected into cats, as sulfate conjugates. some carbaryl can be absorbed intact from the (Casper et al . , 1973). The glucuronidation of was also observed (Bock and Winne, 1975). 1-naphthol was excreted in urine almost entirely When injected in pigs, 1-naphthol was excreted as the glucuronide and sulfate in the ratio of 2:1 (Cape! et al . , 1974) Treatment of rats with l-naphthyl-glucoside-14C showed that hydrolysis preceded formation of sulfate and glucuronide formation (Dorough et al . 1974). After 72 h of incubation with HEL (human embryo lung) cell cultures, carbaryl was almost completely altered but not to C02. The major metabolite was 1-naphthol. Other metabolites included 4-hydroxy-, 5-hydroxy-, 1 ,4-di hydroxy-, and 1 ,5-dihydroxy-carbaryl and 5,6-dihydro- 5,6-dihydroxycarbaryl . Other unidentified more polar metabolites were also observed. After acid hydrolysis of the aqueous extraction phase, three compounds freed from conjugates were identified as 4-hydroxy- carbaryl , 1 ,4-naphthalenediol , and 5,6-dihydro-5,6-dihydroxycarbaryl . Carbaryl was also incubated with sonicated HEL cells and cofactors for 3 h. About 90% of the carbaryl was converted to ether soluble metabolites. Cochromatography revealed five spots which were identi- fied as 1-naphthol, carbaryl, 4- and 5-hydroxycarbaryl and 5,6-dihydro- 5,6-dihydroxycarbaryl . The controls also contained 1-naphthol (Lin et al., 1975). Incubation of rat enzyme preparations with carbaryl indicated the formation from carbaryl of C02 and three unidentified hydroxy deriv- atives, free and conjugated (Palut et al . , 1970). In vivo resistance varied substantially with age and sex in the sar- cophagids (S. bullata Parker, S. crassipalpis Macquart, S^. argyrostoma) and there was a corresponding variation in in vitro ring hydroxylation of carbaryl. In Phornia regina (Meigen), carbaryl resistance and ring hydroxylation also increased with age but N-demethylation remained constant. In vitro ring hydroxylation was lower and N-demethylation was higher in Musca autumnal is than in the sarcophagids or Phormia. Optimal incubation was at 30C and pH 7.3 for ring hydroxylation and N-demethylation. The I50 values of carbaryl to brain cholinesterase ranged from 1.2 x 10-7 to 6.6 x 10"7 M (Brattsten, 1972). Houseflies were allowed to feed on 1-naphthol in milk plus sucrose. Ionophoretic studies indicated the presence of a sulfate, glucoside, phosphate and glucoside phosphate conjugate. Blowflies (Lucilia sericata) and grass grubs (Costelytra zealandica) behaved in a similar manner (Heenan and Smith, 1974) . Alfalfa leafcutting bees (Megachile pacifica) were exposed to carbaryl. In the water-soluble fraction, five unidentified metabolites were observed. The organosol uble fraction contained two unidentified metabolites as well as 5,6-dihydro-5,6-dihydroxycarbaryl , N-hydroxy- methyl carbaryl , 4-hydroxy- and 5-hydroxy-carbaryl , N-hydroxycarbaryl and 1-naphthol (Guirquis and Brindley, 1975). Male and female Periplaneta americana metabolized injected 11+C-carbaryl to about the same extent as measured by 1UC02 (Cocks, 1974). In pond water, carbaryl rapidly hydrolyzed to 1-naphthol. One bac- terium, possibly a flavobacterium, rapidly degraded 1-naphthol. Of 57 58 three compounds observed, two were identified as a hydroxycinnamic acid and salicylic acid (Hughes, 1971). In other studies, bacterial isolates from river water were used. When ^C-labeled 1-naphthol was used, 11+C02 was observed, indicating rupture of the naphthyl ring. Also isolated and identified by IR, NMR and mass spectroscopy was 4-hydroxy-l-tetralone (Bollag et al . , 1975). Carbaryl and 1-naphthol are stable in weakly acid solutions. In basic solutions, 1-naphthol turns yellow and then amber. Photo- oxidation of 1-naphthol gave rise to 2-hydroxy-l ,4-naphthoquinone. Hydrolysis studies with carbaryl indicated a difference between sea water and NaOH solution (Wauchope and Haque, 1973). pH °C Obs. T1/2 k2 x 102 10.0 12 10.0 25 10.0 35 9.8 25 9.5 25 9.2 25 9.0 25 Water) 8.0 3.5 8.0 17 8.0 20 8.0 28 99 min 20 8 27 58 116 173 0.7 3.4 9.0 4.3 3.8 3.8 4.0 (Wauchope and Haque, 1973) 1 mo . 0 . 08 4.8 days 1 .0 3.5 days 1 .4 1.0 day 4.6 (Karinen et al . , 1967) In vitro oxidation and N-demethylation of carbaryl was observed in the Udenfriend chemical hydroxylation system. The N-methyl oxidation product, 1 -naphthyl N-hydroxymethyl carbamate, and the N^demethyl product, 1-naphthyl carbamate, were isolated and identified by mass and/or infrared spectrometry (Locke and Mayer, 1974). 59 CARBOFURAN (Furadan) [2,3-Dihydro-2,2-dimethyl-7-benzofuranyl-N-methyl- carbamate] The metabolism of carbofuran in laying hens was studied with ring- and carboxyl-^C labeling. Highest residues occurred in livers. About of ring-11+C and about 20% of carboxyl-11+C appeared in feces. About of the latter appeared as ll+C02. The following metabolites were detected in combined and/or conjugated form: 2,3-dihydro-2,2-dimethyl- 3-hydroxylbenzofuranyl N- hydro xymethyl carbamate (III); 3-hydroxy carbofuran (IV); 2,2-dihydro-2,2-dimethyl-3,7-dihydroxybenzofuran (VII); 3-ketocarbofuran (VIII); 2,3-dihydro-2,2-dimethyl-3-keto-7-hydroxbenzo- furan (IX) (Hicks, 1970). After injection of labeled carbofuran into earthworms (Lumbricus terrestris) , five radioactive materials were excreted. In addition to carbofuran and two unidentified metabolites, 3-hydroxycarbofuran and 3-hydroxycarbofuran phenol were identified (Stenersen et al., 1973). 14C-Carbofuran was applied to solutions in which the roots of 3-4 year old mugho pine were immersed. Radioactivity appeared in needles within 3 days and rose to 3.12% of the total radioactivity after 70 days. In addition to two unidentified compounds, carbofuran phenol and lesser amounts of 3-hydroxyfuran and 3-ketocarbofuran phenol were present. As the content of one compound, tentatively identified as f[-hydroxymethyl' carbofuran, leveled off, the content of carbofuran phenol increased. Although 3-ketocarbofuran was not isolated in these studies, its transient occurrence was suggested by the increase of 3-ketocarbofuran phenol as the 3-hydroxycarbofuran content leveled off. All metabolites were found conjugated as well as free (Pree and Saunders, 1974). 60 CM::;- Conjugate Conjugate 61 N-(2-To1uenesul fenyl )carbofuran [2,3-Dihydro-2,2-dimethyl-7- benzofuranyl -N-methyl -N- (2-tol uenesul fenyl )carbamate] N-(2-Toluenesul fenyl )carbofuran (I) was rapidly metabolized by white mice. Most of the administered radioactivity appeared in urine within 24 h. Most identities were confirmed by cochromatography in at least four different solvent systems. In the urine were: N-(2-toluenesul fenyl )-3-ketocarbofuran (VI ) ; 3-hydroxycarbofuran TVIII); 3-ketocarbofuran (X); 3-hydroxy-N-hydroxymethylcarbofuran (VII); carbofuran phenol (IV); 3-hydroxycarbofuran phenol (IX); 3-ketocarbofuran phenol (XI). In feces, there was the sulfinyl analog of carbofuran (II); carbofuran (III); and compound VI. 11+C02 was also formed (Black et al . , 1973). When compound I was applied to flies, carbofuran and metabolites VII and VIII were observed free. In addition, metabolites VII, VIII and X were found as conjugates (Black et al . , 1973). 62 CARBOXIN (Vitavax) [2,3-Dihydro-5-carboxanil ido-6-methyl-l ,4- oxathiin] OXYCARBOXIN (Plantvax) [2,3-Dihydro-5-carboxanil ido-6-methyl-l ,4- oxathi i n-4 ,4-dioxi de] Carboxin was administered to female rabbits (New Zealand White strain) and female rats (Wistar strain) by stomach tube. Urine and feces were collected and analyzed. In addition to unchanged carboxin, p_- and o-hydroxy derivatives were observed. Trace amounts of the m-hydroxy analog were also found occasionally. Three other minor metabolites observed appeared to be a hydroxylated sulfoxide, a di hydroxy and a di hydroxy sulfoxide of carboxin. The hydroxy metabolites were excreted largely as glucuronides in both species (Waring, 1973). When carboxin was applied to bean plants (Phaseolus vulgaris L.) in nutrient solutions, roots readily oxidized this fungicide to the sulfoxide. The 4,4-dioxide, oxycarboxin, was detectable in roots and unifoliate leaves for 21 days after application. Most of the fungicide residue in the roots was in the form of acetone-insoluble material (Snel and Edgington, 1970). Other studies have indicated that carboxin is hydrolyzed with formation of aniline which is bound probably as a glucosylamine (Newby and Tweedy, 1970). Barley plants formed carboxin-1 ignin complexes in the leaves. These were liberated by hot dimethyl sulfoxide and identified as carboxin (30%) and its sulfoxide (70%) (Chin et al . , 1973). Rhizopus japonicus, a synthetic glucose medium, converted carboxin into the corresponding sulfoxide and sulfone. Under anaerobic conditions the sulfoxide and a substituted anilide (not further identified) were observed. No sulfone was observed (Wallnofer et al . , 1972). Carboxin-treated barley seed was grown in vermiculite saturated with distilled water. Plants were harvested at intervals over a 21-day period and analyzed. Paper chromatography, GLC and mass spectrometry were used to identify metabolites. Young shoots contained carboxin, p_- hydroxy phenyl analog and unidentified dihydroxyl derivatives. Mature plants contained carboxin, £- hydroxy phenyl derivative, polymeric material and traces of the sulfoxide. Hydrolysis of the 1 ignin produced material that gave a chromatographic band coincident with the £-hydroxyphenyl (Briggs et al . , 1974). 63 64 CDAA (Randox) [2-Chloro-jM-dial lylacetamide] CDAA rapidly decomposed in plants. In rumen fluid of cows, it was stable for 24 h. When incubated with beef liver 10,000xg super- natant, CDAA was not detectable after 30 min. No metabolites were identified (St. John and Lisk, 1974). When 1UC-CDAA administered as a single dose to rats, 86% was excreted in the urine during the first 48 h; 16%, in feces. About 89% of the urinary 14C was the mercapturic acid of CDAA. Studies also showed that CDAA reacted non-enzymatically with glutathione (Lamoureux and Davison, 1975). 65 2-CEPA [2-Chloroethylphosphonic acid] In leaf and stem tissue of Hevea brasil iensis , 2-CEPA was converted into 13 and 20 compounds, respectively. One of the compounds obtained from stem and leaf was identified by TLC as 2-hydroxyethyl- phosphonic acid (Archer et al . , 1973). This compound also formed in small amounts when 2-CEPA was incubated for several days in buffer solutions at room temperature, When heated in alkali, ethylene and non-volatile material, identified as 2-hydroxyethylphosphonic acid by autoradiography and TLC, was formed (Audley and Archer, 1973). 66 CHLORAL HYDRATE Within a few days after application to soil, chloral hydrate was oxidized to trichloroacetic acid (TCA). TCA degraded with evolution of C02. Some formaldehyde was also detected at the beginning of the decomposition (Schutte and Stephan, 1969). 67 Chlordane and Related Compounds a - (or cis-) chlordane l-exo,2-exo,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4, 7-methanoindene y- (or trans-) chlordane 1 -exo,2-endo,4,5,6,7,8,8-octachloro-2,3,3a,4,7,7a-hexahydro-4, 7-methanoindene Chlordene 4,5,6,7,8,8-hexachloro-3a,4,7,7a-tetrahyoro-4,7-methanoindene Chlordene epoxide 4,5,6,7,8,8-hexachloro-exo-(cis)-2,3-epoxy-3a,4,7,7a-tetrahydro- 4, 7-methanoindene [also an endo-( trans )-2,3-epoxy- isomer]. Oxychlordane l-exo>2-endo>4,5>6>7,8,8-octachloro-2>3-exo-epoxy-2,3)3a>4,7,7a- hexahydro-4, 7-methanoindene Heptachlor 1 ,4,5,6,7,8,8-heptachloro-3a,4,7,7a-tetrahydro-4,7-methanoindene 68 Human adipose tissue specimens routinely collected from postmortem examinations and therapeutic surgery procedures were analyzed for a series of organochlorine pesticide residues. Oxychlordane was found in 21 of 27 specimens and ranged from 0.03 to 0.40 ppm (Biros and Enos, 1973). HCS-3260"ll4C (a 3:1 cis-chlordane and trans-chlordane) was admin- istered to rats. After a single oral dose, over 90% was eliminated in 7 days. Feces was the main route of excretion. After feeding HCS-3260" 14C to rats for 56 days, cis- and trans-chlordane, oxy- chlordane, dichlorochlordene and seven unidentified compounds were observed. Oxychlordane was observed after single doses of either cis- or trans-chlordane. After feeding a male rabbit HCS-3260" 14C for 2 days, in addition to cis- and trans-chlordane, oxychlordane and dichlorochlordane were observed in liver and kidney. Seven unidentified compounds were also found in urine and feces (Barnett and Dorough, 1974). Sugar beets were grown in soil treated with HCS-3260 or chlordane. Sugar beet pulp processed from these plants was fed to cows. In milk fat, there were detectable amounts of a- and y-chlordane and oxychlordane. The major product in the milk fat was identified as oxychlordane by mass spectrum. Similar residues were found in the fat (Dorough and Hemken, 1973). The hepatic mixed function oxidase (MF0) of several fish was inves- tigated. When chlordene was used as substrate, hydroxylation preceded epoxidation. With preparations from the Kissing Gourami (Helostoma sp.) and pigeon, l-hydroxy-2,3-epoxychlordene formed after the epoxide, Vmaix and K„ were also determined (Garretto and Khan, 1975; Runnels and Khan, 1973; Stanton and Khan, 1973). Chlordene substrate MF0 Vm,v MF0 Km Epoxidation Kissing Gourami Bluegill (Young) 0.26 0.18 15.59 15.00 Hydroxylation Kissing Gourami Bluegill (Young) 0.47 1.25 11.06 13.00 Epox.-Hydrox. 0.08 10.90 69 MFO V max Substrate Chlordene Hyd rox.-Epox. epoxide Hydi "oxychl ordene Chlordene Kissing Gourami 0.16 0.32 0.09 Bluegill fry 0.16 1.05 Trout 0.33 0.38 Bluegill try 0.13 0.99 Pigeon 0.26 0.44 0.10 Mouse 0.23 1.13 — • ™ - A 3-day aquatic system was used to evaluate uptake and biotrans- formation of chlordene, heptachlor and heptachlor epoxide. Results are tabulated. Water samples indicated the rapid formation (^24 h) of heptachlor epoxide and 1-hydroxchl ordene and its epoxide. Compd. Used Oedogonium Physa Culex Gambusia Metabolite (Snai 1) (Snail) (Mosquito) (Fish) Chlordene Chlordene epoxide + + + + 1 -Hydroxychl ordene + + + + 1 -Hydroxychl ordene epox. + + + + Unknown I + + Unknown II + + Polar + + + + Heptachlor Heptachlor epoxide + + + + 1 -Hydroxychl ordene + + + 1 -Hydroxychl ordene epox. + + + Unknown I + + Unknown II + + Unknown III + + Unknown IV + + + Unknown V + + Polar + + + + Heptachlor Epox. 1 -Hydroxychl ordene epox. + + + + Polar + + + + 70 Hexachlorocyclopentadiene was also evaluated ana found in all phases of the system. In addition, four unidentified compounds and polar material were also found in all phases (Lu et al., 1975). Other studies with the salt marsh caterpillar, Estigmane acrea, and sheep liver microsomes were summarized in the following table. Compound Used Metabolite Salt Marsh Caterpillar Sheep Liver Microsomes Chlordene Chlordene epoxide + 1-Hydroxychlordene + 1-Hydroxychlordene epox. + Unknown I + Unknown II Unknown III + Polar + + + + + + + Heptachlor Heptachlor epoxide 1 -Hydroxychl ordene 1-Hydroxychloroene epox. Unknown I Unknown II Polar + + + + + + +( feces only) + +( feces only) + + Heptachlor Epoxide Polar (Lu et al., 1975) In less than one day, heptachlor was converted to heptachlor epoxide in skim milk and try pti case soy broth, with or without the presence of the test bacteria (Collins, 1969). Soil was treated with high purity chlordane (-95% a plus 6 chlordane; cis/trans - 3:1). Alfalfa was grown on the treated soil. It was sampled 2 months after treatment; cut back at 3 months; and then sampled at 4 months and again at 1 year. Analysis by GLC indicated the presence of a-, y- , oxy- and photo-cis-chlordane. Oxychlordane comprised 9 to 13% of the total residues in the alfalfa but was not detected in the soils. The intermediate compound, 1 ,2-dichloro- chloroene, was found at 0.011 ppm in the alfalfa from plots treated at 10 lb a.i./A and in trace quantities at 5 lb a.i./A. Photo-cis- chlordane accounted for 9 to 16% of the total residues in the alfalfa and was also found in the soil (Wilson and Oloffs, 1973). 71 Ultraviolet irradiation of cis- and trans-chloroane in acetone produced 3 products. The half-caged analog of cis-chlorciane, photo- cis-chlordane, was obtained in high yield. Two products were formed from trans-chlordane. One was identified as photo- trans-chl or dane. The other was not identified, but a molecular composition of Cio^Cls appears likely (Onsuka and Comba, 1975). Irradiation of 6-chlordane in acetone produced II and III. Irradiation of IV gave VI (Parlar and Korte, 1973). A mixture of oxychlordane and xanthone was streaked on the surface of silica gel chromatoplates and then exposed to sunlight. Two photo-isomers were formed. Several structures were possible for each compound and this has not been resolved (Ivie, 1973). Chlordene was adsorbed on silica gel and then irradiated with ultra- violet light at x^290 and A^230nm. Differences observed were mainly quantitative. Chlordene required 1.5 h for 50% conversion of the starting materials. Products included: chlordene epoxide, photo- chlordene, 1-exo-hydroxy chlordene, ketochlordene, an unidentified compound and polar and polymer material. When quartz was used, instead of pyrex, heptachlor was also obtained (Gab et al., 1975). The decomposition of heptachlor epoxide in KBr disks with exposure to ultraviolet radiation and sunlight was studied. The products obtained were identical to those obtained by exposure of solid heptachlor epoxide to sunlight and ultraviolet radiation (Graham et al., 1973). 72 .CI "M, -— v 2 ( -)trans-Chlordane Photo- trans-chlordane 'OH CI ^ ^^M« l-Hydroxychlordane Oxychlordane Cls-C^T^CI CI 1 ,2-Dichlorochlordene CI Photoheptachlor hvy Photoheptachlor Epoxide hv OH <$£»-*. %y -+ *££* Heptachlor \ Heptachlor Epoxide Heptachlor diol ^-aft^O^. Chlordene \ Chlordene Epoxide 1 -Hydroxychl ordene 1 -Hydroxy-2 ,3-epoxy- chlordene CI, OH OH Chlordenediol 73 CHLORDIMEFORM (Galecron) [N-(4-Chloro-o-tolyl )- N' -N' - dime thy lformami dine] Chlordimefonn (I) was quite susceptible to degradation by cultures of primary human embryonic lung cells. Dimethyl ation to N-demethyl- chlordimeform (II) preceded cleavage to N-formyl-4-chloro-o-toluidine (III). Three unidentified compounds were also found in addition to 4-chloro-o-toluidine (IV) (Lin et al., 1975b). Aqueous solutions of ]ltC-chlordimeform were administered by stomach tube to Sprague-Dawley rats. Thin-layer chromatography was used to separate the metabolites and IR and UV were employed for identification. Half of the dose was excreted in urine in 24 h; 87.1 and 95.4% in 96 h by males and females, respectively. In addition to I, compounds II, III and IV were found in urine. Five unidentified compounds were also present. In vitro studies with liver homogenates produced the same metabolites (Morikawa et al., 1975). Absorption and metabolism of chlordimeform by the rice stem borer was slow. Analyses, however, indicated the formation of compounds II, III, IV and five unidentified compounds (Morikawa et al., 1975). From cultures of mixed populations of soil microorganisms to which chlordimeform had been added, a new metabolite of the pesticide was isolated and identified as 4'-chloro-2'-methylmalonanilic acid. Confirmation of structure was obtained by synthesis and mas spectral data (Ross and Tweedy, 1973). P=Plants ^Mammals 0=Microorganisms y— I=Insects =CH-N-CH3 N-Glucosyl amine Conjugate H 0 />N-C-CH2-C00H TH CI-/ Vn-cho ^~^C00H VI ^OOH VII 74 CHLORMEQUAT (CCC) [2-Chloroethyl trimethyl ammonium chloride] CCC-14CH3 was metabolized to choline in barley, wheat, tobacco and maize. Choline isolated from these plants contained 10-20% of the applied radioactivity. A small part of the radioactivity was also found in the betaine fraction. In Nlicotiana rustica L., methyl groups of CCC-lt4CH3 were incorporated into the alkaloid nicotine; in Hordeum vulgare, into the alkaloid gramine (Stephan and Schutte, 19701^ Radioactivity from l,2-ll+C-CCC was also found in the choline moiety of phosphatidyl choline in winter barley (Hordeum vulgare L. var. Dover) (Belzile and Willemot, 1972). When applied to coastal bermudagrass (Cynodon dactyl on L. Pers.), 1 ,2-1LfC-CCC was metabolized; and, within 24 to 48 h after application, about 25% of the label was found distributed among choline, betaine hydrochloride, serine, ethanolamine, glucose and C02 (Ayeke, 1969). Wheat seedlings were root-treated with 1 ,2-ll4C-chlormequat. Trans- location was rapid and choline was formed. The latter was metabolized via betaine, which was demethylated, to glycine and serine. These were then incorporated into the plant protein fractions. Some 14C02 was also formed (Dekhuijzen and Vonk, 1974). 75 CHLORODIOXIN (See also Irgasan.) Although these compounds are not pesticides, their presence as contam- inants in phenol based pesticides and their potential hazard to the environment places them in a position of great interest. Consequently, these compounds have been included in this compilation. When fed to rats, 2,3,7,8-tetrachloro-dibenzo-p_-dioxin (TCDD) was stored primarily in the liver. Total retention was dose dependent and varied from 5.5 to 10.0 times daily intake between 14 and 42 days. At steady state, analyses indicated that retention would approximate 10.5 times daily intake. After removal of TCDD from the diet, the half-life for elimination was 12 and 15 days for males and females, respectively (Fries and Marrow, 1974 and 1975). Thermal decomposition of 2,4,5-trichlorophenol gave rise to 2,3,7,8- TCDD (Milnes, 1971). Irradiation of TCDD in methanol produced 2,3,7-trichloro-dibenzo-p_- dioxin and in a dichloro analog. 0ctachlorodibenzo-p_-diox1n yielded a series of dechlorinated dioxins (Plimmer et al., 1971). Irradiation of photosensitized 2,4-dichlorophenol in water yielded dimeric materials primarily and traces of dechlorinated products. Using mass spectrometry, two tetrachlorophenoxyphenols and two tetra- chlorodi hydroxy bi phenyls were detected. A trace of trichlorophenoxy- phenol was also detected but there was no evidence of substituted dibenzo-£-dioxin. The major product was identified as 4,6-dichloro- 2-(2,4-dichlorophenoxy)phenol . An unidentified isomer of this compound was also present. The presence of riboflavin and oxygen was necessary (Plimmer and Klingebiel, 1971). 2-Hydroxy nonachlorodi phenyl ether (pre-dioxin) was found as a contam- inant in PCP. This material is thermally unstable and undergoes ring closure to form octachlorodioxin. An iso-predioxin was also found in a technical organic salt of PCP (Jensen and Renberg, 1972). The persistence of 2,3,7,3-tetrachlorodibenzo-p_-dioxin (TCDD) in Hagerstown and Lakeland (fid.) soils was found to be 56 and 63%, respectively, after one year. When 2,4-dichlorophenol or 2,4,5- trichlorophenol were added to soil, neither the 2,7-dichloro- nor the tetrachloro-dibenzo-p_-dioxin was detected after 70 days. However, a polar metabolite of the dichloro analog was observed but not identified, Neither of these two dioxins was synthesized bv microbial actions (Kearney et al . , 1972). 76 Predioxin Iso-Predioxin Dibenzofuran Dibenzofuran 77 CHLORONEB (Demosan, Tersan SP) [1 ,4-Dichloro-2,5-dimethoxybenzene] After exposure to chloroneb, young bean plants absorbed the chloroneb and accumulated it mostly in roots and lower stem. Chloroneb was metabolized to 2,5-dichloro-4-methoxyphenol (DCMP) and then converted to the 6-D-glucoside (Thorn, 1973). Incubation of chloroneb, and DCMP indicated that methylation of the phenol, as well as demethyl ation of chloroneb, occurred. Twenty- three different microorganisms were studied. Eight organisms de- methyl ated chloroneb and methylated DCMP: Fusarium solani f. pi si Fusarium solani f. phaseoli Mucor ramannianus Cephalosporium gramineum Aspergillus fumigatus Verticil 1 ium albo-otrum Cephalosporium gregatum Chaetomium globosum Six organisms were capable only of demethyl ating chloroneb: Sclerotinia sclerotiorum Helminthosporium victoriae Cory nebacteri urn fascians Stemphyll ium sarcinaeforme Cladosporium cucumerinum Helminthosporium sativum Three organisms were capable of methylating DCMP but did not degrade chloroneb to DCMP: Trichoderma viride Penicillium frequentans Rhizoctonia solani (Wiese and Vargas, 1973) In other studies, however, mycelium of R. solani degraded chloroneb to DCMP, which was identified by IR, NMR, and mass spectrographic analyses. N. crassa metabolized chloroneb slowly to a compound thought to be an aglycoside (Hock, 1969). 78 CHLOROTHALONIL [2,4,5,6-Tetrachloroisophthalonitri le] In cells of Saccharomyces pastorianus, chlorothalonil acted as an alkylating agent. Initial uptake resulted in the formation of glutathione derivatives. The fungicide also reacted with proteins (Tillman et al., 1973). 79 CHLORPROPHAM (CIPC, Isopropyl -m-chlorocarbani late) [Isopropyl N-(3- chlorophenyl )carbamate] PROPHAM (IPC, Isopropyl carbanilate) [Isopropyl N-phenyl carbamate] After dosing a goat and chicken with labeled propham, analyses conducted showed the presence of the £-sulfate derivative in goat milk and goat and chicken carcasses. The glucuronide was also found in chicken carcass (Paulson and Jacobsen, 1974). The main route of excretion of propham by a goat was via the urine. Small amounts appeared in milk and feces. After administration of phenyl-ll,C-labeled propham to a goat, 13 labeled metabolites were obtained and purified. Identification procedures included deriva- tization and chromatography, mass spectrum analyses, enzyme hydrolysis, syntheses and IR spectrometry. The metabolites identified were: 1. glucuronic acid conjugate of 4-hydroxypropham 2. sulfate ester of 4-hydroxypropham 3. glucuronic acid conjugate of 4-hydroxyacetanilide 4. sulfate ester of 2-hydroxyaniline 5. conjugate of 2-hydroxy isopropyl 4-hydroxycarbanilate 6. sulfate ester of 2-hydroxypropham [7. sulfate ester of 4-hydroxyacetanilide — not obtained from goats.] Compounds 1 and 2 were obtained from dosed rats as well as goats. Compound 7 was obtained from rats only. All others appeared in both animals. Partial identification of four other metabolites from the goat indicated the presence of: 1. a 4-hydroxypropham conjugate 2. a 2-hydroxypropham conjugate 3. a £-aminophenol conjugate 4. a 3,4-dihydroxypropham conjugate (Paulson et al., 1973) 80 In rats, the average biological half-life for IPC in internal organs was 5.0 h; in brain, muscle and fat tissue, 13.3 h. Tentative identification was made for the following urinary metabolites: 4- hydroxy-IPC; l-0H-2-propyl-IPC; 1 -carboxy-1 -ethyl -IPC; l,3-(0H)2-2- propyl-IPC; and 4-hydroxy-IPC-sulfate. Several other metabolites were observed but not identified (Fang et al., 1974). Rats and sheep were fed alfalfa which had been root-treated with propham- C. In sheep urine, the major labeled metabolite was 4-OH-IPC sulfate ester. Another metabolite was identified as the glucuronic acid conjugate of 4-OH-IPC. Co-chromatography, IR and mass spectral analyses were used for identification (Paulson et al., 1974). Alfalfa was root-treated with CIPC. Analyses of the root and shoot tissues indicated the presence of two aglycones. After hydrolysis, 2-OH-CIPC was found in root and shoots, 5.1 and 51.3%, respectively. The 4-OH-CIPC was also found, 26.4 and 17.6% in shoots and roots, respectively. The nature of the conjugates was not determined. However, both aglycones were liberated by treatment with hesperidinase, glucuronidase or cellulase (Still and Mansager, 1974). Alfalfa, which had been root-treated with chlorpropham-phenyl-ll*C, contained chlorpropham and glycoside conjugates of 2-OH-CIPC and 4-OH-CIPC. This plant material was fed to rats and a sheep. Little difference was observed in metabolite patterns in urine and feces of the sheep and rats. Sulfate and glucuronic acid conjugates were present in urine from both rat and sheep. The 4-OH-CIPC and 2-OH- CIPC conjugates were most abundant. The 2-OH-CIPC sulfate appeared in sheep urine. Glucuronide or sulfate conjugates of 2-0H-5-chloro- acetanilide and 4-0H-3-chloroacetanilide were found in rat urine (Still et al., 1974a). Soybean [Glycine max (L.) Merr. variety Hawkeye] were germinated, grown and root treated with chlorpropham-1 ^C. A polar metabolite was obtained from the roots and identified by enzymatic studies, derivatization and GLC, mass spectrum and NMR as an 0-glucoside of 2-hydroxychlorpropham. Similar analyses of shoots showed the presence of the 2- and 4-hydroxychlorprophams as 0-glucosides. The latter was found to be unstable to aqueous acid hydrolysis (Still and Mansager, 1973a). In cucumbers, only 4-hydroxychlorpropham conjugates were observed (Still and Mansager, 1973c). In resistant soybeans, the major metabolite of CIPC was 2-hydroxy- CIPC whereas in susceptible soybeans it was the 4-hydroxy analog. The phenolic metabolites were conjugated in both susceptible and resistant plants (Still et al., 1974b). 81 Soybeans were grown in the presence of 14 C-CIPC . Polar extracts of shoots, when subjected to alkaline hydrolysis, yielded some 3- chloroaniline. Analyses also showed the presence of 1-OH-CIPC. When grown in soil, soybeans metabolized CIPC primarily by alkyl hydroxylation and only small amounts of 2-0H- and 4-OH-CIPC were formed. In hydroponic culture, metabolism was primarily to aryl hydroxylated metabolites (Wiedmann and Ecke, 1975). In oats, the 4-OH-CIPC formed is converted to an S-cysteinyl hydro xychlorpropham (Rusness and Still, 1975). Soybean plants were root-treated with propham-14 C. Analyses of the metabolites indicated that they were glycosides of 2-hydroxypropham and that one of these metabolites was probably 6-0-glucoside (Still and Mansager, 1973b). 82 CLOPIDOL [3,5-Dichloro-2,6-dimethylpyridin-4-ol] When administered to rabbits, clopidol was rapidly absorbed and excreted mostly via urine. Less than \% of the dose remained in the tissues at 16 h after dosing. In addition to unchanged clopidol, 3,5-dichloro-2-hydroxymethyl-6-methylpyridin-4-ol and its glucuronide were present in urine. Another metabolite may be the 2,6-dihydroxy- methyl analog (Cameron et al., 1975). 83 CREDAZINE [3-( 2-Methyl phenoxy )pyri dazi ne] When this herbicide was irradiated with sunlight in aqueous solution at pH 6.8, about 65% of the credazine was unchanged after 3 weeks of exposure. The photolytic decomposition was greater at pH 9.0 and produced primarily 3-pyridazinone-(2H) and o-cresol . o-Cresol decom- posed rapidly but pyridazinone was unaffected. Also identified were salicylic acid, hydroxylated credazine, and 3-( 2-methyl phenoxy ) pyridazine-1 -oxide (Nakagawa and Tamari, 1974). 84 CYANIDE Opposums were dosed with sodium cyanide by means of a stomach tube. Feces and urine were collected and analyzed. Analysis indicated that the major route of detoxication of cyanide was via conversion to thiocyanate, which was excreted in the urine. Traces of 2-imino-4-thiazolidine carboxylic acid were observed in the crude concentrated extract of the urine (Turner, 1969). Studies with a basidiomycete showed that ammonia, HCN, and acetalde- hyde condense to form a-aminopropionitrile which can be hydrolyzed by nitrilase to alanine (Strobel , 1966 and 1967). In other studies, HCN was added to cultures of Rhizoctonia solani . a-Aminobutyronitrile was isolated and has been proposed as an intermediate in cyanide fixa- tion by Rhizoctonia solani (Mundy et al . , 1973). Cyanide was administered to C57 Black mice by i.p. injection. When given alone, cyanide was extensively converted to thiocyanate and excreted in the urine. Pretreatment of animals with nitrite and thiosulfate increased thiocyanate excretion. Pretreatment with cobalt compounds alone or in combination with thiosulfate decreased the formation of thiocyanate and gave increased urinary excretion of cobalt ions and strongly bound cyanide complexes (Frankenberg and Sorbo, 1975). 85 CYOLANE [2-Diethoxyphosphinylimino-l ,3-di thiol ane] Cyolane-treated alfalfa hay was fed to a cow one year after treatment of the alfalfa. Cholinesterase was depressed and did not return to normal levels until 3 months after feeding of the cyolane-contaminated hay had been discontinued. Identification of the residues was not made (Tadjer and Egyed, 1974). 86 2,4-D and RELATED COMPOUNDS 2,4-D [2,4-Dichlorophenoxyacetic acid] 2,4-DB [4-(2,4-Dichlorophenoxy)butyric acid] Erbon [2-(2,4,5-Trichlorophenoxy)ethyl 2,2-dichloropropionate] MCPA [4-Chloro-2-methylphenoxyacetic acid] Si 1 vex [2-(2,4,5-Trichlorophenoxy)propionic acid] 2,4,5-T [2,4,5-Trichlorophenoxyacetic acid] CPA [Chlorophenoxyacetic acid] 87 2,4-D [2,4-Dichlorophenoxyacetic acid] Two h after ingestion by human volunteers, 2,4-D appeared in the urine. More than 75% of the dose was excreted within 96 h. No metabolites were detected. Pharmacokinetics C. = A k ' = vd(kf-Ke) Cexp(-ket)-exp(Kft)] After a 5 mg/kg dose: kf x 102(h_1) = 27.4 ± 4.0 k x 102(h_1) e -0.5 (e)(h) = 2.1 ± 0.2 = 33.0 ± 3.1 Where: C. = Plasma concentration at time t A = dose in mg/kg kf = first order rate constant - absorption k = first order rate constant - clearance Vd x 102 (1/kg) = 10.1 ± 0.3 Vd = Volume of distribution (Kohli et al., 1974) Bovine serum albumin and 2,4-D interact. Binding of 2,4-D is rather extensive but is greatly reduced in the presence of palmitic acid (Kolberg et al . , 1973). The properties of the binding site resemble the properties of the amino acid sequence adjoining the tryptophan at the binding site of bovine serum albumin (Mason, 1975). After feeding 2,4-D to sheep and cattle, analysis of muscle, fat, liver and kidney showed the presence of 2,4-dichlorophenol (Clark et al., 1975). The butyl ester of 2,4-D is unstable in water and undergoes hydrolysis in 9 to 10 days with formation of 2,4-D. If fish are present, high residue levels may accumulate within a few days and persist for a week or more (Shcherbakov and Pol uboyari nova, 1970). In studies with maize leaf tissues, 2,4-D bonded to some extent with cellular protein (Zemskaya et al . , 1971). Oat, wild cucumber, and to a lesser extent cocklebur were able to bind or alter large amounts of 2,4-D (Dexter, 1970). Yellow nutsedge (Cyperus esculentus L.) did not absorb 2,4-D as well as some of the susceptible broadleaf plants. Analysis of methanol -soluble extracts indicated that yellow nutsedge does not appreciably degrade the 2,4-D (Bhan et al . , 1970). 88 Shortly after exposure of Ribes sativum leaves to 1 -ll+C-2,4-D, 37.8% of the label appeared in glycolic acid in the water-soluble metabolites. 11+C-Glycine was also observed (Fleeker, 1973). Soybean (Glycine max L. var. Acme) cotyledon callus stock cultures were grown on an agar medium. After 2 ,4-D-l -1£+C was added, 2,4-D- glutamic acid and 2,4-D-aspartic acid were the major amino acid conjugates found. In addition to these, five other conjugates were isolated and observed: alanine, leucine, phenylalanine, tryptophan, and valine. Two other conjugates were not identified. When 2,4-D- glutamic acid was added to the media, 2,4-D and the aspartate complex were formed. The aglycones 4-hydroxy-2,5-D and 4-hydroxy-2,3-D were also formed. These studies also indicated a more rapid conversion of the glutamate complex to the foregoing inactive aglycones than of 2,4-D itself (Feung et al . , 1973). Additional studies were conducted with callus tissues of carrot, jackbean (Canavalia ensiformis), sweet corn (Zea mays) , tobacco and sunflower (Helianthus annusT After the five plant callus species were exposed to 2,4-D, metabolism produced amino acid conjugates and hydroxylated metabolites as glucosides. After 3- glucosidase treatment of water soluble extracts, 2,4-D, 4-0H-2,3-D and 4-0H-2,5-D were found in callus tissue of all five plants. Corn callus tissue alone contained 4-hydroxy-2-chlorophenoxyacetic acid and 3-0H-2,4-D. The glutamate conjugate of 2,4-D was found in all five plants; and the aspartate conjugate, in corn, tobacco and jackbean (Feung et al . , 1975). In studies with labeled 2,4-D and seedlings of wheat, insoluble complexes of protein and 2,4-D formed. Water-soluble compounds also formed (Hallmen and Eliasson, 1972). Other studies have also shown that plants form water-soluble complexes and hydroxylated 2,4-D derivatives (Eidel'nant and Mostovaya, 1972). After treatment of tomato plants of the variety "Eurocross A," acid hydrolysis of the n-butanol extracted glycosides yielded 4-0H-2,3-D and smaller amounts of 4-0H-2,5-D, 2,4-D and an unidentified metabolite (Muller and Schuphan, 1975). In potatoes, the differences between total and free residue levels of 2,4-D were small but statistically significant and indicated the presence of conjugated 2,4-D. Residues of 2,4-dichlorophenol were also present (Bristol et al . , 1974). The results of studies in susceptible rape (Brassica napus L. cv. Nilla) and sunflower (Helianthus annus L. var. uniflorus) indicated that 2,4-D existed mainly in the free state and only to a small extent in water-soluble complexes (Hallmen, 1974). Similar results were obtained with wheat (Triticum aestivum L. cv. Starke) and Norway spruce [Picea abies (L.) H. Karst] (Hallmen, 1975). 89 The influence of four algae on 2,4-D residues in water was studied. Of the four algae used [Chlorella pyrenoidosa Chick., Chlamydomonas reinhardtii Dangeard, Euglena gracilis Krebs. 'urophora', and Scenedesmus quadricanda (Turp.) Breb.], only the latter was effective in removing the herbicide. When ring-labeled 2,4-D was incubated with Scenedesmus, the main metabolite observed was 3-0H-2,4-D (26% of total radioactivity). The 5-hydroxy analog was also identified. Two other metabolites having higher R^ values than 2,4-D were not identified (Valentine and Bingham, 1974). Molds grown in culture broths containing 2,4-D analogs produced growth- inhibiting principles. Active principles were isolated as crude yellow oils (Naito, 1958; Naito and Kojima, 1957; Naito and Tani , 1955 and 1956a and b). When the molds Gloeosporium olivarum, Gloeosporium kaki and Schizophyllum commune were grown on media containing 2,4-D, color- less needles were isolated and identified by IR spectrum, mass spectrum, elemental analysis and M.P. as the ethanol analog (Nakajima et al . , 1973). Arthrobacter sp. cultures were grown on 2,4-D. An enzyme preparation prepared from these cultures converted cis,cis-2,4-dich1oromuconate to chloromaleyl acetate. The enzyme that converts dichloromuconate to 2-chloro-4-carboxymethylene but-2-enolide was separated from the enzyme that opens the butenolide lactone (Sharpee et al . , 1973). In other studies with an enzyme preparation from Arthrobacter sp., the ether linkage of 2,4-D was cleaved to produce initially 2,4- dichlorophenol and glyoxylate. Evidence for the latter was indirect with observation of the formation of a-alanine. Neither acetate nor glycol ate was metabolized by the bacterial enzyme preparation. Catechols were cleaved to cis,cis-muconic acids. The products of 4-chloro- and 3,5-dichloro-catechol were the 6-chloro- and a,Y-dichloromuconic acids, respectively. The latter was proposed on the basis of its UV spectrum and analogous formation of 3-chloromuconic acid from 4-chlorocatechol . Acidification caused lactonization to the corresponding butenolides. Some cis,trans-B-chloromuconic acid also formed. a-Chloromaleyl acetate, formed from a,Y-dichloromuconic acid, was identified by GLC, UV and mass spectrometry. This compound decarboxylated readily to form the lactol of cis-a-chloro-Y-ketopent-2-enoic acid and was identified by GLC, IR, mass spectrometry and nuclear magnetic resonance. In the presence of NADH, a-chloromaleyl acetate was metabolized to yield succinate. Prelim- inary studies indicated a-chloro-y-ketoadipate and chlorosuccinate as intermediates (Tiedje, 1969). In studies with 2,4-D and MCPA, applications of either to soil affected a cross adaptation. After a period of 19 years, repeated applications reduced the time for 50% degradation for 2,4-D and MCPA from 10 and 20 weeks to 4 and 7 weeks, respectively (Torstensson et al . , 1975). 90 The irradiation of aqueous solutions of 2,4-D and several of its esters indicated differences in mode of decay. The free acid undergoes mono- and di-dechlorination, ortho and para hydroxylation, and polymer formation. Intact esters (ethyl, butyl and 2-methylheptyl ) undergo monodechlorination. In light stronger than sunlight, further dechlor- ination and rearrangement occurs (Binkley and Oakes, 1974a and b, Binkley et al . , 1974). Irradiation of 2,4-D aqueous solutions with UV above 280 nm gave little reaction. When a sensitizer such as riboflavin was also used, the products included tetrachlorophenoxyphenols and two isomeric tetra- chlorodihydroxybi phenyls. The major product was 4,6-dichloro-2- (2,4-dichlorophenoxy)phenol . A trace of a trichlorophenoxy phenol was also observed (Plimmer and Klingebiel, 1971). Studies have also shown that photochemical degradation of 2,4-D derivatives follows two paths. In water, the predominant path, except for esters, involves removal of a chlorine and replacement with a hydroxyl group and cleavage of the ether to form the phenol. In methanol, a chlorine is abstracted from the ring (Binkley et al . , 1974). 2,4-D was formulated as a urea type polymer and exposed to irradiation at 356 nm. This form of 2,4-D was less resistant to degradation than conventional 2,4-D. UV degradation of the polymerized 2,4-D was eliminated by incorporation of UV absorbers. Resistance to thermal degradation, however, was greater in the polymerized form than in non-polymerized 2,4-D (Baur and Bovey, 1974). Pyrolysis of amine salts of 2,4-D produced corresponding amides. Above 160C, 2,4-dichlorophenol , imines, lactones, and other compounds also formed. Above 200C, the amides seemed to decompose (Hee and Sutherland, 1974). Basic and acid hydrolysis of 2,4-D esters yielded 2,4-D and the corresponding alcohol. The hydrolysis half-life of the butoxyethyl ester at 25C increased from 9 h at pH 8 to more than one year at pH 5. The major photoreaction of 2,4-D esters at \<290 nm involved cleavage of the ortho C-Cl bond. Calculated sunlight photolysis half-lives of butoxyethyl ester, at latitude 34°N ranged from 59 h in summer to 430 h in winter, and 13 h and 109 h, respectively, in hexadecane (Zepp et al., 1974). 91 MCPA [4-Chloro-2-methylphenoxyacetic acid] MCPA was applied to a rice field. About 70% of the material reaching the target area was lost by evaporation and soil percolation. Photo- lysis of MCPA with an indoor photoreactor or sunlight yielded 4-chloro- 2-methyl phenol and lesser amounts of o-cresol and 4-chloro-2-formyl- phenol (Soderquist and Crosby, 1975). 92 2,4,5-T [2,4,5-Trichlorophenoxyacetic acid] Bovine serum albumin bound 2,4,5-T extensively. Palmitic acid reduced the binding (Kolberg et al . , 1973). The binding site properties resembled those the amino acid sequency adjoining the tryptophan residue of human serum albumin. There was evidence, too, of the presence of tryptophan at the high affinity binding site of bovine serum albumin (Mason, 1975). Human male volunteers ingested a single dose of 5 mg/kg. Excretion of 2,4,5-T was essentially in unchanged form. Clearance from the plasma and excretion both followed first-order kinetics with a half-life of 23.10 and 23.06 h, respectively (Gehring et al . , 1973). [1-UC]2,4,5-T was administered by stomach tube to pregnant and non- pregnant rats. The rate of elimination was the same for both groups. Urinalysis revealed that 90-95% of the label excreted was in the form of unchanged 2,4,5-T. Two non-polar and one water soluble metabolite were observed. Acid hydrolysis of the latter produced 2,4,5-T. The biological half-life in the various organs was essentially the same but differed between adult and newborn rats: 3.4 h vs. 97 h, respectively (Fang et al . , 1973). The plasma and elimination half- lives for Sprague-Dawley rats was 4.7 and 13.6 h, respectively, when a 5 mg/kg dose was administered (Piper et al . , 1973). When adult beagle dogs were administered 5 mg/kg doses, the half-life for plasma clearance and elimination was 77.0 and 86.6 h, respectively. Three unidentified metabolites were detected in the urine (Piper et al . , 1973). Photolytic decomposition of 2,4,5-T by sunlight in distilled water at pH 8 was studied. The principal reaction was ether cleavage and replace- ment of ring chlorines by hydroxyl and hydrogen. The products identified were: 2,4,5-trichlorophenol > lactone of 4,5-dichloro-2-hydroxyphenoxy- acetic acid > 2,5-dichlorophenol , 4-chlororesorcinol and 4,6-dichloro- resorcinol. Unidentified and polymer material accounted for as much as all metabolites combined except the 2,4,5-trichlorophenol (Crosby and Wong, 1973). 93 DBNPA (2,2-Dibromo-3-nitrilopropionamide) [2,2-Dibromo-2-cyanoacetamide] The rate of hydrolysis of DBNPA at various pH levels was determined at 25C and the hydrolysis products determined. PH ti/2> h 3.9 2140 (2: 6.0 155 6.7 37 7.3 8.8 7.7 5.8 8.0 2.0 8.9 0.34 9.7 0.11 As DBNPA decreased, dibromoacetonitrile increased. Dibromoacetamide formed by hydrolysis of the latter. Dibromoacetic acid and C02 formed under more stringent conditions and hydrolysis of the acid yielded bromide ions and glyoxylic acid. Two unexpected compounds were iden- tified as tribromoacetonitrile and tribromoacetamide. These must have arisen via a bimolecular reaction and hydrolysis. These latter products occurred because of the high (12000-15000 ppm) concentrations used in these studies. At use levels of 1-10 ppm, these should not occur. When a solution of DBNP was mixed with sodium bisulfite, cyanoacetic acid was obtained. DBNPA was also exposed, in water and in a quartz tube, to a G.E. sunlamp for 3 days. A residual oil was obtained which contained cyanoacetic acid, malonic acid amide, malonic acid and oxalic acid. IR and mass spectral analyses were employed for identi- fication (Exner et al . , 1973). 94 DCB [Dichlorobenzene] When dichlorobenzenes were fed to rabbits, the compounds were slowly metabolized over a 3-6-day period. o-DCB The o- isomer yielded glucuronides (48%), sulfates (21%), mercapturic acid (5%) and catechols (4%). The major metabolites were 3,4- and 2,3-dichlorophenol conjugates (2:1, respectively). 4,5-Dichloro- catechol and traces of 3,4-dichlorocatechol comprised the major portion of the catechol fraction and 3,4-dichloro phenylmercapturic acid was the probable mercapturic acid (Azouz et al . , 1954). m-DCB When fed to rabbits, the m-DCB yielded glucuronides (31%), sulfates (11%), mercapturic acid (9%) and catechols (4%). The major product was 2,4-dichlorophenol . Traces of 3,5-, but no 2,6-, dichlorophenol were observed. 2,4-Dichlorophenylmercapturic acid and 3,5-dichloro- catechol were also observed (Azouz et al . , 1954). p-DCB Rabbits fed ^-dichlorobenzene excreted glucuronides (37%) and sulfates (27%). No mercapturic acid or catechols were observed. 2,5-Dichloro- phenol and a quinol, probably 2,5-dichloroquinol , were observed (Azouz et al., 1954). 95 DDOD (Dichlozoline) [3-(3,5-Dichlorophenyl )-5,5-dimethyloxazolidine- 2,4-dione] Labeled DDOD was administered orally to 200g male Wistar rats. Urine and feces were collected and analyzed. Approximately equal amounts of radioactivity appeared in urine and feces. Most of the radioactivity in feces was unchanged DDOD. About 85% of the radioactivity was extractable from urine with ether and contained eight metabolites. Five were identified: N-(3,5-dichloro-4-hydroxy)-5,5-dimethyloxazolidine-2,4-dione N-(3,5-dichloro-4-hydroxyphenyl )-a-hydroxyisobutyramide N-(3,5-dichloro-4-hydroxyphenyl )-N-(a-hydroxyisobutyryl)carbamic acid N-(3,5-dichlorophenyl ) -N-( a- hydroxy isobutyryl )carbamic acid N-(3,5-dichloro-4-hydroxyphenyl )lactamide Two fractions treated with glucuronide or sulfatase released compounds, one of which was identified as N^(3,5-dichloro-4-hydroxyphenyl )lactamide (Sumida et al . , 1973a). Bean plants were treated with labeled DDOD. After root treatment, DHCA and HDA were observed. Neither compound was observed when DDOD was injected into the bean plant. Other unidentified metabolites were observed. After injection of DDOD into grape plants, analysis of the leaves showed the presence of DMDOD, HDA and unidentified material. In soil, DDOD degraded to DHCA, HDA, DCA and unidentified material. No TCAB was found (Sumida et al . , 1973b). 96 E 10 i- 10 •— o 11 II II z: o. uo i. a; O ■!-> C ••-> O c J- o 3 O 97 DDT and RELATED COMPOUNDS DDT [2,2-Bis(]D-chlorophenyl )-1 ,1 ,1-trichloroethane] DDD (TDE, Rhothane) [2,2-Bis(£-chlorophenyl )-l ,1-dichloroethane] Kel thane (Dicofol) [2,2-Bis(])-ch1oropheny1 )-l ,1 ,1-trichloroethanol] DDE [2,2-Bis(£-chlorophenyl )-l ,1-dichloroethylene] 98 Studies with human serum has shown that p^p^-DDE can be bound to proteins. This binding increased with aged serum (Schoor, 1973). When ring-labeled 1I+C-DDT was incubated with human embryonic lung cells, reductive dechlorination produced DDD. The only other meta- bolite found was DDA (North, 1972; North and Menzer, 1972). Binding of p^p^-DDA with human and bovine serum has also been observed (Ross and Biros, 1975). Syrian golden hamsters were fed p_,p} -DDT in their diet for 4 months. Urine and feces were collected. Autoradiography of thin-layer plates on which urine had been spotted indicated the presence of at least 10 radioactive bands. The major metabolite (80%) apparently was DDA, free and as the glucuronide. Other bands were identified as the DDA conjugates of glycine and alanine. DDD was observed in urine and feces (Wall cave et al . , 1974). After Swiss albino mice were fed £,£1-DDT, analysis of urine revealed the presence of DDE and DDA as the glucuronide, alanine and glycine conjugates. DDD was found in the feces (Wall cave et al . , 1974). In other studies with mammals, oral dosing of mice with metabolites of fj.p^-DDT indicated that DDE is not an intermediate in DDT metabolism to DDA. Administration of p^p^-DDD produced increased levels of d_>E.1- DDA. However, DDMU led to a decrease in DDA production in the urine over that found from DDD administration. This would not be expected if DDMU was a metabolite of DDT or DDD leading to production of DDA. When administered intraperitoneally, jd^-DDT dosing led to a decrease in DDA production and indicated that the intestines may play a major role in DDT degradation to DDA (Apple, 1969). Other studies with hepatic microsomes also indicate that the pathway for DDT in birds may differ from that in mammals. A pathway involving DDMU to a highly active liver inducer may be involved (Bunyan and Page, 1973). Oral dosing of mammals with p^p^-DDT gave rise to o.p^-DDA. No fJ.j).1- isomer was observed (Apple, 1969). 14C-Labeled o^-DDD was administered orally to Sprague-Dawley rats. Urine and feces were collected at 6, 12 and 24 h and then at 24 h intervals. Rats were sacrificed at 15 days. Urine contained: o,^.1- DDA and its 3-hydroxy, 4-hydroxy and 3, 4-di hydroxy analogs; the serine and glycine conjugates of DDA; monomethyoxy- and dimethoxy-o^-DDD (Reif and Sinsheimer, 1975). After mice were administered DDT, urine and feces were collected and analyzed. In addition to DDE, DDT, DDMS, DDD, DBP, DDA and kelthane, five unidentified metabolites and some conjugates were observed (Kapoor et al . , 1972). In other studies, DDT was incubated with ovine (Ovis aries) rumen fluid. DDD, DDE and DDMU were observed (Sink et al . , 1972) 99 After mule deer fawns, Odocoileus hemionus, were fed jD.p^-DDT, DDD was found in the serum and in feces^ p_,£!-DDE was found in fecal matter but not in serum (Watson et al . , 1975). Studies with a worker exposed to DDT indicated that the human liver excretes DDT into the bile (Paschal et al . , 1974). A common loon (Gavia immes), found in a moribund state in a soybean field, was autopsied and tissue was analyzed. In addition to p_>P1- DDE, p^-DDD, jd.j^-DDMU, p^-DCBP, jj.^-DDMS, 0,^-DDD, and o.fP-DDE another compound was observed and identified by synthesis and mass spectrum as 1 ,l-bis(]3-chlorophenyl )-2,2-dichloroethanol (Prouty et al . 1975). Chickens, modified surgically to facilitate collection of urine and feces were administered single oral doses of ring-^C-labeled o,^1- DDT. Feces contained o^-DDT and o.p^-DDD, predominantly. The following metabolites were also observed: S-hydroxy^^-DDD 4-hydroxy-2, 41-DDD 4-hydroxy-3-methoxy-2,41-DDD o,£} -DDE 3-hydroxy-2,4!-DDE 4-hydroxy-2,41-DDE 4-hydroxy-3-methoxy-2 ,4! -DDE 3-hydroxy-2,41-DDT 4-hydroxy-3-methoxy-2,41-DDT 0,^-DDA 3-hvdroxy-2,41-DDA o,jr-DDA methyl ester Methyl ester of a methoxy o^p^-DDA (probably 3-isomer) 4-hydroxy-3-methoxy-2,41-DDA (Feil et al., 1974 and 1975) 12,000xg Liver preparations, to which NADPH and riboflavin had been added, were incubated with DDT. Percentage conversion of DDT to DDD was in order: hamster > mouse > pigeon > Wistar rat > quail > cockerel; after heating and then supplementing: Wistar rat > mouse > quail > hamster > cockerel > pigeon (Hassall, 1975). In other studies, incubation of pigeon liver preparations with DDT and DDD gave rise to analogs showing loss of one chlorine (Hassall and Manning, 1972). When pooled fat extracts from tissues of guillemots and grey seals were analyzed, two hydroxylated DDE analogs were observed. The 4,4*- dichlorobenzophenone and 2-bis(p_-chlorophenyl ) acetic acid were also present in some samples (Jansson et al . , 1975). The hydroxylated DDE 100 analogs were identified by mass spectra and synthesis as: 1 ,1-dichloro- 2-(4-chloro-3-hydroxyphenyl )-2-(4-chlorophenyl )ethylene; 1 ,1-dichloro- 2-(3-chloro-4-hydroxyphenyl )-2-(4-chlorophenyl jethylene. When rats were fed p_,p_i-DDE, these two and a third compound identified as the 2-(4-chloro-2-hydroxyphenyl ) analog were isolated (Jansson et al . , 1975; Sundstrom et al . , 1975). When tadpoles of the common frog (Rana temporaria) were exposed to £,£1- DDT, no DDE was detected. The only metabolite observed was DDD and post-mortem breakdown was suspected (Cooke, 1970). In the environment, conversion of DDT to DDD has been observed in a wide variety of biological systems, living and dead. The mechanism has not been clearly established but existing data indicates the involvement of reduced porphyrins. A series of studies demonstrated that the DDT to DDD conversion was affected whenever DDT and reduced porphyrins were brought together in solution (Zoro et al., 1974). Agricultural loam soils were treated with DDT in 1954 and sampled periodically. Analyses in 1970 showed the presence of DDD, DDE and dicofol (Lichtenstein et al . , 1971). In flooded soil, p.p^DDT was dechlorinated to p.p^DDD. Some DDE was also observed (Bhulya, 1969). When DDT was added to an Everglades muck, the amount of degradation was related to the changes in redox potential. Under aerobic or flooded anaerobic conditions in substrate- amended muck, where the redox potential dropped to +350 and +180 mV, respectively, little DDT degradation occurred. Where the redox poten- tial dropped to 0 and -250 mV, considerable degradation occurred (Parr and Smith, 1974). E_. col i , B. subtil is and S. aureus degraded DDT to DDD and DDE in trypticase soy broth (Collins, 1969). Anaerobiosis was found to be an environmental factor in the degradation of DDT to DDD. The ability to make this conversion was demonstrated by 27 bacterial species from the following genera: Achromobacteria, Aerobacter, Agrobacterium, Bacillus, Clostridium, Erwinia, Kurtha, Pseudomonas and Xanthomonas (Johnson, 1969). Reductive dechlorination of £,p_1-DDT to DDD has been observed under both aerobic and anaerobic conditions (French, 1969). Bacillus megaterium converted a small amount of DDT to DDD (Hicks, Jr., and Corner, 1973). When DDT was added to raw sewage, DDD, DDE and DBP were produced. Addition of glucose enhanced the rate of DDD formation but reduced DBP formation. Addition of di phenyl - methane reduced formation of DDD and DBP (Pfaender and Alexander, 1973). Membrane-bound enzymes from Hydrogenomonas sp. appeared to mediate initial anaerobic degradation of DDT to DDD. Soluble cell fractions and flavin enzymes stimulated the reaction. Enzyme preparations from Hydrogenomonas sp. were capable of degrading DDT to DDD, DDMS, DBP. Addition of fresh cells to the anaerobically incubated extract and 101 aerobic incubation of the mixture produced p_-chloropheny1acetic acid (PCPA). An isolated Arthrobacter sp., that could use PCPA as a sole carbon source, produced p_-ch1orophenyl glycol aldehyde during growth on PCPA (Pfaender, 1972). In studies with adult catfish (Heteropneustes fossil is) exposed to DDT, only DDE was observed (Agarwal and Gupta, 1974). The thorny skate (Raja radiata) metabolized ^C-p^p^-DDT to DDD and DDE (Darrow and Addison, 1973). Ring-labeled p^p^-DDT- 3H was force-fed to mature brook trout (Salvelinas fontinal is) one dose each week for five weeks. The eggs were collected, fertilized and incubated. Analyses of the eggs and fry indicated metabolism to £,p_1-DDD and p_,p_1-DDE. Distribution of the three compounds was determined from the day of fertilization until 80 days post- fertilization: p_,p>DDT 92.4 to 61.7% £,£1-DDD 0.4 to 5.1% p^-DDE 7.2 to 33.2% (Atchison and Johnson, 1975) When 14C-labeled DDT was given orally to common soles [Solea solea (L.)]» there was a characteristic distribution pattern of accumulated DDT that was independent of dosage. Brain, liver and gastro-intestinal tract ranked highest. More than 80% of the accumulated DDT remained unchanged and DDE, DDD and a polar compound occurred as metabolites (Ernst and Goerke, 1974). After oral application of yg-amounts of DDT to the polychaete Nereis diversicolor, analysis indicated that most of the DDT (51 to 67% of the initial dose) was stored unchanged. There was only slight metabolism, probably to DDA (Ernst, 1969). Studies with the freshwater planarian Phaqocata velata indicated that it was capable of metabolizing DDT to DDD and DDE (Phillips et al . , 1974). All algae tested converted DDT to DDE. No other metabolites were observed. Algae used included: Chlorella vulgaris Ankistrodesmus braunii Anacystis nidulans Nostoc muscorum Synechococcus elongatus Synechococcus cedrorum Anabaena variabilis 102 Anabaena flos-aquae Calothrix parieatina Phormidium luridum var. olivacea Skeletonema costatum Cyclotella nana Isochrysis galbana Olisthodiscus luteus Amphidinium carteri Tetraselmis chuii (Rice, 1972; Rice and Sikka, 1973) In other studies with the unicellular freshwater alga (Ankistrodesmus amalloides), after exposure to ll+C-DDT for 30 days, both DDE and DDD were recovered. When daphnids (Daphnia pulex) were exposed for 24 h, DDE was recovered (Neudorf and Khan, 1975). Collembola, Folsomia Candida, was fed brewer's yeast spiked with 100,000 ppm DDT. These were then released into fenced plots in a beech-maple forest. Arthropod fauna were sampled at intervals. Reductive dechlorination of DDT gave DDD and dehydrochlorination gave DDE (Klee, 1972). Vitamin B12 has been suggested as having a role in the degradation of DDT. To study this possibility, macrocyclic alkyl -cobalt complexes were synthesized and reacted with DDT. In one of these studies, the Co(II) complex was prepared, reduced to Co(I) species, and allowed to react with DDT. A maroon powder was isolated. Infrared spectra indicated that the complex contained a carboxyl group. After a few days in sunlight, a solution of the material was extracted. Mass spectrum analysis indicated that the white material obtained was bis(p-chlorophenyl ) ketone (Prince and Stotter, 1974; Prince et al . , 1974). Gamma-radiation of DDT induced loss of chlorine but DDD and DDE were absent. It seems, therefore, that dechlorination proceeds with simul- taneous loss of all three chlorine atoms from the CCl3-group (Woods and Akhtar, 1974). In a laboratory model ecosystem, DDE was extremely stable in the tissues of the living organisms. Analysis of body and feces of the salt marsh caterpillar showed over 95% unchanged DDE. The remainder appeared as unidentified polar metabolites (Metcalf et al . , 1975b). Under laboratory conditions, DDT, DDE, DDD and DDA were chroma to- graphed on silica gel G on glass plates. The studies indicated that degradation of DDT occurred when the spotted plates were exposed to UV. In addition to DDD and DDE, there appeared to be four other components (Ernst, 1972). 103 DDT decomposed when irradiated, whether as a pure solid or in hexane solution, by UV (2537A). In hexane solution, DDD and HC1 were identi- fied. When irradiated in the solid form, DDD, DDE and DBP were formed (Mosier et al . , 1969). When DDT and DDE in pyrex tubes were exposed to UV-irradiation (A>290nm) as solids in an oxygen stream, mineralization products (C02 and HC1 ) were observed in small amounts after 7 days. DDE yielded dichloroben- zophenone and trichlorobenzophenone. No photoproducts from DDT were detected (Gab et al . , 1975). Kel thane residues on apple pomace were subjected to UV irradiation filtered through pyrex glass (A>290nm). Analyses indicated that only DBP was formed from Kel thane (Archer, 1974). After oral administration of Kelthane to rats, analyses of tissues, urine and feces showed the presence of DDE, DBP and 4,41-dichlorobenz- hydrol (Brown et al . , 1969). Recent studies have indicated that colored complexes can form between montmorillonite clay and p.p^-DDT, o.p^-DDT, p^p^-DDE, £,p_1-DDD, js.p^-DDA, dicofol, or 4,4*"-dichlorobenzophenone (Haque and Hansen, 1975). In other studies, larvae of the bollworm H_. zea and tobacco budworm H_. virescens were exposed to DDT. Analyses indicated rapid accumulation of DDE and only small amounts of metabolites more polar than DDT in H_. zea. In H_. virescens, there was only minor accumulation of DDE but rapid accumulation of more polar metabolites (Plapp, 1973). 104 DESTUN (Perfluoridone) [1 ,1 ,l-Trifluoro-N-[2-methyl-4-(phenylsulfonyl ) phenyl ]methanesul fonamide] In sandy loam soil, destun was degraded to 3-methyl-4-[[(l ,1 ,1- trifluoromethyl )sulfonyl]amino]benzenesulfonic acid (II) (Bandal et al., 1974). Peanut seedlings were root treated with ^C-labeled destun. Young developing lateral branches contained the highest concentrations of lkC in foliar tissue. TLC of aqueous extracts of roots gave eight radioactive zones. Hydrolysis of one of the zones yielded destun and a metabolite tentatively identified as 1 ,1 ,l-trifluoro-N-[2-methyl- 4-(3-hydroxyphenylsulfonyl )phenyl]methanesul fonamide (III). The most abundant metabolite, not identified, yielded 2 moles of glucose and one of compound II upon acid hydrolysis, but one mole of II and no glucose when treated with B-glucosidase (Lamoureux and Stafford, 1974) *-r\\ /, CH3 II \ Glucoside III 105 DEXON [p_-Dimethylaminobenzenediazo sodium sulfonate] Pseudomonas fragi metabolizes dexon by a co-metabolic process. One of several compounds that is formed was identified as N,N^-dimethyl-p_- phenylenediamine (DMPDA). The enzyme, a reductase, was found in the soluble fraction and required dithioerythreitol as reductant. When dexon was applied to soil, DMPDA was also found (Karanth et al . , 1974). 106 DIANISYLNEOPENTANE [1 ,l-Bis(£-methoxyphenyl )-2,2-dimethylpropane] In an effort to find a more selective and biodegradable replacement for DDT, analogs of DDT were studied. Metabolic studies were con- ducted with an analog, dianisylneopentane, and the DDT-resistant housefly R5P, the salt marsh caterpillar Estigmene acrea (Drury), female Swiss white mice, and mouse liver microsomes (see Table 1). Additionally a model ecosystem was used to study biodegradation (see Table 2). In the model ecosystem, this compound accumulated in fish to about the same level as has been found in studies with methoxychlor; and the neopentyl group exhibited about the same stability as the trichloromethyl group (Coats et al . , 1974). Table 1 Radioactivity recovered Compound Housefly Caterp ill ar Mouse Liver homogenate I ++++ +++++ +++ ++ II +++ +++ + III ++ ++ +++ IV ++ + + V + + VI + + VII + + + + Conjugates S aci ds +++ + +++ + Unknown A + B ++ + + 107 Table 2 Metabolites found in the model ecosystem Alga Snail Fish Compound H 0 (Oedogonium) (Physa) (Gambusia) I + + + + II + + + III + + + IV + + V + + VI + + + VII + + + + Conjugates & acids + + + + Unknown A + + + + B + + + + CH ■0?-0H / H,C-C-CH, CH, Dianlsylneopentane (I) I (v) H3qtH3 CH3 X 3C0-^C-C-^~^>CH3 H2C CH3 (VII) (IV) 108 DIAZINON [0,0-Diethyl 0-(2-isopropyl-4-methylpyrimidin-6-yl ) phosphorothioate] In the beagle dog, metabolism of diazinon proceeded rapidly. Analyses of urine indicated the presence of two metabolites identified as: 4-hydroxy-2-isopropyl-6-methylpyrimidine (III) and 4-hydroxy-2- isopropanol-6-methylpyrimidine (Vila) (Iverson et al . , 1975). Three diazinon metabolites were isolated from sheep dosed by stomach tube. Identification was made by mass spectra: from urine, the 2- isopropanol diazinon (VI); 4-methanol diazinon (XI); primarily from fat, the isopropenyl analog (VIII) (Janes et al . , 1973; Machin, 1973). Liver microsomes rapidly degraded diazinon to diethyl phosphorothioic and diethyl phosphoric acids. Diazinon was degraded by hydrolases in mitochondrial, microsomal and soluble fractions of rat liver (Yang et al . , 1969; Yang, 1971). Houseflies, susceptible and resistant, degraded diazinon and diazoxon. The major metabolites were diethyl phosphorothioic and/or diethyl phosphoric acids. In addition to the MFO system which was responsible for the foregoing, there is another soluble system in the housefly which used reduced glutathione. The major metabolites were the same (Yang, 1971). Degradation of diazoxon by homogenates of Hokota strain (diazinon- resistant) and NAIDM strain (diazinon-susceptible) houseflies produced diethyl phosphate. Optimal pH was ca. 7.0. Resistant flies degraded more diazoxon than susceptible flies. The homogenate supernate degraded diazinon in the presence of reduced glutathione with no significant difference between rates by the supernatant of Hokota and NAIDM strains. The main degradation products were diethyl phos- phorothioic acid and 5[-(2-isopropyl-4-methyl-6-pyrimidinyl ) glutathione. Optimal pH was 8.5. Microsomal MFO plus NADPH metabolized diazinon to diazoxon and diethyl phosphorothioic acid (Shono, 1973, 1974 a and b). Metabolism of diazinon by gypsy moth larvae (Porthetria dispar L.) was qualitatively the same whether after ingestion or topical appli- cation. The major products were 2-isopropyl-4-methyl-6-pyrimidinol ; diazoxon; hydroxydiazinon; 2-(2-hydroxy-2-propyl )-4-methyl-6-pyrimidinol . Formation of these metabolites was reduced by the synergists 2,6- dichlorobenzyl-2-propynyl ether and piperonyl butoxide (Ahmad and Forgash, 1975). From submerged soild and rice paddies, microorganisms capable of decomposing diazinon have been obtained. These fall into three categories: 109 c o 00 u o 2 o 01 a e PL, I •A no 1. Sole carbon source - flavobacterium sp. 2. Synergism - Arthrobacter sp. plus Streptomyces sp. 3. Co -metabolism Arthrobacter "sp. Corynebacterium sp. , Pseudomonas melophthora, Streptomyces sp. Trichoderma viride Microorganisms accelerated hydrolysis of diazinon and subsequent mineralization of 2-isopropyl-6-methyl-4-pyrimidinol to C02 (Sethunathan, 1972). The inhibition of MFC1 by pesticide synergists was investigated. Piperonyl butoxide and NIA 16824 (O-isobutyl-0-propargyl phenyl phos- phonate) inhibited all oxidative reactions to the same extent. However, l-(2-isopropyl phenyl )imidazole inhibited conversion of thiophosphate to phosphate and oxidative de-arylation. There was no significant effect on hydroxylation of ring side chain (Smith et al., 1974). Ultraviolet irradiation of diazinon gives a mixture of products. One has been identified as 0,0-diethyl 0-(2-acetyl-6-methylpyrimidin-4-yl ) phosphorothioate (Machin and Quick, 1971). Ill DICAMBA (Banvel; 3,6-dichloro-o-anisic acid) [2-Methoxy-3,6-dichloro- benzoic acid] DISUGRAN (Racuza; methyl 3,6-dichloro-o-anisate) [Methyl 2-methoxy- 3,6-dichlorobenzoate] Breakdown of dicamba in bracken litter occurred rapidly. At 25C, of the initial dose (1.25 lb/acre) was lost in 4 days at pH 4. Raising the pH to 7.4 reduced the loss rate (Parker and Hodgson, 1966). Dicamba degraded rapidly in prairie soils when applied at rate of 1.1 kg/ha. At 25C over 50% dissipated in 2 weeks. In other studies over half was lost within 4 weeks and only 1UC02 and 3,6-dichloro- salicylic acid were detected (Smith 1973a and b, 1974b). Incubation of disugran with rumen fluid of ewes produced seven meta- bolites. Four were not identified. However, the three identified metabolites comprised about 95% of the total metabolites. Degradation proceeded primarily via ether cleavage and then ester hydrolysis. The third metabolite was 3,6-dichloro-o-anisic acid (Ivie et al . , 1974a). A radiochemical analytical procedure was used to monitor dicamba break- down in soil. At -5 ± 1C breakdown was not observed but was observed at 5 ± 1C. At temperatures above 15 ± 1C, over 80% of the dicamba was dissipated in 8 days. When heavy clay and sandy loam were used, 14 days and temperatures above 20 ± 1C were needed to degrade similar amounts of the herbicide (Smith and Cullimore, 1973). 112 DICHLOBENIL [2,6-Dichlorobenzonitrile] The fate of dichlobenil in alligator weed and parrot feather (Myriophyllum brasiliense) was investigated. In the latter, the major metabolite was the 3-hydroxy analog. Small amounts of the benzamide and benzoic acid analogs of dichlobenil were also observed as was 3-hydroxy-2,6-dichloro- benzamide. Conjugates of the 3-hydroxy compounds also occurred. There was other material not identified (Sikka et al . , 1974). In soil, degradation of dichlobenil was determined at 6.7 and 26.7C. At 6.7C, the half-life was 28 weeks after a ten-week lag; 19 weeks at 26. 7C. Only 2,6-dichlorobenzamide was detected (Montgomery et al . , 1972). In a farm pond treated with dichlobenil at 10 lb a.i. per surface acre, the concentrations in water and hydrosoil had decreased by 85 and 87%, respectively, after 7 weeks (Rice et al . , 1974). In other studies with pond water, more than 75% of the added dichlobenil disappeared because of volatilization. Some dichlobenil was metabolized microbiological ly to 2,6-dichlorobenzamide and other unidentified metabolites. A cell suspension of Arthrobacter sp. metabolized up to 71% of added dichlobenil in 6 days to dichlorobenzamide and small amounts of other compounds not identified. Evolution of lt+C02 from labeled dichlobenil indicated that some of this herbicide could be completely degraded in the environment (Miyazaki et al., 1975). 113 DICHLOROPROPENE (Component of DD) [Trans- and cis-dichloropropene] At 15 to 20C in sandy soils, 1 ,3-dichloropropenes exhibited an average half -life of 24 days and disappeared at the rate of 2 to 3.5% per day with no marked isomer difference. Some chloride was released but this slowed to about 3% after an initial rapid release. Chloroallyl alcohols are assumed to arise from dichloropropenes in soil. The trans- isomer {th = Ca+2 > H+ > Mn+2 > Co+2 > Zn+2 > Ni+2 > Cu+2 > Fe+3 > Al+3 (Khan, 1974) In studies with sandy loam, paraquat was degraded only slightly, if at all, over a seven-year period (Fryer et al . , 1975). 126 DISYSTON [0,0-Diethyl-S-(2-ethylthio ethyl )phosphorodithioate] Disyston was rapidly converted to its oxidative metabolites in soils. Conversion in soil was predominantly by side chain oxidation of the sulfur. The oxygen analogs form in small amounts only. Oxidation in flooded conditions was at a much faster rate than in upland soils (Takase et al . , 1972). 127 DITHIOCARBAMATES Under acid conditions, dithiocarbamates may form significant amounts of carcinogenic nitrosamines. In the presence of sodium nitrite and ziram, the carcinogen dimethyl nitrosamine formed in small amounts at pH 1.5 to 2.0 (Eisenbrand et al . , 1974). MANEB [Manganese ethyl enebisdithiocarbamate] After treatment of beans and tomatoes with maneb, residues were measured at intervals until 14 days post treatment. Residues on beans were higher than on tomatoes for unchanged maneb as well as ETU, ETM and EDA. Residues of these three metabolites were also found in soil 15 days after treatment (Newsome et al., 1975). Maneb was suspended in buffer pH=6 and aerated. Degradation products identified by TLC included ETM, ETU, EDA, CS2 and sulfur (Hylin, 1973). ZINEB [Zinc ethylenebisdithiocarbamate] When fruits and vegetables containing zineb were boiled, ETU was formed (Newsome and Laver, 1973). Maneb and Zineb formulations were studied under laboratory conditions of controlled heat and humidity. At elevated temperatures, zineb was less stable than maneb. The zinc-manganese coordination products, however, were considerably more stable than either zineb or maneb (Bontoyan and Looker, 1973). ETU [Ethylenethiourea) Although not a pesticide, there is considerable interest in its occurrence as a breakdown product of a group of ethylenebisdithiocarbamate fungicides very widely used. There is considerable interest too in its fate in the environment. 128 ll+C-ETU was injected into corn, lettuce, pepper and tomato seedlings. Some ETU was present after 14 days. Some 1UC02 was formed but the major degradation product in all plant tissues was identified as ethyleneurea (EU) (Hoagland and Frear, 1976). When ETU was administered to rats and guinea pigs, elimination was rapid. About 50% was eliminated within 24 h in urine. Elimination in feces was negligible (Newsome, 1974). Photolysis of ETU (x>285 nm) on a solid substrate produced 2-imidazolidone as the major product, bis (imidazolin-2-yl ) sulfide and an unidentified product. Aqueous solutions of ETU undergo slow photolysis but are stable to hydrolysis in the pH range 5.0 to 9.0 at 90C (Cruickshank and Jarrow, 1973). Although aqueous solutions of ETU were stable to sunlight, in the presence of dissolved oxygen and sensitizers, ETU was rapidly degraded. When less than 5% of the ETU remained, a compound was indentified as glycine sulfate. When the reaction was stopped while there was more than 50% of the ETU remaining, 2-imidazolidone was obtained (Ross and Crosby, 1973). 129 DS-15647 (Thiofanox) [3,3-Dimethyl-l-methylthio-2-butanone 0- (methyl carbamoyl ) oxime] Fully expanded leaves of cotton plants grown in the field were treated individually with 35S-labeled DS-15647. The sulfone and sulfoxide were formed. Metabolism to the sulfoxide was essentially complete in 4 days. Polar compounds not identified, the oxime and the oxime sulfoxide, also formed. Similar results were obtained with excised cotton leaves. Seedlings grown from treated seed gave the same results as those obtained in mature plants and in soil. The rate of the initial reaction was more rapid than that of the second, particularly in plants (Whitten and Bull, 1974a). 130 DYFONATE [O-Ethyl S-phenyl ethyl phosphonodithioate] The degradation of dyfonate was studied with a series of fungi: Aspergillus flavus, Aspergillus fumigatus, Fusarium oxysporum, Trichoderma viride , Aspergillus niger, Mucor alternans, Rhizopus arrhizus and Mucor plumbeus. All species degraded dyfonate to some extent. Degradation by P. notatum was slowest; M. alternans, R^ arrhizus and M. plumbeus were the most active species in producing water-soluble metabolites. In addition to dyfonate, the extracts contained dyfoxon, thiophenol , diphenyl disulfide, MPSO2 (methyl phenyl sulfone), ethylethoxyphosphonic acid (EOP) and ethylethoxy- phosphonothioic acid (ETP) and methyl phenyl sulfoxide (MPSO) (Flashinski and Lichtenstein, 1974a and b). Factors affecting the ability of soil fungi to degrade dyfonate included nturient supply, temperature, pH and incubation time. The studies indicated that the mycelium absorbed dyfonate and that meta- bolism of dyfonate occurred in the mycelium. Degradation apparently involved formation of the ethyl acetate-soluble metabolites: ethyl- ethoxyphosphonic acid, ethylethoxyphosphonothioic acid, methyl phenyl sulfoxide and methy phenyl sulfone. These were then metabolized to water-soluble compounds. For R. arrhizus, the optimum was at 15-25C and pH 6.0 to 7.0 (Flashinski and Lichtenstein, 1975). When plants were grown in nitrogen deficient nutrient solutions, concentrations of dyfoxon in greens were reduced due to deficiencies of all elements (potassium, calcium, and magnesium) except nitrogen (Talekar and Lichtenstein, 1973). Dyfonate was incorporated into soil at the rate of 5.6 and 11.2 kg/ha as granules or emulsifiable concentrate; and its persistence and absorption by plants was observed. Four months after application, 33-35% of the granular application and 38-41% of the emulsifiable concentrate application (both 5.6 kg/ha) remained in the soil. No dyfoxon was detected in soil. Potatoes, beets, and rutabagas had little or no detectable residue at either application rate. Wheat had 0.01-0.07 ppm dyfonate but little or none in the mature plant or in the grain. Carrots grown in soil treated at the lower rate had 0.35 and 0.04 ppm dyfonate and dyfoxon, respectively (Saha et al . , 1974). 131 EDB [Ethylene dibromide] In vitro studies of the enzyme catalyzed reaction between EDB and conducted. Chromatography and comparison with indicated the Dresence of S-(B-hydroxyethyl ) le main product (93%) and S^S^-bisCglutathione) [n vivo studies indicated that the reaction occurs (B-hydroxyethyl glutathione, glutathione were synthetic samples glutathione as th ethylene (7%). I primarily in the S- ( B-hydroxyethyl Later degradation ethyl ) mercapturi liver with formation of S; , glutathione sulfoxide and J[,S_ -bis(glutathione)ethylene. occurs primarily in the kidneys to yield ^-(B-hydroxy- c acid and its sulfoxide (Nachtomi, 1970). Br-CH2-CH2-Br + 6SH >- GS-CH2-CH2-Br + Br" + HH GSH. HOH GS-CH2-CH2-SG GS-CH2-CH2-0H + H+ + Br' Mercap-CH2-CH20H GS-CH2-CH2-0H 132 ENDOSULFAN (Thiodan) [6,7,8,9,10,10-Hexachloro-l ,5,5a,6,9,9a-hexahydro- 6,9-methano-2,4,3-benzo[e]dioxathiepin-3-oxide] Endosulfan residues on alfalfa were exposed to ultraviolet light and to sunlight while drying for 10 days. A third lot was dried in the dark. Residue analyses showed the presence of endosulfan isomers I and II, endosulfan diol (XI), endosulfan ether (VII), endosulfan a-hydroxy ether (XIV) and endosulfan sulfate (IX). No lactone was observed (<0.1%). In all three groups, the sulfate percentage of the total residue increased but the increase was most dramatic in the dark drying lot (Archer, 1973). In temperature stressed rats orally dosed with endosulfan I or II, endosulfan sulfate was the metabolite most commonly recovered from tissues, organs and feces regardless of temperature stress. The diol, a-hydroxy ether and lactone (X) were found in most urine and feces samples. Studies with the diol showed this to be converted to the a-hydroxy ether and that both diol and a-hydroxy ether were metabolized to the lactone in small amount (Whitacre, 1970). Degradation of endosulfan by a soil microorganism of the family Pseudomonad was studied. The alcohol was the main metabolite from either isomer. The 6- isomer also yielded small amounts of the endo- sulfan ether as well as i somen zed to the more stable a-isomer (Perscheid et al . , 1973). Endosulfan isomers (a and 3.) were incubated with Aspergillus niger. Endosulfan alcohol was formed from both isomers (El Zorgani and Omer, 1974). These same authors refer to studies by Domsch and coworkers in which endosulfan sulfate was also observed after exposure of microbes and fungi to endosulfan. After incorporation of endosulfan into soil, analyses indicated a half- life for the a-isomer of about 60 days and about 800 days for the B-isomer. Endosulfan sulfate formed in amounts equivalent to the endosulfan that decomposed. Potato tubers grown in the treated soil contained residues of both isomers and the sulfate (Stewart and Cairns, 1974). UV irradiation of endosulfan isomers gave a variety of products, depending on the medium used. a-Endosulfan (I) yielded compound III in n-hexane; compound IV in dioxane-water; and compounds VII to XIII in gas phase. e-Endosulfan (II) gave compound V and VI in dioxane- water and compound V in n-hexane-acetone (Schumacher et al . , 1973). 133 VIII / ' If xiv / Endosulfan H / Hydroxy — ch2oh Ether XIII XII XI E'ndosulfandiol 134 ENDOTHALL [7-Oxabicyclo(2.1 .1 )heptane-2,3-dicarboxyl ic acid] Aquatic microorganisms readily degrade endothall . One species of Arthrobacter, isolated from lake water and sediment, utilized endo- thall as a sole source of carbon for cell growth. When luC-endothall labeled in the oxabicyclo ring was used, the 14C was found in cellular amino acids, proteins, nucleic acids and lipids. Citric, aspartic, alanine and glutamic acid were labeled as well as C02 (Sikka and Saxena, 1973). When exposed to luC-endothall in tap water, bluegill absorbed the labeled material but only unchanged herbicide was found in the alcohol extractable fraction of the fish (Sikka et al . , 1975). 135 ETHION (Diethion) [S,S-Methylene bis(0,0-diethyl phosphorodithioate)] When sediment samples from a saline lagoon were incubated with ethion for 20 days, ethion degradation was slow. Analyses indicated the formation of sulfide from ethion. In these studies, ethion was the sole sulfur source (Sherman et al . , 1974). 136 Ethylene oxide (EO, ETO) When wheat is fumigated with ethylene oxide, S5% of the bound EO was converted to water soluble compounds. The EO residue concentration in the wheat was between 14 and 37.5 ppm and was distributed among water-soluble and water-insoluble proteins, organic acids, mono-oligo- saccharides, lipids, lipoproteins, starch, and bran (Pfeil sticker and Rasmussen, 1974). 137 FENAZAFLOR (Lovozal) [Phenyl 5,6-dichloro-2-trifluoromethylbenzimidazole- 1-carboxylate] NC-2983 [5,6-Dichloro-2-trifluoromethylbenzimidazole] A major degradation product of the acaricide fenazaflor was found to be 5,6-dichloro-2-trifluoromethylbenzimidazole (NC-2983). After application of NC-2983 to field plots, soil analyses indicated no significant disappearance in fall, winter or early spring but a rapid decline during the summer. About 85% of an NC-2983 application in summer disappeared within 135 days. When applied in the autumn, disappearance of a comparable amount required about one year (Ercegovich et al., 1972). 138 FENSULFOTHION (Dasanit, Terracur P) [0,0-Diethyl 0-(p_-methylsulfinyl ) phenyl phosphorothioateT After application to a sandy loam soil, fensulfothion degraded rapidly to the corresponding sulfone. Traces of the sulfone were found in rutabagas grown in fensulfothion-treated soil. It was also found in carrots, in which it persisted during a 4-year storage period when the carrots were frozen (Chisholm, 1974). 139 FLUENETHYL (Fluenetil, Flu, Lambrol ) [2-Fluoroethyl 2-(4-biphenylyl ) acetate] FLUOROACETIC ACID (1080) [2-Fluoroacetic acid] Studies with mice, houseflies and the two spotted spider mite clearly indicate that the toxicity of Flu depends on the release of monofluor- ethanol by ester cleavage of fluenethyl and subsequent oxidation to the monofluoroacetic acid. The latter is converted to fluorocitrate which inhibits aconitase (Johannsen and Knowles, 1974). Seeds of Acacia georginae, peanut (Arachis hypogaea L.) and bean (Phaseolus vulgaris L. var. Pinto) were treated with 1I+C-sodium fluoroacetate. Labeling was found in the lipids and in the water- soluble fractions. lltC02 also evolved (Preuss et al . , 1968). When lettuce plants were incubated with labeled fluoroacetate, a labeled material was obtained and identified as S-carboxymethyl- glutathione (Ward and Huskisson, 1972). 140 FLUORODIFEN (C-6989, Preforan) [2,41-dinitro-4-trifluoromethyl di phenyl ether] Rats, given a single oral dose of lltCF3-fluorodifen, excreted 48% of the dose in 48 h in urine; 23% in feces. Most (83%) of the urinary radioactivity in the 24-h sample was 2-nitro-4-trifluoromethyl phenyl - mercapturic acid. In vitro studies with rat liver homogenates indicated the formation of S-T2-nitro-4-trifluoromethyl phenyl )gluthathione after cleavage of fluorodifen (Lamoureux and Davison, 1974). From epicotyl tissues of pea seedlings, a soluble glutathione S-transferase was obtained. The enzyme, capable of cleaving the ether, had a pH optimum of 9.3-9.5. With labeled substrates, the cleavage products were separated and identified as p_-nitrophenol and S_-(2-nitro-4-trifluoro- methyl phenyl )gluthathi one (Frear and Swanson, 1973). This glutathione conjugate was also formed by peanut (Arachis hypogaea L.). O-Conjugates of p-nitrophenol and traces of the 2-amino analog of fluorodifen also formed. Other unidentified metabolites were observed (Shimabukuro et al . , 1973a). In other studies with peanut seedlings, metabolites identified included 2-ami no-4-trifluoromethyl phenol , 2-amino-fluorodifen and traces of p_-aminofluorodifen and 2,41-diaminofluorodifen. The major product was not identified (Eastin, 1971a and c). Cucumber seedlings were also exposed to labeled fluorodifen. Leaves, stem, cotyledons and root were analyzed. Metabolites identified included p_-nitrophenol , 2-aminofluorodifen, p_-aminophenol , 2,41-diaminofluorodifen and p_-aminofluorodifen (Eastin, 1971b). 141 FLURECOL (Flurenol, EMD-IT 3233) [9-Hydroxyfluorene-9-carboxylic acid] FLURECOL-n-BUTYL ESTER (IT-3233, Am' ten, Florencol, Flurenol -n-butyl ester) [r^-Butyl 9-hydroxyfluorene-9-carboxylate] 14C-labeled fluorecol -n-butyl ester was applied to leaves of Phaseolus vulgaris. Five metabolites were observed: two isomeric e-glucosides and three amino acid conjugates. The aglycone moieties were identified as 21- and 31 -hydroxy analogs of flurecol-ivbutyl ester (Wotschokowsky, 1972). 142 FORMETANATE [m-{ (Dimethylaminomethylene)amino}phenyl N-methyl carbamate] About 84% of formetanate injected into houseflies was metabolized in 4 h. The major metabolite was 3'-hydroxyformanilide. Microsomes from housefly abdomen plus NADH resulted in only 10% metabolism of formetanate. Incubation of labeled formetanate with alkaline soil resulted in a 50% decomposition in less than two days. The major products were 3-formamido- phenyl methyl carbamate, 3'-hydroxyformanilide and m-aminophenol . Irradiation of formetanate with UV (254 my) produced 3'-hydroxyformanilide (the main product), 3-formamidophenyl methyl carbamate and m-{ (dimethyl - aminomethylene)amino}phenol . N^-Demethylation of formetanate was of minor importance photochemical ly (Arurkar, 1971). 143 FRESCON (Trifenmorph, WL 8008) [N-Trityl morpholine] Rats eliminated 97% of a single dose within 96 h. Within the gut, frescon was probably hydrolyzed prior to absorption. The morpholine was excreted largely unchanged. Tri phenyl carbi no! was metabolized to a glucuronide in part and also hydroxylated (mainly para). The latter was conjugated with glucuronic acid (Beynon, 1971). When fish were exposed to frescon at 0.2 ppm, the only residue observed in fish after 30 min was unchanged frescon (Beynon, 1971). Rice plants grown in treated water contained residues of triphenyl- carbinol and hydroxytriphenylcarbinols (o-, m-, and p_-) and their glycosides. In water frescon hydrolyzes to tri phenyl carbi nol . Mud and sediment gradually adsorb frescon and the carbinol. In soil, within a few weeks frescon is aerobically converted to the carbinol which undergoes slow hydroxylation (Beynon, 1971). Hydrolysis t^ at 0.05 ppm PH 6.5 7.1 7.4 8.0 9.0 time in hours 3 10 28 ca. 100 ca. 1000 144 GARDONA [Dimethyl 2-chloro-l-(2' ,4' ,5'-trichlorophenyl )vinyl phosphate] Exposure of gypsy moth larvae to gardona produced metabolites, both free and bound, identified as 2,4,5-trichloroacetophenone, l-(2',4',5'- trichlorophenyl )ethan-l-ol , 2,4,5-trichlorophenacyl chloride and l-(2\ 4' ,5'-trichlorophenyl)-2-chloroethan-l-ol (Tomlin, 1972). 145 GLYPHOSATE [N-(Phosphonomethyl )glycine] When applied to clay loam or muck soil, 56 kg/ha of glyphosate was rapidly inactivated. This inactivation was probably the result of reversible adsorption to clay and organic matter (Sprankle et al . , 1975a). Iron and aluminum clays and organic matter adsorbed more glyphosate than sodium or calcium clays and was readily bound to kaolinite, illite, bentonite, charcoal and muck but not to ethyl cellulose. ll4C-Labeled glyphosate was degraded in soil and 11+C02 was released (Sprankle et al . , 1975b). 146 GRISEOFULVIN (Fulvicin) [7-Ch1oro-4,6-dimethoxycoumaran-3-one-2-spiro- 1 - ( 2 ' -methoxy-6-methyl cycl ohex-2 ' -en-4 ' -one ) ] Liver homogenates prepared from Charles River male mice and rats were incubated with griseofulvin. Analyses showed the presence of 4-desmethyl griseofulvin and 6-desmethyl griseofulvin (Chang et al . , 1973). Pre- treatment with phenobarbital increased both 4- and 6-desmethylation of griseofulvin whereas 3-methylcholanthrene increased only 6-demethylation in rats (Lin et al . , 1973). 147 HCB [Hexachlorobenzene] Single doses of 10 ppm of hexachlorobenzene were administered to rats and several Rhesus monkeys. In rat feces and liver, pentachlorobenzene (PCB) and unchanged HCB were identified by GLC-MS. Pentachlorophenol (PCP) and PCB were identified in urine and feces by GLC-MS. Tetra- chlorobenzene (TCB) was identified by GLC in rats and monkeys (Rozman et al., 1975). In other studies, after administration of a single oral dose of 14C-HCB to adult male rats, primary excretion was via feces (16%). No metabolites appeared to be present. In urine, less than 1% of HCB was excreted but analyses indicated the presence of PCB, TCB, PCP and 2,4,5-trichloro- phenol . Homogenates of liver, lung, kidney and small intestines were incubated with HCB. Trace amounts of chlorobenzenes were produced. Liver microsomal preparations with added NADPH produced chlorophenols. Pentachlorophenol probably formed a glucuronide or other conjugate. The studies also indicated the formation of glutathione conjugates (Mehendale et al . , 1975). Hexachlorobenzene was slowly decomposed by a mold that was capable of decomposing lindane. The only metabolite detected after 52 days was pentachlorobenzene. When pentachlorobenzene was added to a culture of the mold, degradation produced the following metabolites: pentachloro- phenol; 2,3,4,5- and 2,3,4,6-tetrachlorophenol ; 1 ,2,3,4-tetrachloro- benzene; 1,2,4,5- and/or 1 ,2,3,5-tetrachlorobenzene; 2,3,4-, 2,4,6- and 3,4,5-trichlorophenol ; and 1 ,3,5-trichlorobenzene (Engst et al . , 1975). Irradiation of HCB by UV (A>290nm) in quartz produced C02, HC1 and CI 2 (Gab et al . , 1975a). When sheep were dosed with HCB, residues in omental fat were approx- imately proportional to dose rates. Although about 1000 times lower in HCB concentration, blood also reflected the residue in fat. Similarly, tissue levels in pigs and chickens reflected feeding levels of HCB. The half-life for HCB in sheep, chickens and pigs was 10 to 18 weeks, 8 to 14 weeks and 10 to 12 weeks, respectively (Avrahami , 1975; Avrahami and Steele, 1972a and b). 148 HINOSAN (Edifenphos) [O-Ethyl S,S-diphenyl phosphorodithiolate] Hinosan was incorporated in fodder and fed to female goats for 10 days. Several goats were also administered hinosan orally via gelatin capsules. Urine, feces and milk were collected for analyses. At a dose level of 1 mg/kg, no hinosan appeared in the milk. At 10 mg/kg, residues appeared at extremely low levels but disappeared rapidly after 3 days. Low residue levels also appeared in tissues after 4 days. Analyses of urine, after administration of 10 mg/kg of hinosan, showed the presence of 13 metabolites but no hinosan was observed. The following metabolites were identified in urine by co-chroma tography by TLC and GLC: 0-ethyl S-phenyl hydrogen phosphorothiolate (ESP) (V) S_,S-di phenyl hydrogen phosphorodithiolate (SSP) (VII) 0-ethyl S-phenyl hydrogen phosphorodithiolate (ESSP (XII) 0-ethyl di hydrogen phosphate (EP) (X) S-phenyl di hydrogen phosphorothiolate (SP) (VI) phosphoric acid (PA) (XI) diphenyl disulfide (DPDS) (IV) methyl phenyl sulfide (MPS) (XIII) methyl phenyl sulfoxide MPSO) (XIV) methyl phenyl sulfone (MPS02) (XV) m- and p_-(hydroxyphenyl )methyl sulfoxide (m- and p-(OH)-MPSO) (XVII) m- and p_-(hydroxyphenyl (methyl sulfone (m- and p_-(0H)-MPS02) (XVIII) Since some of the metabolites were not determined without acid hydrolysis, they were probably conjugated. In feces, only MPS02 and some unchanged hinosan were observed (Ueyama and Takase, 1975). When administered to a rat and dog, hinosan was rapidly metabolized. Diphenyl disulfide was found in urine but benzenethiol was not observed. The 0-conjugate of hydroxyphenyl methyl sulfone was also present (Eben and Kimmerle, unpubl . , 1972). When applied to rice plants (Oryza sativa L. v. hatsukinode and v. jukkoku), hinosan persisted somewhat longer than many phosphorus insecticides. The half-life on rice leaves was about 4 days (Ishizuka et al . , 1973). Degradation of hinosan was primarily by cleavage of the P-S bond. 35S- and 32P-labeled hinosan was used to elucidate the metabolic pattern. Co -chroma tography indicated the presence of 0,0- diethyl S-phenyl phosphorothiolate (I), triphenyl phosphorotrithiolate (II), diphenyl disulfide (IV), S_-phenyl dihydrogen phosphorothiolate (VI), 0-ethyl S-phenyl hydrogen phosphorothiolate (V), S,S-diphenyl hydrogen phosphorodithiolate (VII), benzenethiol (III), benzenesulfonic acid (VIII), sulfuric acid (IX) and phosphate (XI) (Ueyama et al . , 1973). In other studies ethyl phosphate (X) was also observed (Takase et al . , 1973). 149 (H) :2Ht® IV t 0-sh DPDS III PSH , y S03H VIII t H2S0., IX X v>4 Hinosan / MX9 O-f-s-G ■SH C2H5 ESSP XII II 0 C2H50-P-SQ ESP OH V 0 HO-P 1 S 6 + SSP VII 8 C2H50-P-0H OH EP G>-sh PSH III HO-P-sQ OH VI SP H3PO„ m-/p- HO' PA XI "J^^-S-CH3 -*" je OH-f* m-/p-H0^S-C XVI -MPS O-5- , MPS |XIII "CHq j/ OH-MPSO m-/p-H0-Qi-CH3 -e~~ 0H-MPS02 XVIII XVII OS_ch3 XV MPSO, -S-CH. v/-j-CH3 MPSO XIV 150 IMIDAN [0,0-Dimethyl S-phthalimidomethyl phosphorodithioate] In diethyl ether, photolysis of imidan produced N-methylphthalimide (II) and N-methoxy methyl phthal imide (III). Further irradiation of N-methylphthalimide produced approximately another six compounds, three of which were identified as 3-hydroxy-2-methyl phthal imidine (IV) and the two isomers of 3-(l ' -ethoxyethyl )-3-hydroxy-2-methyl- phthal imidine (V). The latter appear to arise from the reaction of product IV and the ether solvent (Tanabe et al . , 1974). S II -CH2-S-P-0CH3 iCH3 J-CH2-0CH3 HC ^OH H3d\)-CH9- Va H OH 151 IRGASAN DP 300 [5-Chloro-2-(2,4-Dichlorophenoxy)phenol ] Technical formulations of tri-, tetra-, and penta-chlorophenols contain dimeric impurities. The main constituent of these impurities are 2-phenoxyphenols with 4-9 chlorine atoms. The bactericide known as Irgasan DP 300 contained 2,3,4-trichloro-6-(2,4-dichlorophenoxy)phenol . This compound undergoes ring closure with application of heat or when irradiated with UV (xmax = 290-430 nm). When Irgasan was subjected to heat and irradiation, only heat produced 2,7-dichlorodioxin (Nilsson et al., 1974). CI A1C1 OH CI Irgasan DP 300 or UV 2,7-Dichlorodioxin 1 ,2,3,7-Tetrachlorodioxin 152 ISOXATHION (Karphos) [0,0-Diethyl 0-(5-phenyl-3-isoxazolyl )phosphoro- " thioate] Isoxathion-ll+C was administered to Wistar strain rats. Radioactivity was eliminated rapidly mainly in the urine. Four major and seven minor metabolies were detected. Because of the small amounts available, the minor products were not identified. The major metabolites were identified as: (III) 3-hydroxy-5-phenyl i soxazol e ; (XIV) 5-phenyl-3-isoxazolyl sulfate; (XV) 3-(B-D-glucopyranuronosyloxy)-5-phenylisoxazole; and (XVI) hippuric acid. Compounds III, XIV and XV were also found in the tissues (Ando et al . , 1975). Persistence of isoxathion in soil was influenced by soil type and moisture content with an approximate half-life of 15 to 40 days in nonflooded soils and a much faster disappearance in flooded soil. In addition to C02, biochemical degradation produced: 3-hydroxy-5- phenyli soxazol e (HPI) (III); the rearrangement product, 5-phenyl-4- oxazolin-2-one (VII); benzoylacetamide (X); and benzoic acid (XII). Six non-persistent metabolites were tentatively identified as: isoxathion oxon (II); 3-methoxy-5-phenyli soxazol e (V); 2-methyl-5- phenyl-4-i soxazol in-3-one (VI); 2-acetyl-5-phenyl-4-i soxazol in-3-one (IV); 2,5-diphenylpyrazine (IX); and acetophenone (XI). There were strong indications also of conjugated material. Hydrolysis with boiling 6N HC1 for six h released HPI, benzoic acid and a-aminoaceto- phenone. The latter arises from 5-phenyl-4-oxazolin-2-one and its metabolites or degradation products (Nakagawa et al . , 1975). HPI (III) was stable when exposed to sunlight. When exposed to UV, HPI decomposed to yield primarily 5-phenyl-4-oxazolin-2-one (VII). Benzoic acid (XII) and benzoylacetamide (X) were also produced (Nakagawa et al . , 1974). 153 154 KEPONE [Decachloropentacyclo[5.3.0.02>6.03>9.01+'8]decan-5-one] MIREX [Dodecachloropentacyclo[5.3.0.02'6.03'9.04>8]decane] KELEVAN [Decachloropentacyclo[5.3.0.02>6.03>9.04'8]decan-5-ol-5- levulinic acid] Kepone hydrate was irradiated in cyclohexane with ultraviolet. There were two major products identified as compounds XI and XIa (Alley et al., 1974a). Mirex was absorbed more rapidly from digestive tract of female quail than of the males and was rapidly excreted. Male quail excreted more via feces than did female quail. No metabolism of mirex was observed (Ivie et al . , 1974c). In other studies, after administration of 14C- mirex, the half-life in fat of female and male quail was about 20 and 30 days, respectively, and in whole body of fish, 130 days. In fat of female rats, 10 months after being returned to a "clean" diet, residues of mirex had declined by only 40% (Ivie et al . , 1974d). In studies with young leghorn roosters, the amount fed correlated well with amount accumulated over a 20-week period. If: X = ppm in feed Y = ppm in fat Then: Y = a+bX and Y intercept a = 1.0508 slope b = +73.7628 correlation coefficient r = +0.9999767 (Medley et al . , 1974) When mallard duck eggs containing mirex were irradiated with UV and y irradiation, seven and eight products were formed, respectively. Two were identified and tentative identification of two other products was made (Lane et al . , 1976). Cows were fed rations containing mirex. Analyses of fat and milk were then conducted. Residue levels over a 31-week feeding period did not exceed 0.08 ppm in milk and 1.87 in omental fat when mirex was fed at 1.00 ppm (Bond et al . , 1975). In eggs of hens fed 1.06 ppm mirex, the residue level reached 2.03 ppm at 28 weeks and then began declining (Woodham et al . , 1975). Anaerobic incubation of sewage sludge with mirex gave indications of degradation. After two months incubation in the dark at 30C, the sludge was centrifuged and the supernatants were extracted. Gas chromatography in three columns, chromatography in two solvent systems 155 isf1" 11 i 11 ii n in IV 10 Kepone f gem-D1ol V vi OH 10 CI J -A >rJ> ^ "-C1. ■-C1. (trans) V^ (cis) XX ' XXI > 17' •*fch *^fZ7--Cl8,H /xxiv yw R=CH2-C-CH2-CH2-C-0CH,-CH i2-on3 156 on silica gel thin layer plates, and mass spectra were used to identify the metabolite as the 10-monohydro analog of mirex (Andrade and Wheeler, 1974a; Andrade et al . , 1975). Other studies with soil microorganisms were conducted with nine aerobic soils and four anaerobic lake sediments No mirex degradation occurred (Jones and Hodges, 1974). Photolytic degradation of mirex in cyclohexane or isooctane produced two compounds. The monohydro was narrowed to III or IV; the di hydro is believed to be one of four compounds XII, XIII, XIV or XV (Alley et al . , 1973). In other studies, the monohydro photoproduct was identified as compound III (Alley et al., 1974a). When mirex in tri ethyl amine was irradiated with UV, the major photo- product was compound II. A second compound was identified as III. A mixture of dihydro photoproducts formed was believed to be XX or XXI (Alley et al., 1974b). Pyrolysis of mirex produced hexachlorobenzene as the major product and hexachlorocyclopentadiene in small amounts. The vapor phase contained CO, C02, HC1 , Cl2, CC1 ^ and C0C12 (Holloman et al., 1975). Mirex was exposed on silica gel thin-layer chroma topi ates to sunlight or ultraviolet light. Slow degradation occurred. The major photo- product was identified as the monohydro derivative III. Another compound more polar than mirex was identified as kepone hydrate (VI). A compound appearing in small amounts was identified as the monohydro- kepone hydrate XI. Exposure of compound III to artificial light resulted in conversion to compound VII (Ivie et al . , 1974b). Irradiation (x>300nm) of kelevan in n-hexane produced compounds XXII, XXIII and V. Identification was made by chromatography, IR and mass spectra. When kelevan was irradiated in methanol, compounds XXIII and the methyl esters of kelevan and XXII were observed. In acetone, XXII was formed. When quartz filter was used, XXIV and XXV were formed. After prolonged {Sh h) irradiation of kelevan, mirex and kepone were found in 15 and 28% yield (Begum et al . , 1973). In other studies, kelevan was applied to potato leaves and to soil. Analysis after 11 weeks indicated the same metabolites were present in both. In addition to unchanged kelevan, kelevan acid, kepone and kepone acetic acid and some unextractable material were present. Similar results were obtained when the soil was analyzed one year later. GC/MS was used for identification (Sandrock et al . , 1974). 157 HO CI 0 0 ii n H2-C-CH2-CH2-C-0CH2-CH3 Kelevan CH2-C-CH2-CH2-COpH CH2-C00H Kelevan acid Kepone acetic acid CI 10- / Kepone 158 KITAZIN P [0,0-Diisopropyl S-benzyl phosphorothiolate] 32P and 35S-labeled Kitazin P was applied to rice plants. When applied as a spray, Kitazin P disappeared fairly rapidly. When applied to the water, the disappearance rate increased. The water-soluble metabolites were separated into five fractions. Products identified were: 0,0- diisopropyl hydrogen phosphorothioate (V); phosphoric acid (IX); isopropyl di hydrogen phosphate (VIII); diisopropyl hydrogen phosphate (VI); 0-isopropyl S-benzyl hydrogen phosphorothiolate (VII); and dimethyl sulfate. When the toluene-soluble fractions were chromatographed, eight metabolites were observed on TLC. 0,0-Diisopropyl 0-benzyl phosphoro- thionate (IV) and dibenzyl disulfide Jill) were identified by GLC (Yamamoto et al . , 1973). 159 u CO DC X ro ro U U 1 1 X u > 1 M o 1 X o r- tv X S3 ro ro U O ft. A X 33 ro ro U U 1 1 1 •H -H 1 1 J- O CO / 00 °A o •o r>» IV W X ro ro 1 1 X ss o I X otpm-o i o tv X ro U I X o °f\ t-- X IV X u u I •H I •H PM X! I H 160 LANDRIN [3,4,5- and 2,3,5-Trimethylphenyl N-methyl carbamate] The persistence of landrin in eight soils was studied. The half-life varied between <4 to >40 days. As pH increased above pH 7, the break- down rate increased. Although microorganisms played a role in the breakdown, alkaline hydrolysis was a major cause of landrin degradation (Asai et al . , 1974). Photolysis of landrin in ethanol or cyclohexane produced 3,4,5-tri- methyl phenol (Addison et al . , 1974). 161 N-Lauryl-L-valine Many organisms could utilize the sodium salt of this compound as carbon and nitrogen sources for growth. Pseudomonas aeruginosa AJ 2116 apparently cleaved the N-acyl linkage with release of 1 auric acid. Gas chromatography also produced two peaks corresponding to caprylic and capric acids. When 1LtC-labeled ^-lauryl-L-valine sodium salt was used, 11+C02 was also observed (Shida et al . , 1973). 162 LEPTOPHOS (VCS-506, Phosvel , Abar) [0-(4-Bromo-2,5-dichlorophenyl )■ 6-methyl phenyl phosphonothioate] After application of leptophos to tomato plants, initially degradation was very slow but accelerated three weeks after treatment. The phenol metabolite increased in fruit and leaves during the initial three weeks but then decreased. The oxon analog was detected in leaves but not fruit. In grapes, results were similar. The phenol increased during the first three weeks and then decreased (Aharonson and Ben-Aziz, 1974) 163 LUPROSIL [Propionic acid] Luprosil breaks down completely in the citric acid cycle. Successive reactions involving CoA, methyl ma lonyl CoA and succinyl CoA bring the luprosil into the cycle (Anon., BASF, 1974). 164 MALATHION [0,0-Dimethyl S-(l ,2-dicarbethoxy)ethyl phosphorodithioate] After topical application of 32P-malathion to adult larva of the cotton leaf worm (Spodoptrea littoral is), 32P-activity was distributed between hemolymph, gut and fat. About 23% of the applied dose was metabolized in 24 h. A major site of enzymatic attack occurred at the P-0-alkyl bond and then hydrolysis of the P-S bond to give thio- phosphoric acid. Oxidation of P=S to P=0 produced malaoxon. Hydrolysis of the esters gave mono- and di- acid derivatives. 0,0-Dimethyl phos- phorodithioic acid was isolated in small amount. Oxidation of this could give rise to the 0,0-dimethylphosphorothioic acid found. Dimethyl phosphate was also found. The latter gave rise to monomethyl phosphate and inorganic phosphate (Zayed et al . , 1973). With resistant and non-resistant housefly strains, in vitro studies showed that resistant strains degraded malaoxon oxidatively at a rate lOx higher than that of the susceptible strain. The oxidation product was malaoxon 3-monocarboxylic acid when a susceptible strain was used. The resistant strain produced some 3-monoacid but the malaoxon a- monoacid was probably the main metabolite. Positive identification, however, was not made (Welling et al . , 1974). Studies with an Arthrobacter sp. showed that this organism was capable of degrading malathion. Laboratory studies identified the metabolites as malathion half ester, the dicarboxylic acid, dimethyl phosphoro- dithioate and dimethyl phosphorothioate. O-Demethyl malathion was also observed but was non-biological in origin. Identification by TLC was confirmed by infrared spectroscopy (Walker, 1972). When larval homogenates of a malathion-resistant and malathion-susceptible strain of the Indian meal moth (Plodia interpunctella Hubner) were tested for esterase activity, the resistant strain had greater a-napthyl acetate esterase than the susceptible strain; less carboxyl esterase and butyryl- cholinesterase; and similar acetylcholinesterase activity (Zettler, 1974). A heterogeneous bacterial population was isolated from river water and incubated with malathion as a sole carbon source. About 1% of the malathion was converted to the dicarboxylic acid, diethyl maleate, and 0,0-dimethyl phosphorothioic acid. The major metabolite was the 3- monoacid. The bacteria present were identified as Flavobacterium meningosepticum, Xanthomonas sp., Comamonas terrigeri , and Pseudomonas cepacia (Paris et al . , 1975). 165 ■ CH3°\il J> p-s-ch— cr ch or N)c h H5C2^H 25 '» CH Csj CH30>"SH S CH3°J ^ ^*- CHj0;p-S-(jH-C>OC2H5 + Malathion ch3oJ 0_ / CHa-^C2H5 o-Malath1on monoadd N. / 6-Malath1on monoadd kc N-i CH33C^-SH * \JHH"^°H H5C2cf r ch3oJ Ji CH3(r"S~fH~'C;OH CH2"S)H Malathion dladd / CH3oJ CH3O>-0H + V HS-CH— C^qH CH2-C^H "5 -1 -1 4.8 x 10 M sec T pH 67 4.0 S kb 1 yr ka+b 5.5 + 0.3 27 8.0 36 h kc+d 3.1 + 0.2 27 8.0 24 d ke 1.8 ± 0.2 27 8.0 1 yr (Wolfe et al., 1975) 166 MALEIC HYDRAZIDE (MH) [1 ,2-Dihydropyridazine-3,6-dione] Activated carbon delayed decomposition of maleic hydrazide in soil. Degradation followed first order kinetics. The Freundlich k determined for adsorption on activated carbon was 2300 yg/g (Helweg, 1975). 167 MATACIL [4-Dimethyl ami no-3-tolyl -N-methyl carbamate] Matacil was added to an ascorbic acid system containing L-ascorbic acid, ferrous ions, EDTA and dissolved oxygen. After 2 h at 37C, the mixture was extracted and analyzed. Isolated compounds were identified by co-chroma tography and/or IR and MS. About 12 compounds formed. Seven of 12 products could not be identified. One was iden- tified as 4-amino-3-tolyl -N-methyl carbamate. Tentative identification was made for two compounds: hydroxy matacil and the N-hydroxymethyl matacil. Another compound co-chroma tographed with 4-monodemethylamino matacil. IR and mass spectrometry confirmed its identity. Another compound was identified as 4-N_-dimethyl ami no-3-methyl phenol (Balba and Saha, 1974). The major photoproduct from matacil irradiation (x>300nm) in ethanol or cyclohexane was 4-dimethylamino-3-methyl phenol (Addison et al . , 1974) 168 MEOBAL [3,4-Xylyl-N-methyl carbamate] Photolysis of meobal in cyclohexane produced only phenol and some polymer. In ethanol , in addition to the 3,4-dimethyl phenol , three other compounds were identified: 4,5-dimethyl-2-hydroxy-N-methylbenzamide; 2,3-dimethyl-6-hydroxy-N-methylbenzamide; and o- xylene (Kumar et al., 1974). H 0 H3C-A-C 169 MERCURY COMPOUNDS In studies with 48 patients who had ingested seeds treated with mercurials, methyl mercury was determined and its biological half- life in man was calculated to vary from 35 to 189 days with an average of 72 days (Al-Shahristani and Shihab, 1974). In the squirrel monkey, four days after administration of a single dose of methyl mercury chloride, blood and brain concentrations came into equilibrium. The biological half-time was found to be about 49 days and 134 days, respectively, in blood and whole body. Biotransformation of the methyl mercury produced inorganic mercury. In the liver, 20% of the total mercury was inorganic; in the kidney, 50%; in the bile, 30% to 85%; but in the brain less than 5% of the mercury was inorganic (Berlin et al . , 1975). Biotransformation of methyl mercury in the guinea pig produced a high mercuric level in the kidney and a low liver level (50% and 5%, respectively) (Iverson and Hierlihy, 1974). After exposure of bovine erythrocytes to methyl mercury chloride, rapid and almost complete uptake of mercury occurred. Over 90% of the mercury penetrated the bovine cell membrane and associated with intracellular hemoglobin. Various sulfhydryl agents elicited release from cells. Cysteine alone induced a transient release of methyl mercury from erythrocytes but did not facilitate equilibrium with albumin. Rat red cells released much less methyl mercury to albumin than human red cells (White and Rothstein, 1973). Single doses of 203Hg-methyl mercury chloride were administered into the rumen of a milk goat and a milk cow. Less than 20% of the dose appeared in the feces within 72 hours and no radioactivity was detected in the cow's milk. The half-time retention of the 203Hg from methyl mercury chloride was 22 days in goats (Sell and Davison, 1975). Methyl mercury chloride was incubated with intact and ghost erythro- cytes and reticulocytes of adult New Zealand white rabbits. Within 5 min these cells accumulated almost all of the available mercury (Garrett and Garrett, 1974). In cats administered a single oral dose of 203Hg-labeled methyl mercury chloride, the half-period of methyl mercury for whole body was 117.7 t 1.4 days including hair and 76.2 t 1.6 days excluding the hair (Hoi 1 ins et al . , 1975). 170 After injection of 203Hg-methyl mercuric chloride into adult Wistar rats, 3% to 6% of the total brain mercury was present in the inorganic form. This was more than from an equal dose of mercuric chloride. Myelin and mitochondrial fractions accumulated more inorganic mercury than other fractions (Syversen, 1974). When x ttCH3203HgCl was force fed to rats, the amount of C-Hg bond cleavage was calculated to be between 5.1% and 10.6% in blood fractions. Highest concentration of mercury was in the hemoglobin one day after force-feeding (Garcia et al., 1974a). In milk of lactating Sprague-Dawley rats which had been force fed labeled methyl mercury chloride, there was an average of 4.5% bond breakage in the milk; 6.2% in the cerebrum; 6.2% in the liver; 8.0% in the kidney (Garcia et al . , 1974b). Brains of Wistar rats, given CH3HgCl intraperitoneal ly ewery second day from 5 to 27 days of age, were analyzed. The myelin fraction contained a larger proportion of inorganic mercury than found in other fractions (Syversen, 1974). In rat bile, the principal methyl mercuric compound observed was methyl mercuric glutathione. This compound also formed in vitro with bile. A small amount of methyl mercuric cysteine also occurred in the bile. This increased with storage of the bile (Refsvik and Norseth, 1975). When ^-acetyl- homocysteine was intravenously administered, after methyl mercury chloride, urinary excretion of mercury increased. The corresponding thiol actone turned out to be more effective in removing mercury from the body (Aaseth, 1975). Administration of methyl mercuric chloride in the presence of selenium greatly increased the concentration of the mercury in the brain of rats and reduced uptake by kidneys (Chen et al . , 1975). Methyl mercury-203 was orally administered to Jersey cows. About 59% was absorbed. Tissue concentrations were kidney > liver > skeletal muscles > heart > smooth muscle > spleen > lung > brain > ovaries > pancreas. Of the total mercury body burden, 72% was in muscle and 7% in liver and only 0.17% appeared in milk in 14 days (Neathery et al . , 1974). Aspergillus niger and Penicillum notatum were able to grow and reproduce in limited amounts of methyl mercury chloride. Twenty- five and 20 ug Hg per gm fungal tissue was absorbed (Hardcastle and Mavichakana, 1974). Bacteria were obtained from river bottom sediments in an area highly polluted with inorganic mercury. When incubated with methyl mercury chloride, mineralization of the mercurial occurred (Billan et al . , 1974). Some enteric bacteria were capable of causing volatilization of 203Hg-methyl mercuric chloride (Schottel et al . , 1974). When methyl mercuric chloride was anaerobically incubated with human feces, Ch3Hg+ disappeared at a constant rate during a 7-day test. Methane was not observed (Edwards and McBride, 1975). 171 In studies with plasmalogens, methyl mercury chloride was soluble in this phospholipid. The methyl mercuric ion catalyzed rapid hydration and hydrolysis of the vinyl ether linkage to give a mixture of palmitic and stearic aldehydes plus the linolenic monoglyceride product (Segal 1 and Wood, 1974). Guppies accumulated methylmercury from solution but converted very little to inorganic mercury. When the guppy (Labistes resticulatus) and coontail (Ceratophyllum demersum) were exposed to water containing 203Hg-ethyl -mercuric chloride (EMC), the uptake of EMC was related to exposure time and concentration. Internal organs of the guppy contained the highest concentration of 203Hg and the half-life of 203Hg was about 20 to 23 days. The guppy and coontail were both capable of converting EMC to inorganic mercury (Fang, 1974). After a single oral dose to rats, methylmercury dicyandiamide was slowly excreted in feces and urine, primarily i-n organic form. Methylmercury dicyandiamide slowly broke down in kidneys and liver to inorganic mercury. Methylmercury dicyandiamide was rapidly absorbed into circulation and bound by the tissues, particularly by blood cells (Rusiecki and Osicka, 1972). Methylmercury hydroxide was shown to have a lower affinity than Cd++ or Hg++ for thionein. When Hg(0Ac)2 was intravenously injected into laying quail, the mercury was bound to lipovitellin and transported into ovarian follicles (Nishimura and Urakawa, 1972). A microorganism, found in activated sludge and identified as Pseudomonas oval is, tolerated mercury acetate (Tomoyeda et al . , 1973~T In other studies, R- factor systems in enteric bacteria were able to reduce Hg+ from Hg(0Ac)2 to elemental mercury (Schottel et al . , 1974). When solutions of mercuric acetate were irradiated with a 20 watt black- light having the spectral distribution of sunlight, methylmercurlc compound formed. In this reaction mercuric oxide can replace mercuric acetate. The studies indicated that mercuric acetate was hydrolyzed to mercuric oxide and acetic acid in water. The mercuric oxide stimulated the light-induced methylation of inorganic mercury (Akagi and Takabatake, 1973). A metallic mercury-releasing enzyme (MMR-Enz), which catalyzes the reduction of mercurials to metallic mercury, was induced when Pseudomonas sp. were incubated with PMA, PCMB, merzonin, mercuric chloride, and metallic mercury (Furukawa and Tonomura, 1972). In a study of organisms capable of degrading methyl mercury, 207 organisms from sediments and fish were screened with methyl mercury bromide. Thirty isolates were capable of degrading methylmercury with volatilization of labeled mercury (Spangler et al . , 1973a). In addition to Hg°, methane also formed (Spangler et al . , 1973b). 172 Liver preparations from rat, mouse, and guinea pig degraded methoxy- ethyl mercury chloride (MEMC) with formation of ethylene. No evidence of Hg° formation was observed. Preparations from rat brain and kidneys of rat, guinea pig, ferret, and chicken also degraded MEMC (Lefevre and Daniel, 1973). When phenyl mercuryacetate (PMA) was incubated with liver preparations from rat, mouse, guinea pig, ferret, and chicken, benzene was formed. Brain preparations from rat, guinea pig, and ferret and kidney preparations of rat, guinea pig, ferret, and chicken also degraded PMA (Lefevre and Daniel, 1973). A number of bacterial isolates were tolerant of PMA (Tomoyeda et al . , 1973) or capable of volatilizing 203Hg-PMA (Schottel et al . , 1974). In addition to Pseudomonas sp., Arthrobacter sp., Citrobacter sp., Enterobacter sp., Vibrio sp., and Flavobacterium sp. also degraded PMA. Elemental mercury vapor and benzene were observed products of degradation (Nelson et al.. 1973). When guppies, snails, elodea, and coontail were exposed to 2(53Hg-PMA in water, PMA was readily taken up and converted mainly to inorganic mercury. Small amounts of ethylmercuric chloride (EMC) were also formed. The biological half-life of 203Hg in guppies, coontail, and elodea was between 43 and 56 days but was dependent on the initial concentration. At higher concentrations the half-life was between 7 and 11 days. In snails, the biological half-life was about 10.8 days (Fang, 1973). When river sediments were incubated with PMA, some methylmercury formed. More was formed under more acidic conditions (Jacobs and Keeney, 1974). Phenyl mercuric salts were converted to diphenylmercury as the main product. Simultaneously, phenylmercuric chloride was produced in amounts related to the amount of chloride contaminations (Dressman, 1972). Incubation of liver preparations of rat, mouse, guinea pig, ferret, and chicken with £-chloromercury benzoate (PCMB) produced benzoic acid. Rat brain and rat, guinea pig, and chicken kidney preparations also degraded PCMB (Lefevre and Daniel, 1973). Photolytic half-lives of phenyl mercurials are summarized: Compound ti/2, hrs. Diphenyl mercury 8.5 ± 1.8 PMA 16.0+2.0 PMN 20.0 + 1 .0 Phenyl mercury B03 14.0 + 2.0 Phenyl mercury hydroxide 16.0 t 2.0 (Zepp et al., 1973). 173 The mechanism of mercury elimination in waste water was studied. Mercury removal rates were over 99.8% when waste water containing mercuric chloride was treated with acclimated sludge. It was found that the added mercuric chloride was removed rapidly by volatilization after reduction to metallic mercury. Optimum pH and temperature were 8 to 9 and 42 to 43C, respectively (Nakamura et al . , 1974a,b). In other studies, the mercury-resistant bacterium Pseudomonas K62 strain was incubated in culture medium for 6 h with various mercurials. Results are summarized in the following table. Mercury removal by Pseudomonas K62 (6x1 08 cells/ml) Hg-Compound Concentration (ppm) % Removal added mercury Added Without Ps. K62 With Ps. K62 HgCl2 30 11 65 Hg(CN)2 30 0 72 Hg(N03)2 30 0 47 Hg(0Ac)2 30 15 45 HgSO^ 30 25 73 Hg(SCN)2 30 9 55 Hgl2 30 14 69 HgO 15 29 69 PMA 100 0 80 Uptake of mercury in these studies was severely inhibited by sodium chloride, sodium nitrate, KH2P0it and K2HP04 (Suzuki et al . , 1968). Mature specimens of dungeness crabs, Cancer magister, were exposed to dissolved inorganic mercury in aquarium water, returned to unpolluted sea water, and then analyzed for total mercury. Experimental data indicated that inorganic mercury has a biological half-life of 20-25 days in the dungeness crab (Sloan et al . , 1974). In the mollusc, Tapes decussatus, the half-life was 5-10 days (Unlii et al . , 1972). When elemental mercury was incubated with pure culture of micro- organisms, oxidation and accumulation of mercury occurred. Six cultures were tested: P_. aeruginosa |_. coli P_. fluorescens B_. subtil is Citrobacter sp. B_. mega teri urn Concentration factors calculated for E_. coli , P_. fluorescens, and Citrobacter sp. were 196, 1202 and 222, respectively. The distribution of mercury in aquatic biota from a stream receiving a continuous input of Hg++ was also determined. Dragonfly nymphs (Neurocordulina alabamensis) and damselfly nymphs (Argia sp.) exhibited highest total 174 mercury levels. Methyl mercury was highest in mosquito fish (Gambusia affinis) , predaceous diving beetles (Dytiscidae) and water boatmen (Hesperocorixa sp.). No methylmercury was found in algae, fungi and bacteria (Holm and Cox, 1974). Studies with bovine serum albumin indicated that mercury (II) was bound at sites in addition to the carboxyl and thiol groups (Katz and Samitz, 1973). Within 5 min after exposure to mercuric chloride, intact and ghost erythrocytes and reticulocytes accumulated approxi- mately 30% (intact) and 50% (ghost) of the available mercury (Garrett and Garrett, 1974). Kinetic studies of mercuric chloride indicated that mercury was contained in three compartments of short, medium, and long retention time within the rat. Kidneys were the largest compart- ment for mercury and kidney retention probably accounted for the long- term compartment. The biological half-life was about 30-33.5 days (Phillips, 1972). When a goat was given 203HgCl2, less than 30% of the dose was absorbed. Excretion of 203Hg in milk accounted for 0.22% of the dose. Half-time of retention by goats of 203Hg given 203HgCl2 was 78 days (Sell and Davison, 1975). Suspensions of rat caecal and small intestinal contents were incubated with HgCl2. Analyses indicated that these materials were able to synthesize methylmercury (Rowland et al . , 1975). The ability of algae to grow in media containing HgCl2 was studied. Lag periods of 3 or more days were observed. The growth rate was then similar to that of controls without Hg. The rate of decrease of mercury content was not dependent on initial Hg concentrations except at the lowest concentration (2 pM) (Ben-Bassat and Mayer, 1975). In the presence of sublethal amounts of HgCl2, small amounts of methyl- mercury were produced during 7 days aerobic growth by the following bacteria: Pseudomonas fluorescens Aerobacter aerogenes Mycobacterium phlei Bacillus megaterium Escherichia coli and by mycelium of the fungi: Aspergillus niger Scopulariopsis brevicaul is Saccharomyces cerevisiae 175 A yeast, isolated from a stream and identified as Cryptococcus sp., was grown in media containing HgCl 2. Analyses indicated the presence of high levels of mercury in viable cells. The form of the mercury was not determined but is believed to be elemental (Brunker and Bott, 1974). When 203HgCl2 was incubated anaerobically with human feces, methyl- mercury was produced in amounts directly related to the amount of Hg+2 added. The disappearance of methylmercury occurred at a constant rate during the 7-day test. lhCHh was not observed (Edwards and McBride, 1975). One mercury resistant strain of E_. coli converted 95% of 10" 5 M Hg+2 (HgCl2) to metallic mercury at a rate of 4 to 5 n moles Hg+2/min/108 cells. Metallic mercury was eliminated as a vapor (Summers and Silver, 1972). In addition to the E_. col i , S_. aureua and P_. aeruginosa were also capable of carrying out these reactions (Summers and Lewis, 1973). Methylation activity is higher in tuna liver than in other fishes. Fractionation studies with tuna liver strongly suggested that the factor was methyl cobal ami n, a known methyl donor in many biological systems (Pan et al . , 1973). Studies have shown that Hg+2 may be non-enzymatically reduced to elemental mercury by humic acid (Alberts et al . , 1974) or by reducing agents such as ethylene and acetylene (DeFilippis and Pallaghy, 1975). In the presence of sulfur, inorganic mercury may be alkylated in aquatic environments. Sulfur photooxidation to sulfate couples with reduction of mercuric ions. A basic mercuric sulfate formed and was an effective photosensitizer for the methylation (Akagi et al . , 1974). The possibility that sediment materials might cause symmetrization and conversions of monomethyl mercurials into dimethyl mercury was inves- tigated. Results of this study indicated that alkylmercuric halides are not symmetrized under the test conditions although arylmercuric halides were. The procedure used consisted of placement of the mercurial halide on a basic Al 203 column and eluting with a hydro- carbon solvent (Cross, 1973). Studies were conducted to determine the kinetics of microbially mediated methylation of mercury in aerobic and anaerobic aquatic environments. From these studies the following was concluded: 1. Methylation can occur under aerobic or anaerobic conditions. 2. Methylation under both conditions is dependent on growth rate or metabolic activity of the methyl ating organisms, mercuric ion concentration, and availability of mercuric ions. 176 3. At neutral pH, monomethyl mercury is the main product but dimethyl - mercury forms in small amounts. 4. The rate of formation of the mono- and dimethyl mercury can be described by NSMR = YBn(Hgtotal)n where NSMR = net specific methylation rate y = coefficient of microbial activity 3 = coefficient of mercuric ion availability n = reaction order 5. The average reaction order value (n) is 0.15 and 0.28 for anaerobic and aerobic systems, respectively. 6. Methylation is temperature dependent only to the extent that it affects microbial activity. 7. Large amounts of Hg° are formed and removed from the aqueous phase when a gas is forced through the system. (Bisogni and Lawrence, 1975). 177 MESUROL [4-Methylthio-3,5-xylyl-N-methyl carbamate] Photodecomposition of mesurol produced only the compound 4-methylthio- 3,5-dimethyl phenol . This is the same product obtained by basic hydrolysis of mesurol (Kumar et al . , 1974). In alkaline soils, mesurol was rapidly hydrolyzed and CO2 evolved. Hydrolysis in acid soil was shown. The half-life varied between 4 days at pH 7.6 to more than 56 days at pH 4.1. While hydrolysis the main route of degradation in alkaline soil, in acid soil the primary route appeared to be oxidation to the sulfoxide prior to hydrolysis to the phenol (Starr and Cunningham, 1974b). 0=C-N-CH3 0 M was H,C alkaline soil -CH3 Mesurol Lacid soil H,C 0=S-CH3 0=S-CH3 178 METHAZOLE (Oxydiazol , Probe, VCS-438) [2-(3,4-Dichlorophenyl )-4-methyl 1 ,2,4-oxadiazol idine-3,5-dione] Wheat plants and Bermuda onions were placed in water containing lkC- methazole for 24 h and then removed and analyzed after being washed. Radioautography and ultraviolet light were used to visualize the materials on silica gel. With TLC, about seven compounds were resolved: two metabolites were not identified- however, acid hydrolysis (HC1 for 1 h at 90C) released methazole-methylurea (III) and methazole-urea (IV). In onions, metabolite II was in greater concentration than I; in wheat, metabolite I was in greater concentration. Acid hydrolysis of I gave predominantly methazole-urea and small amounts of methazole-methylurea. With metabolite II, the reverse was true. Two metabolites were not identified but did chromatograph similar to 6,7-dichloro-l-methyl-2- benzimidazolinone (VI) and the 5,6-dichloro analog (VII). Other conju- gates were present as evidenced by acid treatment of plant solids after methanol treatment and the release of metabolites I, III and IV. In wheat, 50 to 60% of the dose was accounted for by metabolites III and IV. In onions, methazole-methylurea was the predominant metabolite and methazole-urea (IV) was present only at low concentrations. Treatment of wheat seedlings with methazole-3-ll+C and methazole-phenyl-ll4C gave similar results. This showed that methazole was metabolized in wheat to form 11+C02 and the methyl urea metabolite (III). Some methoxymethyl- urea was also detected in extracts of wheat and onions (Dorough, 1974). Beans and cotton were treated with labeled methazole. Quantitative rather than qualitative differences were indicated. From cotton, 1- (3,4-dichlorophenyl )-3-methylurea (III) and 3,4-dichlorophenylurea (IV) were obtained. The latter was the major metabolite. In addition to these compounds, the hydroxymethyl derivative and three conjugates were observed (Dorough et al . , 1973). In other studies with cotton and prickly sida (Sida spinosa L. ) , compounds III and IV were also observed (Butts and Foy, 1974). After application of VCS-438 to cotton (Gossypium hirsutum L. 'Acala 4-42-77'), foliar penetration occurred within 3 h and increased with time. Cotton tissue readily metabolized VCS-438 to l-(3,4-dichloro- phenyl)-3-methylurea (DCPMU) and l-(3,4-dichlorophenyl jurea (DCPU). When plants were treated through the roots with VCS-438, DCPMU, DCPU and unidentified polar material formed. Digestion of plant residues with the proteolytic enzyme pronase indicated that some of the unex- tractable lkC may be complexes of DCPMU and DCPU with proteins (Jones, 1972). When metabolites I and II were fed to rats, nearly 50% of a single dose was excreted in the urine and 11% in feces within i day after treatment; 65 and 21%, respectively, in 6 days (Dorough et al . , 1973). 179 Water solutions of methazole-phenyl-^C were exposed to sunlight for 7 days. Analyses indicated that compounds III, VI and VII were present. In methanol, compounds VI, VII and VIII were observed (Dorough et al . , 1973). In other studies, irradiation of methazole in water also formed VI, VII and III and compound VIII in methanol (Ivie et al . , 1973). 180 CI VII V" VI ci-^ — 'o=c: c=o ch3 Methazole Compounds I & II CI _y . VjJ-C-fi-CH -OCH c^_y 8 VIII ci-J — ' o IV 4^V ^1 ^ \ii-C-l5-CH3 +C02 i-c-3 CIA' o I N-Con jugate III N-Conjugate -(\ /Vn-C-N-CHjOH —^O-Con Jugate ci ^_^ v >», J=\ 8 CI-/. . Vn-c-n-ch ^och 3 P1-" ' ' VIII 181 METHIDATHION (Supracide, GS 13005) [S-(2-Methoxy-5-oxo-A2-l ,3,4- thiadiazolin-4-yl )methyl 6,0-dimethyl phosphorodithioate] Methidathion was irradiated with UV of A = 254 my. TLC, IR, mass spectra and synthesis were used to isolate and identify nine products. The proposed breakdown scheme is indicated (Dejonckheere and Kips, 1974). 182 Methidathion was fed to a cow as a residue in forage. No intact methidathion was found in the milk and was found to be stable in rumen fluid for 24 h. Incubation with beef liver 10,000xg supernatant fraction degraded methidathion 74-86% within 30 min. Urinalyses showed the presence of dimethyl dithiophosphate and dimethyl thiophosphate (St. John, Jr., and Lisk, 1974). 183 METHOHYL (Lannate, DuPont 1179) [S-Methyl N- (methyl carbamoyl oxy) thioacetamidate] Charles River-CD rats were administered labeled methomyl . lltC02 and acetonitrile were observed. Urine metabolites were not identified (Harvey et al . , 1973). Radiolabeled methomyl was applied to tobacco, corn and cabbage. Rapid degradation occurred to produce CO2 and acetonitrile with a methomyl half-life of 3 to 6 days. Labeled lipids, Krebs cycle acids, sugars and other materials were also present (Harvey and Reiser, 1973). The half-life on cotton was found to be between 2 and 4 days (Bull, 1974). Radiolabeled methomyl was injected into 5th-instar cabbage loopers [Trichoplusia ni (Hubner)]. Unidentified water soluble metabolites were formed. Acetonitrile and other volatiles also probably formed (Kuhr, 1973). In soil, labeled methomyl was degraded to ll|C02 and other materials, some of which were reincorporated into normal components of soil organic matter (Harvey and Pease, 1973). 184 METHOXYCHLOR [2,2-Bis(p_-methoxyphenyl )-l ,1 ,1-trichloroethane] ETHOXYCHLOR [2,2-Bis(p_-ethoxyphenyl )-l ,1 ,1-trichloroethane] When 11+C-ring-labeled methoxychlor was incubated with a sheep liver microsomal preparation for 30 min at 39C, two products were identified: 2-(p_-hydroxyphenyl )-2-(p_-methoxyphenyl )-l ,1 ,1-trichloroethane (8.13%) and 2, 2-bis(p-hydroxyphenyl )-l ,1 ,1-trichloroethane (3.44%) (Hirwe et al., 1975). Chemical decomposition of methoxychlor was slow in water. The half- live at pH 5 to 9 and 27C was 100 days. The photolytic half-life in distilled water was 37 days. In some river waters, methoxychlor photolysis in sunlight was rapid with a half-life of 2 to 5 h. The ethylene analog (DMDE) was formed in each case (Zepp et al . , 1975). Methoxychlor was administered orally to mice in olive oil and topically in acetone to flies. Excrement was collected. Identification of metabolites was by thin-layer chromatography. O-Demethylation was observed with both species and the monohydroxy and dihydroxy metabolites were observed. Similar results were obtained with mouse liver and housefly microsomes (Hansen et al., 1974). CH30-Q-|hQ-0CH, ■CH.0- 1 cfS0H X CH3O-Q-C-0. 0CH3 CH30^|- 0CH3-^ CH30^C-Q-0CH; •13 Methoxychlor H0-Oi- h°- t-°h ci2 (VI) (IV) ho- (V) CI. :ia (VII) 188 Table 2 Methyl chl or distribution in model ecosystem Compound H20 Algae Snail Mosquito Fish II III IV V VI VII + + + + + + Unknown I II III IV V + + + + + + Conjugates Polar metabol ites + + + + + + 189 METHYLENEDIOXYPHENYL COMPOUNDS PIPERONYLIC ACID Pseudomonas fluorescens strain PM 3 was used to prepare a soluble fraction containing oxidative activity. When this was incubated with piperonylic acid, oxidative attack produced protocatechuate and formate. One mole of 0? was consumed per mole piperonylate and NADH or NADPH was required (Buswell and Cain, 1973). 190 MOBAM [4-Benzo[b]thienyl N-methyl carbamate] Resistant and susceptible strains houseflies rapidly metabolized mobam. Differences were quantitative rather than qualitative. Of the five to six metabolites produced, one was identified as 4-hydroxybenzothio- phene (Morallo, 1970). 191 MOCAP (Ethoprop) [O-Ethyl S,S-di propyl phosphorodithioate] When mocap was administered to rats, the urine contained despropyl mocap, 0-ethyl phosphoric acid, S-propyl phosphorothiolic acid and desethyl mocap. Rat and rabbit liver supernatant enzymes de-ethyl ated mocap in the presence of glutathione and formed S-ethyl glutathione. Despropyl mocap was also isolated from liver microsomes and supernatant and from plants, ^-propyl phosphorothiolic acid was also present in plants. Methylene chloride extracts of bean and corn plants, grown in mocap-treated soil, contained ethyl propyl sulfide, ethyl propyl sulfoxide, ethyl propyl sulfone and propyl disulfide. Traces of S^ methylation products and subsequent oxidation were observed: methyl propyl sulfide, methyl propyl sulfoxide and methyl propyl sulfone (Iqbal, 1971). 192 MONITOR (Methamidophos, acephate-met, Tamaron, Ortho 9006) [0,S-Di methyl phosphoramidothioate] ORTHENE (Acephate) [0,S_-Dimethyl N-acetyl phosphoramidothioate] Within 1 h, 130 day-old loblolly pine seedlings absorbed and distributed ll*C-orthene from nutrient solution. Metabolites were separated by TLC. Cochromatography and GLC were used to identify the main metabolite as 0,S_-di methyl phosphoramidothioate (Monitor) and another unidentified compound (Werner, 1974). In plant tissue, orthene is partially metabolized to 0,S-dimethyl phosphoramidothioate, the active ingredient in the insecticide monitor (Leary, 1974). The alkaline hydrolysis of monitor was investigated. P-0 bond cleavage occurred in aqueous potassium hydroxide. In the methanol and acetone solutions, P-S bond cleavage occurred. In the aqueous solution, S- methyl phosphoramidothioate formed; in the less polar methanol and acetone, 0-methyl phosphoramidate. The potassium salt of 0-ethyl and 0-propyl phosphoramidate were the main products formed in ethanolic and propanolic potassium hydroxide. Dimethyl sulfide also formed. The second order rate constants for P-0 and P-S cleavage were determined in potassium hydroxide at 27C for monitor and two closely related analogs k, M"1 rnin"1 0,S-dimethyl phosphoramidate 0,S-dimethyl t^-methyl phosphoramidate 0,S-dimethyl M,N-dimethyl phosphoramidate P-0 P-S 8.4 1.0 x 10"3 0.6 4.4 x 10-2 1.5 x 10"1* (Fahmy et al . , 1972) 193 NAA [a-Naphthaleneacetic acid] Conjugation of NAA in plant tissue studied. Eleven to 14-day- old cowpea plants (Vigna sinensis, Endl . , cultivar Black Eye, Early Ramshaw) were used. Leaves, floating on a-NAA-buffer solution, quickly formed NA-glucose. The formation of NAA-aspartate followed a 2 to 4 h lag (Goren and Bukovac, 1973). When Kinnow mandarin fruits were dipped in aqueous solutions of NAA, four metabolites were formed. Two of these were in small amounts and were not identified. The other two, in larger amounts, were identified as the a-NAA-aspartate and a-naphthylacetyl-e-D- glucose (NA-glucose) (Shindy et al . , 1973). 194 NEMACUR (Bay 68138) [O-Ethyl 0-(4-methylthio-m-tolyl ) N-isopropyl phosphoramidate] After application to turf grass, nemacur was oxidized to its sulfoxide and sulfone (Bowman, 1972). 195 NEODECANOIC ACID (NDA) [Mixture of di-a-branched decanoic acids] 14 C-Carboxy labeled neodecanoic acid was applied to onions to dry the tops. Some C02 was formed during the first 12 days. Thereafter ll+C02 formation was negligible. When onion foil age containing 1UC-NDA was applied to muck soil, 11+C02 was formed over a 30-day period with little change in the rate of evolution. (Gilbert et al . , 1974). 196 NIAGARA 10637 [Ethyl propyl phosphonate] When pea seedlings were treated with ethyl propyl phosphonate, ethylene was apparently produced. In ancillary studies, ethylene and propylene were produced when this phosphonate was exposed to oxygen in combination with a reduced metal. Of the three systems studied, the cuprous system was most effective; ferrous system, least; and metallic copper intermediate (Dollwet and Kumamoto, 1970) 197 N-SERVE (Nitrapyrin) [2-Chloro-6-trichoromethylpyridine] N-Serve was incubated at 20C and IOC in three soils. The half-life at 20C for the three soils was 9, 15 and 16 days for coarse sandy loam, loamy sand and loam, respectively; and 43, 77 and 43 days, respectively, at IOC (Herlihy and Quirke, 1975). Carboxy-labeled 6-chloropicolinic acid(6-CPA), administered to a rat, was rapidly eliminated. Urine collected during the first 8 h showed the presence of 6-CPA and the N-(6-CPA) glycine conjugate. The half-life of 6-CPA in the rat was 2.4 h (Ramsey et al., 1974). C-Cl Cl-^N^S COOH CI 6-CPA N-6-CPA Glycine IN|-CH2-C00H H 198 ORYZEMATE [3-Allyloxy-l ,2-benzisothiazole-l ,1-dioxide] When applied to rice plants, oryzemate was preferentially accumulated in plant leaves. Acetomitrile extracts of rice shoots showed the formation of products which were identified as: ally o-Sulfamoylbenzoate, saccharin and its N^g-D-glucopyranosyl conjugate (Uchiyame et al . , 1973). -CH2 -CH=Cn2 Oryzemate C-0-CH2-CH=CH2 -NH: Conjugate 199 OXADIAZON [2-tert-Butyl-4-(2,4-dichloro-5-isopropoxypheny1-A2- 1 ,3,4-oxadiazol in-5-one] 11+C-Oxadiazon was applied to submerged soil in which rice plants (Oryza sativa L. v. kimmaze or v. nihombare) were grown. Once taken into root tissue, oxadiazon was translocated to shoots and leaves. Metabolism of oxadiazon in plants involved the side chain primarily and produced dealkylated metabolites, an alcholol, and an acid in shoots of seedlings and straws of plants at harvesting. Most of the radioactivity in the roots, shoots or straws, however, was unchanged oxadiazon. The metabolites were identified as the following derivatives: -4-(2,4-dichloro-5-methoxyphenyl )- (III) -4-(2,4-dichloro-5-hydroxyphenyl )- (IV) -4-(2,4-dichloro-5-ethoxyphenyl )- (II) 2-[2-(2-methyl propanoic acid)]-4-(2,4-dichloro-5-hydroxyphenyl )- (V) 2-(2-methylisopropanol)- (I) A sixth metabolite, wherein the nitrogen ring had been opened, was also found and identified as l-(2,4-dichloro-5-isopropoxyphenyl )-l- methoxycarbonyl-2,2-dimethylpropanoylhydrazine (VI) (Hirata and Ishizuka, 1975; Ishizuka et al . , 1975). 200 CH3 I R2 ■ C-CH20H CH, II R1 - C2H50- III R] - CH30 IV R1 - -OH V R, VI -OH m3 ■C-COOH \ CH, H CH,-C-CH, 3 i 3 Cl-fVfUc'-fcHj ^( H CH, CI 201 PARATHION [0,0-Diethyl 0-p_-nitrophenyl phosphorothioate] Mixed function oxidase enzymes metabolized parathion to phosphate and diethyl phosphorothioate. Desethyl parathion was identified (Wolcott, 1971). When 35S-parathion was incubated with rabbit and rat hepatic microsomes, a good portion of the released sulfur in paraoxon formation became bound to microsomal macromolecules. This was decreased by Cu2+ which is known to inhibit MFO (Poore and Neal , 1972). Over 90% of the radioactivity administered to rats as 14C-ethyl parathion was eliminated within 72 h. In urine, the principal radioactive meta- bolites of paraoxon were diethyl phosphoric acid and desethyl paraoxon. Some bound p_-nitrophenol in urine was indicated. In vitro studies with microsomal enzymes degraded li+C-paraoxon to desethyl paraoxon, diethyl phosphoric acid, monoethyl phosphoric acid and an amino acid conjugate of paraoxon. Ethanol and acetaldehyde were also found in small amounts. When rats were pretreated with microsome inducers, the microsomes prepared from these rats produced ethanol from the paraoxon. When NADPH was added to the incubation mixture, paraoxon degrading activity was greater than without NADPH or with NADH (Ku and Dahm, 1973). In other studies with rat liver cells, data indicated that the soluble fractions obtained at 105000xg and 500000xg were primarily responsible for the degradation of parathion to water-soluble metabolites. Analyses indicated that aminoparathion was the primary metabolite produced by soluble cell fractions, followed by paraoxon. Small amounts of p_-nitro- phenol were also detected. Parathion was reduced to aminoparathion and oxidized at the same time to paraoxon. The data indicated that paraoxon was more readily degraded than parathion. It appeared that parathion and paraoxon were degraded to water-soluble materials primarily by soluble fractions. Enzymes in the soluble fraction reduced parathion to aminoparathion. Some oxidation to paraoxon was also affected. Paraoxon was degraded mostly by particulate-associated enzymes through hydrolysis to p_-nitrophenol . The largest amounts of water-soluble metabolites were produced by the soluble fractions which also reduced paraoxon to aminoparaoxon (Lichtenstein et al . , 1973). The nature of the serum enzyme catalyzing paraoxon hydrolysis was partly characterized. The enzyme, paraoxonase, apparently has a single binding site (Lenz et al . , 1973). Weanling Holtzman rats, male and female, were injected with parathion. Cochromatography was used to identify tissue residues as consisting of diethyl phosphorate (DEPA), diethyl phosphorothioate (DEPTA), paraoxon and parathion. Whereas liver, kidney, skeletal muscle and plasma contained residues of all four compounds, only parathion and paraoxon 202 were found in brain and fat tissues. DEPA and DEPTA occurred as the major metabolites in urine with parathion and paraoxon present as traces only. Higher paraoxon levels were present in plasma and brain of weanlings than of adult rats. In vitro studies with liver homogenates showed that adult male rats possess higher activity than weanlings or adult females for both the oxidative and hydrolytic metabolic pathways of parathion (Gagne and Brodeur, 1972). The comparative metabolism of parathion to p_-nitrophenol in rats and lobsters was measured j_n vitro. The rate was considerably greater in rats than in lobsters. No paraoxon could be detected (Carlson, 1973). Oxidative activation of methyl parathion and ethyl parathion in vitro by NADP-glucose-6-phosphate-fortified mouse and liver homogenates were measured. Fish liver homogenates did not differ in their ability to cleave both parathions to p_-nitrophenol and the respective dialkyl phosphorothioates. In these studies, enzymatic hydrolysis of the oxygen analogs was negligible. Fish liver homogenates without added cofactors degraded less than 10% of methyl parathion and no ethyl parathion. Addition of GSH increased methyl parathion degradation but did not enhance ethyl parathion degradation (Benke et al . , 1974). Dearylation of parathion occurred predominantly via microsomal MFO. In resistant fish, highest MFO levels correlated with highest parathion tolerance (Chambers and Yarbrough, 1973). Parathion was applied to peach trees. Residue analyses showed the presence of S-ethyl parathion and paraoxon as well as parathion. Degradation of S-ethyl parathion was very rapid with EC, WP and encap- sulated parathion formulations (Winterlin et al . , 1975). After application of parathion to cotton, analyses indicated a constant increase in photoalteration products. Products found on the foliage included S-ethyl parathion, S-phenyl parathion, paraoxon and p_-nitro- phenol (Joiner and Baetcke, 1973). When parathion was applied to spinach in the field, paraoxon, diethyl phosphate and p_-nitrophenol residues increased. Aminoparathion, S-ethyl parathion and ^-phenyl parathion did not increase in percentage of harvest residues or were undetectable (Archer, 1974). In other studies, parathion was incubated with spinach homogenate. TLC and gas chroma- tography were used to demonstrate the presence of parathion, amino- parathion, hydroxylaminoparathion, and nitrosoparathion. Non-enzymatic reduction of nitrosoparathion by NADPH to hydroxylaminoparathion was also demonstrated (Suzuki and Uchiyama, 1975). In submerged soils, parathion degraded to aminoparathion. In upland conditions, aminoparathion was not detected. Addition of Flavobacterium sp. to the soil accelerated decomposition of parathion to p_-nitro- phenol (Sethunathan and Yoshida, 1973). A bacterium obtained from 203 flooded alluvial soil was identified as a Pseudomonas sp. When this organism was incubated with parathion, hydrolysis to p_-nitrophenol occurred within 3 h. Release of nitrite from p_-nitrophenol occurred within 24 h. A Bacillus sp., also obtained from flooded alluvial soil, liberated nitrite from p_-nitrophenol but not from parathion (Sethunathan, 1973; Siddaramappa et al . , 1973). When Rhizobium japonicum and R. meliloti were incubated with parathion, 95% of the parathion was not detectable after 50 h. Degradation proceeded primarily via aminoparathion which accounted for about 85% of the initial parathion. Diethyl phosphorothioic acid (DEPTA) accounted for 10%. The remaining 5% was unreacted parathion. No paraoxon was detected (Mick, 1969). Microorganisms from Lake Tomahawk were incubated with parathion. Degra- dation to aminoparathion occurred under aerobic and anaerobic conditions. Aminoparathion underwent further degradation aerobically but not under anaerobic conditions (Graetz, 1970). In some studies, after addition of methyl parathion to soil, the oxon was identified (Baker and Applegate, 1970). The persistence of parathion was partially dependent on soil type. In some soils degradation was rapid and probably through a combination of hydrolysis and strong microbial activity. In other soils, parathion loss was slow and attributable to hydrolysis. In Madera sandy loam, after parathion was added at 200 ppm, aminoparathion was not observed although parathion residues declined after 10 days. However, with parathion at 20 ppm in this soil and submerged under water, 3 ppm aminoparathion was recovered after 7 days (Iwata et al . , 1973). At exaggerated levels (30000 to 95000 ppm), parathion was applied to field soil plots as an emulsifiable concentrate or wettable powder. Degrada- tion was slower than anticipated and persisted at relatively high levels for 5 years after gross topical contamination with parathion (Wolfe et al., 1973). Degradation of parathion proceeded via hydrolysis to p_-nitro phenol and diethyl phosphorothioate when adsorbed on kaolinites. Ca-kaolinite was most active (Saltzman et al . , 1974). After exposure of parathion for 35 days to ultraviolet irradiation, 12 products were identified: paraoxon 0,S-di ethyl 0-p_-nitrophenyl phosphate 0,0-di ethyl S-p_-nitrophenyl phosphate p_-nitrophenol p_-aminophenol diethyl phenyl phosphate 204 0,0-diethyl O-phenyl phosphorothioate 0-ethyl 0 ,0-bi s (£-ni trophenyl )phosphorothioate ethyl bis(p_-ni trophenyl phosphate) diethyl phosphate, free acid monoethyl phosphate, free acid phosphate (Joiner and Baetcke, 1974). Parathion was dissolved in 80% aqueous ethanol or 80% aqueous tetra- hydrofuran and irradiated at 2537a. Photolysis in either solvent produced 0,0,S_- triethyl phosphorothioate as the major product and lesser amounts of triethyl phosphate, paraoxon, ethanethiol , and p_-nitrophenol . Photolysis of paraoxon under identical conditions yielded triethyl phosphate (Grunwell and Erickson, 1973). In other studies, photolysis of parathion produced 15 products of which 12 were identified and confirmed by infrared spectroscopy: ethyl paraoxon, S-ethyl parathion, S-phenyl parathion, p_-aminophenol , diethyl phenyl phosphate, diethyl phenyl phosphorothioate, ethyl bis(£-ni trophenyl) phosphate, ethyl bis(p_-ni trophenyl )phosphorothioate, diethyl phosphate and monoethyl phosphate. After application of 14C- parathion to cotton plants exposed under different environmental conditions, identification of photo-alteration products after extraction was by thin- layer chromatography and liquid scintillation spectroscopy: paraoxon, £-nitrophenol , S_-ethyl parathion and ^-phenyl parathion. As much as 15.4% of the applied ^C-parathion remained after 28 days (Joiner, 1972; Joiner and Baetcke, 1973). Sampling of air downwind from a parathion-treated prune orchard revealed the presence of parathion and paraoxon as well as some p_-nitrophenol (Woodrow et al . , 1975). Methyl parathion was incubated with isolated bacteria strains from water from the Vistula River (Poland) and from municipal sewage. These studies indicated that degradation of this pesticide was due to Bacillus cereus and to Bacillus sp. 8. The presence of other organic material apparently accelerated the biodegradation. Most rapid degradation was observed when serine, threonine, asparagine, and alanine were present (Maleszewska, 1974). In other studies, p_-nitrophenol , a metabolite of parathion, in milk was fed to houseflies. An observed conjugated metabolite behaved like the glucose-6-phosphate analog of p-nitrophenol (Heenan and Smith, 1965). 205 PCB (Aroclor, Clophen, KC, Kanechlor, Phenoclor) [Polychlorinated bi phenyl] Following intravenous administration to rats of 4-chloro, 4,41-dichloro, 2,21,4,5,51-pentachloro- and 2,2i,4,41,5,5Lhexachlorobiphenyl , these PCBs were initially rapidly removed from blood and stored in liver and muscle primarily. Redistribution to skin and adipose tissue followed. Half-lives were calculated for each compound: Half-life, h Bi phenyl Blood Liver Muscle Skin Adipose Feces 4-chloro- 4.7 120.0 4.9 85.6 1.26 68.2 4.78 74.0 0.79 15.7 4,4!-dichloro- 5.25 39.6 6.1 99.2 0.131 35.2 11.4 87.4 5.46 50.6 22.2 2,21,4,5,51- pentachloro- 0.53 27.7 256.7 0.25 2.8 40.1 193.0 2.23 613.4 43.0 613.0 51.3 389.0 39.2 211.0 2,21,4,41,5,51- hexachloro- 3.77 27.1 1359.0 2.4 18.3 1308.0 49.0 642.0 Following administration of the PCBs, there was an initial very rapid phase when part of the dose was removed from the tissue. This was followed by a much slower rate of removal. The respective decay rates are summarized (Matthews and Anderson, 1975b). After intraperitoneal injection of 4-chlorobiphenyl in young male rats, urine and feces were collected. A mono- and dihydroxychlorobi phenyl was observed (Hutzinger et al . , 1972a). When 4-chlorobiphenyl was fed to rats, 4-chloro-4i-hydroxybi phenyl was obtained (Safe et al . , 1974). In subsequent studies, this metabolite was administered intraperitoneal ly to rats. Urine and feces were collected and analyzed. Mass and NMR spectroscopy identified the major urinary compound as 4i-chloro-3,4-dihydroxybiphenyl . Two other dihydroxy compounds were observed but could not be separated by chromatographic procedures. However, demethylation of urinary chloromethoxy analogs gave only one product, 4i-chloro-3,4-dihydroxybiphenyl . This indicated that the two components were 4i-chloro-3-methoxy-4-hydroxybiphenyl and 4i-chloro-4-methoxy-3-hydroxybi phenyl . A fourth urinary compound was identified as 4i-chloro-4-methoxy-3,5-dihydroxybiphenyl . No fecal metabolites were observed (Safe et al., 1975a). 206 When 4-chlorobiphenyl was administered to rabbits, the compound was metabolized to 41-chloro-4-hydroxybiphenyl and 41-chloro-3,4-dihydroxy- biphenyl. The 4-hydroxy compound was metabolized by rabbits to the 3,4-dihydroxy analog and small amounts of 41-chloro-4-hydroxy-3- methoxybi phenyl and 41-chloro-3-hydroxy-4-methoxybiphenyl . The results of this study were consistent with the formation of an arene oxide intermediate (Safe et al . , 1975c). After intravenous injection of 4-chloro- and 4,41-dichlorobiphenyl to goats and a cow, urine was collected. After extraction and cleanup of the urine samples, mass spectrometry was used to identify the metabolites of 4-chlorobiphenyl as 41-chloro-4-hydroxybiphenyl and 41-chloro-3,4-dihydroxybiphenyl . The 4-chlorobiphenyl was also identified in urine of cow. Confirmation of metabolite structure identity was made by NMR spectrometry and by comparison with samples of metabolites identified in the rat and confirmed by synthesis (Safe et al . , 1975b). 4-Chlorobi phenyl was fed to male albino rabbits. Urine was collected and analyzed. About 50% of the ingested dose was excreted as a gluco- siduronic acid derivative. Free phenol accounted for 3% and sulfate for 11%. No mercapturic acid derivatives were observed (Block and Cornish, 1959). When pigeons were fed 4-chlorobiphenyl, a monohydroxylated chloro- bi phenyl was found. Trout excreted no detectable metabolites into the water when exposed to 4-chlorobiphenyl (Hutzinger et al . , 1972b and c). Thorny skate (Raja radiata) and winter skate (Raja ocellata) were intravenously administered 2-, 3-, and 4-chlorobiphenyl. The 3-isomer cleared more readily from plasma than did the other two. Accumulation varied considerably from fish to fish but was highest in muscle and liver (Zinck and Addison, 1974). li+C-Labeled 2,41-dichlorobiphenyl was administered intravenously to 4 female rhesus monkeys. Biological ti^l.l to 2.9 days. An average of 73.5% of the administered dose was recovered within 14 days. About 70% of the recovered material appeared in urine and 30% in feces. Blood levels were negligible after 14 days but about 7% of the dose was in the fatty tissue (Greb et al . , 1973). Metabolites in urine and feces were identical. About 17% of the metabolites were conjugated as the sulfate or glucuronide. Three (of six) monohydroxy and three dihydroxy dichlorobiphenyls formed (Greb et al . , 1975b). When fed to rats, 4,41-dichlorobiphenyl yielded the 3-hydroxy analog (Safe et al . , 1974). After intraperitoneal injection of an oil solution of 4,41-dichlorobiphenyl into young male rats, a monohydroxylated chlorobiphenyl was observed. Pigeons, when fed the 4,41-compound, 207 gave similar results. Trout did not excrete any metabolite into the water when fed this material (Hutzinger et al . , 1972b and c). When this 4,41-dichloro compound was intravenously injected into a goat and a cow, the 3-hydroxy analog was found in the urine (Safe et al . , 1975b). Adult female rats (Swiss Webster strain) were treated with phenobarbital for 3 days to increase MFO activity. On the fourth day, the animals were killed and the livers removed and homogenized. The supernatant from 10,000g centrifugation was centrifuged at 100,000q. The resultant pellet was used to assay conversion of PCBs. When 2,2*-dichlorobiphenyl was incubated with the liver enzyme system, four monohydroxy and four dihydroxy dichlorobiphenyls were found. When 2,41-dichlorobiphenyl was used, only 2 of 6 monohydroxy derivatives were found. Two dihydroxy- dichlorobiphenyls also formed. When 2,21,5-trichlorobiphenyl was incubated with the liver enzyme system, 3 monohydroxy (of seven possible) and 2-dihydroxy trichlorobiphenyls were produced (Greb et al . , 1975a). Within 14 days after 2,21,5-trichlorobiphenyl was intravenously admin- istered to a rhesus monkey, about 82% of the dose was excreted. Urine and feces contained about equal amounts of radioactivity. The t\, was 2.1 days (Greb et al . , 1973). Three monohydroxy, two dihydroxy and one tri hydroxy derivative was formed (Greb et al . , 1975b). 2,21,5,51-Tetrachlorobiphenyl in oil was injected intraperitoneal^ into young male rats. A monohydroxy! ated chlorobi phenyl was observed. A similar observation was made when the compound was fed to fish. Trout did not metabolize this material (Hutzinger et al . , 1972b and c). A 1% suspension of 2,4,31,41-tetrachlorobiphenyl in Tween 80-saline (1:3) was intravenously injected into adult male Wistar King rats. About 0.6% of the dose was excreted unchanged daily into the gastroin- testinal tract through the wall of the small intestine (Yoshimura and Yamamoto, 1975). After oral administration of this 2,4,31,41-isomer to adult male Wistar strain rats, urine and feces were collected. At least four phenolic compounds were excreted into feces in addition to unchanged material. No evidence of conjugated metabolites was obtained. About 43% of the administered dose was excreted within 12 days after treatment. Synthesis and spectrophotometric analyses identified the major metabolite as the 5-hydroxy derivative and the minor metabolite as the 3-hydroxy derivative (Yamamoto and Yoshimura, 1973; Yoshimura et al., 1973). ' Tritiated 2 ,5 ,22 ^-tetrachlorobiphenyl was administered to male infant rhesus monkeys by gastric intubation. At 72 h, the animals were sacri- ficed. Urine was collected and analyzed. Identification of metabolites involved IR, GLC-MS and derivatization. Four metabolites were isolated and identified as a monohydroxytetrachl orobi phenyl , a di hydroxy tetra- chlorobiphenyl , trans-3,4-dihydro-3,4-dihydroxy-2,5,21 ^-tetrachloro- biphenyl, and a hydroxylated derivative of the latter with the additional hydroxy group on the aromatic ring (Hsu et al . , 1975a and b). 208 Sprague-Dawley rats were administered a single dose of 3H-2,5,21,51- tetrachlorobi phenyl by gastric intubation. Of six metabolites observed, one from feces was identified as the 3-hydroxy analog by mass and IR spectra. Three other compounds had mass spectra indicative of mono- hydroxy analogs also but were not further identified (Van Miller et al . , 1975). When rabbits were fed 2,5,21,51-tetrachlorobiphenyl , three hydroxylated compounds were identified by gas chromatography, mass spectra and IR spectra. Two compounds were identified as 3- and 4-hydroxy-2,5,21,51- tetrachl orobi phenyl . The third compound was identified as trans-3,4- dihydro-S^-dihydroxy-Z.S^^-tetrachlorobiphenyl (Gardner et al . , 1973). 3,4,31,41-Tetrachlorobiphenyl was administered orally to male Wistar rats every third day for 9 days. The fecal extract contained three metabolites. One of these was isolated and identified as either 2- or S-hydroxy-S^^^-tetrachlorobiphenyl (Yoshimura and Yamamoto, 1973). Rats, mice and quail were administered 2,2* ,3,5! ,6-pentachlorobiphenyl . Analyses of collected feces indicated differences in metabolism of this compound between mammals and birds. Quail excreted the 41-hydroxy analog as the major monophenol whereas with rats and mice, the major monophenol excreted was the 5-hydroxy analog. In rat feces, 17 hydroxy- lated derivatives were observed. Of these, eight were identified as the following hydroxylated analogs of 2,2* ,3,5* ,6-pentachlorobiphenyl : S^hydroxy- 31 ,4-dihydroxy- 41-hydroxy- S^-dihydroxy- 4-hydroxy- 4,41-dihydroxy- 5-hydroxy- 41 ,5-dihydroxy- A resume of the metabolites found in rat feces in this study follows: Description of bi phenyl No. derivatives Monohydroxytetrachloro- 3 Monohydroxypentachloro- 7 Dihydroxytetrachloro- 1 Dihydroxypentachloro- 5 (Sundstrom and Jansson, 1975) A phenolic metabolite of 2,2* ^^^-pentachlorobiphenyl was isolated from feces of rats given this compound. Mass spectrum, synthesis, elaborate chemical studies and chromatography showed that the metabo- lite was the 3!-hydroxy analog (Sundstrom and Wachmeister, 1975). 209 In other studies with ll+C-label ing, single doses were administered intravenously to rats. Most of the material was excreted in the form of glucuronides, primarily a 3l-hydroxy or 3 l, 4 i-di hydroxy derivative. More than 90% of the total dose was removed from the blood within 10 min. Prior to translocation to skin and adipose tissues, the material was initially deposited in the liver and muscle. Most of the radioactivity was excreted in the bile and feces. Excretion in the urine accounted for less than 7% of the dose and ceased after 8-9 days (Matthews and Anderson, 1975). Uniformly lltC-labeled 2,4,5,21,51-pentachlorobiphenyl was administered intravenously and orally to mice. Autoradiography and scintillation counting after intravenous administration showed that most radio- activity left the circulation within 1 h. Peak concentrations were highest in brown fat. Excretion of radioactivity occurred mainly via bile with a half-time of six days. During the first 20 min after injection, in addition to appearing in the fat, radioactivity also appeared mainly in liver and kidneys. Analyses after oral administration indicated that the major metabolite was an unidentified monohydroxylated compound, which occurred free and conjugated (Berlin et al . , 1975). For five weeks 50 pg of 2,4,6,21,41-pentachlorobiphenyl was adminis- tered daily to four male and female rats. Urine and feces were collected daily. Two compounds were isolated but not identified. Mass spectra indicated a hydroxy and a methoxy derivative (Lay et al . , 1975). In other studies when labeled material was fed to rats, most of the radio- activity was found in the feces. The metabolites found in the urine were conjugated. Monohydroxylation predominated and all three meta- hydroxy compounds formed. Mo 2- or 4-hydroxybi phenyl was observed (Goto et al., 1975). When labeled 2,4,6,21,61-pentachlorobiphenyl was fed to rats, most of the label appeared in the feces. Metabolites found in the urine were conjugated. Two m-hydroxy derivatives were found and identified by mass spectra and gas chromatography. No 2- or 4-hydroxy analogs were observed. A dihydroxy compound was identified as the 31 ^-dihydroxy derivative. The main conjugate was identified as the 3-glucuronide by incubation with g-glucuronidase (Goto et al . , 1975). Feeding of 2,4,6,31,41-pentachlorobiphenyl to rats yielded the 3- hydroxy derivative. The Si-analog was not definitely known to be present (Goto et al . , 1975). When 2,4,6,3! ^-pentachlorobiphenyl was fed to rats, a trace of the 3-hydroxy derivative was observed (Goto et al . , 1975). No excreted hydroxylated metabolites were observed after intraperitoneal injection of 2,21,4,41 ^^-hexachlorobiphenyl in rats, feeding of pigeons or feeding of trout (Hutzinger et al . , 1972b and c). When this 210 compound was fed to rats, a hydroxy metabolite was found in the feces but not in urine. Mass spectra data favored the 3-hydroxy structure (Jensen and Sundstrom, 1974). After feeding this hexachloro compound to rabbits for 7 days, collected urine was analyzed. Three metabolites were observed and corresponded to hydroxylation, hydroxylation and mono- dechlorination, and a monodechlorinated analog that contained a hydroxy and a methoxy group (Hutzinger et al . , 1974). Feeding of labeled 2,4,6,21 ,4i,6i-hexachlorobiphenyl to rats yielded the meta-hydroxy derivative (Goto et al . , 1975). When fed to rats, decachlorobiphenyl remained unchanged (Goto et al . , 1975). Studies of extracts of human fat and animal material indicated that many PCBs were metabolized (indicated by + in the following table). Many of the individual PCBs have been identified. In this study, the products were not identified (Schulte and Acker, 1974). 2,5,2i,5i- + 2,3,4,21 ,51 2,3,6,2^ ,51 2,4,5,21 ,51 2,4,5,21 ,31 2,3,4,21 ,31 2,3,4,21 ,41 2,3,4,5 21, 2,3,5,6 21, 2,3,6,21 ,31 2,3,6,21 ,41 2,4,5,21 ,41 2,3,4,5 21, 2,3,4,5 ,21, 2,3,4,5 ,21, 2,3,4,5 ,6,2 2,3,5,6 ,2i, 2,3,4,5 ,21, 2,3,5,6 .21, 2,3,4,5 ,21, + + + + + + + + + + Neg. Neg. (+) Neg. (+) Neg. Neg. Neg. Neg. When rats were fed Aroclor 1016 and 1242, measurable residues were still present five and six months, respectively, after exposure was discontinued (Burse et al . , 1974). Studies also indicated that components of Aroclor 1254 were metabolized at different rates (Grant et al . , 1971). Twenty-seven PCBs in Aroclors 1221, 1242, and 1254 were separated and identified by GLC and IR comparison with known prepared compounds (Webb and McCall , 1972). ,41- ,51- 51- 51- ,61- ,51- ,5i- 3i,4i- 31,61- 41,51 i,5i- 41,51 3i,4i ,51 31,51 ,61 3i,5i ,61 211 The main components of Kanechlor-400 (KC-400) were identified as 2,4,31,41-, 2,5,3m1-, 2,3,4,41-, and 3,4,31,41-tetrachlorobiphenyl and 2,3,4,31,41-pentachlorobiphenyl (Saeki et al . , 1971). Single doses of KC-400 were orally administered to female DDD strain mice. The results indicated that each component was almost equally absorbed and distributed in tissues. Skin concentration of chlorobiphenyls one day after injection was about twice as high as that of liver and kidneys; and chlorobiphenyls were retained longer in the skin than in other tissues. While tetrachlorobi phenyls were almost completely eliminated from liver and kidney in 3 to 4 weeks, the minor components penta- and hexachlorobi phenyls were still retained in small amounts after 9 to 10 weeks (Yoshimura and Oshima, 1971). In other studies using rats and 3H-labeled KC-400, distribution and excretion radio- activity was measured at 3, 28 and 56 days. Levels were higher in skin, adipose tissue, liver, adrenal gland and GI tract than in plasma. Skin and adipose tissues were highest. Although most of the radio- activity was eliminated from the tissues after four weeks, a significant amount was still present after eight weeks. During four weeks of obser- vation, 2% of the dose was excreted via urine and 70% via feces (Yoshimura et al . , 1971). Cows were fed Aroclor 1254 for 60 days. PCB concentrations in milk fat approached equilibrium after 40 days. After feeding stopped, the PCB concentration in milk fat declined 50% within 15 days. The average rate constant was 0.010 day-1 and varied from 0.005 to 0.016 day-1. The decline in body fat concentration of PCB paralleled that in milk (Fries et al . , 1973). C = 30.6e"°-32t + 32.3e°-010t Studies with sheep and pigs yielded the following with Aroclor 1254: (Blood Concentration) CA = Ae"at + Be-^t Sheep Pig a B B VA (Borchard et al . , 1974) Aroclor 1254 was fed to bobwhite quail for 14 days. Absorption of all components occurred at the same rate. Two peaks containing six chlorines showed a distinct increase but a third peak declined. Some 0.616 ppm 0.465 1 .213 ppm .537 0.115 ppm 0.047 .252 ppm .046 284.54 65.60 212 dechlorination occurred but no products were identified (Bagley and Cromartie, 1973). Leghorn hens and a rooster were given 50 yg/ml of the PCB mixture Aroclor 1254. Elimination of PCB isomers was studied. It was found that 3,4,2! ,3l ^-pentachlorobiphenyl was eliminated more rapidly than 3,4,21,41,51-pentachlorobiphenyl and 2,3,4,2! .41 ^-hexachloro- biphenyl. Chlorination in the 4-position in penta- and hexachloro- bi phenyls was associated with slow clearance of PCB isomers from hen, embryo, and chick (Bush et al . , 1974). Fish, exposed to Clophen A50, accumulated residues up to 70 ppm. When transferred to fresh water, half of the PCB residues was eliminated in 20 days (Hattula and Karlog, 1973). Baltic herring (Clupea harengus) were shown to carry high PCB residue levels. Since the guillemot (Uria algae) and the grey seal (Halichoerus grypus) feed heavily on the Baltic herring, studies were undertaken to determine PCB residues in droppings of the guillemot and seal. These studies showed a difference in the metabolism of PCB and are summarized in the following table. Compounds were identified by GC-MS (Jansson et al., 1975). Compou inds found in the phenol ic fraction from feces after me thylation. Compound Number • of : Isomers Seal Gu- illemot Methoxytrichlorobi phenyl 2 Methoxytetrachlorobi phenyl 5 . 6 Methoxypentachlorobi phenyl 9 8 Methoxyhexachlorobi phenyl 7 7 Methoxyheptachlorobi phenyl 2 3 Dimethoxypentachlorobi phenyl - 1 Dimethoxyhexachlorobi phenyl 1 1 Grass shrimp (Palaemonetes pugio) , exposed for 3 months to sediments contaminated with Aroclor 1254, concentrated the Aroclor to about the level observed when exposed to 0.09 yg/1 in water for 2 weeks in the laboratory (Nimmo et al . , 1974). A laboratory ecosystem used to study the fate of ll+C-labeled PCBs consisted of water, alga (Oedogonium cardiacum), snail (Physa), plankton, water flea (Daphnia magna) , mosquito (Culex pipiens quinquefasciatus) and fish (Gambusia affinis). After introduction of 2,5,21-trichlorobiphenyl into the system, six compounds were observed: in water, compounds I, II, IV, V, VI; in alga, compounds I, II, VI; 213 in snail, I through VI; in mosquito, I; and in fish, I and II. When 2,5,2* ^-tetrachlorobiphenyl was introduced, two compounds were observed in all phases except fish, where only one was found. After introduction of 2,5,21,41 ^-pentachlorobiphenyl , five compounds were observed in the system. Compounds II, III, IV, and V in water; I, II, III and V in alga; I, II and III in mosquito; I, II, III and V in fish; and all five in snail. All three compounds were biomagnified in all components of the system. All three compounds were also degraded by the salt marsh caterpillar larva: five compounds from the trichloro-; three compounds from the tetrachloro-; and three compounds from pentachlorobiphenyl . None of the metabolites observed were identified (Metcalf et al . , 1975b). Two plants, Ranunculus fluitans and Callitriche sp., which grow submerged in water, were exposed to 2,21-dichlorobiphenyl . In the water where the plants had been cultured; one di hydroxy compound free and conjugated, and a dechlorinated product (Moza et al., 1974). 11+C-2,21-Dichloro- biphenyl was also applied directly to leaves of Veronica beccabunga. After 6 weeks, the plants were homogenized with methanol and extracted for 48 h in a Soxhlet. Thin-layer chromatography indicated four compounds, one of which was conjugated. Mass spectra indicated mono- methylation of a phenol when it was reacted with diazomethane. A second compound gave similar results, indicating a second monophenol . These phenols were also observed after acid hydrolysis of the conjugated fraction (Moza et al . , 1973). The soil fungus Rhizopus japonicus was incubated in a medium containing 4-chlorobiphenyl , 56 Mg/30 ml culture medium. A compound having a melting point of 145C was isolated. NMR and mass spectra were identical with that of 4-chloro-4-hydroxybi phenyl (Wallnofer et al . , 1973). 4,41-Dichlorobiphenyl was hydroxylated by Rhizopus japonicus. The metabolite was not identified (Wallnofer et al . , 1973 pomcus. Two strains of Achromobacter were isolated from sewage effluents using biphenyl and p_-chlorobi phenyl as sole carbon sources. Achromobacter BP grew only on biphenyl but did co-metabolize the mono- and dichloro- bi phenyls. Achromobacter pCB, grown on p_-chl orobi phenyl , grew better on biphenyl than on £-chl orobi phenyl and co-metabolized meta- and ortho- chlorobiphenyl and dichlorobiphenyls. Achromobacter pCB metabolized p_-chl orobi phenyl to benzoic acid and p_-chlorobenzoic acids. The latter probably arises also from jd^jd1 -dichl orobi phenyl . The two acids were also produced by Achromobacter BP. Chloride was not produced by either strain during degradation of the chlorobiphenyls. Washed cell suspensions of both isolates oxidized biphenyl, o-phenyl phenol, phenyl pyruvate, catechol, fj-chl orobi phenyl , m-chlorobi phenyl , o-chlorobiphenyl , o,^1- and p^p^-dichlorobiphenyl (Ahmed and Focht, 1973b). Using resting cell suspensions of Achromobacter pCB, they were first grown on p_-chl orobi phenyl Except for 2,5,3* ^-tetrachlorobiphenyl which was not oxidized at all, 214 and S^-dichlorobiphenyl which was oxidized after a brief lag, all other PCBs tested were oxidized without lag: 2,3-, 2,4-, 3,4- and 3,5-dichlorobiphenyl ; S^^-trichlorobiphenyl ; 2,3,21,31-tetrachloro- biphenyl; 2,3,4,5,6-pentachlorobiphenyl . Products were not identified (Ahmed and Focht, 1973a). In studies with microorganisms, various PCBs were incubated with Nocardia spp. (NCIB 10603) and Pseudomonas spp. (NCIB 10643) for varying periods of 7 to 73 days. Nocardia spp. degraded at least 50% of the following PCBs: 2,41-dichloro- 2,3,21-trichloro- 2,3-dichloro- 2,3,41-trichloro- 3,4-dichloro- S^^-trichloro- When biphenyl was added to the incubation mixture, 2,5,41-trichloro- biphenyl was also metabolized. Similarly, a mixture of 2,3,4,5,21,31- hexachloro-, 2,3,21-trichloro-, and 2.31 ^-trichlorobiphenyl plus biphenyl was metabolized. Mot metabolized with or without added biphenyl were 2,4,6-trichloro-, 2,4,21,41-tetrachloro- and 2,4,6,21-tetrachloro- biphenyl. Pseudomonas spp. metabolized only 2,41-dichloro-, 4,4*- dichloro, and 2,5,4i-trichlorobiphenyl . Both strains also metabolized 85% or more of Aroclors 1016 and 1242 in 100 days (Baxter et al . , 1975). Lake bacteria used Aroclor 1221 and 1242, but not 1254, as sole carbon and energy sources for growth. Aroclor 1221 was completely degraded into several low molecular weight compounds after one month. Of the seven bacterial isolates capable of degrading Aroclors, five were Achromobacter sp. and two were Pseudomonas sp. (Wong and Kaiser, 1975). In other similar studies with bacteria from Hamilton Harbour, Ontario, a solution containing 0.1% Aroclor 1242 was incubated at 20C for two months. After extraction, the metabolites were isolated and identified by gas chromatography and mass spectrometry. No phenols or chlorine- containing metabolites were observed. Metabolites identified included: iso-hexane, iso-octane, ethyl benzene, isobutyl benzene, n-butyl benzene and iso-nonane (Kaiser and Wong, 1974). Aroclor 1254 was added to a loam soil at the rate of 10 ppm. After one year, 95% was recovered. In other soils, 25-50% of some of the peaks were lost (Iwata et al . , 1973). Unsymmetrical PCBs were irradiated in quartz with UV above 287 nm. Mono- and di -dechlorination was observed. 215 Starting bi phenyl 2,4,5-trichloro- 2,4,6-trichloro- 21,3,4-trichloro- 2,3,4,5-tetrachloro- 2,3,5,6-tetrachloro- Bi phenyl product 4-chloro- 3,4-dichloro- 4-chloro- 2,4-dichloro- 3,4-dichloro- 3,4-dichloro- 3,4,5-trichloro- 3,5-dichloro- 2,3,5-trichloro- (Ruzo et al., 1975) With irradiation of PCBs at 300 nm in cyclohexane, stepwise, dechlor- ination occurred. Where ortho-chlorines were present, PCBs yielded products arising from loss of the chlorines. The two main products accounted for more than 98% of PCB reacted. Less than 1% of the products arose from the loss of a meta-chlorine in the presence of ortho-chlorine. Para-chlorines were not cleaved after 20 h of irradi- ation. After more than 50 h of irradiation, S^^^-tetrachloro- biphenyl yielded some 3,31,4-trichlorobiphenyl in addition to 3,4,4*- trichlorobiphenyl . In methanol solution, dechlorination was the major reaction; but some methoxylated products were also observed. In all cases, these comprised less than 3% of the reacted PCB. Results have been summarized in the following table (Ruzo et al . , 1972, 1974a and b) Bi phenyl Products Biphenyl used 4,41-C12 2,21,5,51-Cl^ 2,2i,4,4!-CV 2,2i,3,3i-CV Dechlorinated 4-C1- 2,3i,5-Cl3- 3,3i-Cl 2-(286 nm) of 2,21,4,41,5,51-hexachlorobiphenyl in methanol in sealed borosilicate tubes for 1 h, about 10% of the biphenyl reacted to give 3.31 ,4,4 i-tetrachlorob1 phenyl (70%) and 2,31,4,41,5- pentachlorobi phenyl (30%) (Ruzo and Zabik, 1975). In other studies the 2,21,4,41,5,51-hexachloro- and 2,21,5,51-tetra- chlorobi phenyls were adsorbed on silica gel and then exposed to UV irradiation at x>290 nm. When quartz was used, mineralization occurred with the hexachlorobiphenyl but not with the tetrachlorobiphenyl (Gab et al., 1975a). A sample of 2,21,4,41,6,61-hexachlorobiphenyl in hexane was irradiated at max 3100a for 100 min. Thin-layer chromatography showed two bands and gas liquid chromatography revealed 11 major peaks. Mass spectrum analysis of one band indicated the presence of di-, tri-, tetra-, penta- and hexa-chlorobiphenyls. Irradiation in methanol produced similar results but also yielded some more polar material containing oxygenated polychlorinated compounds (Safe and Hutzinger, 1971). Chlorinated bi phenyls in a small volume of methanol were suspended in distilled water. These were then irradiated for 15-26 days in sunlight or 1-2 weeks in an aerated photoreactor (F40 BL lamp). GC/MS analyses indicated the formation (about 0.2%) of 2-chloro- dibenzofuran from 2,5-dichloro- and 2,21,5,51-tetrachlorobiphenyl (Crosby and Moilanen, 1973). Product Test biphenyl Reduced 2,4-Cl2 - 2,5-Cl2 + 3,4-Cl2 - 4,41-C12 + 2,4,5-CT3 2,21,3,3f-Cl4 - + 2,21,4,41-C11+ - Hydroxylated + + + + 217 PCB (not identified) in 2-propanol and sodium hydroxide was irradiated with 100 W-high pressure mercury lamp under nitrogen and at about 30C. PCB was dechlorinated about 80, 95 and 100% after 5, 10 and 15 min, respectively. Biphenyl and sodium chloride were identified (Nishiwaki et al., 1972). The photolysis of chlorobiphenyls was studied under laboratory conditions and in sunlight. Progressive dechlorination and polymerization occurred in hexane. In hydroxylic solvents and at pH 9, irradiation of Aroclor 1254 produced compounds corresponding to the addition of water as well as more polar carboxylic material. When thin films of Aroclors were photolyzed in the presence of water, the major products were those resulting from dechlorination and/or polymerization. Polar compounds having little or no chlorine were also produced. 4,41-di-, 2,2*,5,51- tetra-, 3,31,4,41-tetra, 2,21,4,41,5,51-hexa-, 2,21,3,31 AAK5,5l-oct" CO. V"2 V HOOC ^ XC-C1 «2 N s -COOH HOOC^ yr COOH \r> NH„ ci HOOC cC ,ci ft ^ HN^ C-COOH V :-cooh H20 HOO I COOH SI NH CH2 "^CH I CHO CO„ ^7~ HOOC CHO HC1 + CO 225 PIRIMIPHOS-METHYL [0,0- Dimethyl 0-(2-dimethylamino-4-methylpyrimidin- 6-yl )phosphorothionate] Pirmiphos-methyl was applied to a clean wooden plank upon which a new cloth-wrapped cheese was placed. Very little pesticide was absorbed by the cheese and TLC analyses indicated only traces of the oxon and pyrimidinol derivatives in the wrapping (Thomas and Rowlands, 1975). 226 PROLAN [1 ,l-Bis(p_-chlorophenyl )-2-nitropropane] 14C-Prolan was administered in olive oil orally to mice. Urine and feces were collected and analyzed. Results of these analyses are tabulated. 1I+C-Labeled prolan was incubated with a preparation of sheep liver microsomes. After 30 min incubation at 39C, 99% intact prolan was recovered. In a comparative study with methoxychlor, about 88% remained intact. When larva of the salt marsh caterpillar (Estigmene acrea) ingested 11+C-prolan, 9% degraded to the 2-propanone and acetic acid analogs. After topical application to the Sn/\idm female housefly (Musca domestica) , 14C-prolan was degraded to polar compounds which comprised 83% of the label in excreta and 75% in body homogenates. In addition to prolan, the acetic acid and benzophenone analogs were indicated. Conjugation was also indicated by the release of the 2- amino analog after hydrochloric acid treatment of the polar material. ite Mou< ;e Fly Salt Marsh Metabol Urine Feces Caterpillar I + + + + II + + + III + + + IV + + + + V + + + VI + + + + VII + + + The degradation and accumulation of prolan in a model ecosystem was also studied. Oedo- gonium Daphnia Physa Culex Gambusia Compound (alga) (Waterflea) (Snail) (Mosquito) (Fish) I + + + + + II + + + + III + + + IV + + + + V + + VI + + + VII + In all studies, polar conjugated materials were also observed as well as several unidentified compounds (Hirwe et al . , 1975). 227 R= CI W A ^CH-CH-N03 ft Eh 3 Prolan I >CH-CH-NH2 *' in, II N >- ^C=CH-CH3 III [ pCH-(fH-CH3] OH V COOH VI ^CH-C-COOH R/ II K 0 l\ ^CH-C- CH, IV R \ VII c=o 228 PRONAMIDE (Kerb) [3,5-Dich1oro-N-(l ,1 -dimethyl -2-propynyl )benzamide] The metabolism of pronamide in soil was studied with ^C-carbonyl labeling. It was shown that formation of ll+C02 was biologically mediated. The treated soils were extracted after 33 days and the extracts were chroma to- graphed. No 3,5-dichlorobenzoic acid was detected/ In addition to pronamide and two unidentified metabolites, five metabolites indentified were compounds I, II, III, VII, and VIII (Fisher, 1974). CHc tttH, -C^CH Pronamide I R-C IJ-C-CHo I 1 H3C 0 r R-C-N-C-C-CH I - -3 H3 U\ CHq ,-i. CH, ->-[R-C-N-C- CH, C^ 1 XN-C- 0-CH-CH20H N-C-CH3 tH3 III H3C OH -C-N-C-C-CH,0H VI H3g o ii R-g-N-C-C-CH2OH *- R-C-N-C-C-COOH 0 H CH 0 rt :h3 IV IX ->- R-C-N-C C-N-C-CH2-CH2OH { H3 V \ C\\: ■I R-C-N-C-CH2-C00H Fl & :h3 vii I H3C OH ->- R-fi-N-C-f H-COOH Mh3 XII ■>• R- CH3 •N-C-COOH ^CH3 VIII R= 229 PROPANIL [3,4-Dichloropropionanilide] In studies with propanil and 3,4-DCA (3,4-dichloroaniline) , it was observed that in different soils there were differences in the amount of tetrachloroazobenzene (TCAB) formed. Formation of TCAB did not correlate with soil pH. With five soils of pH 4.5 to 5.5, TCAB was formed from both compounds; pH 5.8 and 7.4, TCAB formed from 3,4-DCA only; pH 3.4 and 6.4, no TCAB from either substrate (Hughes and Corke, 1974). In soil, the conversion of 3,4-DCA to TCAB increased with an increase in peroxidase activity (Lay and Ilnicki, 1974). Propanil was hydrolyzed by Corynebacterium pseudodi phtheri ti cum NCIB 10803 (Grant and Wilson, 1973). A strain of Fusarium solani used propanil as a sole source of carbon and energy for growths and the primary product of degradation was 3,4-DCA. This acylamidase did not catalyze hydrolysis of dicryl , karsil, fenuron, monuron or IPC. It seems to be different than acylamidases isolated from rice, rat liver and chick kidney (Lanzi- lotta, 1969). Studies with rice have shown that diazinon and carbaryl , absorbed from soil and translocated, could inhibit propanil hydrolysis (El-Refai and Mowafy, 1973). 230 PROXIMPHAM [0-(N-Phenyl carbamoyl )isopropyloxime] Hydrolysis of proximpham in acid produced diphenylurea, aniline and isopropoxime. In alkaline solution, the salt of carbanilic acid and isopropoxime formed. Model tests of proximpham degradation in soil indicated a half-life of 7-10 days. In soil, aniline was degraded much more rapidly than proximpham and was not detected (Spengler and Jumar, 1969). 231 PYRAZON (Pyramin) [5-Amino-4-chloro-2-phenyl-3(2H)-pyridazinone] A photochemically controlled process was involved in the degradation of pyrazon in the leaves of beets. No degradation occurs in the dark. In sugar beets and red beets, pyrazon formed N-glucosylpyrazone (I). In addition 5-amino-4-chloro-3(2H)-pyridazinone (II) and a strongly hydrophilic compound were formed (Anon., BASF 1973; Stephenson et al . , 1971). In soil pyrazone is degraded by bacteria with formation of compound II and is not detectable in soil after 20 weeks (Anon., BASF 1973). A strain of Azotobacter sp., capable of using pyrazon as a sole source of carbon, was used to study bacterial decomposition of pyrazon. Incubation of the bacteria with pyrazon produced 5-amino-4-chloro-2- (2,3-cis-dihydroxycyclohexa-4,6-diene-1-yl )-3(2H)-pyridazinone (III) ; 2-(5-amino-4-chloro-3-oxo-2,3-dihydro-2-pyridazino-cis,cis-muconic acid (IV); 2-pyrone-6-carboxylic acid (VII); and 5-amino-4-chloro- 3(2H)-pyridazinone (V) (de Frenne et al . , 1973). Analogs of pyrazon were co-metabolized by Azotobacter sp. When o- methyl pyrazon was used, the 2-hydroxymethyl phenyl derivative was formed and with m-methylparazon, the 3-hydroxymethyl phenyl derivative. The p_-methyl pyrazon was not metabolized (de Frenne et al . , 1974). 232 Pyrazon 1 NH2 III H Glucosyl \ / N NH, > J CI VII 233 PYRETHRINS BIO-ALLETHRIN [3-Allyl-2-methyl-4-oxocyclopent-2-enyl (±)-trans- chrysanthemate] BIORESMETHRIN [(±)-trans-resmethrin] FURAMETHRIN [5-Propargyl -2-furyl methyl (+)-trans-chrysanthemate] PHENOTHRIN [3-Phenoxybenzyl (+)-trans-chrysanthemate] RESMETHRIN [5-Benzyl -3-furyl methyl (±)-cis,trans-crysanthemate] TETRAMETHRIN [3,4,5,6-Tetrahydrophthalimidomethyl (±)-trans- chrysanthemate] 234 Mouse liver microsomal preparations were capable of hydrolyzing the ester link of pyrethroids made with primary alcohols. The enzyme system did not hydrolyze the esters formed with secondary alcohols. Several relationships were observed. 1. Cleavage of (+)-trans chrysanthemate esters: rate decreased in order of: 5-propargyl-2-furyl methyl 5-benzyl -3-furyl methyl 3-phenoxybenzyl tetrahydrophthal imidomethyl 2. Hydrolysis rate of benzyl furyl methyl esters decreased in order of: (+)- or (-)-trans chrysanthemate (+)-trans-ethanochrysanthemate tetramethyl cycl opropanecarboxyl ate (+)- or (-)-c is -chrysanthemate or (+)-cis-ethanochrysanthemate 3. Trans- isomers of the above were hydrolyzed up to 50-fold more rapidly than the c is- isomers. (Abernathy et al . , 1973) In other studies, pyrethroids were decomposed in solution by tabu powder. Decomposition was caused by the prophyrin ring in the pheophytin in solution (Iguchi et al., 1974). 235 BIOALLETHRIN Irradiation of a 0.15% solution of a diastereoisomeric mixture of commercial bioallethrin in rv-hexane produced a single photoproduct in up to 90% yield. Mass, NMR and IR spectral data were used to identify the product as corresponding to a rearrangement in the prop-2-enyl side chain of the alcohol moiety (Bullivant and Pattenden, 1973). Bioallethrin was not cleaved by esterases in acetone powder preparation from milkweed bugs, cockroaches (Blattella germanica L.), houseflies, cabbage loopers (Trichoplusia ni Hubner), yellow meal worms (Tenebrio molitor L.) or mouse liver (Jao and Casida, 1974). -COO 236 FURAMETHRIN Purified furamethrin (I) was heated at 120-140C for 10 h. Chyrsanthemic acid (II) and an unidentified compound were formed in very small amounts, At 150C for 8 h, about 0.5% pyrocin (III) and cis-dihydrochrysanthemo- 6-lactone (IV), chrysanthemic acid and an unidentified compound were formed. At 200C for 7 h, in addition to four unidentified compounds, chrysanthemic acid and two aldehydes (V and VI) were formed (Abe et al . , 1974). CH,-C=CH ->. Polymerization C00H II III / \\ -CH0 R-<. J>-CH=CH-CH0 VI 237 PHENOTHRIN (S 2539) 11+C-Phenothrin, labeled at the hydroxymethyl group of the alcohol moiety, was orally administered at the rate of 200 mg/kg to male Sprague-Dawley rats. Absorption and elimination was rapid. About 60% of the radio- activity was eliminated in urine and 40% in feces in 3 days. In addition to phenothrin, 3-phenoxybenzyl alcohol and 3-phenoxybenzoic acid were found in brain, liver, kidney and blood. Unidentified water and ether solubles were also present. Urine contained low levels of 3-phenoxy- benzoic acid and its glycine conjugate and some ether and water soluble material. In addition to these, 3-(4'-hydroxyphenoxy)benzoic acid was present and accounted for 42.3% of the radioactivity originally applied. This compound was also the major metabolite in feces but accounted for only 11.9% of the initially applied radioactivity. In addition to unchanged phenothrin and unidentified water and ether solubles, feces contained 3-phenoxybenzoic acid and the glycine- conjugate. 3-Phenoxy- benzyl alcohol was not observed in urine or feces (Miyamoto et al . , 1974). 238 RESMETHRIN Mouse hepatic microsomal esterases cleaved the (+)-trans ester more rapidly than the (+)-cis_- isomer (Abernathy and Casida, 1973). Acetone powder preparations of milkweed bugs, cockroaches (Blatella germanica L.), houseflies, cabbage loopers (Trichoplusia ni Hubner) and yellow mealworms (Tenebrio molitor L.) also hydrolyzed both (+)-trans- and (+)- cis-isomers. Of these, the (+)- trans- isomer was cleaved more rapidly than the (+)-ci_s_- isomer (Jao and Casida, 1974). Other studies indicated that microsomal esterases were important in hydrolyzing trans- but not cis-isomers (Ueda et al . , 1975b). Resmethrin isomers were metabolized in microsome-NADPH systems to the extent of 95 to 98%. The extent to which trans- and cis-isomers were metabolized differed. In the presence of NADPH, ester cleavage was much greater with TEPP-treated microsomes. An oxidative ester cleavage seemed to be most important with (-)-ci_s_- resmethrin. In the latter case, alcohol moieties released include unstable compounds and protein-bound metabolites. Seventeen percent of the initial radiocarbon appeared in 11 ester metabolites (not identified) of (+)-trans-resmethrin. These were recovered only with TEPP-treated microsomes fortified with NADPH. Oxidized chrysanthemic acid derivatives (VIII to XXII and XXVI) were comparatively stable. The metabolites IV and VII were major products only in the presence of NADPH and the supernatant fraction. Compounds II, III, V and VI were not isolated (Ueda et al . , 1975b). Six days after administration of ll+C-resmethrin to rats at a dose of 1 mg/kg, 53-73% was accounted for in urine and feces. Low residue levels were observed in tissues. In urine, there were almost equal parts of free and conjugated metabolites. Much of the conjugated material was released after incubation at pH 5, in buffer, with or without glusulase. When the aqueous phase was acidified to pH 2, more of the metabolites were recovered. Differences were observed between the metabolism of (+)-trans- and (+)-cis-resmethrin. When the alcohol was labeled, compounds BFCA, a-OH-BFCA and 4'-0H-BFCA were found in urine after administration of ( + )-trans_- isomer whereas only BFCA was observed after the (+)-cj_s_- isomer. With the latter, all three compounds were released by incubation with glusulase but only BFCA and 4'-0H-BFCA were released when the (+)-trans-isomer was used. After administration of acid labeled (+)-trans-resmethrin, tE-CDA and t-CA were found in urine. The t-CHA found probably consisted of t-CHA from both (+)-trans- and (+)-cis- resmethrin. The (+)-cj_s_- isomer yielded c-CA, cE-CHA, cE-CDA and cZ-CDA when the acid moiety was labeled (Ueda et al., 1975a). 239 H3( H3C. /CHs C =CH/\ N:H-CH2-c-d' N CH2 CH-CH N(K TH2 H3C CH >QH/\ p H3C nch-ch2-(;s Ri R2 R3 Ru ■CH3 ■CH20H ■CHO -C00H Resmethrin BFA- -CD Alcohol BFA- -CD Aldehyde BFA- -CD Acid Ri R2 R3 R4 -CH3 -CH20H -CHO -C00H CA CHA CAA CDA HOOC *J a-keto BFCA XXVIII HOOC jcxox OHC- ULfjO HOOC- HOCHf a-OH-BFA XXIII oh ^ H0CH2- BFA XXII OH BFCA XXV BFCA XXVI a-OH BF Aldehyde XXIV ^-OH BFCA XXVII BFA-Z-CDA VII [VI] [V] BFA-E-CDA < IV t-CA VIII t-E-CHA X 1 + t-E-CAA - XI t-E-CDA XII [BFA-E-CD Aldehyde]<-[BFA-E-CD Alcohol ]«f(+)trans- & (+)cis- Resmethrin (I) c-E-CHA XIII ■*- [c-E-CAA] XIV I c-E-CDA XV c-CA IX I c-Z-CHA XVI It [c-Z-CAA] -^r XVII 4 c-Z-CDA XVIII t-Z-CHA XIX If -*«-{t-Z-CAA] XX I [t-Z-CDA] XXI 240 Observed Acid derivatives J_n Vitro In Vivo t-CA + + c-CA + + tE-CHA + + tE-CAA + + tE-CDA + + cE-CHA + + cE-CAA + cE-CDA + + cZ-CHA + + cZ-CAA + cZ-CDA + + tZ-CHA + tZ-CAA + ± tZ-CDA + ± Alcohol derivatives BFA-E-CDA + BFA-Z-CDA + BFA + a-OH-BFA + BFCA + + a-OH-BFCA + 4'-0H-BFCA + Photodecomposition of (+)-cis-resmethrin produced cis-chrysanthemic acid; benzaldehyde; phenylacetic acid; 5-benzyl-5-hydroxy-2-oxo-2,5- dihydro-3-furylmethyl cis-chrysanthemate and 4-benzyl-5-hydroxy-3- oxo-cyclopent-1 ,2-enyl methyl cis-chrysanthemate (Ueda et al . , 1974). Irradiation of the (+)-trans-isomer produced 11 photoproducts. The major component was trans-chrysanthemic acid. Other compounds observed included benzaldehyde (VIII); 2-benzyloxy-5-oxo-2,5-dihydro-3-furyl methyl trans-chrysanthemate (IV); compound III, compound V, benzyl alcohol, benzoic acid, phenylacetic acid and two epoxyresmethrin isomers (see following figure) (Ueda et al . , 1974). 241 C C-C-C-0-CH,-C - Cv " C^ \ ° \ / \ o o- CH„-C00H VI CnAC\ / r/"c\ K C C-C-C-0-CH,-C=C II 0 HO-C fc=0 0 cv c c oc c V C-C-C-0-CH,-C=C, III 0 HO-C' C»0 o /C=C\A C C-C-C-0-CH2-C=C IV o CH20H VII 0-°» VIII / C00H IX C C-C-C-0-CH,-OC 1 0=V\"cH2"O " OH 242 TETRAMETHRIN (Phthal thrin, Neo-Pynamin, NIA 9260, FMC 9260, SP 1103) The microsomal fraction of rat liver homogenates was incubated with tetramethrin (I). The major metabolites were chrysanthemumic acid (V) and tetradydrophthalimide (X). Addition of NADPH2 decreased formation of compound (X), increased tetramethrin oxidation and produced primarily the propenol derivative II and the hydroxychrysanthemumic acid VI. Only a small amount of the hydrolysis product N-hydroxymethyl phthal imide (IX) was observed. This product went non-enzymatically to compound X. Minor amounts of compounds III, IV, VII and VIII were also observed (Suzuki and Miyamoto, 1973). Studies conducted with homogenates of three strains of houseflies showed that the major microsomal metabolites were compounds V and X. Addition of NADPH2 did not affect formation of compound X. Small amounts of compounds III, IV, VII and VIII were observed. Similar results were obtained when tetramethrin was applied to flies by injec- tion (Miyamoto and Suzuki, 1973; Suzuki and Miyamoto, 1974). Acetone powder preparations of milkweed bugs, cockroaches (Blattella germanica L.), houseflies, cabbage loopers (Trichoplusia ni Hubner) and yellow mealworms (Tenebrio molitor L.) hydrolyzed both (+)-trans- and (+)-cis-isomers of tetramethrin. Of these two isomers, the (+)- trans-isomer was cleaved more rapidly (Jao and Casida, 1974). 243 H3C >CH3 I II III IV R= -CH3 -CH2OH -CHO -COOH /R Hs^ ch3 0^ /\/CH=C X-CH-CH X HOT H3 V VI VII VIII ■CH3 •CH2OH -CHO -COOH t ->- VI I ■*- II ■>- VII t III IX VIII 1 ->- IV 244 R-7465 [2-(a-naphthoxy)-l^,N^-diethy1 propionamide] Labeled R-7465 was applied to roots of tomato plants. Translocation of the material throughout the leaves occurred within 8 h. Extraction of the plants and analyses revealed the presence in the organic fraction of three metabolites identified as: 2-(a-naphthoxy)-N-ethyl propionamide; 2- ( 5-hydroxy-l -naphthoxy ) -N-ethyl propi onami de ; 2- ( 5-hydroxy-l -naphthoxy ) - N,N-diethyl propionamide; and 1 ,4-naphthoquinone. The aqueous fraction contained a conjugate of 4-hydroxy R-7465 identified as a hexose con- jugate. Two other compounds, which gave positive glycoside tests, were identified as different hexose conjugates of 4-hydroxy R-7465 and a hexose conjugate of the monodesethyl 4-hydroxy R-7465. The 5-hydroxy R-7465 and its desethyl analog were also present in small amounts after enzymatic hydrolysis of the conjugates. However, the sources of these two compounds after hydrolysis were unresolved (Murphy et al . , 1973). 245 ?Conj. C 0 Et i u I Q-C-C-N-Et ?Conj. C 0 H i ii • O-C-C-N-Et 4- HO- Con j. (hexose-2) C 0 H « ' » > O-C-C-N-Et OH 4-HO-N-desethy? Naphthoquinone 246 RQBENZ (Robenidine hydrochloride) [1 ,3-Bis(p_-chlorobenzylideneamino) guanidine hydrochloride] Carbonyl-1I+C-labeled robenz was administered as a single dose to rats. A small amount was converted to C02. The major urinary metabolite (88%) was identified as p_-chlorohippuric acid. A minor metabolite, about 2% of urinary radioactivity, was identified as p_-chlorobenzoic acid. About 12 other unidentified materials were also present. More than 60% of the radioactivity in feces was unreacted robenz. Liver, kidney and muscle contained p_-chlorohippuric acid, £-chlorobenzoic acid and robenz (Zulalian and Gatterdam, 1973). Chickens were administered robenidine (I) ll*C-labeled in the a-carbon of p_-chlorobenzylidene or in the aminoguanidine carbon. Within 24 h, 82% of the label had been excreted, mostly as unchanged robenidine. After solvent extraction, column chromatography and mass spectral analyses, the metabolites were identified as p_-chlorobenzoic acid (II), 3-amino-4-(p-chlorobenzylideneamino)-5-(p_-chlorophenyl )-(4H)-l ,2,4- triazole (X), and compounds III to IX (Zulalian et al . , 1975). 247 cl"{3"CH=N"NHi"NH"N=CH'(~^cl — ►• C1,CV^ II II NHHC1 *-* ' *-f\) Robenz (I) IUhQ (X) oO< — * Q<-—>H 2222 ^ ^ Ornithine lvsinP N2 N5 N2 N, VI ""• "OC ""Ok" V 248 ROTENONE Rotenone is stable in the solid state but degradation is accelerated by the presence of organic solvents. Air and light are required (Cahn et al . , 1945). The rate of decomposition varies with solvents, temper- ature and access of air. Decomposition produced the yellow crystalline dehydrorotenone and rotenonone and a complex mixture of other oxidation products of rotenone (Jones and Haller, 1931). 249 S-1358 [S-n_-Butyl S'-(p-tert-butyl benzyl )-N-3-pyridyldithiocarbon- i mi date] Male Sprague-Dawley rats were intubated with an aqueous suspension of labeled S-1358 in 10% Tween 80. Excretion of radioact-vity was almost complete within 4 days. Depending on the dose level, 36 to 43% was excreted in urine and 54 to 57% in feces. After separation of meta- bolites by TLC, identification procedures included the use of NMR, IR, MS and derivatization: I. S-n-butyl S/-(p_-2-methyl isopropanol ) benzyl P[-3-pyridyldithio- carbonimidate II. 3-aminopyridine III. 2-(3'-pyridylimino)-4-carboxythiazolidine IV. 4-(2-methyl isopropanol )benzyl methylsulfide V. 4-(2-methyl isopropanol jbenzyl methyl sulfone. VI. 4-[2-(2-methylpropanoic acid)]benzyl methylsulfide VII. 4-[2-(2-methylpropanoic acid)]benzyl methylsulfone VIII. bi s (p-tert-butyl benzyl disulfide) IX. S- (p-tert-butyl benzyl )N-3-pyridyldithiocarbamate Urine contained metabolites I, IV, V, VI and VII. The latter four were also present probably as glucuronide conjugates. Feces also contained metabolites I, II, IV, V, VI and VII. Analysis of bile indicated the presence of compounds IV, V, VI and VII both free and as glucuronides, metabolite I free and conjugated, metabolites VIII and IX. In each case, there was also some unidentified material (Ohkawa et al . , 1975). 250 CH^ CH, ™>{yyy> ^v^^Ot- VIII ^ IX / ^-CH2-CH2-CH2-CH3 11 S-1358 3 X I /S-CH2-CH2-CH2-CH3 | V-CH-COOH "*— ] \ /=\ I GLUC. Ill i CH. CH3 CH, =nSH ch>-s-c^O"["cH2°h — *■ ch'_s"ch'Oi" COOH CH. IV VI. / \ / \ GLUC. [Sulfoxide] [Sulfoxide] GLUC. 9 _ ?H3 P CH, CH3 0 CH, '2-Oi"cH2°H — *■ cH4cHfO"i" CH3-S-CH2-<\ /K-CH20H ►" CH,-S-CH^V >C-C0OH v X / vii GLUC. GLUC. 251 SALITHION [2-Methoxy-(4H)-l ,3,2-benzodioxaphosphorin-2-sulfide] After oral administration of 32P-salithion to mice, analyses indicated that this material was rapidly degraded and excreted. In houseflies, salithion persisted for a comparatively long time. Analysis of the chloroform-soluble fraction of houseflies indicated the presence only of the oxo analog (Ohkawa et al . , 1970). 252 SAN-6706 [4-Chloro-5-dimethylamino-2-(a,a,a-trifluoro-m-tolyl)-3(2H)- pyridazinone] SAN-9789 (Norflurazone) [4-Chloro-5-methylamino-2-(a,a,a-trifluoro- m-tolyl-3(2H)-pyridazinone] Both compounds were readily absorbed from nutrient solution by cotton (Gossypium hirsutum L. "Coker 203"), corn (Zea mays L. "WF9") and soybean (Glycine max (L.) Merr. "Lee") plants. In corn and soybean plants, these compounds were translocated more rapidly and in greater amount than in cotton. SAN-6706 was not degraded to any great extent in cotton. In corn and soybean, significant amounts of the mono- and des-methyl derivatives were seen after 24 h. Metabolism of SAN-9789 also was more rapid in corn and soybean than in cotton (Strang and Rogers, 1974). 253 SUMITHION (Fenitrothion, Accothion) [0,0-Dimethyl 0-(3-methyl-4- nitrophenyl )phosphorothioate] Labeled sumithion was applied to apple tree. After 21 days, nearly 86% of the residue on the apple surface was sumithion. In the tissues degradation was more rapid, and approximately 45% of the radioactive carbon was in the form of degradation products. In addition to sumioxon, the S-methyl isomer of sumithion, p_-nitrocresol and its 3-glucoside, and desmethyl sumithion were also found. The latter product was detected only in fruit harvested on the 21st day (Hosokawa and Miyamoto, 1974). Irradiation of sumithion in various solvents produced considerable photodecomposition rate variations. Solvent/Surface Product Bean leaves Water Acetone 1* 2* + sunlight Carboxysumithion + + + + + Methyl parathion + Sumioxon + + + + + Carboxysumioxon + + + 3-methyl -4-ni trophenol + + + + + 3-carboxy-4-ni trophenol + + + + Sumithion S- isomer + C02 + Unknowns + + + + + (Ohkawa et al . , 1974b) 1* Silica gel chroma topi ates + UV 2* Silica gel chromatoplates + sunlight Solvent Half-life (min) Air Nitrogen Water 50% Aq. CH30H Acetone CH3OH Benzene <5 <5 20 60 50 100 100 >240 >360 >360 (Ohkawa et al . , 19741 Sumithion can isomerize to the S_-methyl analog. The latter is a more potent cholinesterase inhibitor. The I50 varied from 2.34 x 10"5 (human blood serum) to 1.47 x 10"6 for fly head for sumithion and 9.04 x 10"8 to 5.26 x 10"9, respectively, for S-methyl sumithion. The hydrolysis rate was also determined at pH 10.99 and 25C: KHyd(min_1) for sumithion = 3.54 x 10_l+ and for S-methyl sumithion = 2.96 x 10"1 (Kovacicova et al . , 1973). 254 [Methoxy-ll+C]sumithion was used to assay glutathione-dependent demethyl- ation. Results of these studies indicated the presence of a glutathione- dependent enzymatic breakdown of sumithion in both Heliothis zea and Heliothis virescens but was lower in the latter (Plapp, 1973). Sumithion has been used over a period of years for spruce budworm control. Some studies have shown that, although 70-85% of the initial dose deposited on trees was lost within two weeks after spraying, about 10% persists for at least 10 months. In view of these findings, a survey was made to check residue accumulations in areas of N.B., Canada, which had been treated for up to 5 consecutive years. No measurable amounts of sumithion or known breakdown products were found in any tested soils. Balsam fir foliage contained measurable year-end residues but no major breakdown products. Total residues appeared to have accumulated in foliage in relation to dosage and number of applications. Maximum residue observed was 1 ppm sumithion in Spring 1973 in fresh balsam fir foliage (Yule, 1973 and 1974; Yule and Duffy, 1972). 255 TERBUFOS (Counter) [0,0-Diethyl S-(tert-butylthiomethyl )phosphoro- dithioate] In soil, terbufos exhibited a half-life of 4 to 5 days. The sulfoxide formed by oxidation reached a maximum at about 14 days. The sulfone appeared one week after the start of incubation of soil with terbufos. Some other compounds observed in less than 1% amounts were the thiolophosphate, thiolophosphate sulfoxide and the thiolophosphate sulfone (Laveglia and Dahm, 1975). 256 TFM [4-Nitro-3-trifluoromethyl phenol] When rainbow trout were exposed in vivo to 11+C-labeled TFM, only the glucuronide conjugate was detected and was excreted primarily in bile. The highest glucuronide levels were found in liver (Lech, 1972 and 1973: Lech and Costrini, 1972). Coho salmon exposed to TFM excreted about 35 times more conjugated than free TFM in a 24-h study period (Hunn and Allen, 1975a). When rainbow trout were exposed to 5 mg/1 solution of TFM, the concen- tration of free TFM in gallbladder bile rose to 4.12 yg/ml after 2 h and the TFM glucuronide rose to 196 yg/ml . Plasma concentration of TFM was 2.73 yg/ml and of TFM glucuronide, 0.87 yg/1 (Hunn and Allen, 1974). Within 24 h after transfer to fresh water, TFM disappearance from the fish plasma was complete. Concentration of free TFM in the bile remains stable during 12 h of withdrawal but the conjugated TFM concentrations rise. Then, between 12 and 24 h of withdrawal, the levels of both declined (Hunn and Allen, 1975b). Chironomid larvae (Chironomus tentans Fabricius) were exposed to TFM. TFM accumulation from water was dependent on concentration and water hardness. The half-life varied from 3.6 to 15.3 h. Analyses of homo- genates of exposed larvae indicated the presence of TFM glucuronide and sulfate as well as another conjugate which was hydrolyzed by 0.25M HC1 and 0.25M NaOH but not by g-glucuronidase or by sulfatase. RTFM was also observed (Kawatski and Bittner, 1975). In other in vitro studies, all fish tissue homogenates (except trout brain) produced metabolites. Except bluegill liver, all homogenates produced TFM glucuronide (Kawatski and McDonald, 1974). When rainbow trout were pre-exposed to sal icyl amide, TFM toxicity was increased; blood levels of TFM increased and TFM glucuronide decreased. The half-life of i.p. administered TFM was increased from 1.59 to 4.13 h (Lech, 1974). Administration of novobiocin produced similar effects (Lech et al . , 1973). Administration of salicylamide to the sea lamprey did not increase TFM toxicity. ' In vitro studies indicated lower glucuronyl transferase than in rainbow trout and in vivo studies showed a higher free to conjugated TFM ratio in sea lamprey than in trout (Lech and Statham, 1975). Studies were conducted with li+C-TFM in a model stream community. Uptake and accumulation by several plant and animal components was basically an adsorption phenomenon consisting of a rapid initial uptake and then a reduced linear uptake phase. Elimination of TFM accumulations was rapid: in riffle dwelling species, an average half-life of 17.8 h; in pool-dwelling species, 140 h (Maki , 1974). 257 Scud (Gammarus pseudolimnaeus) concentrated TFM by a factor of about 58 in 7 days. After being transferred to TFM-free water, they elim- inated half of the accumulated TFM in 3.5 days and 98% after 14 days (Sanders and Walsh, 1975). When TFM was was released. incubated with isolates from river muds, some fluoride The organisms seemed to be Pseudomonas sp. Although cultures degraded TFM somewhat, isolates were unable to do so (Kempe, 1973). TFM was exposed to sunlight and to UV lamp. TFM half-life in aqueous solution exposed to sunlgith was about 100 h; on silica gel plates, 71 h. A number of degradation products were observed. One chroma- tographed the same as RTFM. None were identified (Dawson, 1973). OH OH Microorganism -»- no TFM Rat, Trout liver & kidney prep. CF, NH? RTFM Trout liver & kidney prep, OH Rat Trout Rat Trout liver & kidney prep. Glucuronide Glucuronide 258 THIABENDAZOLE (TBZ) [2-(4*-thiazolyl )benzimidazole] 14C- and 35S-labeled thiabendazole was orally administered to sheep. Within 96 h, sheep excreted 75% of the dose via urine and 14% in feces. Chromatography indicated that nearly all of the radioactivity was in the form of metabolites. Residues were distributed throughout most body tissues initially. 35S was detectable in only a few tissues at less than 0.2 ppm by the 16th day and 0.06 ppm or less after 30 days. The metabolites were identified as the 5-hydroxy analog and the sulfate and glucuronide esters (Tocco et al . , 1964). In pepper plants, thiabendazole (TBZ) accumulated only in the leaves. Disappearance of TBZ from the leaves exceeded that of methyl -2- benzimidazolecarbamate (MBC) by three to fourfold. 2-Aminobenzimidazole, a degradation product of MBC, was also present at levels up to 2% of the parent compound (Ben-Aziz and Aharonson, 1974). ^C-Thiabendazole was sprayed on sugar beet leaves. The plants were grown for 34 days under incandescent and fluorescent illumination. Analyses accounted for 97-98% of the radioactivity as unchanged thiabendazole. When treated beet leaves were exposed to sunlight for the equivalent of 14 8-hr days, only 78% of the radioactivity was present as unchanged thiabendazole. The remainder appeared to be photoproducts. In addition to benzimidazole-2-carboxamide, benzimidazole and polar and polymer products were formed. When photo- lysis was conducted on glass plates, benzimidazole-2-carboxamide and benzimidazole were observed (Jacob et al . , 1975). Thiabendazole was not metabolized by potatoes or cotton (Tisdale and Lord, 1973). 259 THIOLCARBAMATES BENTHIOCARB [S- (4-Chl orobenzyl ) -N ,N-di ethyl thiol carbamate] BUTYLATE [S-Ethyl-N,N-(di-2-methyl propyl ) thiol carbamate] CYCLOATE [S-Ethyl-N-ethyl-N-cyclohexyl thiol carbamate] DIALLATE [S- ( 2 , 3-Di chl oroal lyl ) -N ,N-di i sopropyl thiol carbamate] EPTC [^-Ethyl-N,N-dipropylthiolcarbamate] MOLINATE [S-Ethyl-N,N-hexamethylenethiol carbamate] PEBULATE [S-Propyl -N-butyl -N-ethyl thiol carbamate] TRIALLATE [S- ( 2 ,3 ,3-Tri chl oroal lyl -N ,N-di i sopropyl thiol carbamate] VERMOLATE [S-Propyl-N,N-di propyl thiol carbamate] Thiocarbamates are detected in the liver of mice 20 min after i.p. treatment with EPTC, molinate, pebulate, and vernolate at 1 m mole/ kg but not after administration of benthiocarb, butyl ate, or cycloate (Casida et al . , 1974). 260 EPTC (Eptam) 1,2,3,4 Pebulate (Tillam) 1,2,3 Benthiocarb (Saturn) 1 Butyl ate (Sutan) 1,5 Cycloate (Ro-Neet) 1 Molinate (Ordram) 1,2 Vernolate (Vernam) 1,2 ♦Formed with DEGRADATION PRODUCTS* Sulfoxide Sulfone C02 EtS02-CH3 N-depropyl 2 2 2 1 1. Mouse liver microsome - NADPH system 2. Living mice 3. Photolysis 4. Corn 5. Soil After oxidation to the sulfoxide, cleavage by the GSH-S-transferase system occurred with EPTC and pebulate. Mercaptans were released. (Casida et al . , 1974 and 1975) 261 BENTHIOCARB (Saturn) [4-Chlorobenzyl N,N-diethylthiol carbamate] The fate of lltC- labeled benthiocarb was studied with white mice in vivo and in vitro. After oral administration, benthiocarb was rapidly translocated into organs. There was rapid urinary excretion of labeled material; slight excretion in feces; and only a little expired. The major metabolites identified were: 4-chlorohippuric acid, 4-chlorobenzoic acid, glucuronide of 4-chlorobenzoic acid, and 4-chlorobenzyl alcohol. In liver homogenates, the microsomal fraction exhibited highest activity and NADP accelerated the degradation. In vitro metabolites were identified as: N-desethyl benthiocarb, bis(4- chlorobenzyl )mono- and di-sul fides, and 4-chlorobenzoic acid (Ishikawa et al . , 1973). 11+C-Benzyl methylene labeled benthiocarb was taken up through the roots and translocated into whole plants by rice, barnyard grass, wild amaranth, smartweed, and lambsquarters plants. It was trans- located from a leaf into other leaves also. When applied to seeds, it was rapidly absorbed and accumulated mostly in the embryo. The plants degraded benthiocarb rapidly. No metabolites were identified (Nakamura et al . , 1974). 262 0 II Cl\ />-CH2-S-C-N-(C2H5)2 C1-"cooh i 2,5-TIBA COOH MIBA COOH 2-OH-MIBA COOH 3,5-DIBA COOH 2-0H-3,5-DIBA 265 TIN COMPOUNDS FENTIN ACETATE [Tri phenyl tin acetate] When fentin was added to soil, the amount that could be extracted with methanol decreased with time. Some fentin acetate was adsorbed to the soil. When [ll+C]triphenyltin acetate was incubated with soil, 50% of the label evolved as lt+C02 in 140 days. In sterile soil, only 0.47% evolved in 60 days. Several Aspergillus sp. were able to degrade fentin in liquid culture with release of il*C02. A Gram-negative bacteria was also able to metabolize fentin (Barnes et al . , 1973). Photochemical degradation of fentin at X>250 produced diphenyltin, monophenyltin, and inorganic tin (Chapman and Price, 1972; Barnes et al., 1973). In distilled water, fentin underwent rapid hydrolysis with formation of triphenyltin hydroxide (Barnes et al . , 1973). When rats were exposed p.o. to labeled tin, it was found that 50% of absorbed tin was excreted within 48 h (Hiles, 1974). 266 TIRPATE (Ent 27696) [2,4-Dimethyl-l ,3-ditholane-2-carboxaldehyde 6- (methyl carbamoyl )oxime] The half-life of tirpate, when administered to young tobacco plants (Nicotiana tobacum) in hydroponic culture, was about 8-9 h. ^C- Tirpate was readily taken up and translocated throughout the shoot but was not rapidly retranslocated to new young leaves. The initial metabolite was the sulfoxide. The sulfoxide nitrile was also found. Identification was by GC-MS. The conjugated materials were not identified. Some were released by sulfatase or glucosidase. One material released by sulfatase exhibited an Rf similar to that of the sulfoxide (Hill and Krieger, 1975). 267 TOXAPHENE (Camphene chlorinated to 67-69% chlorine by weight and an average C10H8C110 composition) Technical toxaphene is a complex mixture consisting of at least 175 C10 polychloro compounds (Casida et al . , 1974b; Khalifa et al . , 1974). Male rats were orally administered 36Cl-toxaphene. Within 9 days after dosing, the rats excreted over 50% of the administered dose. About 30% of this was in the urine and 70% in the feces. Although excretion in feces plateaued early, excretion in urine continued upward. Ionic chloride was excreted in large amount (Crowder and Dindal , 1974). Other studies confirm the rapid elimination of chloride with a half-time of 2 to 3 days. When 14C- toxaphene was used, only low 11+C-levels were observed in tissues several days after administration. Similar observations were made after administration of toxicant B from toxaphene. Urinary and fecal metabolites included CO2, dechlorinated materials and acidic compounds (Ohsawa et al . , '1 975) . Most of the 36C1 -toxaphene was metabolized before excretion. Less than 1% of the 36C1 in the urine and less than 3% in feces appeared as unmetabolized toxaphene. Subfractions of toxaphene did not differ greatly (Casida et al . , 1974a). The only urinary metabolite identified when *6C1- toxaphene was administered to rats was chloride ion. Tissue residues were very low when 1UC- toxaphene was used (Casida et al . , 1974c). The closely related polychlorinated norbornenes were also studied. Hexachloronorbornene (II) was added to a culture of Clostridum butyricum. Analyses of the medium showed the presence of compounds III, IV and V. The pentachloronorbornene VI gave rise to compounds III and IV. Tetrachloronorbornene (III) gave rise to compound IV (Schuphan and Ballschmitter, 1972). Toxaphene was applied to alfalfa, range grass and winter wheat. Analyses gave no evidence of toxaphene metabolism (Carl in et al . , 1976). Toxaphene reacted rapidly with hematin in aqueous media to produce dechlorinated toxaphene derivatives. About half of the carbon- chlorine bonds were broken. Toxicant fractions A and B underwent dechlorination, dehydrochlorination and a combination of both (Holmstead et al . , 1975). 268 H2 rU A-S C^Cl 2,2,5-endo-6-exo-8,9,10 heptachl oronorbornane (Toxicant B) I II IV 269 TRIAZINES Ametryne Atrazine Bromosimazine Cyanazine Cyprazine Fluorosimazine Iodoatrazine Iodopropazine Iodosimazine Metribuzin Prometone Prometryne Propazine Simazine Simetryne WL 9385 270 Photodecomposition of symmetrical triazines was found to be dependent on the nature of the substituent and the solvent. The rate constant ^decreased in the order: I>Br>Cl>F; ethyl > propyl; and methanol > n-butanol . Decomposition exhibited zero-order rate constants. Materials tested included: Ametryne Atrazine Bromosimazine Fluorosimazine Iodoatrazine Iodopropazine Iodosimazine Prometryne Propazine Simazine Simetryne (Ruzo et al., 1973) 271 AMETRYNE [2-Ethyl ami no-4-i sopropyl ami no-6-methyl thi o-s_- triazi ne] In nutrient solution-sugarcane system, ametryne degraded rapidly (90% in 30 days) to more polar materials. Dealkylated ametryne was the major product at 20 days. 2-Methylthio-4,6-diamino-s_-triazine and ammeline formed in substantial amounts by 30 days. When ring-ll+C- ametryne was applied to sugarcane, some ^C02 was formed. Ametryne was not metabolized to hydroxyametryne in sugarcane. In addition to C02> another volatile metabolite was observed but not identified. In soil, ametryne was degraded through N^-dealkylation and 2-hydroxy- lation (Goswami, 1972; Goswami and Green, 1974). 272 ATRAZINE [2-Chloro-4-ethylamino-6-isopropylamino-s-triazine] Canada thistle (Crisium arvense L. ) plants were treated with labeled atrazine. Analyses indicated that over 90% of the material was present in the shoot where the atrazine was applied. TLC showed that most (64%) of the chloroform extracted material was unaltered atrazine; 6%, 2-amino-4-chloro-6-isopropylamino-s-triazine; 5%, 2-amino-4-chloro- 6-ethylamino-s^-triazine; and 25% unidentified. The water-soluble fraction contained 42% of the lkC in the form of 2-ethyl aminos-hydroxy- s'isopropyl ami no-s-triazine; 2-amino-4-hydroxy-6-isopropylamino-s^- triazine; and 2-amino-4-ethylamino-6-hydroxy-s-triazine. About 58% was unidentified (Burt, 1974). The degradation of atrazine in submerged soil was measured. When ring- C-atrazine was used, some lt+C02 evolved. A metabolite, hydroxy- atrazine, was degraded more rapidly than atrazine by microorganisms. Products of microbial degradation of atrazine and hydroxyatrazine, an atrazine metabolite, included the product 2-amino-4-chloro-6- isopropylamino-s_-triazine. These studies indicated that two pathways may be simultaneously operative: (1) biological, with dealkylation; and (2) chemical, with hydrolysis of the halide followed by microbial degradation (Goswami and Green, 1971). Atrazine was applied to shoots of fall panicum, Texas panicum (P_. texanum Buckl . ) , witchgrass (P. capillare L. ) , giant foxtail (Setaria faberii Herrm.), yellow foxtail (S. glauca L. Beauv.), green foxtail (S. viridis L. Beauv.), giant green foxtail (S_. viridis var. major Gaud Posp. ) , robust white foxtail (S^. viridis var. robusta-alba Schreiber) and robust purple foxtail (S^. viridis var. robusta-purpurea Schreiber). Analyses of plant extracts indicated the presence of hydroxyatrazine, monodealkylated hydroxyatrazine, and amino acid or peptide conjugates (Thompson, 1972). Further studies were conducted to elucidate the metabolism of atrazine in sorghum (Sorghum vulgare Pers., N.D. 104). The major pathway was shown to involve the glutathion conjugate. ' Subsequent reactions removed the glycine moiety and then glutamic acid in that order. From the S-cysteine derivative, rearrangement produced the N-analog t[-(4-ethylamino-6-isopropyl-s_-triazinyl-2)cysteine (VIII) . Addition of alanine produced the N-lanthionine derivative (IX). Two other compounds were observed in sorghum for the first time: 2-amino-4- hydroxy-6-isopropylamino-s-triazine (III) and 2,4-diamino-6-hydroxy- £-triazine (ammeline) (IVj. The two mono-N-dealkylated products and ammeline (IV) were observed and one more new metabolite identified as NUIV-bis(4-ethylamino-6-isopropylamino-s-triazinyl )cystine (X) (Lamoureux et al . , 1973; Shimabukuro et al . , 1973b). 273 The degradation of atrazine by rat liver preparations was investigated. Cochromatography with standards was used for identification. These studies indicated that dealkylation was the predominant reaction and preceded conjugation with glutathione. Removal of the isopropyl group apparently occurred more easily than removal of the ethyl group. However, addition of MADPH to 10800xg supernatant and the microsomal fraction brought about removal of the second alkyl group to produce 2-chloro-4,6-diamino-s_-triazine (XIV). When GSH as well as NADPH was added to the mixture, GSH-conjugates were formed with atrazine and the two mono-N-dealkylated derivatives but not with the diamino analog. However, when the desethyl or diamino derivatives were used as substrates, some GSH-conjugate of the diamino derivative was formed (Dauterman and Muecke, 1974). In soil, atrazine hydrolysis proceeded with a second-order kinetics under non-sterile conditions and first-order kinetics under sterile conditions. Laboratory studies indicated that about half to two- thirds of applied atrazine was hydrolyzed non-biological ly by soil samples (Agnihotri, 1971). After application to soil, atrazine degradation produced both mono-N-dealkyl derivatives and the hydroxy- atrazine (II) (Sirons et al . , 1973). The major metabolite, hydroxy- atrazine, probably occurred through non-biological processes. Degra- dation was greater at pH 5.5 than at pH 7.5 (Best and Weber, 1974). In the presence of nitrite and acid, atrazine reacts to form an N[- nitrosamine (NNA). Maximum NNA formation occurs at pH 1 . Thermal decomposition on GLC produces atrazine (Wolfe et al . , 1975). 274 ti 0 COOH CH,-CH-N-C-CH,-CH,-CH-NH, i-Pr J ' fcOOH '2 vn2 S-G N^ N S-G H2N^N ])■( XIII K ? N H S-CH2-fH-C00H X HJJ-CH-CH2SH ,.pr^H/^t i-Pr>^N^tt .N H VIII IV G-S = Glutathione 275 CYANAZINE [2-Chl oro-4- ( 1 -cyano-1 -methyl ethyl ami no ) -6-ethyl ami no-s_- triazine] When applied to soil, cyanazine degraded primarily to des-isopropyl atrazine. The anticipated amide, the initial hydrolysis product of the nitrile, was also seen (Sirons et al . , 1973). Using a system developed by R. Metcalf, 1HC-ring-labeled cyanazine was introduced into an aquatic model ecosystem. After 35 days, analyses of the components were conducted. In addition to unchanged cyanazine (I), N-deethyl cyanazine (II), cyanazine amide (III), f[-deethyl cyanazine amide (IV), and three unknowns were found in the water. Radioactivity did not increase in the food chain of algae to mosquitoes to fish (a decrease from 1.3 to 0.05 ppm was observed), indicating that this compound does not concentrate through the food chain (Yu et al . , 1975a). Compound Organism Found Algae [Oedogonium cardiacum (Huss.)] Ue Crab (Uca Minax]~ II, U^ Uc, Ue Daphnia (Daphnia magna Strauss.) Ue El odea (Elodea canadensis) Uc, Ue Mosquito (Culex pi pi ens quinquefasciatus Say) Ue Fish (Gambusia affinis Baird and Girard) Ue Snail (not identified) Ua» Ub, Uc = Three unidentified metabolites Ue ' = Unextractable 14C 276 CYPRAZINE [2-Chloro-4-cyclopropylamino-6-isopropylamino-s-triazine] ll+C-Ring-labeled cyprazine (I) was administered by stomach tube to rats which were sacrificed after 3 days. Feces and urine were collected daily and pooled. About 98% of the radioactivity was excreted within 72 h. Very little (<0.1%) appeared as ll*C02 and carcass and hide contained 7.5% of the lkC. Paper, thin-layer and gas chromatography, derivatization and mass spectral analyses were used to separate and identify the metabolites. Compounds II to IV were identified and VI to IX were characterized (Larsen and Bakke, 1975). i-C3H7NH- -NH2 -NH2 i-C3H7NH- i-C3H7NH- CH3 I H0-CH2-CH-NH- -NH2 CH3 HOOC-CH-NH- CH3 CI- lo-CH-NH- I. Cl- II. H0- III. Cl- IV. H0- V. Cl- VI. Cl- VII. Cl- VIII. Cl- H2C— -CH— -NH -NH2 -NH2 -NH2 -NH2 -NH2 CH2 CH- NH- CH? — CH- •NH- CH, — CH-NH- HO-CHo-a 277 METRIBUZIN (BAY-94337, SEMCOR) [4-Amino-6-tert-butyl-3-methylthio- as-triazin-5(4H)-one] Metribuzin was added to nutrient solutions in which sugarcane cuttings of cultivar H50-7209 had been established. After one week, very little parent material was present in the nutrient solution or plant tissue. The deaminated product II, the hydrolysis product III, and the diketo product IV were detected in small amounts. Most of the metribuzin metabolites present in sugarcane were not identified (Hilton et al . , 1974). Preliminary greenhouse studies with metribuzin indicated that soybean cultivars exhibited different responses to exposure through nutrient solutions. The major portion of the metabolites was water-soluble. The "Semmes" and "Coker" cultivars produced primarily 6-tert-butyl- a£-triazin-3,5-(2H,4H)-dione (IV). The major metabolite from "Bragg" roots and stems was an N-glucoside conjugate (Smith and Wilkinson, 1974). The rates of degradation of metribuzin and two analogs were studied. All three herbicides exhibited pseudo first-order kinetics. (CH3) 3^3" (CH3) 3J3' II -CH, (CH3)3-C N-NH, (CH3)3-C 278 k x lO"2 tl/2 AEa R °C day"1 (days) (kcal/mole) t-butyl 5 20 1.84 1.52 377 46 12.7 35 4.40 16 i -propyl 5 20 2.07 1.50 335 46 13.3 35 4.56 15 cyclohexyl 5 20 2.53 1.75 274 40 10.5 35 4.21 17 (Hyzak and Zimdahl , 1974) A number of asymmetric triazin-5(4H)-ones were irradiated in carbon tetrachloride, methanol, benzene and water. Photolysis yielded essentially identical results in each case. The major product was identified as the 5-hydroxy triazine. Chromatography and mass spectra indicated minor products resulting from oxidation and desulfurization. Compounds tested were the 6-t-butyl , 6-isopropyl and 6-cyclohexyl analogs. Photolysis produced the following derivatives of these three compounds: 4-amino-3,5-diketo- 3-hydroxy-5-keto- 5-hydroxy-3-keto- 4-amino-5-keto- 4-azo-5-keto- and 5-hydroxy-as-l ,2,4-triazine. (Pape and Zabik, 1972) -NH: S-CH, 279 PROMETONE [2 ,4-Bi s ( i sopropyl ami no) -6-methoxy-s-triazi ne] Rats were administered ^C-ring-prometone. Urine was collected and analyzed and eight metabolites were identified or characterized by mass spectrometry or trimethylsilyl derivatives. The major metabolites identified were ammeline (31.5%) and 2,4-diamino-6-methoxy-s_-triazine (10-14%). Other metabolites included: 2-amino-4-(l-carboxyethylamino)- 6-methoxy-s-triazine; 2-amino-4-(l-carboxyethyl ami no) -6- hydroxy -s-triazine; 2-amino-4-methoxy-6-(2-propan-l-ol)amino-s_-triazine; 2-amino-4-hydroxy- 6-(2-propan-l-ol )amino-s-triazine; and 2-amino-4-hydroxy-6-i sopropyl amino- s-triazine (Bakke and Price, 1973). 280 PROPAZINE [2,4-Bis(ethylamino)-6-chloro-s_-triazine] Propazine was applied to six species and varieties of Setaria and three species of Panicum. In all cases, the hydroxypropazine was formed (Thompson, 1972). 281 SIMAZINE [2-Chloro-4,6-bis (ethyl amino )-s_-triazine] Six species and varieties of Setaria and three Panicum species were exposed to 1I+C-simazine. After absorption, simazine was metabolized to water-soluble compounds. Hydroxy derivatives were detected but peptide conjugates apparently were the only major metabolites formed by each species or variety. Hydroxysimazine was detected by chroma- tographic analysis (Thompson, 1972). Simazine was added to a nutrient solution in the presence of citrus tree roots. Hydroxysimazine was not observed. Monodealkylation was followed by di-dealkylation of the simazine (Jordan and Jolliffe, 1973). Simazine was applied three times at the rate of 2.8 kg/ha and five times at the rate of 5.6 kg/ha. After 12 and IS months, respectively, the total simazine residue was less than 10% of the annual dose (Clay and Stott, 1973). Black walnut (Juglans nigra L. ) and yellowpoplar (Liriodendron tulipifera L. ) 1-year-old seedlings were placed in nutrient solutions to which simazine had been added. Analyses after 3 days exposure showed the presence of simazine and monodealkylated simazine in leaves, stems and roots. The concentration of the monodealkylated simazine was greater in the yellowpoplar than in black walnut. Other degradation products found included 2-chloro-4,6-diamino-s_-triazine, found in higher concentrations in yellowpoplar than black walnut, and hydroxy- simazine which was found in yellowpoplar but not in black walnut. Two other compounds found in both plants were not identified (Wichman and Byrnes, 1975). 282 WL 9385 [2-Azi do-4- t-butyl ami no-6-ethyl ami no-s_-triazi ne] In the presence of moisture, in all soils tested, WL 9385 decomposed with formation of the corresponding 2-amino derivative. The rate constant is about 1.5 to 2.0 mg/g soil/day with some dependence on soil pH indicated. The reaction is not of a biological nature. In the solid state, this herbicide changes from white to yellow-brown when exposed to daylight or ultraviolet light. A half-life of about 240 h was observed. Decomposition followed first order kinetics (Barnsley and Gabbott, 1966). 283 TRIDEMORPH (Calixin) [2,6-Dimethyl N-tridecylmorpholine] After the use of tridemorph on cereals, residues in grain were not detectable (less than 0.05 ppm) after 48 days. The half-life is about 5 or 6 days. Tridemorph is almost completely adsorbed from aqueous solution by soil at pH 6.7 and 7.5. Within 30 days, 80% of tridemorph added to Limburgerhof soil was degraded. The degradation was initiated by formation of tridemorph-N-oxide. Carbon dioxide and 2,6-dimethylmorpholine formed subsequently. Tridemorph half-life in loamy sand soil was about 8 weeks (Anon., BASF 1974). 284 TRIFLURALIM [2,6-Dinitro-N,N-dipropyl-a,a,a-trifluoro-p_-toluidine] Trifluralin readily decomposed when aqueous solutions were exposed to sunlight. Under acidic conditions, the main product was 2-amino- 6-nitro-a,a,a-trifluoro-p_-to1uidine (XIII). Under alkaline pH, 2- ethyl-7-nitro-5-trifluoromethylbenzimidazole (XI) was the main compound (80%) of the photolytic products. Two other compounds, which were present under all conditions were identified as 2,3-dihydroxy-2-ethyl- 7-nitro-l-propyl-5-trifluoromethylbenzimidazole (II) and 2-ethyl-7- nitro-5-trifluoromethylbenzimidazole-3-oxide (VII). These latter two degraded readily by heat or irradiation. Further irradiation of compounds II and VII helped elucidate the photolytic degradation of trifluralin. About 25 compounds were detected; 14 were identified (Crosby and Leitis, 1973; Leitis and Crosby, 1974). Photolysis of trifluralin vapor produced II, III, VI, VII, XI, XII, XV and XVI (Soderquist et al . , 1975). 285 HN t-C-CH (VIII) 3 HN_ _c-0H 02tKJ\^) (XV) CH I || 2 5 HN C-C H F 2 5 3 (VII) HN C-CH=CH 286 TRIFORIME (Cela W524) [N,N'-Bis(l-formamido-2,2,2-trichloroethyl ) piperazine] A soil drench application of triforine was applied to barley plants in pots. The biological half-life was 9 to 10 days when applied at the rate of 5 mg/plant but rose to 25 to 26 days with 50 mg. In the shoots four metabolites were observed. One was identified as piperazine and another was tentatively identified as N-monoglyoxyl -piperazine (Bruchhausen and Stiasni, 1973; Fuchs et al . , 1972). 287 URACILS BROMACIL [5-Bromo-3-sec-butyl -6-methyl uraci 1 ] Aqueous solutions of bromacil were irradiated 6 days in the laboratory and for 4 summer months outdoors. In sunlight, a low yield of 5-bromo- 6-methyl uracil was obtained. Laboratory photolysis yielded this compound also. Other studies indicated the formation of four volatile substances after irradiation of a 10 ppm aqueous bromacil solution for 6 days. The major product (37%) was 6-methyl uraci 1 . The mass spectrum of a second compound was identical to that of 5-bromo-6-methyl uraci 1 . The mass spectra of the two other products were consistent with the addition of a water molecule to 6-methyl uracil to form 5-hydroxy-6- methyl-5,6-dihydrouracil and photooxidation of the latter to form 2-hydroxyimidazole (Moilanen and Crosby, 1974). Of 55 fungal and 73 bacterial cultures isolated from soil, only four fungi were capable of degrading bromacil. One culture was identified as Penicillium paraherquei Abe. (Torgeson and Mee, 1967). Bromacil was incubated in various soils to determine its persistence. The half -life in flooded soil was 155 days; in flooded soil plus bean straw, 198 days (Wolf and Martin, 1974). UREAS Buturon Chlorbromuron Dimilin Fluometuron Linuron Methbenzthiazuron Monolinuron Monuron 289 BUTURON [N-(4-Chlorophenyl )-N ' -methyl -N ' -(1 -methyl prop-2-ynyl )urea] After application of buturon to leaves, no p_-chloroaniline was observed. Other metabolites less polar than buturon were not demonstrated and the unextractable material was not characterized (Haque et al . , 1974). Ultraviolet irradiation of buturon in methanol, methanol /water and benzene produced dechlorobuturon and ^-phenyl -N' -methyl urea. Highly polymerized material was also present (Kotzias et al . , 1973). When buturon was incubated with Rhizopus japonicus, the methyl propynyl group was lost to form the 1 - (4-chl orophenyl ) -3-methyl urea (Wallnofer et al., 1973a). 290 CHLORBROMURON [3-(3-Chloro-4-bromophenyl )-l-methoxy-l -methyl urea] After application of chlorbromuron to corn and pigweed, the desmethyl and phenyl urea metabolites were present in greater amount than the desmethoxy and unidentified metabolites (Palm, 1971). 291 DIMILIN (Diflubenzuron, TH 60-40, OMS 1804, PH-6040) [l-(4-Chlorophenyl )-3-(2,6-difluorobenzoyl )urea] Dimilin was incubated for 1 h with sheep microsomes. Slightly more than 99% of the parent compound was unchanged. Metabolites identified included compounds II, III, V, VI, VII and IX. When the salt marsh caterpillar, Estigmene acrea, was fed 11+C-labeled dimilin, 99+% of the parent material was recovered unchanged in both feces and body homo- genates. Incubation of dimilin with the soil microorganism (Pseudomonas putida) produced no evidence of degradation. When incubated with soil, dimilin degradation was very low. Traces of products cochromatographed with 4-chlorophenylurea (V) and 4-chloroaniline (VI) (Metcalf et al . , 1975a). A model ecosystem was constructed and contained water, alga (Oedogonium cardiacum) , snail (Physa sp.), mosquito larva (Culex pipiens quinque- fasciatus) , fish (Gambusia affinis), plankton (Daphnia magna), sorghum (Sorghum "vulgare) and the salt marsh caterpillar (Estigmene acrea). Fourth instar caterpillars fed on dimilin treated sorghum leaves and dispersed the material into the aquatic portion of the system. In addition to those metabolites identified, there were nine unidentified compounds. No azobenzenes were observed (Metcalf et al . , 1975a). SYSTEM Found in Ecosystem Compou nd Sheep Found Microsomes I + II + III + IV V + VI + VII + VIII IX + Soil Water Alga Snail Mosquito Fish + + + + + + + + + + + + + + + + + + + + + (Metcalf et al . , 1975a) Dimilin was irradiated in methanol for 9 h at 254 nm. Some colored material was produced. TLC analysis showed the presence of 2-difluoro- benzamide (II), methyl phenyl carbamate (XI), and methyl 4-chlorophenyl- carbamate (X). In aqueous dioxane, a dark brown solution formed after 4-h irradiation. In addition to compound II, 4-chloroaniline (VI) and aniline (XII) were found. Cochromatography, IR and mass spectrometry were used in the identification of these compounds (Metcalf et al . , 1975a). In other studies, irradiation in methanol produced compounds II, X, XI and XIII (Ruzo et al . , 1974c). 292 F VII i IX '^Q^1 VIII OCN o° XIII 293 FLUOMETURON [1 ,1 -Dimethyl -3- (m-trifluoromethyl phenyl )urea] The metabolism of fluometuron in corn (Zea mays var. Dixie 18) and wheat (Triticum aestivum var. Wakeland) was studied. In both species, metabolism involved two-step demethylation and then hydrolysis to the aniline. Ring hydroxylation was indicated. Further metabolism of the aniline derivative into numerous metabolites occurred with an indication of formation of the hydroxyaniline derivative (Neptune, 1970). Sour orange (Citrus auranthium L.) or sweet lime (C. limetioides Tanaka) were exposed to 14C-fluometuron. After 4 days, analyses showed the presence of desmethyl fluometuron, 3-trifluoromethyl phenyl urea, and 3- trifluoromethylaniline (Menashe and Goren, 1973). After incubation of fluometuron with Rhizopus japonicus, desmethyl- fluometuron was observed (Wallnofer et al . , 1973c). 294 LINURON [3-(3,4-Dichlorophenyl)-l-methoxy-1-methylurea] When linuron was applied to corn or pigweed, the desmethyl and phenyl urea metabolites were present in larger amounts than the desmethoxy and unidentified metabolites (Palm, 1971). Data derived from studies of adsorption of linuron on humic acid, saturated with Fe3+, Al3+, Cu2+, Zn2+, Ni2+, Ca2+, H+ was found to be consistent with a physical type of adsorption. Infrared spectro- scopy showed no coordination of linuron to the cations on humic acid (Khan and Mazurkewich, 1974). 295 METHBENZTHIAZURON (MBT, Tribunil) [W2-Benzothiazolyl )-l ,3-dimethylurea] MBT was applied to hydroponic cultures of Triticum vulgare and allium cepa. Analyses indicated that MBT was metabolized to the 1-hydroxymethyl analog initially and subsequent loss of the hydroxymethyl group (Pont et al . , 1974). In other studies with sensitive and resistant plants, MBT passed rapidly from roots towards leaves where active metabolism seemed to occur. Metabolites identified include the 3 -hydroxymethyl analog and its glucoside and the 3-demethylated analog. The 1-OH-methyl analog was suggested as another metabolite. One other metabolite was characterized and the structure most compatible with the information was that of a l,2-bis(MBT) ethane (Collet and Pont, 1974). 296 MONOLINURON (Aresin) [3- (4-chl orophenyl )-l-methoxy-l -methyl urea] Monolinuron was sprayed on ground waste. After 3 weeks of composting, the material was extracted and analyzed. Most of the residue was unreacted monolinuron. About 0.4% was demethyl monolinuron (Muller and Korte, 1975). Incubation of monolinuron with Rhizopus japonicus produced desmethyl monolinuron (Wallnofer et al., 1973c). 297 MONURON [3- (4-Chlorophenyl) -1,1 -dimethyl urea] Young leaves were cut from 2-week-old plants of bean (Phaseolus vulgaris L. var. Black Valentine) and corn (Zea mays L. var. Batam Cross) and exposed to carbonyl-11+C-labeled monuron in water. After monuron uptake by the leaves, analyses showed the presence in both plants of: l-(4- chlorophenyl )-3-methylurea; 4-chlorophenylurea; an unidentified conjugate: and 1 ,1 -dimethyl -3-(2-hydroxy-4-chlorophenyl ) urea. Although the conjugates were not identified, these studies indicated the presence of a monuron- polypeptide larger than 5000 and three glucose conjugates. The latter were identified as mono-B-D-glucose conjugates of 2-hydroxy-4-chloro- phenylurea; l-(2-hydroxy-4-chlorophenyl )-3-methylurea; and 1 ,1-dimethyl- 3-(2-hydroxy-4-chlorophenyl ) urea (Lee and Fang, 1973; Lee et al . , 1973). Incubation of monuron with Rhizopus japonicus produced l-(4-chlorophenyl )- 3-methylurea (Wallnofer et al . , 1973c). 298 polypeptide complexes H 0 CH, CI OH CH„ H 0 CH, A-?-lJ-CH3 ci-v y— n-c-n-ch3 °<5-fi CH, , - ^OGl CI C-N-CH, H«H 3 *■ CI H 0 // N-C-NH„ T^O-GT C.-TV- N-C-NH, ^1=' H 0 299 WARFARIN [3- (a-Acetonyl benzyl )-4-hydroxycoumarin] In vivo studies with Wistar-derived warfarin susceptible strain (TAS) rats indicated that warfarin metabolism was the limiting step with regard to toxicity. Using in vitro studies, 6-, 7-, 8-, and 4'-hydroxy- warfarins were separated by means of thin-layer and paper chromatography and identified by mass spectrometry and UV spectra (Townsend et al . , 1975). 300 ZECTRAN (Mexacarbate) [4-Dimethylamino-3,5-Xylyl N-methyl carbamate] Bacteria, mold and fungi were screened for their ability to degrade zectran. All organisms tested were able to metabolize this pesticide. A bacteria (HF-3) and a fungus (Trichoderma viride) were further investigated. The major T. viride metabolite was 4-dimethylamino-3,5- xylenol (DMAX). Methylamino zectran (MAZ) and methyl formami do zectran (MFZ) were formed by HF-3. Other degradation products identified by TLC were amino zectran (AZ) and formamido zectran (FZ). Addition of cofactors and carbon sources altered the metabolic patterns. Decar- bamylation predominated in the presence of ATP, NADP+ and NADPH; demethylation, in the presence of NAD+ and FAD. Thus, T. viride could be induced to degrade zectran via -demethylation of the N-dimethyl group whereas metabolism of zectran normally proceeds principally via decarbamylation in this organism (Benezet and Matsumura, 1974). Irradiation of zectran in cyclohexane or ethanol by a high-pressure xenon-mercury lamp produced a number of compounds. Three major products were produced: MAZ, DMAX and 2,6-dimethyl-4-hydroxy-N-methyl benzamide (HMB) (Silk and Unger, 1973). A scheme was proposed by Meikle (1973) to explain the gradual flow of zectran metabolites to water-soluble compounds and other plant substances, 301 \ -g o +-> 3 oj -a -* o •r- i. ■— Q. CT1 / o 302 BIBLIOGRAPHY Aaseth, J. 1975. The effect of N-acetyl homocysteine and its thiolactone on the distribution and excretion of mercury in methyl mercuric chloride injected mice. Acta Pharmacol. Toxicol., 36(3) : 1 93-202 . Abe, Y., N. Itaya, Y. Fujita, and N. Muramoto. 1974. Studies on Pyrethroidal Compounds. Part IV. Thermal Behavior of Furamethrin. Botyu-Kagaku, 39(1):1-10. Abernathy, CO., and J.E. Casida. 1973. Pyrethroid insecticides: Esterase cleavage in relation to selective toxicity. Science, 179:1235-1236. Abernathy, CO., K. Ueda, J.L. Engle, L.C Gaughan, and J.E. Casida. 1973. Substrate-specificity and toxicological significance of pyrethroid-hydrolyzing esterases of mouse liver microsomes. Pest. Biochem. Physiol., 3(3):300-311. Adams, C.H.M., and K. Mackenzie. 1969. Dehalogenation of Isodrin and Aldrin with alkoxide bases. J. Chem. Soc, (C):480-486. Addison, J.B., P.J. Silk, and I. Unger. 1974. The photochemical reactions of carbamates. II. The solution photochemistry of Matacil (4-dimethyl-amino-m- tolyl-f\[-methyl carbamate) and Landrin (3,4,5-trimethylphenyl- N-methyl carbamate). Bull. Environ. Contam. Toxicol., 11:250-255. Agarwal , H.C, and B. Gupta. 1974. Distribution and metabolism of DDT in the catfish Heteropneustes fossil is in relation to the signs of poisoning. Toxicol. Appl . Pharmacol., 29:204-209. Agnihotri , N.P. 1971. Relative biological and non-biological inactivation of Atrazine in soil. Diss. Abstr., 31B (Pt. 1):7042. Agosin, M., N. Scaramelli, L. Gil, and M.E. Letelier. 1969. Some properties of the microsomal system metabolizing DDT in Triatoma infestans. Comp. Biochem. Physiol., 29:785-793. Aharonson, N., and A. Ben-Aziz. 1973. Determination of residues of Benomyl , its hydrolysis produce, and Thiabendazole in various crops. J. Assoc. Off. Anal. Chem., 56(6) :1330-1334. Aharonson, N., and A. Ben-Aziz. 1974. Persistence of residues of Velsicol VCS-506 and two of its metabolites in tomatoes and grapes. J. Agric. Food Chem., 22(4):704-706. Aharonson, N., and U. Kaf kaf i . 1975. Adsorption of Benzimidazole fungicides on Mont- morillonite and Kaolinite Clay surfaces. J. Agric. Food Chem., 23(3):434-437. Ahlborg, U.G., J.E. Lindgren, and M. Mercier. 1974. Metabolism of Pentachlorophenol . Arch. Toxicol., 32:271-281. 303 Ahmad, S., and A.J. Forgash. 1975. Metabolism of 11+C-Diazinon by gypsy moth larvae. J. Econ. Entomol., 68(5) : 571 -576. Ahmed, M. , and D.D. Focht. 1973a. Oxidation of polychlorinated biphenyls by Achromobacter pCB. Bull. Environ. Contain. Toxicol., 10(2) :70-72. Ahmed, M. , and D.D. Focht. 1973b. Degradation of polychlorinated biphenyls by two species of Achromobacter. Can. J. Microbiol., 19:47-52. Akagi, H., and E. Takabatake. 1973. Photochemical formation of methyl mercuric compounds from mercuric acetate. Chemosphere, 3:131-133. Akagi, H., and E. Takabatake. 1974. Photochemical methylation of inorganic mercury in the presence of solid sulfur. Chem. Lett. : 761 -764. Akira, K. , and J.S. Hart. 1974. Uptake of inorganic mercury by bed sediments. J. Environ. Qual., 3(3):273-278. Akitake, H., and K. Kobayashi . 1975. Studies on the metabolism of chlorophenols in fish--III. Isolation and identification of a conjugated PCP excreted by goldfish. Bull. Jpn. Soc. Sci . Fish., 41 (3) :321-327. Alberts, J.J., J.E. Schindler, and R.W. Miller. 1974. Elemental mercury evolution mediated by humic acid. Science, 184:895-897. Alley, E.G., D.A. Dollar, B.R. Layton, and J. P. Minyard, Jr. 1973. Photochemistry of Mi rex. J. Agric. Food Chem., 21(1): 138-139. Alley, E.G., B.R. Layton, J. P. Minyard, Jr. 1974a. Identification of the photoproducts of the insecticides Mirex and Kepone. J. Agric. Food Chem., 22(3) :442-445. Alley, E.G., B.R. Layton, J. P. Minyard, Jr. 1974b. Photoreduction of Mirex in aliphatic amines. J. Agric. Food Chem., 22(4) :727-729. Al-Rubae, A.Y., and CO. Knowles. 1972. Metabolism of chloropropylate and bromopropylate acaricides by twospotted spider mites and houseflies. J. Econ. Entomol., 65(6):1600-1603. Al-Shahristani , H., and K.M. Shihab. 1974. Variation of biological half-life of methylmercury in man. Arch. Environ. Health, 28:342-344. Altom, J.D., and J.F. Stritzke. 1973. Degradation of Dicamba, Picloram and four phenoxy herbicides in soils. Weed Sci., 21 (6) :556-560. Aly, O.M., and M.A. El-Dib. 1971. Studies on the persistence of some carbamate insecticides in the aquatic environment-I. Hydrolysis of Sevin, Baygon, Pyrolan, and Dimetilan in waters. Water Res., 5:1191-1205. 304 Anderson, J.P.E. 1971. Factors influencing insecticide degradation by a soil fungus, Mucor alternans. Diss. Abstr., 32B. (6) :3414-3415. Ando, M., T. Nakamura, and M. Makagawa. 1974. Metabolism of Hymexazol , 3-Hydroxy-5-methylisoxazole, in the rats. Agric. Biol. Chem. , 38(12) :2451-2456. Ando, M., M. Nakagawa, T. Nakamura, and K. Tomita. 1975. Metabolism of Isoxathion, 0,0-Di ethyl 0-(5-Phenyl-3- isoxazolyl )phosphorothioate in the rats. Agric. Biol. Chem., 39(4):803-809. Andrade, P.S.L., Jr., and W.B. Wheeler. 1974a. Mirex transformation products in the environment. Abstracts 168th ACS Meeting, Atlantic City, N.J., September 9-13, PEST 44. Andrade, P.S.L., Jr., and W.B. Wheeler. 1974b. Biodegradation of Mirex by sewage sludge organisms. Bull. Environ. Contam. Toxicol., 11 (5) :415-416. Andrade. P., Jr., W.B. Wheeler, and D.A. Carlson. 1975. Identification of a Mirex metabolite. Bull. Environ. Contam. Toxicol., 14(4) :473-479. Andrawes, N.R., and H.W. Dorough. 1970. Metabolism of temik in boll weevils and houseflies. Tex. Agric. Exp. Stn. Prog. Rep., PR-2833, 1-8. Andrawes, N.R., R.R. Romine, and W.P. Bagley. 1973. Metabolism and residues of temik aldicarb pesticide in cotton foliage and seed under field conditions. J. Agric. Food Chem., 21(3):379-386. Anon. 1973. Basagran, a new herbicide. Publication of BASF Aktiengesellschaft, Agricultural Research Station, D 6703 Limburgerhof , GPE/IF, 44 pages. Anon. 1974. Luprosil. Publication of BASF GPE/IF, Limburgerhof, 47 pages. Apple, E.J. 1969. The metabolism and detoxification of DDT in mammals. Diss. Abstr., 29B(10) :3606. ApSimon, J.W., J. A. Buccini, A.S.Y. Chau. 1974. The acid-catalyzed Wagner-Meerwein rearrangement of Dieldrin. Tetrahedron. Lett. No. 6:539-542. Archer, B.L., B.G. Audley, and N.P. Mann. 1973. Decomposition of 2-Chloroethylphosphonic acid in stems and leaves of Hevea brasiliensis. Phytochemistry, 12:1535-1538. Archer, T.E. 1973. Endosulfan residues on alfalfa hay exposed to drying by sunlight, ultraviolet light and air. Pestic. Sci., 4:59-68. Archer, T.E. 1974a. The effect of ultraviolet radiation filtered through pyrex glass upon residues of Dicofol (kelthane; 1 ,1 '-bis-(p_-chloro- phenyl ) 2,2,2-trichloroethanol ) on Apple Pomace. Bull. Environ. Contam. Toxicol., 12(2) :202-203. 305 Archer, T.E. 1974b. Dissipation of Parathion and related compounds from field sprayed spinach. J. Agric. Food Chem., 22(6) :974-977. Arurkar, S.K. 1971. Metabolic and stability studies of Formetanate Acaricide. Diss. Abstr., 32B(3):1633. Asai, R.I., F.A. Gunther, and W.E. Westlake. 1974. Influence of some soil characteristics on the dissipation rate of Landrin insecticide. Bull. Environ. Contam. Toxicol., ll(4):352-358. Atchison, G.J., and H.E. Johnson. 1975. The degradation of DDT in brook trout eggs and fry. Trans. Am. Fish. Soc, 104(4) :782-784. Atlas, R.M., and R. Bartha. 1972. Biodegradation of petroleum in seawater at low temperatures. Can. J. Microbiol., 18(12) :1851-1855. Audley, B.G., and B.L. Archer. 1973. Decomposition of 2-chloroethylphosphonic acid in aqueous solution: formation of 2-hydroxyethylphosphonic acid. Chem. Ind., 634-635. Avrahami , M. 1975. Hexachlorobenzene. IV. Accumulation and elimination of HCB in pigs after oral dosing. N.Z. J. Exp. Agric, 3:285-287. Avrahami, M., and R.T. Steele. 1972a. Hexachlorobenzene. I. Accumulation and elimination of HCB in sheep after oral dosing. N.Z. J. Agric. Res., 15(3): 476-481 . Avrahami, M., and R.T. Steele. 1972b. Hexachlorobenzene. II. Residues in laying pullets fed HCB in their diet and the effects on egg production, egg hatch- ability, and on chickens. N.Z. J. Agric. Res., 15(3) :482-488. Ayeke, C.A. 1969. The metabolism of (l-2-Clt+Chloroethyl )trimethyl ammonium chloride and its nitrogen interaction effects on forage quality in coastal bermuda-grass (Cynodon dactylon (L) Pers.). Diss. Abstr., 29B(8):2689. Azouz, W.M., D.V. Parke, and R.T. Williams. 1954. The metabolism of Dichlorobenzenes. Biochem. J., 57:XII. Babiker, A.G.T., and H.J. Duncan. 1975. Mobility and breakdown of Asulam in the soil and the possible impact on the environment. Biol. Conserv., 8(2): 97-104. Bagley, G.E., and E. Cromartie. 1973. Elimination pattern of Aroclor 1254 components in the bobwhite. J. Chromatogr., 75:219-226. Baker, R.D., and H.G. Applegate. 1970. Effect of temperature and ultraviolet radiation on the persistence of methyl parathion and DDT in soils. Agron. J., 62:509-512. 306 Bakke, J.E., and C.E. Prince. 1973. Rat urinary metabolites from 2-Methoxy-4,6-bis(iso- proplyamino)-s-triazine (Prometone). J. Agric. Food Chem., 21(4):640-644. Balba, M.H., and J.G. Sana. 1974a. Metabolism of Lindane-14 by wheat plants grown from treated seed. Environ. Lett., 7(3) : 181 -1 94. Balba, M.H., and J.G. Saha. 1974b. Degradation of Matacil by the ascorbic acid oxidation system. Bull. Environ. Contam. Toxicol., 1 1 (2) : 193-200. Baldwin, M.K. 1971. The metabolism of the chlorinated insecticides Aldrin, Dieldrin, Endrin, and Isodrin.. Thesis for degree of Doctor of Philosophy, University of Surrey, Guildford. Baldwin, M.K. 1973. Structural studies and photochemical rearrangement of an animal metabolite of HEOD, the active component of Dieldrin. Pestic. Sci., 4:227-237. Baldwin, M.K., A. Porter, W.P. Hayes, and D.T. Burns. 1974. Synthesis and structural studies of 9-Anti -Hydroxy HEOD. Pestic. Sci., 5:121-134. Ballester, M., J. Riera, and C. Badia. 1974. A rearrangement in the synthesis of Perchloro-1 ,1- Diphenylethylene from DDE, and related results. Tetrahedron Lett., 12:1199-1202. Bandal , S.K., H.B. Clark, and S.C. Anderson. 1974. Leaching and metabolism of 1 ,1 ,l-Trifluoro-N_-[2-methyl- 4- ( phenyl sul fonyl ) phenyl] methanesulfonamide (Destun Herbicide) in a sandy loam soil. Abstracts, 167th ACS Meeting PEST 61. Barkes, L., and R.W. Fleming. 1974. Production of dimethyl selenide gas from inorganic selenium by eleven soil fungi. Bull. Environ. Contam. Toxicol., 12(3) :308-311 . Barnes, D., A.T. Bull, and R.C. Poller. 1973. Studies on the persistence of the organotin fungicide fentin acetate (triphenyltin acetate) in the soil and on surfaces exposed to light. Pestic. Sci., 4:305-317. Barnett, J.R., H.W. Dorough. 1974. Metabolism of Chlordane in rats. J. Agric. Food Chem., 22(4) :612-619. Barnsley, G.E., and P. A. Gabbott. 1966. A new herbicide 2-Azido-4-ethylamino-6-t-butylamino- 1 ,3,5-triazine. Proc. Eighth Brit. Weed Control Conf., 2:372-376. Bartl , P., and F. Korte. 1975a. BEITRAGE ZUR 0K0L0GISCHEN CHEMIE XCVIII. Photo- chemisches Verhalten des Herbizids Sencor (4-Amino-6-tert.- butyl-3-(methylthio)-l ,2,4,triazin-5-(4H)-on) in Losung. Chemosphere, 4(3) :169-172. 307 Bartl , P., and F. Korte. 1975b. BEITRAGE ZUR OKOLOGISCHEN CHEMIE IC. Photochemisches und thermisches Verhalten des Herbizids Sencor (4-Amino-6- tert.-butyl-3-(methylthio)-l ,2,4-triazin-5-(4H)-on) als Festkorper und auf Oberflachen. Chemosphere, 4(3) : 1 73-1 76. Baude, F.J., J. A. Gardiner, and J.C.Y. Han. 1973. Characterization of residues on plants following foliar spray application of Benomyl . J. Agric. Food Chem., 21(6): 1084-1090. Baude, F.J., H.L. Pease, R.F. Holt. 1974. Fate of Benomyl on field soil and turf. J. Agric. Food Chem., 22(3):413-418. Baughman, R.G., and R.A. Jacobson. 1975. Crystal and molecular structure of organophosphorus insecticides. I. Ronnel . J. Agric. Food Chem., 23(4) :811. Baur, J.R., and R.W. Bovey. 1974. Ultraviolet and volatility loss of herbicides. Arch. Environ. Contam. Toxicol. 2(3):275-288. Baxter, R.A., P.E. Gilbert, R.A. Lidgett, J.H. Mainprize, and H.A. Vodden. 1975. The degradation of polychlorinated biphenyls by micro- organisms. Sci . Total Environ., 4:53-61. Beckert, W.R., A. A. Moghissi, F.H.F. Au., E.W. Bretthauer, and J.C. McFarlane. 1974. Formation of methylmercury in a terrestrial environment. Nature, 249(5458) :674-675. Bedford, J.W. 1971. Uptake, metabolism, and elimination of DDT and Dieldrin by freshwater mussles. Diss. Abstr., 23B(1):416. Begum, S., S. Gab, H. Parlar, and F. Korte. 1973. BEITRAGE ZUE OKOLOGISCHEN CHEMIE LXIV. Reaktions- verhalten Von Kelevan in Losung, Als Festkorper Und in Der Gasphase Bei Uv-Bestrahlung. Chemosphere, 6:235-238. Begum, S., J. P. Lay, W. Klein, und F. Korte. 1975. BEITRAGE ZUE OKOLOGISCHEN CHEMIE CIII. Ausscheidung Speicherung und Verteilung von Chloroalkylen-9 lkC Futterung an Ratten. Chemosphere 4(4) : 241 -246. Beland, F.A., S.O. Farwell, and R.D. Geer. 1974. Anaerobic degradation of 1 ,1 ,1 ,2-Tetrachloro-2,2-bis (p_-chlorophenyl )ethane (DTE). J. Agric. Food Chem., 22(6): 1148-1149. Ben-Aziz, A., and N. Aharonson. 1974. Dynamics of uptake, translocation, and disappearance of thiabendazole and methyl -2-benzimidazolecarbamate in pepper and tomato plants. Pest. Biochem. Physiol., 4:120-126. Ben-Bassat, D., and A.M. Mayer. 1975. Volatilization of mercury by algae. Physiol. Plant., 33:128-132. Benezet, H.J., and F. Matsumura. 1973. Isomerization of y-BHC to a-BHC in the environment. Nature , 243 ( 5407 ) : 480-481 . 308 Benezet, H.J., and F. Matsumura. 1974. Factors influencing the metabolism of mexacarbate by microorganisms. J. Agric. Food Chem., 22(3) :427-430. Benke, G.M., K.L. Cheever, F.E. Mirer, and S.D. Murphy. 1974. Comparative toxicity, anticholinesterase action and metabolism of methyl parathion and parathion in sunfish and mice. Toxicol. Appl . Pharmacol., 28:97-109. Benke, G.M., and S.D. Murphy. 1974. Effect of TOTP pretreatment on paraoxon and methyl paraoxon detoxification in rats. Res. Commun. Chem. Pathol. Pharmacol., 8(4) :665-672. Benke, G.M., and S.D. Murphy. 1975. The influence of age on the toxicity and metabolism of methyl parathion and parathion in male and female rats. Toxicol. Appl. Pharmacol., 31:254-269. Berck, B. 1974. Fumigant residues of carbon tetrachloride, ethylene dichloride, and ethylene dibromide in wheat, flour, bran, middlings, and bread. J. Agric. Food Chem., 22(6) :977-984. Berlin, M., J. Gage, and S. Holm. 1975. Distribution and metabolism of 2,4,5,2' ,5'-penta- chlorobiphenyl . Arch. Environ. Health, 30:141-147. Best, J. A., and J.B. Weber. 1974. Disappearance of s-triazines as affected by soil pH using a balance-sheet approach. Weed Sci., 22(4) :364-373. Beynon, K.I. 1971. The fate and effects of frescon molluscicide in aquatic systems. Schriftenreihe Verein fur Wasser. - Boden., und Lufthygiene, 34:95-107. Benynon, K.I., K.E. Elgar, B.L. Mathews, and A.N. Wright. 1973. The analysis of crops to determine neutral conjugates of an N-hydroxymethyl derivative of monocrotophos insecticide. Analyst, 98:194-201. Beynon, K.I., D.H. Hutson, and A.N. Wright. 1973. The metabolism and degradation of vinyl phosphate insecticides. Residue Rev., 47:55-142. Beynon, K.I., T.R. Roberts, G. Stoydin, and A.N. Wright. 1974a. The fate of the herbicide Benzolyprop-ethyl in crops grown in treated soils. Pestic. Sci., 5:443-450. Beynon, K.I., T.R. Roberts, and A.N. Wright. 1974b. The degradation of the herbicide Benzoyl prop-ethyl following its application to wheat. Pestic. Sci., 5:429-442. Beynon, K.I., T.R. Roberts, and A.N. Wright. 1974c. Degradation of the herbicide Benzoyl prop-ethyl in soil. Pestic. Sci., 5:451-463. Beynon, K.I., T.R. Roberts, and A.N. Wright. 1974d. The degradation of the herbicide Benzoyl prop-ethyl on the foliage of cereal seedlings. Pest. Biochem. Physiol., 4:98-107. 309 Bhan, V.M., E.W. Stoller, and F.W. Slife. 1970. Toxicity, absorption, translocation, and metabolism of 2,4-D in yellow nutsedge. Weed Sci . , 18(6) :733-737. Bhulya, Z.H. 1969. Factors affecting persistence of DDT in arrendondo fine sand. Diss. Abstr., 30B(1 ) :22-23. Billen, G. 1973. Etude De L'Ecometabolisme Du Mercure Dans Un Milieu D'eau Douce. Hydrobiol . Bull., 7:60-68. Billen, G., C. Join's, and R. Wollast. 1974. A bacterial methylmercury-mineralizing activity in river sediments. Water Res., 8:219-225. Binkley, R.W., and T.R. Oakes. 1974a. Photochemical reactions of Alkyl 2,4-Dichlorophenoxy- acetates. Chemosphere, 3(1 ) :3-4. Binkley, R.W., and T.R. Oakes. 1974b. Photochemical reactions of methyl phenoxyacetates. J. Org. Chem., 39(1 ) :83-86. Binkley, R.W., T.R. Oakes, and E. Siebert. 1974. Photochemical reactions of 2,4-Dichlorophenoxy acetic acid derivatives. Abstracts, 167th ACS Meeting, PEST 69. Biros, F.J., and H.F. Enos. 1973. Oxychlordane residues in humas adipose tissue. Bull. Environ. Contam. Toxicol., 10(5) :257-260. Bishara, R.H., G.S. Born, and J.E. Christian. 1972. Radiotracer distribution and excretion study of chloro- phenothane in rats. J. Pharm. Sci., 61 (12) : 1 91 2-1916. Bisogni, J.J., Jr., and A.W. Lawrence. 1975. Kinetics of microbially mediated methylation of mercury in aerobic and anaerobic aquatic environments. J. Water Pollut. Control Fed., 47(1 ) :35-50. Black, A.L., Y.C. Chiu, T.R. Fukuto, and T.A. Miller. 1973. Metabolism of 2,2-Dimethyl-2,3-Dihydrobenzofuranyl-7 NHTiethyl-N-(2-Toluenesulfenyl )carbamate in the housefly and white mouse. Pest. Biochem. Physiol., 3(4) :435-446. Bladel, R. Van, and A. Moreale. 1974. Adsorption of Fenuron and Monuron (substituted ureas) by two montmorillonite clays. Soil Sci. Soc. Am. Proc, 38(2): 244-249. Blake, J., and D.D. Kaufman. 1975. Characterization of Acylanilide-Hydrolyzing Enzyme (s) from Fussarium oxysporum Schlecht. Pest. Biochem. Physiol., 5:304-313. Block, W.D., and H.H. Cornish. 1959. Metabolism of bi phenyl and 4-chlorobi phenyl in the rabbit. J. Biol. Chem., 234(12) :3301-3302. Bock, K.W., and D. Winne. 1975. Glucuronidation of 1-naphthol in the rat intestinal loop. Biochem. Pharmacol., 24:859-862. 310 Bollag, J-M., E.J. Czaplicki, and R.D. Minard. 1975. Bacterial metabolism of 1-Naphthol. J. Agric. Food Chem.. 23(l):85-90. Bond, C.A., D.W. Woodhan, E.H. Ahrens, and J.G. Medley. 1975. The cumulation and disappearance of Mirex residues. II. In milk and tissues of cows fed two concentrations of the insecticide in their diet. Bull. Environ. Contam. Toxicol., 14(1):25-31. Bontoyan, W.R., and J.B. Looker. 1973. Degradation of commercial ethylene bisdithiocarbamate formulations to ethylenethiourea under elevated temperature and humidity. J. Agric. Food Chem., 21 (3) : 338-341 . Borchard, R.E., L.G. Hansen, W.H. Huber, R.L. Metcalf, M.E. Welborn. 1974. Pharmacokinetics of Aroclor 1254 components after intravenous administration to swine and sheep. Arch. Environ. Contam. Toxicol., 2(2) : 1 79-192. Bordeleau, L.M. 1972. Biochemical transformations of herbicide-derived anilines in soil. Diss. Abstr., 32B(9) :5341-5342. Borg, L., K. Erne, E. Hanko, and H. Wanntorp. 1970. Experimental secondary methyl mercury poisoning in the goshawk (Accipiter G. gentilis L.). Environ. Pollut. 1:91-104. Bosik, J.J. 1971. Metabolism of C-2307 (dimethyl phosphate, ester with 3-Hydrox,y-N-Methoxy-N-Methyl-cis-Crotonamide) in rats. Diss. Abstr., 32B(6):3415. Bowman, M.C. 1972. Determination and persistence of Bay 68138 and two of its metabolites in turf grass. Int. J. Environ. Anal. Chem., 1:307-316. Boyer, A.C. 1975. Sorption of tetrachlorvinphos insecticide (Gardona) to the hemolymph of Periplaneta americana. Pest. Biochem. Physiol., 5:135-141. Brattsten, L.B. 1972. Role of mixed function oxidases of insects in their response to xenobiotics. Diss. Abstr., 32B(8):4645. Braun, H.E., F.L. McEwen, R. Frank, and G. Ritcey. 1975. Residues of leptophos and its metabolites following application to various crop plants. J. Agric. Food Chem., 23(l):90-95. Briggs, D.E., R.H. Waring, and A.M. Hackett. 1974. The metabolism of carboxin in growing barley. Pestic. Sci., 5:599-607. Bristol, D., L. Cook, M. Koterba, and D.C. Nelson. 1974. Determination of trace residues of 2,4-D and 2,4- Dichlorophenol in potato tubers. Abstracts 168th ACS Meeting, Atlantic City, N.J., September 9-13, PEST 44. 311 Brown, B.S., J. Mills, and J.M. Hulse. 1974. Chemical and biological degradation of waste plastics. Nature, 250(5462) :161-163. Brown, J.R., and H. Hughes, and S. Viriyanondha. 1969. Storage, Distribution and Metabolism of 1,1 -Bis (4- chlorophenyl )-2,2,2-trichloroethanol . Toxicol. Appl . Pharmacol., 15(l):30-37. Brown, N.J., and A.W.A. Brown. 1970. Biological fate of DDT in a sub-arctic environment. J. Wildl. Manage., 34(4) :929-940. Bruce, R.B., W.R. Maynard, G.D. Cloyd, and D.L. Gilbert. 1974. Fenfluramine residues in chickens and eggs. J. Agric. Food Chem., 22(6) : 1108-11 11 . Bruchhausen, V.V., and M. Stiasni. 1973. Transport of the systemic fungicide Cela W 524 (Triforine) in barley plants. II. Uptake and Metabolism. Pestic, Sci . , 4:767-773. Brunker, R.L., and T.L. Bott. 1974. Reduction of mercury to the elemental state by a yeast. Am. Soc. Microbiol., 27(5) :870-873. Buchenauer, H., L.V. Edgington, and F. Grossmann. 1973. Photochemical transformation of thiophanate-methyl and thiophanate to alkyl benzimidazol-2-yl carbamates. Pestic. Sci., 4:343-348. Buckland, J.L., R.F. Collins, M.A. Henderson, and E.M. Pullin. 1973a. Radiochemical distribution and decline studies with bromoxynil octanoate in wheat. Pestic. Sci., 4:689-700. Buckland, J.L., R.F. Collins, and E.M. Pullin. 1973b. Metabolism of bromoxynil octanoate in growing wheat. Pestic. Sci., 4:149-162. Bull, D.L. 1974. Fate of methomyl on cotton. Environ. Entomol . , 3(4): 723-724. Bullard, R.W., G. Holguin, and J.E. Peterson. 1975. Determination of chlorophacinone and diphenadione residues in biological materials. J. Agric. Food Chem., 23(1 ) :72-74. Bullivant, M.J., and G. Pattenden. 1973. Photolysis of bio-allethrin. Tetradhedron Lett. , 38:3679-3680. Bunyan, P.J., and J.M.J. Page. 1973. Pesticide-induced changes in hepatic microsomal enzyme systems. Some effects of 1 ,1-di (p_-chlorophenyl )-2,2-dichloro- ethylene (DDE) and 1 ,1-di (p_-chlorophenyl )-2-chlorothylene (DDMU) in the rat and Japanese Quail. Chem. -Biol. Interact., 6:249-257. Burse, V.W., R.D. Kimbrough, E.C. Villanueva, R.W. Jennings, R.E. Linder, and G.W. Sovocool . 1974. Polychlorinated biphenyls: Storage, distribution, excretion, and recovery; liver morphology after prolonged dietary ingestion. Arch. Environ. Health, 29:301-307. 312 Burt, G.W. 1974. Translocation and metabolism of Atrazine in Canada Thistle. Weed Sci., 22(2): 11 6-11 9. Burt, P.E., M. Elliott, A.W. Farnham, N.F. Janes, P.H. Needham, and D.A. Pulman. 1974. The Pyrethrins and related compounds. XIX. Geometrical and optical isomers of 2,2-Dimethyl-3-(2,2-dichlorovinyl )- cyclopropane carboxylic acid and insecticidal esters with 5-benzyl-3-furyl methyl and 3-phenoxybenzyl alcohols. Pestic. Sci., 5:791-799. Burt, P.E., and R.E. Goodchild. 1974. Knockdown by pyrethroids: Its role in the intoxication process. Pestic. Sci., 5:625-633. Buser, H.-R., and H.-P. Bosshardt. 1975. Studies on the possible formation of polychloroazobenzenes in Quintozene treated soil. Pestic. Sci., 6:35-41. Bush, B., C.F. Tumasonis, and F.D. Baker. 1974. Toxicity and persistence of PCB homologs and isomers in the avian system. Arch. Environ. Contam. Toxicol., 2(3): 195-212. Buswell, J. A., and R.B. Cain. 1973. Microbial degradation of piperonylic acid by Pseudomonas fluorescens. FEBS Lett., 29(3) :297-300. Butts, E.R. , and C.L. Foy. 1974. Comparative uptake and metabolism of methazole in prickly sida and cotton. Pest. Biochem. Physiol., 4(1 ):44-55. Cahn, R.S., R.F. Phipers, and E. Broadaty. 1945. The stability of Derris in insecticidal dusts. The solvent—powder effect. J. Soc. Chem. Ind., 64(1 ) :33-40. Cameron, B.D., L.F. Chasseaud, and D.R. Hawkins. 1975. Metabolic fate of Clopidol after repeated oral adminis- tration to rabbits. J. Agric. Food Chem., 23(2) :269-274. Capdevila, J., E.D. Villar, and P. Poblete. 1973. The effect of DDT treatment on the levels of DDT- Dehydrochlorinase in Musca domestica. Comp. Biochem. Physiol., 44b:441-450. Capel , I.D., P. Millburn, and R.T. Williams. 1974. The conjugation of 1- and 2-Naphthols and other phenols in the cat and pig. Xenobiotica, 4(10) :601-615. Carl in, F.J., J.J. Ford, and L.R. Kangas. 1976. The nature of toxaphene residues on crops. Abstracts, 168th ACS Meeting, PEST 22. 313 Carlson, G.P. 1974. Epoxidation of Aldrin to Dieldrin by lobsters. Bull. Environ. Contam. Toxicol., 11(6): 577-582 . Carlson, G.P. 1973. Comparison of the metabolism of Parathion by lobsters and rats. Bull. Environ. Contam. Toxicol., 9(5) :296-300. Case, F.H., and R.U. Schock, Jr. 1943. The nitration of certain halobiphenyls. II. Di- and Tetra-nitro derivatives of 2,2'-dichlorobiphenyl . J. Am. Chem. Soc, 65:2086-2088. Casida, J.E., R.A. Gray, and H. Tilles. 1974a. Thiocarbamate sulfoxides: Potent, selective, and biodegradable herbicides. Science, 184:573-574. Casida, J.E., R.L. Holmstead, S. Khalifa, J.R. Knox, T. Ohsawa, K.J. Palmer, and R.Y. Wong. 1974b. Toxaphene insecticide: A complex biodegradable mixture. Science, 183:520-521. Casida, J.E., S. Khalifa, J.R. Knox, and T. Ohsawa. 1974c. Studies of toxaphene: Component toxicities and metabolic fate in mammals. Abstracts, 168th ACS Meeting PEST 21. Casida, J.E., E.C. Kimmel , H. Okkawa, and R. Ohkawa. 1975. Sulfoxidation of thiocarbamate herbicides and metabolism of thiocarbamate sulfoxides in living mice and liver enzyme systems. Pest. Biochem. Physiol., 5:1-11. Casper, H.H., J.C. Pekas, and W.E. Dinusson. 1973. Gastric Absorption of a pesticide (1-naphthyl N-methyl- carbamate) in the fasted rat. Pest. Biochem. Physiol., 2(4): 391-396. Catelani, D., and A. Colombi. 1974. Metabolism of biphenyl. Biochem. J., 143:431-434. Catelani, D., A. Colombi, C. Sorlini, and V. Treccani . 1973. Metabolism of biphenyl. Biochem. J., 134:1063-1066. Catelani, D., G. Mosselmans, J. Nienhaus, C. Sorlini, and V. Treccani. 1970. Microbial degradation of aromatic hydrocarbons used as reactor coolants. Experientia, 26(8) :922-923. Catelani, D., C. Sorline, and V. Treccani. 1971. The metabolism of biphenyl by Pseudomonas putida. Experientia, 27:1173-1174. Chadwick, R.W., L.T. Chuang, and K. Williams. 1975. Dehydrogenation: A previously unreported pathway of lindane metabolism in mammals. Pest. Biochem. Physiol., 5:575-586. Chadwick, R.W. and J.J. Freal . 1972. Comparative acceleration of Lindane metabolism to chlorophenols by pretreatment of rats with Lindane or with DDT and Lindane. Food Cosmet. Toxicol., 10:789-795. Chakrabarti, J.K., and O.M. Friedman. 1973. Studies on the hydrolysis of cyclophosphamide. II. Isolation and characterization of intermediate hydrolytic products. J. Heterocycl . Chem., 10:55-58. 314 Chambers, J.E., and J.D. Yarbrough. 1973. Organophosphate degradation by insecticide-resistant and susceptible populations of Mosquitofish (Gambusia affinis). Pest. Biochem. Physiol., 3(3) : 31 2-316. Chambon, P., M. Riotte, M. Daudon, R. Chambon-Mongenot, and J. Briquier. 1971. Study of the metabolism of dibutyl and diethyl phthalates in the rat. C.R. Acad. Sci. Paris, 273 Series D:2165-2168. Chan, T.M., J.W. Gillett, and L.C. Terriere. 1967. Interaction between microsomal electron transport systems of trout and male rat in cyclodiene epoxidation. Comp. Biochem. Physiol., 20:731-742. Chang, R.L., S. Symchowicz, and Chin-Chung Lin. 1973. Oxidative demethylation of 11+C-griseofulvin by liver microsomes of rats and mice. Biochem. Pharmacol., 22:1389-1392. Chang, S.C., C.W. Woods, and A.B. Borkovec. 1970. Metabolism of C-labeled N2, N2, N\ N^-tetramethylmel amine in male house flies. J. Econ. Entomol . , 63X5) : 1 51 0-1 51 3. Chapman, A.H., and J.W. Price. 1972. Degradation of triphenyltin acetate by ultra-violet light. Int. Pest Control, 14(1):11-12. Chasseaud, L.F., D.R. Hawkins, B.D. Camerson, B.J. Fry, and V.H. Saggers. 1972. The metabolic fate of bentazon in the rat. Xenobiotica, 2(3):269-276. Chen, P.R.S. 1972. Studies on the amidase which hydrolyzes dimethoate. Diss. Abstr., 32B(8) :4645-4646. Chen, R.W., H.E. Ganther, and W.G. Hoekstra. 1973. Studies on the binding of methylmercury by thionein. Biochem. Biophys. Res. Commun., 51 (2) :383-390. Cheng, H.M., and J.E. Casida. 1973. Metabolites and photoproducts of 3-(2-Butyl )phenyl N-methyl carbamate and !N-benzenesulfenyl-N-methyl carbamate. J. Agric. Food Chem., 21 (6) :1037-1047. Chiba, M., and F. Doornbos. 1974. Instability of benomyl in various conditions. Bull. Environ. Contam. Toxicol., 11 (3) :273-274. Chin, B., J.M. Eldridge, and L.J. Sullivan. 1974. Metabolism of carbaryl by selected human tissues using an organ-maintenance technique. Clin. Toxicol., 7(1 ) : 37-56. Chin, W., N. Kucharczyk, and A.E. Smith. 1973. Nature of carboxin (Vitavax)-derived bound residues in barley plants. J. Agric. Food Chem., 21 (3) :506-507. Chisholm, D. 1974. Persistence of fensulfothion in soil and uptake by rutabagas and carrots. Can. J. Plant Sci., 54:667-671. 315 Chopra, S.L., and C.L. Arora. 1974. Infrared spectra of the complexes of malaoxon with some anhydrous metal chlorides. Pestic. Sci., 5:271-274. Chow, A.Y.K., and S.D. Murphy. 1974. Production of a methemoglobin-forming metabolite of 3,4-dichloraniline by liver in vitro. Bull. Environ. Contam. Toxicol., 13(1):9-13. Clark. A.G., S. Murphy, and J.N. Smith. 1969. The metabolism of hexachlorocyclohexanes and penta- chlorocyclohexenes in flies and grass grups. Biochem. J., 113:89-96. Clark, D.E., J.S. Palmer, R.D. Radeleff, H.R. Crookshank, and F.M. Farr. 1974. Residues of chlorophenoxy acid herbicides and their phenolic metabolites in tissues of sheep and cattle. J. Agric. Food Chem., 23(3) :573-578. Clay, D.V., and K.G. Stott. 1973. The persistence and penetration of large doses of Simazine in uncropped soil. Weed Res., 13(1 ) :42-50. Clegg, D.E. 1974. Residues of Clenpirin [2-(3,4-dichlorophenylimino)-10 r^-butyl pyrrolidine] in the fatty tissues of steers and in butter fat. Pestic. Sci., 5:769-779. Clegg, D.E., and P.R. Martin. 1973. Residues of the carbamate acaricide, 3-methyl-5-isopropyl- phenyl-N-(n-butanoyl )-N-methyl carbamate (promacyl) and two metabolites in the tissues and milk of cattle. Pestic. Sci., 4:447-457. Cliath, M.M., and W.F. Spencer. 1972. Dissipation of pesticides from soil by volatilization of degradation products. Environ. Sci. Toxicol., 6(10):910-914. Coats, G.E., and C.L. Foy. 1974. Effect of petroleum oils on the uptake of Atrazine-11+C by corn. Weed Sci., 22(3) :220-225. Coats, J.R., R.L. Metcalf, and I. P. Kapoor. 1974. Metabolism of the methoxychlor isostere, dianisylneopentane, in mouse, insects, and a model ecosystem. Pest. Biochem. Physiol., 4:201-211. Cocks, J. A. 1974. The metabolism of 1-naphthyl methyl carbamate by Periplaneta americana. Pestic. Sci., 5:505-510. Cole, E.R., G. Crank, and A-Salam Sheikh. 1973. Photochemistry of heterocyclic compounds I. Photo- dehydrodimerization of Benzimidazole. Tetrahedron Lett. No. 32:2987-2988. Collet, G.F., and V. Pont. 1974. Distribution et Metabolisme du Methabenzthiazuron chez des Especes Vegetal es. Weed Res., 14:151-165. 316 Collins, J. A. 1969. Chlorinated hydrocarbon pesticides: Degradation and effect on the growth of bacteria. Diss. Abstr. 30B(4) :1426-1427. Collins, R.F. 1973. Perfusion studies with Bromoxynil Octanoate in soil. Pestic. Sci., 4:181-192. Cooke, A.S. 1970. The effect of p_,p_'-DDT on tadpoles of the common frog (Rana temporaria). Environ. Pollut., 1(1): 57-71 . Cox, D.P., and M. Alexander. 1973. Production of trimethylarsine gas from various arsenic compounds by three sewage fungi. Bull. Environ. Contam. Toxicol., 9(2):84-88. Craine, E.M., M.J. Parnell, and L.R. Stone. 1974. A method for analysis of swine tissue for the primary metabolite of dimetridazole at the 2-ppb level. J. Agric. Food Chem., 22(5) : 377-881 . Creaven, P.J., and D.V. Parke. 1966. The stimulation of hydroxylation by carcinogenic and non-carcinogenic compounds. Biochem. Pharmacol., 15:7-16. Crosby, D.G., and E. Leitis. 1973. The photodecomposition of trifluralin in water. Bull. Environ. Contam. Toxicol., 10(4) : 237-241 . Crosby, D.G., and K.W. Moilanen. 1973. Photodecomposition of chlorinated biphenyls and dibenzo- furans. Bull. Environ. Contam. Toxicol., 10(4) :372-377. Crosby, D.G., and K.W. Moilanen. 1974. Vapor-phase photodecomposition of aldrin and dieldrin. Arch. Environ. Contam. and Toxicol., 2(l):62-74. Crosby, D.G., and A.S. Wong. 1973a. Photodecomposition of p_-chlorophenoxyacetic acid. J. Agric. Food Chem., 21 (6) : 1049-1052 . Crosby, D.G., and A.S. Wong. 1973b. Photodecomposition of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in water. J. Agric. Food Chem., 21 (6) :1052-1054. Cross, R.J. 1973. Organomercurials in the environment. Chem. Ind., 719-721. Crowder, L.A., E.F. Dindal. 1974. Fate of 36Cl-Toxaphene in rats. Bull. Environ. Contam. Toxicol., 12(3):320-327. Cruickshank, P. A., and H.C. Jarrow. 1973. Ethyl enethiourea degradation. J. Agric. Food Chem., 21:333-335. Currie, R.A. 1974. Determination of leptophos, leptophos oxon and a possible phenolic photoconversion metabolite in rapeseed grain. J. Assoc. Off. Anal. Chem., 57:1056-1060. 317 Daly, R.W. , Jr. 1972. Degradation of 2,4-DBEE in an aquatic environment. Diss. Abstr., 32B(7):3806. Daniel , J.W. 1972. The biotransformation of organomercury compounds. Biochem. J., 130(2] 1:64-65. Daniel, J.W. and H. Bratt. 1974. The adsorption, metabolism and tissue distribution of Di(2-ethylhexyl )phthalate in rats. Toxicology, 2:51-65. Dannals, L.E., R.J. Puhl , and N. Kucharczyk. 1974. Dissipation and degradation of Alar in soils under greenhouse conditions. Arch. Environ. Contam. Toxicol., 2(3) .-213-221. Darrow, D.C., and R.F. Addison. 1973. The metabolic clearance of 1J*C-p_,p_' -DDT from plasma and its distribution in the thorny skate, Raja radiata. Environ. Physiol. Biochem., 3:196-203. Dauterman, U.C., and W. Muecke. 1973. In vitro metabolism of Atrazine by rat liver. Pest. Biochem. Physiol., 4:212-219. Davidek, J., J. Seifert. 1973. The stability of phaltan and captan in wort. Z. Lebensm.- Unters.-Forsch., 153:301-304. Davis, A.C., J.B. Bourke, and R.J. Kuhr. 1974. Disappearance of Monitor residues from cole crops. J. Econ. Entomol., 67(6) :766-768. Dawson, V.K. 1973. Photodecomposition of the piscicides TFM(3-trifluoro- methyl-4-nitrophenol) and antimycin. Master's Thesis presented to U. of Wisconsin, La Crosse, 62 pages. DeBaun, J.R., J.B. Miaul lis, J. Knarr, A. Mihailkovski , J.J. Menn. 1974a. Metabolism of the trichloromethylthio (TMT) moiety of Captan in the rat: Inactivation of the putative fungal toxophore, Abstracts, 167th ACS Meeting, April 1-5, PEST 45. DeBaun, J.R., J.B. Miaul lis, J. Knarr, A. Mihailovski, and J.J. Menn. 1974b. The fate of N-Trichloro (li+C) methyl thio-4-cyclohexene- 1 ,2-dicarboximide (["^C] Captan) in the rat. Xenobiotica, 4(2):101-119. de Frenne, E., J. Eberspacher, and F. Lingens. 1973. The bacterial degradation of 5-Amino-4-chloro-2-phenyl- 3(2H)-pyridazinone. Eur. J. Biochem., 33(2) :357-363. de Frenne, E., J. Eberspacher, F. Lingens, and W. Schafer. 1974. Bacterial hydroxylation of pyrazon compounds. Z. Naturforsch., 296:283-285. Dejonckheere, W., and R.H. Kips. 1974. Photodecomposition of methidathion. J. Agric. Food Chem., 22(6):959-968. Dejonckheere, W., W. Steurbaut, R. Dynoodt, and R.H. Kips. 1974. Uptake and translocation of dimefox and schradan in hops. Pestic. Sci . , 5(5) :549-559. 318 Dejonckheere, W. , W. Steurbaut, and R.H. Kips. 1975. Residues of quintozene, hexachlorobenzene, dichloran, and pentachloroaniline in soil and lettuce. Bull. Environ. Contam. and Toxicol., 13(6) :720-729. Dekhuijzen, H.M., and C.R. Vonk. 1974. The distribution and degradation of chlormequat in wheat plants. Pest. Biochem. Physiol., 4:346-355. DeLacy, T.P., and C.H.L. Kennard. 1972a. Insecticides. Part I. Crystal structires of 1,1-Bis- (fJ-chlorophenyl ) -2, 2-dimethyl propane. J. Chem. Soc, Perkin Transactions II., 2121-2147. DeLacy, T.P., and C.H.L. Kennard. 1972b. Insecticides. Part II. Crystal structures of 1,1-Bis- (p_-chlorophenyl )-2,2,2-trichloroethene(p_,p_'-DDT) and l-(o- chlorophenyl )-l -(p_-chlorophenyl )-2,2,2-trichloroethane (o,p_'-DDT) . J. Chem. Soc, Perkin Transactions II., 2148-2153. Demint, R.J., J.C. Pringle, Jr., A. Hattrup, V.F. Burns and P. A. Frank. 1975. Residues in crops irrigated with water containing trichloro- acetic acid. J. Agric. Food Chem., 23(l):31-84. Desaiah, D. , L.K. Cutkomp, and R.B. Koch. 1974. A comparison of DDT and its biodegradable analogues tested on ATPase enzymes in cockroach. Pest. Biochem. Physiol., 4:232-238. Devonshire, A.L., and P.H. Needham. 1974. The fate of some organophosphorus compounds applied topically to peach-potato aphids (Myzus persicae (Sulz.)) resistant and susceptible to insecticides. Pestic. Sci . , 5:161-169. deVos, R.H., M.C. ten Noever deBrauw, and P.D.A. Olthof. 1974. Residues of pentachloronitrobenzene and related compounds in greenhouse soils. Bull. Environ. Contam. Toxicol., 11 (6) : 567-571 . Dexter, A.G. 1970. Fate of 2,4-Dichlorophenoxyacetic acid in several plant species. Diss. Abstr., 30(7) :2988-2989. DiCuollo, C.J., J. A. Miller, W.L. Mendelson, and J.F. Pagano. 1974. Metabolic and tissue residue studies on Parabendazole in sheep. J. Agric. Food Chem., 22:948-953. Dieter, S., and A. Jumar. 1969. Model luntersuchungen uber den Abbau des herbiziden Wirkstoffes Proximpham. Arch. Pflanzenschutz, 5(6) :445-453. Dimond, J.B., R.B. Owene, Jr., and A.S. Getchell. 1975. DDT residues in forest biota: Further Data. Bull. Environ. Contam. Toxicol., 13(1 ) :117-122. Dinamarca, M.L., A. Ramirez, E.D. Villar, and J. Capdevila. 1974. DDT-dehydrochlorinase. III. Enzymic oxidation of gluta- thione. Int. J. Biochem., 5:1-9. Doll-wet, H.H.A., and J. Kumamoto. 1970. Ethylene production of ethyl propyl phosphonate, Niagara 10637. Plant Physiol., 46:786-789. Donaldson, T.W., D.E. Bayer, and O.A. Leonard. 1973. Absorption of 2,4-Dichlorophenoxyacetic acid and 3-(p_- chlorophenyl )-l ,1-dimethylurea (Monuron) by barley roots. Plant Physiol., 52:638-645. 319 Dorough, H.W. 1974. Metabolism of methazole in wheat and onions. Bull. Environ. Contam. Toxicol., 12(4) :493-500. Dorough, H.W., and R.W. Hemken. 1973. Chlordane residues in milk and fat of cows fed HCS 3260 (High Purity Chlordane) in the diet. Bull. Environ. Contam. Toxicol., 10(4):208-216. Dorough, H.W., J. P. McManus, S.S. Kumar, R.A. Cardona. 1974. Chemical and metabolic characteristics of 1-Naphthyl-e D-Glucoside. J. Agric. Food Chem., 22(4) :642-645. Dorough, H.W., D.M. Whitacre, and R.A. Cardona. 1973. Metabolism of the herbicide Methazole in cotton and beans, and fate of certain of its polar metabolites in rats. J. Agric. Food Chem., 21 (5) :797-803. Douch. P.G.C. 1973. The metabolism of benomyl fungicide in mammals. Xenobiotica, 3(6) :367-380. Dressman, R.C. 1972. The conversion of phenylmercuric salts to diphenyl- mercury and phenylmercuric chloride upon gas chromatographic injection. J. Chromatogr. Sci . , 10:468-472. Duff, W.G., and R.E. Menzer. 1973. Persistence, mobility and degradation of 11+C-dimethoate in soils. Environ. Entomol . , 2(3) : 309-318. Duhm, B., W. Maul, H. Medenwald, K. Patzschke, and L.-A. Wegner. 1961. Radioaktive Untersuchungen mit einem neuen Molluscicid. Z. Naturforsch., 16b:509-515. Dumas, T., and E.J. Bond. 1975. Bromide residues in apples fumigated with ethylene dibromide. J. Agric, Food Chem., 23(1 ) :95-98. Dunn, G.L., G. Gallagher, Jr., L.D. Davis, J. R.E. Hoover, and R.J. Stedman. 1973. Metabolites of methyl 5(6)-butyl-2-benzimidazolecarbamate (Parbendazole) . Structure and synthesis. J. Med. Chem., 16(9):996-1002. Eastin, E.F. 1971a. Fate of fluorodifen in resistant peanut seedlings. Weed Sci., 19(3) :261-265. Eastin, E.F. 1971b. Movement and fate of fluorodifen-l-11+C in cucumber seedlings. Weed Res., 11:63-68. Eastin, E.F. 1971c. Movement and fate of p_-Nitrophenyl-a,a,a-trifluoro- 2-nitro-p_-tolyl ether in peanut seedlings. Weed Sci. Soc. Am. Abstr., 44. Eben, A., and G. Kimmerle. 1972. Unpublished data (Bayer AG). Referred to in Ueyama and Takase, Agr. Biol. Chem., 39(9) : 1 71 9-1 727( 1 975) . 320 Edwards, T., B.C. McBride. 1975. Biosynthesis and degradation of methylmercury in human feces. Nature, 253:462-464. Eidel'nant, N.M., and V.E. Mostovaya. 1972. Studies of the metabolism of 2,4-D in plants. Agrokhimiya, 11:121-124. Eisenbrand, G., 0. Lingerer, and R. Preussman. 1974. Rapid formation of carcinogenic N-Nitrosamines by inter- action of nitrite with fungicides derived from Dithiocarbamic Acid in vitro under simulated gastric conditions and in vivo in the rat stomach. Food Cosmet. Toxicol., 12:229-232. Eliasson, L. 1973. Translocation and persistence of 2,4-D in Populus tremula L. Weed Res., 13:140-147. El-Refai, A., and M.M. Mowafy. 1973. Propanil hydrolysis: Inhibition in rice plants by Diazinon and Carbaryl translocated from the soil. J. Assoc. Off. Anal. Chem., 56(5) : 11 78-1 182. El-Zorgani, G.A., and M.E.H. Omer. 1974. Metabolism of Endosulfan isomers by Aspergillus niger. Bull. Environ. Contam. Toxicol., 12(2) :182-185. Englehardt, F., P.R. Wallnofer, and R. Plapp. 1973. Purification and properties of an Aryl Acylamidase of Bacillus sphaericus, catalyzing the hydrolysis of various Phenylamide herbicides and fungicides. Appl . Microbiol., 26(5):709-718. Engst, R., R.M. Macholz, and M. Kujawa. 1974. Metabolismus des Lindan. Abbau von Lindan durch Schimmelpilzkulturen. Unkonjugierte Metabolite. Nahrung, 18(8) :737-745. Engst, R., R.M. Macholz, and M. Kujawa. 1975. Identifizierung von Metaboliten under der Abbauweg des Hexachlorbenzols in einer Schimmelpilzkultur. Die Nahrung, 19(7) :603-606. Ercegovich, CD., N.L. Hartwig, S. Witkonton, and P. Carroll. 1972. Persistence of 5,6-Dichloro-2-trifluoromethylbenzimidazole, a major degradation product of Fenazaflor, in Hagerstown silt loam soil. Environ. Entomol . , 1 (6) : 730-733. Ernst, W. 1969. 10. Metabolism of substituted Dinitrophenols and ureas in mammals and methods for the isolation and identification of metabolites. J. S. Afr. Chem. Inst., XXII, S79-S88. Ernst, W. 1972. Degradation of [llfC]DDT on silica gel G chromatograms under laboratory conditions. J. Chromatogr., 67:179-181. Ernst, W. 1975. Aufnahme, Ausscheidung und Umwandlung Von Lindan-11+C Durch Mytilus edulis. Chemosphere, 4(6) :375-380. 321 Ernst, W., and H. Goerke. 1974. Anreicherung, Verteilung, Umwandlung and Ausscheidung von DDT-lt+C bei Solea solea (Pisces: Soleidae). Mar. Biol. (Berl), 24:287-304. Exner, J.H., G.A. Burk, and D. Kyriacou. 1973. Rates and products of decomposition of 2,2-Dibromo-3- nitrilopropionamide. J. Agric. Food Chem. , 21 (5) :838-842. Fahmy, M.A.H., and T.R. Fukuto. 1972. Oxidative rearrangement of ^-(Dimethoxyphosphinothioyl ) Carbamate esters. Tetrahedron Lett., 41:4245-4248. Fahmy, M.A.H., A. Khasawinah, and T.R. Fukuto. 1972. Alkaline hydrolysis of Phosphoramidothioate esters. J. Org. Chem., 37:617-625. Fang, S.C. 1973. Uptake and biotransformation of Phenyl mercuric Acetate by aquatic organisms. Arch. Environ. Contam. Toxicol., l(l):18-26. Fang, S.C. 1974. Uptake, distribution, and fate of 203Hg-ethyl mercuric chloride in the guppy and the coontail. Environ. Res., 8(1 ):112-118. Fang, S.C, E. Fall in, M.L. Montgomery, and V.H. Freed. 1973. The metabolism and distribution of 2,4,5-Trichlorophenoxy- acetic acid in female rats. Toxicol. App. Pharmacol., 24:555-563. Fang, S.C, E. Fall in, M.L. Montgomery, and V.H. Freed. 1974. Metabolic studies of C-labeled Propham and Chlorpropham in the female rat. Pest. Biochem. Physiol., 4:1-11. Fell , V.J., CH. Lamoureau, E. Styrvoky, R.G. Zaylskie, E.J. Tacker, and G.M. Holman. 1973. Metabolism of o,p_'-DDT in rats. J. Agr. Food Chem., 21(6): 1072-1078. Feil, V.J., CH. Lamoureux, and R.G. Zaylskie. 1974. Metabolism of o,p_'-DDT in chickens. Abstracts, 167th ACS Meeting, PEST 79, April 1-5. Feil, V.J., CH. Lamoureux, and R.G. Zaylskie. 1975. Metabolism of o_,p_'-DDT in chickens. J. Agric. Food Chem., 23(3):382-388. Feiner, E., B. Krauthacker, V. Simeon, and M. Skrinjaric-Spol jar. 1975. Mechanism of inhibition in vitro of mammalian acetyl- cholinesterase and cholinesterase in solutions of 0_,0_-di methyl 2,2,2-trichloro-l-hydroxyethyl phosphonate (Trichlorphon) . Biochem. Pharmacol., 24:717-722. Feit, P.W., and N. Rastrup-Andersen. 1973. 4-Methanesulfonyloxybutanol : Hydrolysis of Busulfan. J. Pharm. Sci., 62(6) :1 007-1 008. Feung, C, R.H. Hamilton, and R.0. Mumma. 1973. Metabolism of 2,4-Dichlorophenoxyacetic Acid. V. Identi- fication of metabolites in soybean callus tissue cultures. J. Agric. Food Chem., 21 (4) :637-640. Feung, C, R.H. Hamilton, and R.0. Mumma. 1975. Metabolism of 2,4-Dichlorophenoxyacetic Acid. VII. Compar- ison of metabolites from five species of plant callus tissue cultures. J. Agric. Food Chem., 23(3) :373-376. 322 Finlayson, D.G., and D.L. Suett. 1975. Persistence and bioactivity of Chlorofenviphos in carrots and soil in greenhouse experiments. J. Econ. Entomol . , 68(2):140-142. Fisher, J.D. 1974. Metabolism of the herbicide Pronamide in soil. J. Agric. Food Chem., 22(4) :606-608. Fiveland, T.J., L.C. Erickson, and C.I. Seely. 1972. Translocation of 11+C-assimilates and 3-Amino-l ,2,4- Triazole and its metabolites in Agropyron repens. Weed Res., 12:155-163. Flashinski, S.J., and E.P. Lichtenstein. 1974a. Metabolism of Dyfonate by soil fungi. Can. J. Microbiol, 20(3): 399-411. Flashinski, S.J., and E.P. Lichtenstein. 1974b. Degradation of Dyfonate in soil inoculated with Rhizopus arrhizus. Can. J. Microbiol., 20(6) :871-875. Flashinski, S.J., and E.P. Lichtenstein. 1975. Environmental factors affecting the degradation of Dyfonate by soil fungi. Can. J. Microbiol., 21(l):17-25. Fleeker, J.R. 1973. Removal of the acetate-moiety of 2,4-Dichlorophenoxy- acetic Acid in Ribes sativum. Phytochemistry, 12:757-762. Fleeker, J.R., H.M. Lacy, I.R. Schultz, and E.C. Houkom. 1974. Persistence and metabolism of Thiophanate-methyl in soil. J. Agric. Food Chem., 22(4) :592-595. Forgash, A.J., and S. Ahmad. 1974. Hydroxylation and demethylation by gut microsomes of gypsy moth larvae. Int. J. Biochem., 5:11-15. Fournier, J.-C. 1975a. Degradation microbienne de la 2,4-Dichlorobenzamide dans des modeles de laboratoire. II. Influence de 1 'addition de substrats carbones simples sur la biodegradation de la 2,4-Dichlorobenzamide. Chemosphere, 4(1 ) :35-40. Fournier. J.-C. 1975b. Degradation Microbienne De L' Isoproturon Dans Des Modeles De Laboratoire. Chemosphere, 4(4) : 207-214. Francis, A.J., R.J. Spanggord, and G.I. Ouchi . 1975. Degradation of Lindane by Escherichia coli . Appl . Microbiol., 29(4):567-568. Frank, A. 1971. Studies on the metabolism of 2-(2-Furyl )benzimidazole in certain mammals. Acta Pharmacol, et toxicol., 29(2):1-124. Frankenberg, L., and B. Sorbo. 1975. Effect of cyanide antidotes on the metabolic conversion of cyanide to thiocyanate. Arch. Toxicol., 33:81-89. Freal , J.J., and R.W. Chadwick. 1973. Metabolism of hexachlorocyclohexane to chlorophenols and effect of isomer pretreatment on Lindane metabolism in rat. - J. Agric. Food Chem., 21 (3) :424-427. 323 Frear, D.S., and H.R. Swanson. 1973. Metabolism of substituted diphenylether herbicides in plants. I. Enzymatic cleavage of fluorodifen in peas (Pi sum sativum L.). Pest. Biochem. Physiol., 3:473-482. Frear, D.S., and H.R. Swanson. 1975. Metabolism of cisanilide (cis-2,5-Dimethyl-l -Pyrrol i- dinecarboxanilide) by excised leaves and cell suspension cultures of carrot and cotton. Pest. Biochem. Physiol., 5:73-80. Freeman, L.R., P. Angel ini, G.J. Silverman, and C. Merritt, Jr. 1975. Production of hydrogen cyanide by Pseudomonas fluorescens. Appl. Microbiol., 29(4) : 560-561 . Freitag, K.-D., and R. Bock. 1974. Degradation of triphenyltin chloride on sugar beet plants and in rats. Pestic. Sci., 5:731-739. French, A. 1969. Reductive dechlorination of p_,p_' -DDT by Escherichia coli and Pseudomonas aeruginosa. Diss. Abstr. , 30B(1 ):240-241 . Fries, G.F. 1972. Degradation of chlorinated hydrocarbons under anaerobic conditions. Adv. Chem. Ser., 111:256-270. Fries, G.F., and G.S. Marrow. 1974. Retention and elimination of 2,3,7,8-tetrachlorodibenzo- p_-dioxin fed continuously to rats. Abstracts, 167th ACS Meeting, PEST 72. Fries, G.F., and G.S. Marrow. 1975. Retention and excretion of 2,3,7,3-Tetrachlorodibenzo- p_-dioxin by rats. J. Agric. Food Chem., 23(2) :265-269. Fries, G.F., G.S. Marrow, Jr., and C.H. Gordon. 1973. Long-term studies of residue retention and excretion by cows fed a polychlorinated biphenyl (Aroclor 1254). J. Agric. Food Chem., 21 (1 ) :117-121 . Fryer, J.D., J.R. Hance, and J.W. Ludwig. 1975. Long-term persistence of paraquat in a sandy loam soil. Weed Res., 15:189-194. Fuchs, A., M. Viets-Verweij, and F.W. de Vries. 1972. Metabolic conversion in plants of the systemic fungicide Triforine Q[,N/-bis-(l-formamido-2,2,2-trichloroethyl )-piperazine; CELA U 524]. Phytopathol . Z., 75:111-123. Fujita, M., A. Ishii, and Y. Sakagami. 1969. Photo-decomposition of Endrin. J. Hyg. Chem., 15(1):9-12. Fukoto, T.R. 1972. Metabolism of carbamate insecticides. Drug Metab. Rev., 1(1):117-151. Furukawa, K. , and K. Tonomura. 1972. Induction of metallic mercury-releasing enzyme in mercury- resistant Psejjd^monas_. Agric. Biol. Chem., 36(13) :2441-2448. Gab, S., W. Klein, and F. Korte. 1973. Photo reaktionen Des Aldrin/Dieldrin-Metaboliten Dihydrochlorden-1 ,3-Dicarbonsaure. Chemosphere, 2(3) : 107-1 10. 324 Gab, S., S. Nitz, H. Parlar, and F. Korte. 1975a. Beitrage Zur Okologischen Chemie CV. Photomineralisation of certain aromatic Xenobiotica. Chemosphere, 4(4) :251 -256. Gab, S., H. Parlar, and F. Korte. 1974. Beitrage Zur Okologischen Chemie - LXI. Photoreaction Des Al dri n/Di el dri n-Metabol i ten Di hydochl ordendi carbonsaure . Tetrahedron, 30:1145-1151. Gab, S., V. Saravanja, and F. Korte. 1975b. Beitrage zue Okologischen Chemi LXXIII. Irradiation studies of Aldrin and Chlordene adsorbed on a silica gel surface. Bull. Environ. Contam. Toxicol., 13(3) :301-306. Gagne, J., and J. Brodeur. 1972. Metabolic studies on the mechanisms of increased susceptibility of weanling rats to Parathion. Can. J. Physiol. Pharmacol., 50(9) :902-915. Garcia, J.D., M.G. Yang, J.H.C. Wang, and P.S. Belo. 1974. Carbon-mercury bond cleavage in blood of rats fed methyl mercuric chloride. Proc. Soc. Exp. Biol. Med., 146:66-70. Gardiner, J. A., J.J. Kirkland, H.L. Klopping, and H. Sherman. 1974. Fate of Benomyl in animals. J. Agric. Food Chem., 22(3): 419-427. Gardner, A.M., J.T. Chen, J.A.C. Roach, and E.P. Ragelis. 1973. Polychlorinated bi phenyls: Hydroxylated urinary metabolites of 2,5,2' ,5'-tetrachlorobiphenyl identified in rabbits. Biochem. Biophys, Res. Commun., 55(4) :1377-1384. Garrett, R.J.B., N.E. Garrett. 1974. Mercury incorporation by mature and immature red blood cells. Life Sci., 15:733-740. Garretto, M., and M.A.Q. Khan. 1975. Hydroxylation and epoxidation of chlordene by the mixed- function oxidase of the tropical and cold fresh water fish. Gen. Pharmacol., 6:91-96. Gehring, P.J., C.G. Kramer, B.A. Schwetz, J.Q. Rose, and V.K. Rowe. 1973. The fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) following oral administration to man. Toxicol. Appl . Pharmacol., 26:352-361. Geier, G., and I.W. Ernt. 1967. Kinetik und Mechanismus von Methyl quecksibler- Komplexbildungen. Chimia, 27(12) :635-637. Getzin, L.W. 1973. Persistence and degradation of carbofuran in soil. Environ. Entomol . , 2(3) :461-467. Gibson, J.R. 1971. Comparative biochemistry of Parathion metabolism in three species of fishes. Diss. Abstr. , 32B(4):2365. Gilbert, M.D., S.P. Monselise, L.J. Edgerton, G.A. Maylin, L.J. Hicks, and D.J. Lisk. 1975. Metabolism studies with Ethephon in cherry leaves. J. Agric. Food Chem., 23(2) :290-292. 325 Gilbert, M.D., A. Pendergrass, F.M. Isenberg, and D.J. Lisk. 1974. Fate of neodecanoic acid in onion and soil. J. Agric. Food Chem., 22(4) : 589-592. Gilman, A. P., and A. Vardanis. 1974. Carbofuran. Comparative toxicity and metabolism in the worms Lumbricus terrestris L. and Eisenis foetida S. J. Agric. Food Chem., 22(4) :625-628. Gledhill, W.E. 1975. Biodegradation of 3,4,4'-Trichlorocarbanil ide, TCC, in sewage and activated sludge. Water Res., 9:649-654. Golab, T., and W.A. Althaus. 1975. Transformation of Isopropalin in soil and plants. Weed Sci., 23(3):165-171. Golab, T., C.E. Bishop, A.L. Donoho, J. A. Manthey, and L.L. Zornes. 1975. Behavior of lhC Oryzalin in soil and plants. Pest. Biochem. Physiol., 5:196-204. Goren, R., and M.J. Burkovac. 1973. Mechanism of Naphthaleneacetic Acid conjugation. Plant Physiol., 51:907-913. Goswami , K.P. 1972. Fate of Ametryne in soil, nutrient solution-sugarcane and soil-sugarcane systems. Diss. Abstr. 33B(6) :2436-2437. Goswami, K.P., and R.E. Green. 1971. Microbial degradation of the herbicide Atrazine and its 2-Hydroxy analog in submerged soils. Enviorn. Sci. Technol . , 5(5):426-429. Goswami, K.P., and R.E. Green. 1974. Ametryne metabolite in transpired/guttated water from sugarcane shoot. J. Agric. Food Chem., 22(2) :340-342. Goto, M., M. Hattori, and K. Sugiura. 1975. Metabolism of Pentachloro- and Hexachloro-bi phenyls in the rat. Chemosphere, 4(3) :177-180. Graetz, D.A. 1970. I. Parathion degradation in lake sediments. II. Adsorption of insecticides by organo-clay complexes. Diss. Abstr., 31B(6):3464-3465. Graham, R.E., K.R. Burson, C.F. Hammer, L.B. Hansen, and C.T. Kenner. 1973. Photochemical decomposition of heptachlor expoide. J. Agric. Food Chem., 21 (5) :824-834. Grant, D.J.W., and J.V. Wilson. 1973. Degradation and hydrolysis of amides by Corynebacterium pseudodiphteriticum NCIB 10803. Microbios., 8:15-22. Grant, D.L., W.E.J. Phillips, and D.C. Villeneuve. 1971. Metabolism of a polychlorinated biphenyl (Aroclor 1254) mixture in the rat. Bull. Environ. Contam. Toxicol., 6(2) :102-112. 326 Greaves, J. 1972. How super rats survive. New Sci . , 56(816) :1 56-168. Greb, W., W. Klein, F. Coulston, L. Golberg, and F. Korte. 1973. Excretion rates of pure Di- and Trichlorobiphenyl-11+C in the rhesus monkey. Chemosphere, 2(4) : 143-146. Greb, W., W. Klein, F. Coulston, L. Golberg, and F. Korte. 1975a. Beitrage zur Okologischen Chemie. LXXXIII. In vitro Metabolism of Polychlorinated bi phenyl s-11+C. Bull. Environ. Contam. Toxicol., 13(4) :424-432. Greb, W. , W. Klein, F. Coulston, L. Golberg, and F. Korte. 1975b. Beitrage zur Okologischen Chemie. LXXXIV. Metabolism of lower polychlorinated biphenyls-1LfC in the rhesus monkey. Bull. Environ. Contam. Toxicol., 13(4) :471-476. Grover, R. 1974. Adsorption and desorption of trifluralin, triallate and dial late by various adsorbents. Weed Sci., 22(4) :405-408. Grunwell, J.R., and R.H. Erickson. 1973. Photolysis of Parathion (0, O-Di ethyl -0- (4-ni trophenyl ) thiophosphate). New Products. J. Agric. Food Chem., 21(5): 929-931 . Guirguis, G.N., and W.A. Brindley. 1975. Carbaryl penetration into and metabolism by alfalfa leaf- cutting bees, Megachile pacifica. J. Agric. Food Chem., 23(2): 274-279. Hall, R.J. 1974. The metabolism of ammonium fluoride and sodium mono- fluoracetate by experimental Acacia georginae. Environ. Pollut., 6:267-280. Hall men, U. 1975. Translocation and complex formation of root-applied 2,4-D and Picloram in susceptible and tolerant species. Physiol. Plant., 34:266-272. Hallmen, U. 1974. Translocation and complex formation of Picloram and 2,4-D in rape and sunflower. Physiol. Plant., 32:78-83. Hallmen, U., and L. Eliasson. 1972. Translocation and complex formation of picloram and 2,4-D in wheat seedlings. Physiol. Plant., 27:143-149. Hamelink, J.L. 1970. The dynamics of DDT in the lentic environment. Diss. Abstr., 30B(12):(part 1), 5312-5313. Hammerschlag, R.S., and H.D. Sisler. 1973. Benomyl and methyl -2-benzimidazolecarbamate (MBC): Biochemical, cytological and chemical aspects of toxicity to Ustilago maydis and Saccharomyces cerevesiae. Pest. Biochem. Physiol., 3(1 ) :42-54. 327 Casida. phenyl epoxygeranyl ether juvenoid Biochem. Physiol., 4:393-406. Hammock, B.D., S.S. Gill, and J.E. 1974. Insect metabolism of a and related compounds. Pest. Handi, Y.A., and M.S. Tewfik. 1969. Decomposition of the herbicide trifluralin by a pseudomonad. Acta Microbiol. Pol., Ser. B., 1 (18) :83-84. Hansen, L.G., I. P. Kapoor, and R.L. Metcalf. 1972. Biochemistry of selective toxicity and biodegradability: Comparative O-Dealkylation by aquatic organisms. Comp. Gen. Pharmacol., 3:339-344. Hansen, L. G., R.L. Metcalf, and I. P. Kapoor. 1974. Biochemistry of selective toxicity and biodegradability. II. Comparative in vivo and microsomal O-Dealkylation by mice and flies. Comp. Gen. Pharmacol., 5:157-163. Haque, A., I. Weisgerber and W. Klein. 1974. Beitrage Zue Okologischen Chemie. LXVIII. Metabolismus von Buturon-luC in Weizenblattern. Chemosphere, 3(1):9-12. Haque, R., and D. Hansen. 1974. Colored chlorinated hydrocarbon-clay complexes: An electron spin resonance study. Abstracts, 167th ACS Meeting, PEST 63, April 1-5. Haque, R., and D. Hansen. 1975. New colored chlorinated hydrocarbon-clay complexes. Bull. Environ. Contam. Toxicol., 13(4) :497-500. Haque, R., and D. Schmedding. 1975. A method of measuring the water solubility of hydropholic chemicals solubility of five polychlorinated biphenyls. Bull. Environ. Contam. Toxicol., 14(1 ) : 13-18. Hardcastle, J.E., and N. Mavichakana. 1974. Uptake of Mercuric chloride and methyl mercury chloride from liquid media by Aspergillus niger and Penicillium notatum. Bull. Environ. Contam. Toxicol., 11(5) :456-460. Harke, H.P., A. Mauch, and B. Frahm. 1975. Dunnschicht-chromatographische Bestimmung von und Nicotinmetaboliten im Urin Harvey, J., Jr., A.G. Jelinek, and H. 1973. Metabolism of methomyl in 21(5):769-775. Jr. , and H.L. Decomposition 21(5):784-786 Jr. , and R.W. Z. Anal Sherman, the rat. Chem., 274 Nicotin :300. J. Agric. Food Pease. of methomyl in soil . J. Agric. Food Chem. Harvey, J. 1973. Chem. Harvey, J. 1973. J. Agric. Hassall , K.A. 1975. Species and sex differences in the reductive dechlori- nation of DDT by supplemented liver preparations. Pest. Biochem. Physiol., 5:126-134. Reiser. Metabolism of methomyl in tobacco, corn and cabbage. Food Chem., 21 (5) :775-783. 328 Hassall, K.A., and D. Manning. 1972. Anaerobic metabolism of DDT analogs by pigeon liver preparations. Pest. Biochem. Physiol., 2(3) :331 -336. Hattula, M.L., and 0. Karlog 1973. Absorption and elimination of polychlorinated bi phenyls (PCB) in goldfish. Acta Pharmacol, et toxicol . 32:237-245. Hawkins, D.R., W.H. Down, L.F. Chasseaud, and J.D. Lewis. 1974. The metabolic fate of tridemorph in rats. Pestic. Sci., 5:535-542. Hawkins, D.R., and V.H. Saggers. 1974. The fate of dinobuton and dinoseb on growing apples. Pestic. Sci., 5:497-504. Hawton, D., and E.H. Stobbe. 1971a. The fate of nitrofen in rape, redroot pigweed and green foxtail. Weed Sci., 19(5) :555-558. Hawton, D., and E.H. Stobbe. 1971b. The fate of nitrofen in echo rape, redroot pigweed and green foxtail. Wed Sci. Soc. Am. Abstr., 44. Hedlund, R.T., and C.R. Youngson. 1972. The rates of photodecomposition of picloram in aqueous systems. Adv. Chem. Ser., 111:159-172. Hee, S.S.Q., and R.G. Sutherland. 1974. The pyrolysis of some amine salts of 2,4-dichlorophenoxy- acetic acid. J. Agr. Food Chem., 22:86-90. Heenan, M.P., and J.N. Smith. 1974. Water-soluble metabolites of p_-Nitrophenol and 1-Naphthyl N- Methyl carbamate in flies and grass grubs. Biochem. J., 144:303-310. Helling, C.S., G. Dennison, and D.D. Kaufman. 1974. Fungicide movement in soil. Phytopathology, 64(8) : 1091 -11 00. Helweg, A. 1975a. Degradation of 14C-labeled maleic hydrazide in soil as influenced by sterilization, concentration and pretreatment. Weed Res., 15:53-58. Helweg, A. 1975b. Degradation of lltC-maleic hydrazide in soil as influenced by adsorption of activated carbon. Weed Res., 15:129-133. Herlihy, M. , and W. Quirke. 1975. The persistence of 2-chloro-6-(trichloromethyl )-pyridine in soil. Comm. in Soil Sci. and Plant Anal., 6(5) : 51 3-520. Herring, J.L., E.J. Hannan, and D.D. Bills. 1972. UV-irradiation of Aroclor 1254. Bull. Environ. Contam. Toxicol., 8(3) :153-157. Heuer, B., B. Yaron, and Y. Birk. 1974. Guthion half-life in aqueous solutions on glass surfaces. Bull. Environ. Contam. Toxicol., 11 (6) :532-537. Hicks, B.W. 1970. Fate of 2, 3-Dihydro-2,2-dimethyl-7-benzofuranyl-N^-methyl car- bamate (furadan) and 2-methyl-2-(methylthio)propionaldehyde-0-(methyl- carbamoyl )oxime (temik) in laying hens. Diss. Abstr., 31 (5) :2741-2742. 329 Hicks, 6.F., Jr., and T.R. Corner. 1973. Location and consequences of 1 ,1 ,l-Trichloro-2,2-bis (p_-chloropheny1 )ethane uptake by Bacillus megaterium. Appl . Microbiol., 25(3) :381-387. Hiles, R.A. 1974. Adsorption, distribution and excretion of inorganic tin in rats. Toxicol. Appl. Pharmacol., 27:366-379. Hill, J.E., and R.I. Krieger. 1975. Uptake, translocation, and metabolism of tirpate in tobacco Nicotiana tabacum. J. Agric. Food Chem., 23(6) :1125-1129. Hilton, H.W., N.S. Nomura, W.L. Yauger, Jr., S.S. Kameda. 1974. Adsorption, translocation, and meatbolism of metribuzin (Bay 94337) in sugarcane. J. Agric. Food Chem., 22(4) :578-582. Hirata, H., and K. Ishizuka. 1975. Identification of the metabolite (M-l ) of 2-tert-Butyl- 4-(2,4-dichloro-5-isopropoxyphenyl )-A2-l ,3,4-oxadiazolin-5-one (Oxadiazon) in rice plants. J. Agric. Biol„ Chem., 39(7): 1447-1454. Hirwe, A.S., R.L. Metcalf, P.-Y. Lu, and L.-C. Chio. 1975. Comparative metabolism of 1 ,l-Bis-(£-Chlorophenyl )- 2-Nitropropane (Prolan) in mouse, insects, and in a model ecosystem. Pest. Biochem. Physiol., 5:65-72. Hoagland, R.E., and D.S. Frear. 1976. Behavior and fate of ethylenethiourea in plants. J. Agric. Food Chem., 24(1 ) :1 29-133. Hoagland, R.E., G. Graf, and E.D. Handel. 1974. Hydrolysis of 3' ,4'-dichloropropionanilide by plant aryl acylamidases. Weed Res., 14:371-374. Hock, W.K. 1969. Studies of the biodegradation and more of antifungal action of chloroneb (1 ,4-dichloro-2,5-dimethoxybenzene). Diss. Abstr., 29B(8):2705. Hodgson, R.H. 1971. Alteration of diphenamid metabolism by ozone. Weed Sci. Soc. Am. Abstr., 44-45. Hodgson, R.H., K.E. Dusbabek, and B.L. Hoffer. 1974. Diphenamid metabolism in tomato: Time course of an ozone fumigation effect. Weed Sci., 22(3) :205-210. Hodgson, R.H., D.S. Frear, H.R. Swanson, and L.A. Regan. 1973. Alteration of diphenamid metabolism in tomato by ozone. Weed Sci., 21 (6) :542-549. Holloman, M.E., B.R. Layton, M.V. Kennedy, and C.R. Swanson. 1975. Identification of the major thermal degradation products of the insecticide mirex. J. Agric. Food Chem., 23(5) :1 011-1012. Holm, H.W., and H.F. Cox. 1974. Mercury in aquatic systems: Methylation, oxidation- reduction, and bioaccumulation. EPA 660/3-74-021:1-29. Holm, H.W. , and M.F. Cox. 1975. Transformation of elemental mercury by bacteria. Appl. Microbiol., 29(4) :491 -494. 330 Holmstead, R.L., S. Khalifa, and J.E. Casida. 1974. Toxaphene composition analyzed by combined gas chroma- tography - chemical ionization mass spectrometry. J. Agric. Food Chem., 22(6) :939-943. Holmstead, R.L., S. Kahlifa, and J.E. Casida. 1975. Studies of the reaction of toxaphene and mirex with ferroprotoporphyrin model systems. Abstracts, 170th ACS Meeting, PEST 131. Hook, G.E.R., T.C. Orton, J. A. Moore, and G.W. Lucier. 1975. 2,3,7,8-Tetrachlorodibenzo-p_-dioxin-induced changes in the hydroxylation of biphenyl by rat liver microsomes. Biochem. Pharmacol., 24:335-340. Hosier, C.F. , Jr. 1974. Degradation of Zectran in alkaline water. Bull. Environ. Contam. Toxicol., 12(5) : 599-605. Hosokawa, S., and J. Miyamoto. 1974. Metabolism of lt+C-labelled sumithion, 0,0-dimethyl 0-(3-methyl-4-nitrophenyl ) phosphorothioate in apples. Botyu- Kagaku, 39(2):49-53. Hsu, I.C., J. P. VanMiller, and J.R. Allen. 1975a. Metabolic fate of 3H-2,5,2' ,5'-tetrachlorobiphenyl in infant nonhuman primates. Bull. Environ. Contam. Toxicol., 14(2):233-240. Hsu, I.C., J. P. VanMiller, J.L. Seymour, and J.R. Allen. 1975b. Urinary metabolites of 2,5,2' ,5'-tetrachlorobiphenyl in the nonhuman primate. Proc. Soc. Explt'l. Biol. Med., 150:185-188. Hsu, J.C., and N.D. Camper. 1975. Degradation of Ioxynil to C02 in soil. Pest. Biochem. Physiol., 5:47-51. Hsu, T.S., and R. Bartha. 1974. Biodegradation of chloroaniline-humus complexes in soil and in culture solution. Soil Sci . , 118(3) :213-220. Huckins, J.N., J.E. Swanson, and D.L. Stalling. 1974. Perchlorination of polychlorinated biphenyls. J. Assoc. Off. Anal. Chem., 57:416-417. Hughes, A.F., and C.T. Corke. 1974. Formation of tetrachloroazobenzene in some Canadian soils treated with propanil and 3,4-dichloroaniline. Can. J. Microbiol., 21(l):35-39. Hughes, L.B. , Jr. 1971. A study of the fate of carbaryl insecticide in surface waters. Diss. Abstr., 32B(6):3108. Hunn, J.B., and J.L. Allen. 1974. Movement of drugs across the gills of fishes. Ann. Rev. Pharmac, 14:47-55. Hunn, J.B., and J.L. Allen. 1975a. Renal excretion in coho salmon (Oncorhynchus kisutch) after acute exposure to 3-trifluoromethyl-4-nitrophenol . J. Fish. Res. Board Can., 32(10) :1873-1876. 331 Hunn, J.B., and J.L. Allen. 1975b. Residue dynamics of quinaldine and TFM in rainbow trout. Gen. Pharmacol., 6:15-18. Hustert, K. , and F. Korte. 1972. Beitrage zur Okologischen Chemie-XXXVIII . Synthese Polychlorierter Biphenyle and ihre Reaktionen bei UV-Bestrahlung. Chemosphere, 1(1): 7-1 0 . Hutacharern, C, and C.O. Knowles. 1975. Metabolism of chlorpyrifos-ll+C in the eastern subterranean termite. Bull. Environ. Contam. Toxicol., 13(3) :351 -356. Hutson, D.H., M.K. Baldwin, and E.C. Hoadley. 1975. Detoxication and bioactivation of endrin in the rat. Xenobiotica, 5(11 ) :697-714. Hutson, D.H., and E.C. Hoadley. 1972. The comparative metabolism of [11+C-Vinyl] dichlorvos in animals and man. Arch. Toxicol., 30:9-18. Hutzinger, 0., W.D. Jamieson, and S. Safe. 1972a. Photochemical degradation of isomerically pure Di-, Tetra-, Octa-, and Deca-chlorobiphenyls. Abstracts, 164th ACS Meeting, WATER 23. Hutzinger, 0., W.D. Jamieson, S. Safe, L. Paulmann, and R. Amnion. 1974. Identification of metabolic dechlorination of highly chlorinated bi phenyl in rabbit. Nature, 252:698-699. Hutzinger, 0., D. Nash, and S. Safe. 1972b. Metabolism of isomerically pure Mono-, Di-, Tetra-, and Hexachloro-biphenyls by Mammal, bird and fish. Abstracts, 164th ACS Meeting, WATER 39. Hutzinger, 0., D.M. Nash, S. Safe, A.S.W. Defreitas, R.J. Norstrom, D.J. Wildish, and V. Zitko. 1972c. Polychlorinated biphenyls: Metabolic behavior of pure isomers in pigeons, rats, and brook trout. Science, 178:312-314. Hutzinger, 0., S. Safe, and V. Zitko. 1972d. Photochemical degradation of chlorobiphenyls (PCBs). Environ. Health Perspect., 1:15-20. Hutzinger, 0., S. Safe, and V. Zitko. 1972e. Polychlorinated Biphenyls. Analabs Res. Notes, 12(2):1-11 Hylin, J.W. 1973. Oxidative decomposition of ethyl ene-bis-dithiocarbamates. Bull. Environ. Contam. Toxicol., 10(4) :227-233. Hyzak, D.L., and R.L. Zimdahl . 1974. Rate of degradation of metribuzin and two analogs in soil. Weed Sci., 22(l):75-79. Ide, A., Y. Niki, F. Sakamoto, I. Watanabe, and H. Watanabe. 1972. Decomposition of pentachlorophenol in paddy soil. Agric. Biol. Chem., 36(11 ) :1937-1944. Iguchi, T., K. Sawazaki , and A. Hayashi. 1974. Stability of pyrethroid insecticides in mosquito coil extract (studies on pyrethroid insecticide part V.). J. Agric. Chem. Soc. Jap. , 48:1-5. 332 Ingram, G.H., and E.M. Pull in. 1974. Persistence of bromoxynil in three soil types. Pestic. Sci., 5:287-291. Intrieri, C, and K. Ryugo. 1974. Uptake, transport and metabolism of (2-chloroethyl )- trimethyl ammonium chloride in seedlings of almond (Primus amygdalus, BATSCH.). J. Am. Soc. Hortic. Sci., 99(4) :349-352. Iqbal, Z.M. 1971. Metabolism of 0-ethyl S^S-dipropyl phosphorodithioate (MOCAP) in plants, rats, and liver microsomal systems. Diss. Abstr., 31B(11):6665. Ishikawa, K. , I. Okuda, and S. Kuwatsuka. 1973. Metabolism of benthiocarb (4-Chlorobenzyl N,N- diethylthiolcarbamate) in mice. Agric. Biol. Chem., 37(1): 165-173. Ishizuka, K. H. Hirata, and K. Fukunaga. 1975. Absorption, translocation and metabolism of 2-tert- Butyl-4-(2,4-dichloro-5-isopropoxyphenyl )-A2-],3,4-oxadiazolin- 5-one (Oxadiazon) in rice plants. Agric. Biol. Chem., 39(7): 1431-1446. Ishizuka, K. , I. Takase, K. Ei Tan, and S. Mitsui. 1973. Adsorption and translocation of 0-ethyl S^,S-Di phenyl phosphorodithiolate (Hinosan) in rice plants. Agric. Biol. Chem., 37(6):1307-1316. Iverson, F., D.L. Grand, and J. Lacroix. 1975. Diazinon metabolism in the dog. Bull. Environ. Contam. Toxicol., 13(5):611-618. Iverson, F., and S.L. Hierlihy. 1974. Biotransformation of methyl mercury in the guinea pig. Bull. Environ. Contam. Toxicol., 11(1):85-91. Ivie, G.W. 1973. Nature and toxicity of two oxychlordane photoisomers. J. Agric. Food Chem., 21 (6) :1 1 13-1115. Ivie, G.W., D.E. Clark, and D.D. Rushing. 1974a. Metabolic transformation of disugran by rumen fluid of sheep maintained on dissimilar diets. J. Agric. Food Chem., 22(4):632-634. Ivie, G.W., H.W. Dorough, and E.G. Alley. 1974b. Photodecomposition of mirex on silica gel chroma topi ates exposed to natural and artificial light. J. Agric. Food Chem., 22(6):933-935. Ivie, G.W., W. Dorough, H.E. Bryant. 1974c. Fate of Mirex-14 in Japanese quail. Bull. Environ. Contam. Toxicol., 11 (2):129-135. Ivie, G.W., H.W. Dorough, and R.A. Cardona. 1973. Photodecomposition of the herbicide methazole. J. Agric. Food Chem., 21 (3) :386-391 . 333 Ivie, G.W., J.R. Gibson, H.E. Bryant, J.J. Begin, J.R. Barnett, and H.W. Dorough. 1974d. Accumulation, distribution, and excretion of Mirex-:ttC in animals exposed for long periods to the insecticide in the diet. J. Agric. Food Chem., 22(4) :646-653. Iwata, Y., W.E. Westlake, and F.A. Gunther. 1973. Persistence of Parathion in six California soils under laboratory conditions. Arch. Environ. Contam. Toxicol., l(l):84-96. Iwata, Y., W.E. Westlake, and F.A. Gunther. 1973. Varying persistence of polychlorinated biphenyls in six California soils under laboratory conditions. Bull. Environ. Contam. Toxicol., 9(4):204-211. Jackson, R.B. 1973. The metabolism of allyl alcohol in Trichoderma viride. J. Gen. Appl. Microbiol., 19:41-54. Jacob, T.A., J.R. Carlin, R.W. Walker, F.J. Wolf, and W.J. A. VendenHeuvel 1975. Photolysis of thiabendazole. J. Agric. Food Chem., 23(4):704-709. Jacobs, L.W., and D.R. Keeney. 1974. Methylmercury formation in mercury-treated river sediments during in situ equilibration. J. Environ. Qual . , 3(2) :121-126. Jamet, P., M.-A. Piedallu. 1975. Etude de l'adsorption et de la desorption de la pyrazone (amino-5-chloro-4-phenyl-2(2H)pyridazinone-3) par differents types de sols. Weed Res., 15:113-121. Jamet, P., M-A. Piedallu, M. Hascoett. 1974. Migration et Degradation de L'Aldicarbe Dans Differents types de sol. Internat'l. Atomic Energy Agency, SM-175/45: 393-415. Jan, J., M. Komar, and M. Milohnoja. 1975. Excretion of some pure PCB isomers in milk of cows. Bull. Environ. Contam. Toxicol., 13(3) :313-315. Janes, N.F., A.F. Machin, M.P. Quick, H. Rogers, D.E. Mundy, and A.J. Cross. 1973. Toxic metabolites of diazinon in sheep. J. Agric. Food Chem., 21(1):121-124. Jansson, B., S. Jensen, M. Olsson, L. Renberg, G. Sundstrom, and R. Vaz. 1975. Identification by GC-MS of phenolic metabolites of PCB and p_,p_'-DDE isolated from baltic guillemot and seal. Ambio, 4(2):93-97. Jao, L.T., and J.E. Casida. 1974. Insect pyrethroid-hydrolyzing esterases. Pest. Biochem. Physiol., 4:465-472. Jeffcoat, B., and W.N. Harries. 1973. Selectivity and mode of action of ethyl (+)-2-(N-benzoyl- 3,4-dichloroanilino)propionate in the control of Avena fatua in cereals. Pestic, Sci., 4:891-899. 334 Jensen, B.L., and R.E. Counsell . 1973. Acid hydrolysis products DDD and DDT precursors. J. Org. Chem., 38:835-838. Jensen, H.L. 1961. Some aspects of biological allyl alcohol dissimilation. Acta Agric. Scand., 11:54-62. Jensen, S., and L. Renberg. 1972. Contaminants in pentachlorophenol : Chlorinated dioxins and predioxins. Ambio, l(2):62-65. Jensen, S., and G. Sundstrom. 1974. Metabolic hydroxylation of a chlorobiphenyl containing only isolated unsubstituted positions--2,2' ,4,4' ,5,5'-hexa- chlorobiphenyl . Nature, 251:219-220. Jhotty, J.S., and H. Singh. 1972. Stability of benomyl in plants. Phytochemistry, 11: 2207-2208. Johannsen, F.R., and CO. Knowles. 1974. Toxicity and action of fluenethyl acaricide and related compounds in the mouse, housefly and twospotted spider mite. Comp. Gen. Pharmacol., 5:101-110. Johnson, B.T. 1969. The degradation of DDT by soil-borne bacteria. Diss. Abstr., 29B(9):3156. Johnson, B.T., and J.0. Kennedy. 1973. Biomagnification of p_,p_'-DDT and methoxychlor by bacteria. Appl . Microbiol., 26(1):66-71. Johnson, B.T., and W. Lulves. 1975. Biodegradation of Di-n-Butyl Phthlate and Di-2-Ethylhexyl Phthalate in freshwater hydrosoil. J. Fish Res. Bd. Can., 32(3) :333-339. Johnson, D.L., and M.E.Q. Pilson. 1975. The oxidation of arsenite in seawater. Environ. Lett., 8(2):157-171. Joiner, R.L. 1972. A study of the photoalteration products of parathion. Diss. Abstr., 32B(7) :4169-4170. Joiner, R.L., and K.P. Baetcke. 1973. Parathion: Persistence on cotton and identification of its photoalteration products. J. Agric. Food Chem., 21(3): 391-396. Joiner, R.L., and K.P. Baetcke. 1974. Identification of the photoalteration products formed from parathion by ultraviolet light. J. Assoc. Off. Anal. Chem., 57(2):408-415. Jondorf, W.R., D.V. Parke, and R.T. Williams. 1958. Studies in detoxication: The metabolism of halogeno- benzenes. 1,2,3,4-, 1 ,2,3,5-Tetrachlorobenzenes. Biochem. J., 69:181-189. 335 Jones, A.S. 1976. Metabolism of Aldicarb by five soil fungi. J. Agric. Food Chem., 24(1 ):115-117. Jones, A.S., and C.S. Hodges. 1974. Persistence of mirex and its effects on soil micro- organisms. J. Agric. Food Chem., 22(3) :435-439. Jones, D.W. 1972. Absorption, translocation, and fate of the herbicide 2-(3,4-dichlorophenyl )-4-methyl-l ,2,4-oxadiazolidine-3,5-dione, in cotton. Diss. Abstr., 32(10:5564. Jones, H.A., and H.L. Haller. 1931. The "Yellow Compounds" resulting from the decomposition of rotenone in solution. J. Am. Chem. Soc, 53:2320-2324. Jordan, L.S., and V.A. Jolliffe. 1973. Simazine dealkylation in conjunction with citrus roots. Pestic. Sci., 4:467-472. Jordan. L.S., A. A. Zurqiyah, A.R. DeMur, and W.A. Clerx. 1975. Metabolism of siduron in Kentucky bluegrass (Poa pratensis L.). J. Agric. Food Chem., 23(2):286-290. Kaiser, K.L.E., and P.T.S. Wong. 1974. Bacterial degradation of polychlorinated biphenyls. I. Identification of some metabolic products from Aroclor 1242. Bull. Environ. Contam. Toxicol., 11 (3) :291-296. Kamada, T. 1971. Hygienic studies of pesticide residues. I. Accumulation of BHC. Nippon Eiseigaku Zasshi , 26(4) :358-364. Kamimura, S., M. Nishikawa, H. Saeki , and Y. Takahi. 1974. Absorption and metabolism of 3-Hydroxy-5-methylisoxazole in plants and the biological activities of its metabolites. Phytopathology, 64(10) :1273-1281 . Kapoor, I. P. 1971. Comparative metabolism of DDT, methoxychlor and methio- chlor in mammals, insects and in a model ecosystem. Diss. Abstr., 31B(9):5408-5409. Kapoor, I. P., R.L. Metcalf, A.S. Hirwe, J.R. Coats, and M.S. Khalsa. 1973. Structure activity correlations of biodegradability of DDT analogs. J. Agric. Food Chem., 21 (2) :310-315. Karanth, N.G.K., S.6. Bhat, C.S. Vaidyanathan, and V.N. Vasantharajan. 1974. Conversion of Dexon (p_-dimethylaminobenzenediazo sodium sulfonate) to l^,N-dimethyl-p_-phenylenediamine by Pseudomonas fragi Bk9. Appl . Microbiol., 27(1 ) :43-46. Karanth, N.G.K., and V.N. Vasantharajan. 1973. Persistence and effect of dexon on soil respiration. Soil Biol. Biochem., 5:679-684. Karapally, J.C., J.G. Saha, and Y.W. Lee. 1973. Metabolism of Lindane-11+C in the rabbit: Ether-soluble urinary metabolites. J. Agric. Food Chem., 21 (5) :811-818. Katz, S.A., and M.H. Samitz. 1973. The binding of mercury to bovine serum albumin. Environ. Res., 6:144-146. 336 Kaufman, D.D., J.R. Plimmer, and U.I. Klingebiel. 1973. Microbial oxidation of 4-chloroanil ine. J. Agric. Food Chem., 21 (1 ):127-130. Kawatski, J. A. 1970. Toxicity and metabolism of two chlorinated hydrocarbon insecticides (Aldrin and Dieldrin) in the freshwater ostracod Chlamydotheca arcuata (Sars). Diss. Abstr., 30B(9):4429. Kawatski, J. A., and M.A. Bittner. 1975. Uptake, elimination, and biotransformation of the lampricide 3-Trifluoromethyl-4-nitrophenol (TFM) by larvae of the aquatic midge Chironomus tentans. Toxicology, 4:183-194. Kawatski, J. A., and M.J. McDonald. 1974. Effect of 3-Trifluoromethyl-4-nitrophenol on in vitro tissue respiration of four species of fish with preliminary notes on its in vitro biotransformation. Comp. Gen. Pharmacol.. 5:67-76. Kearney, P.C., J.R. Plimmer, V.P. Williams, U.I. Klingebiel, A.R. Isensee, T.L. Laanio, G.E. Stolzenberg, and R.G. Zaylskie. 1974. Soil persistence and metabolism of N-sec-butyl -4-tert- butyl-2,6-dinitroaniline. J. Agric. Food Chem., 22(5) :856-859. Kearney, P.C., E.A. Woolson, J.R. Plimmer, and A.R. Isensee. 1969. Decontamination of pesticides in soil. Residue Rev., 29:137-149. Kempe, L.L. 1973. Microbial degradation of the lamprey larvicide 3- trifluoromethyl-4-nitrophenol in sediment-water systems. Technical Report No. 18, Great Lakes Fishery Comm., 16 pages. Kern, A.D., W.F. Meggitt, and D. Penner. 1975. Uptake, movement, and metabolism of cyanazine in fall panicum, green foxtail, and corn. Weed Sci., 23(4):277-282. Ketchersid, M.L., and M. G. Merkle. 1975. Persistence and movement of perfluidone in soil. Weed Sci., 23(5):344-348. Khalifa, S. , T.R. Mon, J.L. Engel , and J.E. Casida. 1974. Isolation of 2,2,5-endo, 6-exo, 8,9,10-heptachloro- bornane and an octachloro toxicant from technical toxaphene. J. Agric. Food Chem., 22(4) :653-657. Khan, S.U. 1974. Adsorption of bipyridylium herbicides by humic acid. J. Environ. Qual . , 3(3) :202-206. Khan, S.U., and R. Mazurkewich. 1974. Adsorption of linuron on humic acid. Soil Sci., 118(5): 339-343. Kiigemagi, U., R.J. Burnard, and L.C. Terriere. 1975. Analytical methods for the detection of the pesticide 1 ,1 '-methyl endi-2-naphthol (Squoxin) in fish and water. J. Agric. Food Chem., 23(4):717. 337 Kilzer, L., S. Detera, I. Weisgerber, and W. Klein. 1974. Beitrage zur okologischen Chemie LXXVII: Verteilung und metabolismus des Aldrin-Dieldrin-metaboliten trans-4,5- dihydroxy-4,5-dihydroaldrin-lltC in Salatpflanzen und Boden. Chemosphere, 3(4):143-148. Kirklan, K., and J.D. Fryer. 1972. Degradation of several herbicides in a soil previously treated with MCPA. Weed Res., 12:90-95. Klaassen, CD. 1974a. Biliary excretion of arsenic in rats, rabbits, and dogs. Toxicol. Appl . Pharmacol., 29(3) :447-457. Klaassen, CD. 1974b. Biliary excretion of manganese in rats, rabbits, and dogs. Toxicol. Appl. Pharmacol., 29(3) :458-468. Klaassen, CD., and D.W. Shoeman. 1974. Biliary excretion of lead in rats, rabbits, and dogs. Toxicol. Appl. Pharmacol., 29(3) :434-446. Klee, G.E. 1972. DDT metabolism and movement in deciduous forest soil microarthropods. Diss. Abstr., 32B(9):5233. Klein, W., J. Kohli, I. Weisgerber, and F. Korte. 1973. Fate of Aldrin-lt+C in potatoes and soil under outdoor conditions. J. Agric. Food Chem. , 21 (2) : 152-1 56. Klein, W. , S. Zarif, and I. Weisgerber. 1972. Beitrage zur Okologischen Chemie XXXVI. Ruckstands- verhalten von IsodrinluC und seiner Umwandlungsprodukte in Weisskohl und Mohren. Chem. Mikrobiol. Technol . Lebensm. , 1:121-125. Knowles, CO., and S.A. Aziz. 1974. Metabolic fate of benzoyl chloride (2,4,6-trichloro- phenyl )hydrazone (Banamite Acaricide) in the twospotted spider mite. J. Econ. Entomol . , 67(5) : 574-576. Kobayashi, l(. , and H. Akitake. 1975a. Studies on the Metabolism of chlorophenols in fish-- I. Absorption and excretion of PCP by goldfish. Bull. Jap. Soc. Sci. Fish., 41(l):87-92. Kobayashi, K. , and H. Akitake. 1975b. Studies on the metabolism of chlorophenols in fish--II. Turnover of absorbed PCP in goldfish. Bull. Jap. Soc. Sci. Fish., 41(l):93-99. Kobayashi, K., H. Akitake, and T. Tomiyama. 1970. Studies on the metabolism of pentachlorophenate, a herbicide, in aquatic organisms-Ill. Isolation and identi- fication of a conjugated PCP yielded by a shell -fish, Tapes philippinarum. Bull. Jap. Soc. Sci. Fish., 36(1 ) : 1 03-1 08. Kocma, E. 1973. Levels of diethyldithiocarbamate in blood serum after intra-peritoneal administration of its sodium salt and tetra- ethylthiuram disulphide. Acta Pol. Pharmacol., XXX(2) :229-234. 338 Kohl i , J.D., R.N. Khanna, B.N. Gupta, M.M. Dhar, J.S. Tandon, and K.P. Sircar. 1974. Absorption and excretion of 2,4-Dichlorophenoxyacetic Acid in man. Xenoxibotic, 4(2) :97-100. Kohl i , J., I. Weisgerber, and W. Klein. 1972. Beitrage zur Okologischen Chemie XLI(l). Umwandlung und Ruckstandsverhalten von Dieldrin-14C in Zweibeln nach Saatgutbehandlung. Chem. Mikrobiol. Technol . Lebensm., 1: 149-150. Kohl i , J., I. Weisgerber, and W. Klein. 1976. Balance of Conversion of [11+C]Lindane in lettuce in hydroponic culture. Pestic. Biochem. Physiol., 6:91-97. Kohl i , J., I. Weisgerber, W. Klein, and F. Korte. 1973a. Beitrage Zur Okologischen Chemie. LIX. Ruckstand- sverhalten und Umwandlun von Dieldrin-ll+C in Kulturpflanzen, Boden und Sickerwasser Nach Bodenapplikation. Chemosphere, 2(4):153-156. Kohli, J., S. Zarif, I. Weisgerber, W. Klein, and F. Korte. 1973b. Fate of Aldrin-^C in sugar beets and soil under outdoor conditions. J. Agric. Food Chem., 21 (5) :855-857. Kolberg, J., K. Helgeland, and J. Jonsen. 1973. Binding of 2,4-Dichloro- and 2,4,5-Trichlorophenoxyacetic Acid to bovine serum albumin. Acta Pharmacol. Toxicol., 33: 470-475. Koransky, W., G. Munch, G. Noack, J. Portig, S. Sodomann, and M. Wirsching. 1975. Biodegradation of a-Hexachlorocyclohexane V. Character- ization of the Major urinary metabolites. Naunyn-Schmiedeberg's Arch. Pharmacol., 288:65-78. Koshy, K.T., A.R. Friedman, A.L. VanDerSlik, and D.R. Graber. 1975. Photolysis of Benzoic acid 2-(2,4,6-Trichlorophenyl ) hydrazide. J. Agric. Food Chem., 23(6) : 1084-1 088. Kossman, K. 1970. Uber Abbaugeschwindigkeit und Verteilung Von Phenmedipham Im Boden. Weed Res., 10:349-359. Kotzias, D., W. Klein, and F. Korte. 1973. Reaktion Des Buturons Bei UV-Bestrahlung. Chemosphere, 2:87-90. Kovacicova, J., V. Batora, and S. Truchlik. 1973. Hydrolysis rate and i_n vitro anticholinesterase activity of fenitrothion and S-methyl fenitrothion. Pestic. Sci., 4:759-763. Kraus, P., G. Noack, and J. Portig. 1973. Biodegradation of alpha-hexachlorocyclohexane. II. Glutathione-mediated conversion to hydrophilic substance by particulate fractions of rat liver and by homogenates of various rat organs. Naunyn-Schmiedeberg's Arch. Pharmacol., 279: 199-202. 339 Krieger, R.I., P.W. Lee, A. Black, and T.R. Fukuto. 1973. Inhibition of microsomal aldrin epoxidation by diquat and several related bipyridylium compounds. Bull. Environ. Contam. Toxicol., 9(l):l-3. Ku, T-Y., and P. A. Dahm. 1973. Effect of liver enzyme induction on paraoxon metabolism in the rat. Pest. Biochem. Physiol., 3(2):175-188. Kuhr, R.J. 1973. The metabolic fate of methomyl in the cabbage looper. Pest. Biochem. Physiol., 3(2):113-119. Kuhr, R.J., and A.C. Davis. 1975. Toxicity and metabolism of carbaryl in the European corn borer. Pest. Biochem. Physiol., 5:330-337. Kumar, Y., G.P. Semeluk, P.J. Silk, and I. Unger. 1974. The photochemistry of carbamates VI: The photodecom- position of meobal (3,4-XYLYL-N-methyl carbamate) and mesurol (4-methylthio-3,5-XYLYL-N-methyl carbamate). Chemosphere, 3(1): 23-27. Kurihara, N., and M. Nakajima. 1974. Studies on BHC isomers and related compounds. VIII. Urinary metabolites produced from y- and 6-BHC in the mouse: Chlorophenol conjugates. Pest. Biochem. Physiol., 4(2) :220-231 . Kurihara, N., M. Uchida, T. Fujita, and M. Nakajima. 1974a. Studies on BHC isomers and related compounds. VI. Penetration and translocation of BHC isomers in the cockroach and their correlation with physicochemical properties. Pest. Biochem. Physiol., 4(1):12-18. Kurihara, N., S. Wakamura, T. Nakamura, and M. Nakajima. 1974b. Isomerization of 1 ,3,4,5, 6-Pentachlorocyclohexene-l . Agric. Biol. Chem., 38(9) :1717-1723. Laanio, T.L., P.C. Kearney, and D.D. Kaufman. 1973. Microbial metabolism of dinitramine. Pest. Biochem. Physiol., 3:271-277. Labrecque, G.C., M.C. Bowman, R.S. Patterson, and J. A. Seawright. 1972. Persistence of thiotepa and tepa in pupae and adults of Culex pi pi ens fatigans Wiedemann. Bull. Org. Mond. Sante (Bull. W.H.O.), 47:675-676. La Hue, D.W., L.D. Kirk, and G.C. Mustakas. 1975. Fate of dichlorvos residues during milling and oil extraction of soybeans. Environ. Entomol . , 4(1 ):1 1-14. Lamoureux, G.L., and K.L. Davison. 1975. Mercapturic acid formation in the metabolism of Propachlor, CDAA, and Fluorodifen in the rat. Abstracts 170th ACS Meeting, Chicago, 111., Aug. 25-29, PEST 1. Lamoureux, G.L., and L. E. Stafford. 1974. The metabolism of 1 ,1 ,l-Trifluoro-N-[2-methyl-4- (phenylsulfonylJphenyl-^C^U)] methanesulfonamide (Destun) in plant seedlings. Abstracts, 167th ACS Meeting, PEST 62. 340 Lamoureux, G.L., L.E. Stafford, R.H. Shimabukuro, and R.G. Zaylskie. 1973. Atrazine metabolism in Sorghum: Catabolism of the glutathione conjugate of Atrazine. J. Agric. Food Chem. , 21(6):1020-1030. Landner, L. 1972. The biological alkylation of mercury. Biochem. J., 130(2) :67-69. Lane, R.H., R.M. Grodner, and J.L. Graves. 1976. Irradiation studies of mallard duck eggs material containing mirex. J. Agric. Food Chem., 24(1 ) : 1 92-1 93 - Lanzilotta, R.P. 1969. Microbial and enzymatic transformations of 3 ' ,4 ' - Dichloropropionanilide and related compounds. Diss. Abstr., 29B(11):4016-4017. Larsen, G.L., and J.E. Bakke. 1975. Metabolism of 2-Chloro-4-cyclopropylamino-6-isopropyl- amino-s_-triazine (Cyprazine) in the rat. J. Agric. Food Chem., 23(3):388-392. Laveglia, J., and P. A. Dahm. 1975. Oxidation of Terbufos (Counter) in three Iowa soils. Environ. Entomol . , 4(5) :71 5-718. Lawley, P.D., S.A. Shah, D.J. Orr. 1974. Methylation of nucleic acids by 2,2-dichlorovinyl dimethyl phosphate (Dichlorvos, DDVP). Chem. -Biol. Interact., 8:171-182. Lay, J. P., I. Weisgerber, and W. Klein. 1975. Conversion of the Aldrin/Dieldrin metabolite dihydro- chlordene dicarboxylic acid - 14C in rats. Pest. Biochem. Physiol., 5:226-232. Lay, M.M., and R.D. Ilnicki. 1974. Peroxidase activity and propanil degradation in soil. Weed Res., 15:111-113. Lay, M.M., and R.D. Ilnicki. 1975. Effect of soil storage on propanil degradation. Weed Res., 15:63-66. Lay, J. P., W. Klein, and F. Korte. 1974. Beitrage zue okologischen Chemie-. LXXXV: Mikrosynthese und in vitro Metabolismus von Dihydrochlorden-Dicarbonsaure-ll+C durch Rattenleberorganellen. Chemosphere, 3(5) :1 93-198. Lay, J. P., W. Klein, and F. Korte. 1975. Beitrage Zue Okologischen Chemie. C. Ausscheidung, Speicherung und Metabolisierung Von 2,4,6,2' ,4'-Pentachloro- biphenyl-11+C Nach Langzeitfutterung an Ratten. Chemosphere, 3:161-168. Lay, J. P., I. Weisgerber, and W. Klein. 1975. Conversion of the Aldrin/Dieldrin metabolite dihydro- chlordene Dicarboxylic Acid-ll+C in rats. Pest. Biochem. Physiol., 5:226-232. 341 Leary, J.B. 1971. Gas chromatographic determination of monitor (0,S-Di methyl Phosphoramidothioate) residues in crops. J. Assoc. Off. Anal. Chem., 54(6): 1396-1 398. Leary, J.B. 1974. Gas-liquid chromatographic determination of acephate and ortho 9006 residues in crops. J. Assoc. Off. Anal. Chem., 57:189-192. Lech, J.J. 1972. Isolation and identification of TFM Glucuronide in bile of TFM exposed rainbow trout. Fed. Proc, 31 (2) :606 . Lech, J.J. 1973. Isolation and identification of 3-Trifluoromethyl-4- nitrophenyl glucuronide from bile of rainbow trout exposed to 3-trifluoromethyl-4-nitrophenol . Toxicol. Appl . Pharmacol., 24:114-124. Lech, J.J. 1974. Glucuronide formation in rainbow trout--effect of salicylamide on the acute toxicity, conjugation and excretion of 3-trifluoromethyl-4-nitrophenol . Biochem. Pharmacol., 23:2403-2410. Lech, J.J., and N.V. Costrini. 1972. In vitro and in vivo metabolism of 3-trifluoromethyl-4- nitrophenol (TFM) in rainbow trout. Compar. Gen. Pharmacol., 3(10):160-166. Lech, J.J., S. Pepple, and M. Anderson. 1973. Effects of Novobiocin on the acute toxicity, metabolism and bi 11 iary excretion of 3-trifluoromethyl-4-nitrophenol in rainbow trout. Toxicol. Appl. Pharmacol., 25:542-552. Lech, J.J., and C.N. Statham. 1975. Role of glucuromide formation in the selective toxicity of 3-trifluoromethyl-4-nitrophenol (TFM) for the sea lamprey: Comparative aspects of TFM uptake and conjugation in sea lamprey and rainbow trout. Toxicol. Appl. Pharmacol., 31:150-158. Lee, S.S. , and S.C. Fang. 1973. Metabolism of monuron in excised leaves of corn and bean plants. Weed Res., 13:59-66. Lee, S.S., D.A. Griffin, and S.C. Fang. 1973. Identification of 3-D-glucosides of ring hydroxylated ureas in monuron- treated bean leaves. Weed Res., 13:234-235. Leesch, J.G., and T.R. Fukuto. 1972. The metabolism of abate in mosquito larvae and houseflies. Pest. Biochem. Physiol., 2(2) :223-235. Lefevre, P. A., and J.W. Daniel. 1973. Some properties of the organomercury-degrading system in mammalian liver. FEBS Lett., 35(1 ) :121-123. Leffingwell, J.T., R.C. Spear, and D. Jenkins. 1975. The persistence of ethion and zolone residues on grape foilage in the central valley of California. Arch. Environ. Contam. Toxicol., 3(l):40-54. 342 Leistra, M., and J.H. Smelt. 1974. Concentration-time relationships for methyl isothiocyanate in soil after injection of metham-sodium. Pestic. Sci . , 5:409-417. Leitis, E., and D.G. Crosby. 1974. Photodecomposition of trifluralin. J. Agric. Food Chem. , 22(5):842-848. Lenz, D.E., L.E. Deguehery, and J.S. Holton. 1973. On the nature of the serum enzyme catalyzing paraoxon hydrolysis. Biochem. Biophys. Acta, 321:189-196. Lewis, D.K. 1969. Residue studies using ^C-benazolin, with special reference to its persistence on foliage under glasshouse conditions. J. Sci. Food Agric, 20:185-190. Lewis, D.L., D.F. Paris, and G.L. Baughman. 1975. Transformation of malathion by a fungus, Aspergillus oryzae, isolated from a freshwater pond. Bull. Environ. Contam. Toxicol., 13(5) :596-601 . Lewis, R.J. 1970. Warfarin metabolism in man: Identification of metabolites in urine. J. Clin. Invest., 49(5) :907-913. Lichtenstein, E.P., T.W. Fuhremann, and K.R. Schulz. 1971. Persistence and vertical distribution of DDT, Lindane, and Aldrin residues, 10 and 15 years after a single soil application. J. Agric. Food Chem., 19(4) -.718-721 . Lichtenstein, E.P., T.W. Fuhremann, and K.R. Schulz. 1974. Translocation and metabolism of [11+C]phorate as affected by percolating water in a model soil -pi ant ecosystem. J. Agric. Food Chem., 22(6) :991-996. Lichtenstein, E.P., A. A. Hochberg, T.W. Fuhremann, R.N. Zahlten, and F.W. Stratman. 1973. Metabolism of [14C] Parathion and [14C] Paraoxon with fractions and subfractions of rat liver cells. J. Agric. Food Chem., 21:416-424. Lin, C, R. Chang, C. Casmer, and S. Symchowicz. 1973. Effects of phenobarbital , 3-methylcholanthrene, and griseofulvin on the 0-demethylation of griseofulvin by liver micromes of rats and mice. Drug Metab. Dispos., 1 (4) : 61 1-618. Lin, T.H., H.H. North, and R.E. Menzer. 1975a. Metabolism of carbaryl (1-Naphthyl N-methyl carbamate) in human embryonic lung cell cultures. J. Agric. Food Chem., 23(2):253-256. Lin, T.H., H.H. North, R.E. Menzer. 1975b. The metabolic fate of chlordimeform [N-(4-chloro-o- tolyl )-N' ,N_' -dimethyl formami dine] in human embryonic lung cell cultures. J. Agric. Food Chem., 23(2) :257-258. Lingens, V.F. 1973. Abbau von Herbiziden und Fungiziden durch Mikroorganismen des Bodens. Chimia, 27:628-635. 343 Locke, R.K., and V.W. Mayer. 1974. Physical evidence for the oxidative demethylation in vitro of 1-naphthyl N-me thy 1 carbamate by the Udenfriend chemical hydroxylation system. Biochem. Pharmacol., 23:1979-1984. Lohs, P., B. Luckas, G. Strege, and H. Wetzel. 1974. Zue Persistenz von Thiuram auf Grunem Salat. Die Nahrung, 18(l):53-57. Lokke, H. 1974. Residues in carrots treated with linuron. Pestic. Sci., 5:749-757. Long, J.W., and M.R. Siegel. 1975. Mechanism of action and fate of the fungicide chloro- thalonil (2,4,5,6-tetrachloroisophthalonitrile) in biological systems. Chem.-Biol. Interact., 10:383-394. Long, J.W., L. Thompson, Jr., and C.E. Rieck. 1974a. Absorption, accumulation, and metabolism of benefin, diphenamid, and pebulate by tobacco seedliags. Weed Sci., 22(1 ) :42-47. Long, J.W., L. Thompson, Jr., and C.E. Rieck. 1974b. Metabolism of 14C-pebulate in seedling tobacco. Weed Sci., 22(l):91-94. Lu, P.-Y., R.L. Metcalf, A.S. Hirwe, and J.W. Williams. 1975. Evaluation of Environmental Distribution and Fate of Hexachlorocyclopentadiene, Chlordene, Heptachlor, and Heptachlor Epoxide in a Laboratory Model Ecosystem. J. Agric. Food Chem., 23(5) :967-973. Machin, A.F. 1973. The isolation and possible significance of some toxic mammalian metabolites of diazinon. Pestic. Sci., 4:425-430. Machin, A.F., M.P. Quick, and N.F. Janes. 1971. 0-2-Acetyl-6-methyl-pyrimidin-4-yl 0,0-diethyl phosphoro- thioate: A new degradation product of diazinon. Chem. Ind. , (42):1198-1199. Maekawa, K., Y. Shuto, E. Taniguchi, and Y. Miyoshi. 1974. Thermal decomposition of Bis-(0,0-diemthyl thionophosphoryl ) disulfide. Botyu-Kagaku, 39:21-27. Maes, R., R.H. Drost, H. Sauer. 1974. GLC determination of ekalux residues in various crops. Bull. Environ. Contam. Toxicol., 1 1(2):121-127. Mahler, J.R., D. Bieniek, and F. Korte. 1973. Beitrage Zur Okologischen Chemie. LIV. Solvolyse von Heptachlor und Dieldrin Unter Hohen Drucken. Chemosphere, 1:31-33. Mahoney, M.D., and D. Penner. 1975. Bentazon translocation and metabolism in soybean and navy bean. Weed Sci. , 23(4) :265-271 . Maki, A.W. 1974. The effects and fate of lampricide (TFM: 3-trifluoromethyl- 4-nitrophenol ) in model stream communities. PhD Diss, submitted to Michigan State Univ., Dept. Fisheries and Wildlife, 162 pages. 344 Mallinckrodt, M.G., and H.P. Schmidt. 1970. Toxicity and metabolism of aminotriazole in man. Arch. Toxikol., 27:13-18. Mansour, M., H. Parlar, and F. Korte. 1975. Beitrage Zur Okologischen Chemie. CI. Reactions- verhalten von 3,4-Dichloranilin und 3,4-dichlorophenol in Losung, als Festkorper und in der Gasphase bei UV-Bestrahlung. Chemosphere, 4(4) :235-240. Marshall, R.S. 1972. Aldrin epoxication by non-enzymatic systems and its inhibition by insecticide synergists. Diss. Abstr., 32(9):5233. Mason, R.W. 1975. Binding of some phenoxyalkanoic acids to bovine serum albumin in vitro. Pharmacol., 13:177-186. Mathur, S.P., and J.G. Saha. 1975. Microbial degradation of lindane-C14 in a flooded sandy loam soil. Soil Sci., 120(4) :301-307. Matsuo, H., and J.E. Casida. 1970. Photodegradation of two dinitrophenolic pesticide chemicals, dinobuton and dinoseb, applied to bean leaves. Bull. Environ. Contam. Toxicol., 5(l):72-78. Matthews, H.B., and M.W. Anderson. 1975a. The distribution and excretion of 2,4,5,2' ,5'-Pentachloro- biphenyl in the rat. Drug Metab. Dispos., 3(3) :211-219. Matthews, H.B., and M.W. Anderson. 1975b. Effect of chlorination on the distribution and excretion of polychlorinated biphenyls. Drug Metab. Dispos., 3(5):371-380. Matthews, H.B., and J.D. McKinney. 1974. Dieldrin metabolism to cis-dihydroaldrindiol by rat liver microsomes. Drug Metab. Dispos., 2(4) :333-340. Maxwell, J., D.S. Kaushik, and C.G. Butler. 1974. Behaviour of an aziridine alkylating agent in acid solution. Biochem. Pharmacol., 23:168-170. McBride, B.C., and R.S. Wolfe. 1969. Biosynthesis of alkylated arsenic from CH3-B12 in cell extracts of methane bacteria. Bacteriol. Proc. (P85). 130. McClure, G.W. 1974. Degradation of anilide herbicides by propham-adapted microorganisms. Weed Sci., 22:323-329. McKinney, J.D., and H.M. Mehendale. 1973. Formation of polar metabolites from aldrin by pea and bean root preparations. J. Agric. Food Chem. , 21(6): 1079-1084. Medley, J.G., C.A. Bond, and D.W. Woodham. 1974. The cumulation and disappearance of mirex residues I. In tissues of roosters fed four concentrations of mirex in their feed. Bull. Environ. Contam. Toxicol., 11:217-223. 345 Mehendale, H.M. 1973. Aldrin epoxidation by plant root extracts. Phytochemistry, 12:1591-1594. Mehendale, H.M., M. Fields, and H.B. Matthews. 1975. Metabolism and effects of hexachlorobenzene on hepatic microsomal enzymes in the rat. J. Agric. Food Chem., 23(2):261-265. Meikle, R.W. 1973. Metabolism of 4-dimethylamino-3,5-xylyl methyl carbamate (Mexacarbate, active ingredient of Zectran insecticide): A unified picture. Bull. Environ. Contam. Toxicol., 10(l):29-36. Meikle, R.W., C.R. Youngson, R.T. Hedlund, C.A.I. Goring, and W.W. Addington. 1974. Decomposition of picloram by soil microorgansims: A proposed reaction sequence. Weed Sci . , 22(3) :263-268. Menashe, J., and R. Goren. 1973. Detoxification of fluometuron by citrus tissues. Weed Res., 13:158-168. Mendoza, C.E., H.A. McLeod, J.B. Shields, and W.E.J. Phillips. 1974. Determination of methomyl in rape seeds, oils and meals. Pestic. Sci., 5:231-237. Metcalf, R.A., and R.L. Metcalf. 1973. Selective toxicity of analogs of methyl parathion. Pest. Biochem. Physiol., 3(2) :149-159. Metcalf, R.L., I. P. Kapoor, and A.S. Hirwe. 1972. Development of biodegradable analogues of DDT. Chem. Technol., 105-109. Metcalf, R.L., P. Lu, and S. Bowlus. 1975a. Degradation and environmental fate of l-(2,6-difluoro- benzoyl)-3-(4-chlorophenyl )urea. J. Agric. Food Chem., 23(3):359-364. Metcalf, R.L., J.R. Sanborn, P.-Y. Lu, and D. Nye. 1975b. Laboratory model ecosystem studies of the degradation and fate of radiolabeled tri-, tetra-, and pentachlorobiphenyl compared with DDE. Arch. Environ. Contam., 3(2) :1 51-1 65. Mick, D.L. 1969. Metabolism of parathion by two species of Rhizobium. Diss. Abstr., 30B(6) :2746-2747. Middaugh, D.P., and C.L. Rose. 1974. Retention of two mercuricals by striped mullet, Mugil cephalus. Water Res., 8:173-177. Mihara, K. , and J. Miyamoto. 1974. Metabolism of sal ithion (2-methoxy-4H-l ,3,2-benzo- dioxaphosphorin-2-sulfide) in rats and plants. Agric. Biol. Chem., 38(10) :1913-1924. Miller, J.H., P.E. Keeley, C.H. Carter, and R.J. Thullen. 1975. Soil persistence of trifluralin, benefin, and nitralin. Weed Sci., 23(3) :211-214. 346 Miller, L.L., G.D. Nordblom, and G.A. Yost. 1974. Photochemistry of N-(a-trichloromethyl -£-methoxybenzyl )-£- methoxyaniline. J. Agric. Food Chem., 22(5) :853-855. Milnes, M.H. 1971. Formation of 2,3,7,8-tetrachlorodibenzodioxin by thermal decomposition of sodium 2,4,5-trichlorophenate. Nature, 232:395-396. Miyamoto, J., and T. Suzuki. 1973. Metabolism of Tetramethrin in Houseflies jn vivo. Pestic. Biochem. Physiol. 3:30-41. Miyamoto, J., and T. Suzuki. 1974. Metabolism of phenothrin or 3-phenoxybenzyl d-trans-chrysan- themumate in mammals. Pest. Biochem. Physiol., 4:438-450. Miyazaki, S., H.C. Sikka, and R.S. Lynch. 1975. Metabolism of dichlobenil by microorganisms in the aquatic environment. J. Agric. Food Chem., 23(3) :365-368. Moilanen, K.W., and D.G. Crosby. 1974. The photodecomposition of bromacil. Arch. Environ. Contam. Toxicol., 2(1): 3-8 . Montgomery, M. , T.C. Yu, and V.H. Freed. 1972. Kinetics of dichlobenil degradation in soil. Weed Res., 12:31-36. Morallo, B.D. 1970. The metabolism of mobam (4-benzy(b)thienyl N-methyl carbamate) in resistant and susceptible houseflies. Diss. Abstr. , 30B(7): 3226-3227. Morikawa, M. , S. Yokoyama, and J. Fukami . 1975. Comparative metabolism of chlordimeform on rat and rice stem borer. Botyu-Kagaku, 40(4) :162-184. Mosier, A.R., and W.D. Guenzi. 1973. Picloram photolytic decomposition. J. Agric. Food Chem., 21(5):835-837. Mosier, A.R., W.D. Guenzi, and L.L. Miller. 1969. Photochemical decomposition of DDT by a free-radical mechanism. Science, 164:1083-1085. Moza, P., I. Weisgerber, W. Klein, and F. Korte 1973. Beitrage Zur Okologischen Chemie. LXIII. Verteilung und Metabolismus von 2,2'-Dichlorobiphenyl-lt+C in der hoheren Sumpfpflanze Veronica beccabunga. Chemosphere, 2:217-222. Moza, P., I. Weisgerber, W. Klein, and F. Korte. 1974. Metabolism of 2,2' -dichlorobi phenyl -lkC in two plant-water- soil systems. Bull. Environ. Contam. Toxicol., 12(5) :541-546. Muller, H., and W. Schuphan. 1975. Zur Anwendung von 2,4-Dichlorphenoxyessigsaure (2,4-D) Bei Tomaten. Qual. Plant., 24(3/4) :405-413. Muller, W.P., and F. Korte. 1975. Contributions to ecological chemistry CI I - Microbial degradation of benzo-[a]-pyrene, monolinuron, and dieldrin in waste composting. Chemosphere, 4(3) : 1 95-1 98 . 347 Muller, W., G. Nohynek, G. Woods, F. Korte, and F. Coulston. 1975a. Comparative metabolism of dieldrin-ll*C in mouse, rat, rabbit, rhesus monkey and chimpanzee. Chemosphere, 4(2):89-92. Muller, W., G. Woods, F. Korte, and F. Coulston. 1975b. Metabolism and organ distribution of dieldrin-^C in rhesus monkeys after single oral and intravenous administration. Chemosphere, 4(2):93-98. Munakata, K., and M. Kuwahara. 1967. Photoche ical degr dation products of pentachlorophenol . Residue Rev., 25:13-23. Mundy, B.P., F.H.S. Liu, and G.A. Strobel. 1973. a-Aminobutyronitrile as an intermediate in cyanide fixation by Rhizoctonia solani. Can. J. Biochem., 51:1440-1442. Munster, J., R.S. Hermann, W. Koranski, and G.-A. Hoyer. 1975. Uber die Rolle von Pentachlorcyclohexen bie Stoffwechsel und Wirkung von Hexachlorcyclohexan. I. Synthese von 3-Pentachlor- cyclohexen und seine Identifizierung als Monodehydrochlorierungs- produkt von a-Hexachlorcyclohexan. Hoppe-Seyler's Z. Physiol. Chem. , 356:437-447. Murphy, J. J., J. Didriksen, and R.A. Gray. 1973. Metabolism of 2-(a-naphthoxy)-N,N-diethyl propionamide in tomato. Weed Sci. , 21 (1 ) :1 1 -1 5. Murray, D.S., P.W. Santelmann, and J.M. Davidson. 1975. Comparative adsorption, desorption, and mobility of dipropetryn and prometryn in soil. J. Agric. Food Chem., 23(3): 578-582. " Nachtomi, E. 1970. The metabolism of ethylene dibromide in the rat. Biochem. Pharmacol., 19:2853-2860. Naito, N. 1958. Production of fungi toxic substance by fungi grown on media containing either 2,4-D or related phenoxy compounds. Jap. J. Bot., 16(2):153-162. Naito, N., and Y. Kojima. 1957. Fungi toxic Substance Production by Gloeosporium ol i varum which was grown on media containing 2-chlorophenoxyacetic acid or 2-methylphenoxyacetic acid. Tech. Bull. Fac. Agr. Kagawa Univ., 9:18-25. Naito, N. , and T. Tani. 1955. On a fungi tstatic substance produced in culture filtrates of Gloeosporium ol i varum on media containing 2,4-D. Ann. Phytopath. Soc. Jap. 19:129-132. Naito, N., and T. Tani. 1956a. An antibiotic isolated from culture filtrates of Gloeo- sporium oli varum grown on media containing 2,4-D. Jap. J. Bot., 1 5(2) :1 52-163. " 348 Naito, N. , and T. Tarn". 1956b. A fungi toxic substance produced in cultures of Gloeo- sporium olivarum on media containing 2,4-D. Ann. Phytopath. Soc. Japan 21774 Nakagawa, M. , M. Ando, and Y. Obata 1975. Fate of isoxathion [0,0-diethyl 0-(5-phenyl -3-isoxazolyl )- phosphorothioate] in soils. Agric. BioT. Chem. , 39( 9) : 1 763-1 773 . Nakagawa, M. , and D.G. Crosby. 1974a. Photodecomposition of nitrofen. J. Agric. Food Chem., 22(5):849-853. Nakagawa, M. , and D.G. Crosby. 1974b. Photonucleophilic reactions of nitrofen. J. Agric. Food Chem., 22(6):930-933. Nakagawa, M. , T. Nakamura, and K. Tomita. 1974. Photolysis of 3-hydroxyisoxazoles. Agric. Biol. Chem., 38(11 ):2205-2208. Nakagawa, M., and H. Tamari. 1974. Photodecomposition of credazine, 3-(2-methylphenoxy ) pyridazine. J. Agric. Chem. Soc. Jap., 48(12) :651 -655. Nakajima, S., N. Naito, and T. Tani. 1973. Microbial transformation of 2,4-D and its analogues. Chem. Pharm. Bull., 21 (3) :671 -673. Nakamura, K., J. Ito, and M. Dazai. 1974a. Mechanism of elimination of mercurials in waste water by activated sludge. J. Ferment. Technol . , 52(11 ) :837-842. Nakamura, K., J. Ito, and M. Dazai. 1974b. Mercury volatilization and the capacity of activated sludge for waste water containing mercurials. J. Ferment. Technol., 52(1 1 ) :843-847. Neathery, M.W., W.J. Miller, R.P. Gentry, P.E. Stake, and D.M. Blackmon. 1974. Cadmium-109 and methyl mercury-203 metabolism, tissue distribution, and secretion into milk of cows. J. Dairy Sci., 57:1177-1183. Nelson, J.D., W. Blair, F.E. Brinckman, R.R. Colwell, and W.P. Iverson. 1973. Biodegradation of phenylmercuric acetate by mercury-resistant bacteria. Appl . Microbiol., 26(3) :321 -326. Nelson, J.O., and F. Matsumura. 1973. Dieldrin (HEOD) metabolism in cockroaches and houseflies. Arch. Environ. Contam. Toxicol., 1 (3) :224-244. Neptune, M.D. 1970. Absorption, translocation, and metabolism of fluometuron in corn and wheat. Diss. Abstr. , 31B(3):1110. Neudorf, S., and M.A.Q. Khan. 1975. Pick-up and metabolism of DDT, dieldrin and photodieldrin by a fresh water alga (Anki strode smus amalloides) and a micro- crustacean (Daphnia pulex). Bull. Environ. Contam. Toxicol., 13(4):443-449. 349 Neville, G.A., and T. Drakenberg. 1974. Mercuric mercury and methyl mercury complexes of glutathione. Acta Chem. Scand., B28(4) :473-477. Newby, L., and B.G., Tweedy. 1970. Comparison of amino acid exudates from leaves of two bean varieties. Photopathology, 60:6. Newland, L.W. 1969. The adsorption and degradation of insecticides by lake sediments. Diss. Abstr. , 30B(3):938. Newland, L.W., G. Chesters, and G.B. Lee. 1969. Degradation of y-BHC in simulated lake impoundments as affected by aeration. J. Water Pollut. Control Fed., 41(5): (part 2):R174-188. Newsom, H.C., and W.G. Woods. 1973. Photolysis of the herbicide dinitramine (N3,N3-diethyl-2, 4-dinitro-6-trifluoromethyl-m-phenylenediamine). J. Agric. Food Chem., 21:598-601. Newsome, W.H. 1974a. A method for determining ethyl enebis (dithiocarbamate) residues on food crops as bis(trifluoroacetamido)ethane. J. Agric. Food Chem., 22(5) :886-889. Newsome, W.H. 1974b. The excretion of ethylenethiourea by rat and guinea pig. Bull. Environ. Contam. Toxicol., 1 1(2): 174-176. Newsome, W.H., and G.W. Laver. 1973. Effect of boiling on the formation of ethylenethiourea in zi neb-treated foods. Bull. Environ. Contam. Toxicol., 10(3): 151-154. Newsome, W.H., J.B. Shields, and D.C. Villeneuve. 1975. Residues of maneb, ethylenethiuram monosulfide, ethylene- thiourea, and ethyl enediamine on beans and tomatoes field treated with maneb. J. Agric. Food Chem., 23(4) :756-757. Nilles, G.P., and M.J. Zabik. 1974. Photochemistry of bioactive compounds. Multiphase photo- degradation of basalin. J. Agric. Food Chem., 22(4) :684-688. Nilles, G.P., and M.J. Zabik. 1975. Photochemistry of bioactive compounds. Multiphase photo- degradation and mass spectral analysis of basagran. J. Agric. Food Chem., 23(3) :410-415. Nilsson, C.-A., K. Anderson, C. Rappe, and S.-0. Westermark. 1974. Chromatographic evidence for the formation of chlorodioxins from chloro-2-phenoxyphenol s. J. Chromatogr. , 96:137-147. Nimmo, D.R., J. Forester, P.T. Heitmuller, and G.H. Cook. 1974. Accumulation of Aroclor 1254 in grass shrimp (Palaemonetes pugio) in laboratory and field exposures. Bull. Environ. Contam. ToxTcol., ll(4):303-308. 350 Nishimura, M. , and N. Urakawa. 1972. A transport mechanism of mercury into ovarian follicles in laying quail. Jap. J. Pharmacol., 22:605-616. Nishiwaki, T., A. Ninomiya, S. Yamanaka, and K. Anda. 1972. Dechlorination of polychlorinated biphenyl by the UV- irradiation. Nippon Kagaku Kaishi, 11:2225-2226. Noack, G., and J. Protig. 1973. Biodegradation of alpha-hexachlorocyclohexane. III. Decrease in liver non-protein thiol after intragastric application of the drug. Naunyn-Schmiedeberg's Arch. Pharmacol., 280:183-189. Noack, G., J. Portig, and M. Wirsching. 1975. Biodegradation of a-hexachlorocyclohexane. IV. The extent of degradation of single doses in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol., 288:57-64. Nolan, J., and H.J. Schnitzerling. 1975. Characterization of acetylcholinesterases of acaricide- resistant and susceptible strains of the cattle tick Boophilus microplus (Can). Pest. Biochem. Physiol., 5:178-188. Norback, D.H. , J.F. Engblom, and J.R. Allen. 1975. Tissue distribution and excretion of octachlorodibenzo-p_- dioxin in the rat. Toxicol. Appl . Pharmacol., 32:330-338. Nordblom, G.D., and L.L. Miller. 1974. Photoreduction of 4,4'-dichlorobiphenyl . J. Agric. Food Chem., 22(1 ):57-58. Norseth, T. 1972. Biotransformation of methyl mercuric salts in the rat with chronic administration of methyl mercuric cysteine. Acta Pharmacol. Toxicol., 31:138-148. North, H.H. 1972. Pesticide metabolism in mammalian cell cultures. Diss. Abstr., 33B(5):2135. North, H.H., and R.E. Menzer. 1973. Metabolism of DDT in human embryonic lung cell cultures. J. Agric. Food Chem., 21 (3) :509-510. Nose, K. 1972. Decachlorination of polychlorinated biphenyl and its application to soil and rice analysis. ■ J. Agric. Chem. Soc. Jap., 46(12) :679-681. Oda, J., and W. Muller. 1972. Identification of a mammalian break-down product of dieldrin. Symp. Chemistry of Pesticides under Metabolic and Environ. Cond., Bonn, Sept. 1970, in Environ. Qual. Safety, 1:248. Ohkawa, H., and J.E. Casida. 1971. Glutathione S-transferases liberate hydrogen cyanide from organic thiocyanates. Biochem. Pharmacol., 20:1708-1711. 351 Ohkawa, H., M. Eto, and Y. Oshima. 1970. Metabolism and toxicity of salithion, 2-methoxy-4H-l,3,2- benzodioxaphosphorin-2-sulfide. Jap. J. Appl. Entomol. Zool., 14(4):191-194. Ohkawa, H., Y. Hisada, N. Fujiwara, and J. Miyamoto. 1974a. Metabolism of N-(3' ,5'-dichlorophenyl )succinimide in rats and dogs. Agric. Biol. Chem., 38(7) : 1359-1 369. Ohkawa, H., N. Mi k ami, and J. Miyamoto. 1974b. Photodecomposition of Sumithion [0,0-dimethyl-0-(3-methyl- 4-nitrophenyl )phosphorothioate]. Agric. Biol. Chem., 38(11): 2247-2255. Ohkawa, H., R. Shibaike, T. Hatanaka, and J. Miyamoto. 1975. Metabolism of the fungicide S-n-butyl S'-p_'-tert- butyl benzyl N-3-pyridyldithiocarbonimidate (S-1358) in rats. Agric. Biol. Chem., 39(8):1605-1615. Ohkawa, H., R. Yoshihara, T. Hohara, and J. Miyamoto. 1974c. Metabolism of m-tolyl N-methyl carbamate (Tsumacide) in rats, houseflies and bean plants. Agric. Biol. Chem., 38(5): 1035-1044. Ohsawa, M. , and L. Magos. 1974. The chemical form of the methylmercury complex in the bile of the rat. Biochem. Pharmacol., 23:1903-1905. Ohsawa, T. , J.R. Knox, S. Khalifa, and J.E. Casida. 1975. Metabolic dechlorination of toxaphene in rats. J. Agric. Food Chem., 23(1 ) :98-106. Oloffs, P.C. 1970. Epoxidation of aldrin by cell-free pea root preparations. Pestic. Sci., 1:228-232. Olson, W.P. 1973. Dieldrin transport in the insect: An examination of Gerolt's hypothesis. Pest. Biochem. Physiol., 3(4) :384-392. Onsuka, F.I., and M.E. Comba. 1975. Isolation and characterization of the photoalteration products of cis- and trans-chlordane. J. Assoc. Off. Anal. Chem., 58(l):6-9. Oppenoorth, S.V., W. Welling, N.W.H. Houx, and J.W. van den Oudenweyer. 1971. Synergism of insecticidal action in inhibition of microsomal oxidation with phosphorothionates. Nat. New Biol., 223:187-188. Otake, N., S. Takeuchi, T. Endo, and H. Yonehara. 1966a. Chemical studies on blasticidin S part II. The structure of cytosinine and uracinine. Agric. Biol. Chem., 30(2) : 1 26-1 31 . Otake, N., S. Takeuchi, T. Endo, and H. Yonehara. 1966b. Chemical studies on blasticidin S part III. The structure of blasticidin S. Agric. Biol. Chem., 30(2) : 132-141 . Ottoboni, A., and J.I. Ferguson. 1969. Excretion of DDT compounds in rat milk. Toxicol. Appl. Pharmacol., 15:56-61. 352 Page, A.C., J.E. Loeffler, H.R. Hendrickson, C.K. Huston, and D.M. DeVries. 1972. Metabolic fate of dichlorvos in swine. Arch. Toxikol., 30:19-27. Palm, H.L. 1971. Effects and fate of linuron and chlorbromuron in plants. Diss. Abstr., 32B(6) :3113-3114. Palut, D. 1970. Investigation of the metabolism of carbaryl- C on animal model system. Rocz. Panstw. Zakl. Hig., 21(4) :41 7-426. Pan, S.-K., N. Imura, and T. Ukita. 1973. Fractionation and characterization of mercury -methyl ati on factor in tuna liver. Chemosphere, 6:247-252. Pape, B.E., and M.J. Zabik. 1972. Photochemistry of bioactive compounds. Solution-phase photochemistry of asymmetric triazin-5(4H)-ones. J. Agric. Food Chem., 20(l):72-75. Paris, D.F., D.L. Lewis, and N.L. Wolfe. 1975. Rates of degradation of ma lathi on by bacteria isolated from aquatic system. Environ. Sci. Technol., 9(2):135-138. Parke, D.V., and R.T. Williams. 1960. The metabolism of halogenobenzenes: (a) Penta- and hexa- chlorobenzenes. (b) Further observations on 1 ,3,5-trichlorobenzene. Biochem. J., 74:5-9. Parker, C, and G.L. Hodgson. 1966. Some studies on the fate of picloram and dicamba in soils underlying bracken. Proc. Eighth Br. Weed Con. Conf . , 2:614-615. Parlar, H., and F. Korte. 1973. Beitrage Zur Okologischen Chemie. LX. Zur Photochemie der Chlordanderivate. Chemosphere, 4:169-172. Parr, J.F., and S. Smith. 1974. Degradation of DDT in an Everglades muck as affected by lime, ferrous iron, and anaerobiosis. Soil Sci., 118(1 ) :45-52. Parr, J.F., G.H. Willis, and S. Smith. 1970. Soil anaerobiosis: II. Effect of selected environments and energy sources on the degradation of DDT. Soil Sci., 110(5): 306-312. Paschal, E.H., C.C. Roan, and D.P. Morgan. 1974. Evidence of excretion of chlorinated hydrocarbon pesticides by the human liver. Bull. Environ. Contam. Toxicol., 12(5) :547-554. Paulson, G.D., and A.M. Jacobsen. 1974. Isolation and identification of Propham (isopropyl carbanilate) metabolites from animal tissues and milk. J. Agric. Food Chem., 22(4):629-631. Paulson, G.D., A.M. Jacobsen, and G.G. Still. 1974. Alfalfa metabolites of isopropyl carbanilate (Propham): Their fate when fed to sheep and rats. Abstracts, 168th ACS Meeting, PEST 3. 353 Paulson, G.D., A.M. Jacobsen, R.G. Zaylskie, and V.J. Feil. 1973. Isolation and identification of Propham (isopropyl carbanilate) metabolites from the rat and the goat. J. Agric. Food Chem. , 21(5):804-811. Pekas, J.C. 1974. Absorption of pesticidal carbamates from perfused intestinal loops in conscious swine. Food Cosmet. Toxicol., 12:377-379. Pekas, J.C, and J.L. Giles. 1974. Effect of dosing technique on absorption of carbaryl. Food Cosmet. Toxicol., 12(1 ): 1 69. Peoples, S.A., and J.U. Lakso. 1973. The methylation of inorganic arsenic in the ruminant and carnivore. Proc. West. Pharmacol. Soc, 16:244. Perscheid, M., H. Schluter, and K. Ballschmi ter. 1973. Aerober Abbau von Endosulfan durch Bodenmikroorganismen. Aerobic degradation of endosulfan by mircoorganisms. Z. Naturforch., 28(11/12) :761-763. Pfaender, F.K. 1972. Metabolism of DDT by axenic cultures and natural microbial communities. Diss. Abstr., 12B(part ) : 71 95 . Pfaender, F.K., and M. Alexander. 1973. Effect of nutrient additions on the apparent cometabolism of DDT. J. Agric. Food Chem., 21(3) :397-399. Pfeilsticker, K., and H. Rasmussen. 1974. Umsetzungen von radioaktiv markiertem Athylenoxyd-l,2-14C mit Weizeninhaltsstoffen. Z. Lebensm. Unters.-Forsch., 156:158-162. Phillips, J., M. Wells, and C. Chandler. 1974. Metabolism of DDT by the freshwater planarian, Phagocata yelata. Bull. Environ. Contam. Toxicol., 12(3) :355-358. Phillips, R.A. 1972. The kinetics of metabolism of mercuric chloride in the rat. Diss. Abstr., 33B(6):2679. Ping, C.L., H.H. Cheng, and B.L. McNeal. 1975. Variations in picloram leaching patterns for several soils. Soil Sci. Soc. Am. Proc, 39(3) :470-473. Piper, W.N., J.Q. Rose, M.L. Leng, and P.J. Gehring. 1973. The fate of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) following oral administration to rats and dogs. Toxicol. Appl. Pharmacol., 26:339-351. Plapp, F.W. , Jr. 1973. Comparison of insecticide absorption and detoxification in larvae of the bollworm, Heliothis zea, and the tobacco budworm. Pest. Biochem. Physiol., 2(4) :447-455. Plimmer, J.R., and U.I. Klingebiel. 1971. Riboflavin photosensitized oxidation of 2,4-dichlorophenol : Assessment of possible chlorinated dioxin formation. Science, 174:407-408. 354 Plimmer, J.R., and U.I. Klingebiel. 1974. Photochemistry of N-sec-butyl-4-tert-butyl-2,6-dinitroani line. J. Agric. Food Chem. , 22(4) :689-693. Plimmer, J.R., and U.I. Klingebiel, D.G. Crosby, and A.S. Wong. 1973. Photochemistry of dibenzo-p-dioxins. Adv. Chem. Ser., 120:44-55. Polles, S.G. 1971. The fate of C11+-labeled endrin in tobacco budworm (Heliothis virescens (Fabricius) larvae. Diss. Abstr. , 31B(7):4115. Pont, V., H.J. Jarczyk, G.F. Collet, and R. Thomas. 1974. Identification de Metabolites du Dimethyl-1 ,3(benzothiazolyl- 2)-3-uree et Etude de sa Stabilite In Vitro. Phytochemistry, 13:785-792. Poore, R.E., andR.A. Neal. 1972. Evidence for extrahepatic metabolism of parathion. Toxicol. Appl. Pharmacol., 23:759-768. Portig, J., P. Kraus, S. Sodomann, and G. Noack. 1973. Biodegradation of alpha-hexachlorocyclohexane. I. Gluta- thi one-dependent conversion to a hydrophilic metabolite by a rat liver cytosol. Naunyn-Schmiedeberg's Arch. Pharmacol., 279:185-198. Potter, J.C., A.C. Boyer, R.L. Marxmiller, R. Young, and J.E. Loeffler. 1973a. Radioisotope residues and residues of dichlorvos and its metabolites in pregnant sows and their progeny dosed with dichlorvos- 14C or dichlorvos-36Cl formulated as PVC pellets. J. Agric. Food Chem., 21(2):734-738. Potter, J.C., J.E. Loeffler, R.D. Collins, R. Young, and A.C. Page. 1973b. Carbon-14 balance and residues of dichlorvos and its metabolites in pigs dosed with dichlorvos-14C. J. Agric. Food Chem., 21(2): 163-166. Pree, D.J., and J.L. Saunders. 1974. Metabolism of carbofuran in mugho pine. J. Agric. Food Chem., 22(4):620-625. Preuss, P.W., A.G. Lemmens, and L.H. Weinstein. 1968. Studies on f luoro-organic compounds in plants. I. Metabolism of 2-14C-f luoroacetate. Contrib. Boyce Thompson Inst., 24:25-31. Prince, R.H., G.M. Sheldrick, D.A. Stotter, and R. Taylor. 1975. Cobaloxime and DDT. X-ray crystal structure of an unexpected vinyl-cobalt (III) complex. J. Chem. Soc. Chem. Commun., 854-855. Prince, R.H., and D.A. Stotter. 1974. Alkyl-cobalt mediation of DDT hydrolysis. Nature, 249:286-287. Prouty, R.M., J.E. Peterson, L.N. Locke, and B.M. Mulhern. 1975. DDD poisoning in a loon and the identification of the hydroxy- lated form of DDD. Bull. Environ. Contam. Toxicol., 14(4) :385-388. Puech, A. A., and J.C. Crane. 1975. Translocation of ethephon in fig (Ficus carica L.) shoots. J. Amer. Soc. Hort. Sci., 100(4) :443-446. 355 Rabenstein, D.L., C.A. Evans, M.C. Tourangeau, and M.T. Fairhurst. 1975. Methylmercury species of equilibria in aqueous solution. Anal. Chem., 47(2) :338-341 . Radwan, M.A., and W.E. Dodge. 1970. Fate of radioactive tetramine in small mammals and its possible use as a seedling protectant. Northwest Sci., 44(1): 25-30. Ragab, M.T.H. 1974. Simazine persistence in soil and effects of its residue on crops. Can. J. Plant Sci., 54:713-716. Raig, P. , and R. Ammon. 1972. Nachweis einiger neuer phenol ischer Stoffwechselprodukte des Biphenyls. Arzneim-Forsch. , 22(8): 1399-1403. Ramsey, J.C., J.Q. Rose, W.H. Braun, and P.J. Gehring. 1974. Fate of 6-chloropicolinic acid following oral administration in rats. J. Agric. Food Chem., 22(5) :870-873. Ray, T.B., and C.C. Still. 1975. Propanil metabolism in rice: A comparison of propanil amidase activities in rice plants and callus cultures. Pest. Biochem. Physiol., 5:171-177. Reddy, G., and M.A.Q. Khan. 1974. In vitro metabolism of [14C]photodieldrin by microsomal mixed-function oxidase of mouse, rat, and houseflies. J. Agric. Food Chem., 22(5) :910-912. Reddy, G., and M.A.Q. Khan. 1975a. Metabolism of photodieldrin in rabbits. Abstracts 170th ACS Meeting, PEST 7, Aug. 25-29. Reddy, G., and M.A.Q. Khan. 1975b. Fate of photodieldrin under various environmental conditions. Bull. Environ. Contam. Toxicol., 13(l):64-72. Reddy, G., and M.A.Q. Khan. 1975c. Metabolism, excretion, and tissue distribution of [ C] photodieldrin in male rabbits, following single oral and intraperitoneal administration. J. Agric. Food Chem., 23(5):861-866. Refsvik, T., and T. Norseth. 1975. Methyl mercuric compounds in rat bile. Acta Pharmacol. Toxicol . , 36:67-78. Reif, V.D., B.C. Littleton, and J.E. Sinsheimer. 1975. In vitro biotransformations of 1 -(o-chlorophenyl )- l-(p-chTorophenyl-2,2-dichloroehtane (o^jT-DDD) and 1,1- bis?£-chlorophenyl )-2,2-dichloroehtane (£,£>' -DDD) by bovine adrenal. J. Agric. Food Chem., 23(5) :996-999. Reif, V.D., and J.E. Sinsheimer. 1975. Metabolism of l-(o-chlorophenyl )-l-(p-chlorophenyl )- 2,2-dichloroethane (o,£'-DDD) in rats. Drug Metab. Dispos., 3(l):15-25. 356 Rhodes, R.C., and J.D. Long. 1974. Run-off and mobility studies on benomyl in soils and turf. Bull. Environ. Contam. Toxicol., 12(4) :385- 393. Rice, C.P. 1972. Degradation of DDT by selected fresh water algae. Diss. Abstr., 33B(4):1427. Rice, C.P., and H.C. Sikka. 1973a. Fate of dieldrin in selected species of marine algae. Bull. Environ. Contam. Toxicol., 9(2) : 11 6-123. Rice, C.P., and H.C. Sikka. 1973b. Uptake and metabolism of DDT by six species of marine algae. J. Agric. Food Chem., 21(2): 148-152. Rice, C.P., H.C. Sikka, and R.S. Lynch. 1974. Persistence of dichlobenil in a farm pond. J. Agric. Food Chem., 22(3) :533-534. Rieck, C.E. 1970. Microbial degradation of 4-amino-3,5,6-trichloropicolinic acid in soild and in pure cultures of soil isolates. Diss. Abstr., 30B(9):3945. Ross, J. A., and B.G. Tweedy. 1973. Malonic acid conjugation by soil microorganisms of a pesti- cide-derived aniline moiety. Bull. Environ. Contam. Toxicol., 10(4):234-236. Ross, R.D., and D.G. Crosby. 1973. Photolysis of ethylenethiourea. J. Agric. Food Chem., 21(3):335-337. Ross, R.D., and D.G. Crosby. 1975. The photooxidation of aldrin in water. Chemosphere, 4(5): 277-282. Ross, R.T., and F.J. Biros. 1975. A study of intermolecular complexes of bis(p-chlorophenyl ) acetic acid and some biologically significant compounds. Mass Spectrometry and NMR Spectroscopy in Pesticide Chemistry. R. Haque and F.J. Biros, eds., pp. 263-272. Rouchaud, J. P., J.R. Decallonne, and J. A. Meyer. 1974. Metabolic fate of methyl-2-benzimidazole carbamate in melon plants. Phytopathology, 64(12) : 1513-1517. Rowland, I.R., M.J. Davies, and P. Grasso. 1975. The methyl ati on of mercury by the gastro-intestinal contents of the rat. Biochem. Soc. Trans., 3:502-504. Rowlands, D.G. 1971. The metabolism of contact insecticides in stored grains. II. 1966-1969. Residue Rev., 34:91-161. Rozman, K., W. Mueller, M. Iatropoulos, F. Coulston, and F. Korte. 1975. Ausscheidung, Koerpervertei lung und Metabol isierung von Hexachlorbenzol nach Oraler Einzeldosis in Ratten und Rhesusaffen. Chemosphere, 4(5) :289-298. 357 Rummens, F.H.A. 1975. Separation and structural assignment of the cj[s and trans isomers of S-(2,3-dichloroal lyl )diisopropylthiocarbamate. Weed Sci., 23(1 ):7-10. Rusiecki, W., and A. Osicka. 1972. Distribution and excretion of mercury in rats intoxicated with methylmercury dicyandiamide. Acta Pol. Pharm. , 29(6) :623-628. Rusness, D.G., and G.G. Still. 1975. S-Cysteinyl-hydroxychlorpropham formation in oat. Abstracts, 170th ACS Meeting, PEST 21. Ruzo, L.O., S. Safe, and M.J. Zabik. 1975. Photodecomposition of unsymmetrical polychl orobi phenyl s. J. Agric. Food Chem., 23(3) :594-595. Ruzo, L.O., and M.J. Zabik. 1975. Polyhalogenated biphenyls: Photolysis of hexabromo and hexachlorobiphenyls in methanol solution. Bull. Environ. Contam. Toxicol., 13(2):181-182. Ruzo, L.O., M.J. Zabik, and R.D. Schuetz. 1972. Polychlorinated biphenyls: Photolysis of 3,4,3' ,4' -tetra- chl orobi phenyl and 4,4'-dichlorobiphenyl in solution. Bull. Environ. Contam. Toxicol., 8(4) : 21 7-21 8. Ruzo, L.O., M.J. Zabik, and R.D. Schuetz. 1973. Photochemistry of bioactive compounds, kinetics of selected s-triazines in solutions. J. Agric. Food Chem. , 21 (6) : 1 047-1 049- Ruzo, L.O., M.J. Zabik, and R.D. Schuetz. 1974a. Photochemistry of bioactive compounds: Photoproducts and kinetics of polychlorinated biphenyls. J. Agric. Food Chem., 22(2) :199-202. " Ruzo, L.O., M.J. Zabik, and R.D. Schuetz. 1974b. Photochemistry of bioactive compounds. Photochemical process of polychlorinated biphenyls. J. Am. Chem. Soc, 96:3809-3813. Ruzo, L.O., M.J. Zabik, and R.D. Schuetz. 1974c. Photochemistry of bioactive compounds. l-(4-Chlorophenyl )- 3-(2,6-dihalobenzoyl)ureas. J. Agric. rood Chem. , 22(6) : 1 106-1 1 08. Saeki, S., A. Tsutsui, I. Oguri, H. Yoshimura, and M. Hamana. 1971. The isolation and structure elucidation of the main com- ponents of kanechlor-400 (chlorobiphenyls). Fukuoka Acta Medica, 62(1 ):20-24. Safe, S., and 0. Hutzinger. 1971. Polychlorinated Biphenyls: Photolysis of 2,4,6,2' ,4' ,6' - Hexachlorobiphenyl. Nature, 232:1541-642. Safe, S., 0. Hutzinger, and D. Ecobichon. 1974. Identification of 4-chloro-4'-hydroxybiphenyl and 4,4'- dichloro-3-hydroxybiphenyl as metabolites of 4-chloro- and 4,4'- dichl orobi phenyl fed to rats. Experientia, 30(7) : 720-721 . Safe, S., 0. Hutzinger, D.J. Ecobichon, and A. A. Grey. 1975a. The metabolism of 4'-chloro-4-biphenylol in the rat. Can. J. Biochem., 53(4) :41 5-420 358 Safe, S., 0. Hutzinger, and D. Jones. 1975c. The mechanism of chlorobiphenyl metabolism. J. Agric. Food Chem., 23(5) :851 -853. Safe, S., N. Platonow, and 0. Hutzinger. 1975b. Metabolism of chlorobiphenyls in the goat and cow. J. Agric. Food Chem., 23(2) :259-261 . Saha, J.G. 1974. The fate of lindane-11+C in wheat flour under normal con- ditions in bread making. J. Inst. Can. Sci. Technol. Aliment., 7(2):101-104. Saha, J.G., R.H. Burrage, Y.W. Lee, M. Saha, and A.K. Sumner. 1974. Insecticide residue in soil, potatoes, carrots, beets, rutabagas, wheat plants and grain following treatment of the soil with dyfonate. Can. J. Plant Sci., 54:717-723. Saha, J.G. , and Y.W. Lee. 1974. Degradation of lindane-11+C by wheat grain. Environ. Lett., 7(4):359-366. Saltzman, S., B. Yaron, and U. Mingelgrin. 1974. The surface catalyzed hydrolysis of parathion on kaolinite. Soil Sci. Soc. Am. Proc, 38(2) : 231 -234. Sanborn, J.R., and C.-C. Yu. 1973. The fate of dieldrin in a model ecosystem. Bull. Environ. Contam. Toxicol., 10(6) :340-346. Sanders, H.O., and D.F. Walsh. 1975. Toxicity and residue dynamics of the lampricide 3-trifluoro- methyl-4-nitrophenol (TFM) in aquatic invertebrates. Investigations in Fish Control. No. 59. U. S.D.I. Fish and Wildlife Service. Washington, D.C. 9 pages. Sandrock, K., D. Bienieck, W. Klein, and F. Korte. 1974. Beitrage zue Okologischen Chemie. LXXXVI. Isolierung und Strukturaufklarung von Kelevan-11+C-metabol iten und Bilanz in Kartoffeln und Boden. Chemosphere, 3(5):199-204. Satch, T. 1973. A liver arylamidase extremely sensitive to organophosphorus compounds. Life Sci., 13:1181-1188. Schafer, D.E., and E.H. Stobbe. 1973. Translocation and metabolism of benazolin in wild mustard and rape species. Weed Sci., 21(1):48-51. Schlagbauer, B.G.L., and A.W.J. Schlagbauer. 1972. Part I. The metabolism of carbamate pesticides--A liter- ature analysis. Residue Rev., 42:1-90. Schoor, W.P. 1973. In vivo binding of p,p'-DDE to human serum proteins. Bull. Environ. Contam. Toxicol., 9(2):70-74. Schottel , J., A. Mandal , Schottel, J., A. Mandal, D. Clark, and S. Silver. 1974. Volatilisation of mercury and organomercurials determined by inducible R-factor systems in enteric bacteria. Nature, 251: 335-337. 359 Schrauzer, G.N., J.H. Weber, T.M. Beckham, and R.K.Y. Ho. 1971. Alkyl group transfer from cobalt to mercury: The reaction of alkylcobalamins, alkylcobaloximes and of related compounds with mercuric acetate. Tetrahedron Lett., 3:275-277. Schulte, E., and L. Acker. 1974. Identifizierung und Metabol isierbarieit von polychlorierten Biphenylen. Naturwissenschaften, 61(2):79-80. Schumacher, H.G., H. Parlar, W. Klein, and F. Korte. 1973. Photochemische Reaktionen von Endosulfan. Chemosphere, 2:65-68. Schuphan, I., and K. Ballschmiter. 1972. Metabolism of polychlorinated norbornenes by Clostridium butyricum. Nature, 237:100-101. Schutte, H.R., and U. Stephan. 1969. Abbau des Herbizids Chloralhydrat im Boden. Z. Pflanzenernahr., Dung., Bodenkd. , 123(3) :212-219. Segall, H.J., and J.M. Wood. 1974. Reaction of methyl mercury with plasmalogens suggests a mechanism for neurotoxicity of metal -alkyl s. Nature, 248:456-458. Seidler, H., R.M. Macholz, M. Hartig, M. Kujawa, and R. Engst. 1975. Untersuchungen uber den Metabolismus einiger Insektizide und Fungizide in der Ratte. 4. Mitt. Verteilung, Abbau und Ausscheidung von 14-C-markiertem Lindan. Die Nahrung, 19(5/6): 473-482. Sell, J.L., and K.L. Davison. 1975. Metabolism of mercury, administered as methyl merucric chloride or merucric chloride, by lactating ruminants. J. Agric. Food Chem., 23(4) :803-808. Sellers, L.G. 1971. Distribution, metabolism and localization of dieldrin in the adult house fly, Musca domesti ca (L.). Diss. Abstr. , 32B(2):999. Sethunathan, N. 1972. Diazinon degradation in submerged soil and rice-paddy water. Adv. Chem. Ser., 111:244-255. Sethunathan, N. 1973. Degradation of parathion in flooded acid soils. J. Agric. Food Chem"., 21 (4) :602-604. Sethunathan, N., and T. Yoshida. 1973. Parathion degradation in submerged rice soils in the Philippines. J. Agric. Food Chem., 21 (3) :504-506. Seto, H., N. Otake, and H. Yonehara. 1966. Biological transformation of blasticidin S by Aspergillus fumigalus sp. Agric. Biol. Chem., 30(9) :877-886. Sharpee, K.W., J.M. Duxbury, and M. Alexander. 1973. 2,4-Dichlorophenoxyacetate metabolism by Arthrobacter sp.: Accumulation of chlorobutenolide. Appl . Microbiol., 26(3) :445-447. 360 Shatoury, H.H. 1972. Fate of internal doses of DDT. Experientia, 28(9) :1062-1063. Shcherbakov, Y.A., and I.V. Pol uboyari nova. 1970. Stability of the butyl ester of 2,4-D. Edsp. Vod. Toksikol. Mater. Vses. Simp., 1:32-35. Sherman, J.C., T.A. Nevin, and J. A. Lasater. 1974. Hydrogen sulfide production from ethion by bacteria in lagoonal sediments. Bull. Environ. Contam. Toxicol., 12(3): 359-365. Shida, T. , Y. Homma, and T. Misato. 1973. Bacterial degradation of N-lauroyl-L-valine. Agric. Biol. Chem., 37(5):1027-1033. Shimabukuro, R.H., G.L. Lamoureux, H.R. Swanson, W.C. Walsh, L.E. Stafford, and D.S. Frear. 1973a. Metabolism of substituted di phenyl ether herbicides in plants. II. Identification of a new fluorodifen metabolite, S-(2-nitro-4-trifluoromethylphenyl glutathione in peanut. Pest. Biochem. Physiol., 3(4) :483-494. Shimabukuro, R.H., W.C. Walsh, G.L. Lamoureux, and L.E. Stafford. 1973b. Atrazine metabolism in sorghum: Chloroform-soluble intermediates in the N-dealkylation and glutathione conjugation pathways. J. Agric. Food Chem., 21 ( 6) : 1 031 -1 036 . Shindy, W.W., L.S. Jordan, V.A. Jolliffe, C.W. Coggins, Jr., and J. Kumamoto. 1973. Metabolism of [ll+C]naphthaleneacetic acid in Kinnow Mandarin. J. Agric. Food Chem. , 21 (4) :629-631 . Shono, T. 1974a. Studies on the mechanism of resistance in diazinon resistant Hokota strain of houseflies. II. In vitro degradation of diazoxon. Botyu-Kagaku, 39{ II): 54-59. Shono, T. 1974b. Studies on the mechanism of resistance in diazinon resistant Hokota strain of houseflies. III. Diazinon degradation by glutathione-S-transferase. Botyu-Kagaku, 39( 1 1 1 ) : 75-80. Shono, T. 1974c. Studies on the mechanism of resistance in diazinon resistant Hokota strain of houseflies. IV. Diazinon metabolism by mixed-function oxidase. Botyu-Kagaku, 39( III) :80-84. Siddaramappa, R., K.P. Rajaram, and N. Sethunathan. 1973. Degradation of parathion by bacteria isolated from flooded soil. Appl. Microbiol., 26(6) :846-849. Siegel, M.R. 1975. Benomyl-soil microbial interactions. Phytopathology, 65(2): 219-220. Siegel, M.R., and A.J. Zabbia, Jr. 1972. Distribution and metabolic fate of the fungicide benomyl in dwarf pea. Phytopathology, 62(6) :630-634. 361 Sikka, H.C., D. Ford, and R.S. Lynch. 1975. Uptake, distribution, and metabolism of endothall in fish. J. Agric. Food Chem. , 23(5) :849-851 . Sikka, H.C., R.S. Lynch, and M. Lindenberger. 1974. Uptake and metabolism of dichlobenil by emersed aquatic plants. J. Agric. Food Chem. , 22(2) :230-234. Sikka, H.C., and J. Saxena. 1973. Metabolism of endothall by aquatic microorganisms. J. Agric. Food Chem., 21 (3) :402-406. Silk, P.J., and I. Unger. 1972. The photodecomposition of 1 ,1 -dichloro-2,2-bis(5' -chloro-2' - methoxyphenyl ) ethylene (MPE), an analogue of DDE. Int. J. Environ. Anal. Chem., 1:301-306. Silk, P.J., and I. Unger. 1973. The photochemistry of carbamates. I. The photodecomposition of Zectran. Int. J. Environ. Anal. Chem., 2:2131-220. Sink, J.D., H. Varela-Alvarez, and C. Hess. 1972. Metabolism of 14C-DDT by ovine rumen fluid in vitro. J. Agric. Food Chem., 20(l):7-9. Sirons, G.J., R. Frank, and T. Sawyer. 1973. Residues of atrazine, cyanazine, and their phytotoxic metabolites in clay loam soil. J. Agric. Food Chem., 21(6): 1016-1020. Slade, M. , G.T. Brooks, H.K. Hetnarski, and C.F. Wilkinson. 1975. Inhibition of the enzymatic hydration of the epoxide HEOM in insects. Pest. Biochem. Physiol., 5:35-46. Sloan, J. P., J.A.J. Thompson, and P. A. Larkin. 1974. The biological half-life of inorganic mercury in the Dungeness crab (Cancer magister). J. Fish. Res. Board Can., 31(10): 1571-1576. Smelt, J.H., and M. Leistra. 1974. Conversion of metham-sodium to methyl isothiocyanante and basic data on the behaviour of methyl isothiocynate in soil. Pestic. Sci., 5:401-407. Smith, A.E. 1971. Degradation of bromoxynil in Regina heavy clay. Weed Res., 11:276-282. Smith, A.E. 1972. The hydrolysis of 2,4-dichlorophenoxyacetate esters to 2,4-dichlorophenoxyacetic acid in Saskatchewan soils. Weed Res., 12:364-372. Smith, A.E. 1973a. Transformation of dicamba in Reqina heavy clay. J. Agric. Food Chem., 21 (4) :708-7l0. Smith, A.E. 1973b. Degradation of dicamba in prairie soils. Weed Res., 13:373-378. Smith, A.E. 1974. Breakdown of the herbicide dicamba and its degradation product 3,6-dichlorosalicylic acid in prairie soils. J. Agric. Food Chem., 22(4) : 601 -605. 362 Smith, A.E., and D.R. Cul limore. 1974. The vn vitro degradation of the herbicide bromoxynil. Can. J. MicrobToTTT 20(5) :773-776. Smith, A.E., and D.R. Cullimore. 1975. Microbiological degradation of the herbicide dicamba in moist soils at different temperatures. Weed Res., 15:59-62. Smith, A.E., andR.E. Wilkinson. 1974. Differential absorption, translocation and metabolism of metribuzin [4-amino-6-tert-butyl -3- (methyl thio)-as-triazine- 5(4H)one] by soybean cultivars. Physiol. Plant., 32:253-257. Smith, B.R., W.C. Dauterman, and E. Hodgson. 1974. Selective inhibition of the metabolism of diazinon and diazoxon J_n vitro by piperonyl butoxide, NIA 16824, and l-(2-isopropyl phenyl ) imidazole. Pest. Biochem. Physiol., 4:337-345. Smith, L.W., and F.-Y. Chang. 1973. Aminotriazole metabolism in Cirsium arvense (L.) Scop. and Pi sum sativum L. Weed Res., 13(4) :339-350. Smith, R.A., W.S. Belles, K.-W. Shen, and W.G. Woods. 1973. The degradation of dinitramine (N3,N3 -diethyl 2,4-dinitro- 6-trifluoromethyl-m-phenylenedi amine) in soil. Pest. Biochem. Physiol., 3(3):278-288. Snell, M., and L.V. Edgington. 1970. Uptake, translocation and decomposition of systemic oxathiin fungicides in bean. Phytopathology, 60(1 2) :1 708-1 716- Soderquist, C.J., and D.G. Crosby. 1975. Dissipation of 4-chloro-2-methylphenoxyacetic acid (MCPA) in a rice field. Pestic. Sci., 6:17-33. Soderquist, C.J., D.G. Crosby, K.W. Moilanen, J.N. Sieber, and J.E. Woodrow. 1975. Occurrence of trifluralin and its photoproducts in air. J. Agric. Food Chem. , 23(2) :304-309. Solel, Z., J.M. Schooley, and L.V. Edgington. 1973. Uptake and translocation of benomyl and carbendazim (methyl benzimidazol-2-yl carbamate) in the symplast. Pestic. Sci., 4:713-718. Sorensen, D.O. 1971. Kolorimetrisch bestimmbare Herbizide: Analyse, Abbau, Toxikologie. Vom Wasser, 38:17-26. Spangler, W.J., J.L. Spigarelli, J.M. Rose, R.S. Flippin, and H.H. Miller. 1973a. Degradation of methylmercury by bacteria isolated from environmental samples. Appl. Microbiol., 25(4) :488-493. Spangler, W.J., J.L. Spigarelli, J.M. Rose, and H.M. Miller. 1973b. Methylmercury: Bacterial degradation in lake sediments. Science, 180:192-193. 363 Spear, R.C., W.J. Popendorf, J.T. Leffingwell, and D. Jenkins. 1975. Parathion residues on citrus foliage. Decay and composition as related to worker hazard. J. Agric. Food Chem., 23(4) :808-810. Spencer, W.F., M.M. Cliath, W.J. Farmer, and R.A. Shepherd. 1974. Volatility of DDT residues in soil as affected by flooding and organic matter applications. J. Environ. Qual., 3( 2) : 1 26-1 29- Spengler, D., and A. Jumar. 1969. Modellunterschunger uber den Abbau des herbiziden Wirkstoffes Proximpham. Arch. Pflanzenschutz, 5(6) :445-453. Spitznagle, L.A. 1970. Metabolism and residue properties of the plant growth regulator, 2,3,5-triiodobenzoic acid in field-growth soybeans. Diss. Abstr., 30B(9) :401 6-401 7. Sprankle, P., W.F. Meggitt, and D. Penner. 1975a. Rapid inactivation of glyphosate in the soil. Weed Sci., 23(3):224-228. Sprankle, P., W.F. Meggitt, and D. Penner. 1975b. Adsorption, mobility, and microbial degradation of glyphosate in soil. Weed Sci., 23(3) :229-234. St. John, L.E., Jr., and D.J. Lisk. 1973. Metabolic studies with chloropropylate acaricide in the dairy cow. J. Agric. Food Chem., 21 (4) :644-646. St. John, L.E., Jr., and D.J. Lisk. 1974a. Feeding studies with randox in the dairy cow. Bull. Environ. Contam. Toxicol., 11 (6) : 529-531 . St. John, L.E., Jr., and D.J. Lisk. 1974b. Feeding studies with supracide in the dairy cow. Bull. Environ. Contam. Toxicol., 12(5) :594-598. St. John, L.E., Jr., and D.J. Lisk. 1975. A feeding study with the herbicide, Kerb (N-(l ,1 -dimethyl - propynyl )-3,5-dichlorobenzamide, in the dairy cow. Bull. Environ. Contam. Toxicol., 13(4) :433-435. Staiff, D.C., S.W. Comer, J.F. Armstrong, and H.R. Wolfe. 1975. Persistence of azinphosmethyl in soil. Bull. Environ. Contam. Toxicol., 13(3): 362-368. Stanton, R.H., and M.A.Q. Khan. 1973. Mixed-function oxidase activity toward cyclodiene insecticides in bass and bluegill sunfish. Pestic. Biochem. Physiol., 3:351-357. Starr, R.I. 1972. The absorption, translocation, and metabolism of lt+C-4- aminopyridine in corn and sorghum: Its movement and degradation in soil systems. Diss. Abstr., 33B(6) :2443-2444. Starr, R.I., and D.J. Cunningham. 1974a. Phytotoxicity, absorption and translocation of 4-amino- pyridine in corn and sorghum growing in treated nutrient cultures and soils. J. Agric. Food Chem., 22(3) :409-413. 364 Starr, R.I., and D.J. Cunningham. 1974b. Dearadation of "^C-labeled mesurol in soil and water. Abstracts 168th ACS Meeting, Atlantic City, NJ, Sept. 9-13, PEST 59. Starr, R.I., and D.J. Cunningham. 1975a. Leaching and degradation of 4-aminopyridine-lttC in several soil systems. Arch. Environ. Contam. Toxicol., 3(l):72-83. Starr, R.I., and D.J. Cunningham. 1975b. Degradation of 4-aminopyridine-11+C in corn and sorghum plants. J. Agric. Food Chem. , 23(2) :279-281 . Steller, W.A., and W.W. Brand. 1974. Analysis of dimethoate-treated grapes for the N-hydroxy- methyl and de-N-methyl metabolites and for their sugar adducts. J. Agric. Food Chem., 22(3) :445-449. Stenerson, J., A. Gilman, and A. Vardanis. 1973. Carbofuran: Its toxicity to and metabolism by earth worm (Lumbricus terrestris). J. Agric. Food Chem. , 21 (2) :166-171 . Stephan, U., and H.R. Schutte. 1970. About the metabolism of chloroethyl trimethylammoniumchloride in higher plants. Biochem. Physiol. Pflanz., 161:499-510. Stephenson, G.R., L.R. Baker, and S.K. Ries. 1971. Metabolism of Pyrazon in susceptible species and inbred lines of tolerant red beet (Beta vulgaris L.). J. Am. Soc. Hortic. Sci., 96(2):145-147. Stewart, D.K.R., and K.G. Cairns. 1974. Endosulfan persistence in soil and uptake by potato tubers. J. Agric. Food Chem., 22(6) :984-986. Stewart, D.K.R., and D. Chisholm. 1971. Long-term persistence of BHC, DDT and chlordane in a sandy loam soil. Can. J. Soil Sci., 51:379-383. Still, G.G., and E.R. Mansager. 1973a. Soybean shoot metabolism of isopropyl -3-chlorocarbanilate: Ortho and para aryl hydroxylation. Pest. Biochem. Physiol., 3(1): 87-95. Still, G.G., and E.R. Mansager. 1973b. Metabolism of isopropyl carbanilate by soybean plants. Pest. Biochem. Physiol., 3(3) : 289-299. Still, G.G., and E.R. Mansager. 1973c. Metabolism of isopropyl-3-chloracarbanilate by cucumber plants. J. Agric. Food Chem., 21(5): 787-791 . Still, G.G., and E.R. Mansager. 1974. Metabolism of isopropyl -3-chlorocarbanialte by alfalfa plants. Abstracts, 168th ACS Meeting, PEST 1. Still, G.G., E.R. Mansager, and G.D. Paulson. 1974a. Alfalfa metabolites of isopropyl-3-chlorocarbanilate (chlorpropham) : Their fate in rats and sheep. Abstracts, 168th ACS Meeting, PEST 2. 365 Still, G.G., D.G. Rusness, and E.R. Mansager. 1974b. Carbanilate herbicides and their metabolic products- their effect on plant metabolism. Abstracts, 167th ACS Meeting, PEST 40. Stillwell, W.G., M.J. Carman, L. Bell, and M.G. Horning. 1974. The metabolism of safrole and 2' ,3' -epoxysafrole in the rat and quinea pig. Drug Metab. Dispos., 2(6) :489-498. Stoller, E.W., L.M. Wax, L.C. Haderlie, and F.W. Slife. 1975. Bentazon leaching in four Illinois soils. J. Agric. Food Chem., 23(4):682-684. Strang, R.H., and R.L. Rogers. 1974. Behavior and fate of two phenyl pyridazi none herbicides in cotton, corn, and soybean. J. Agric. Food Chem., 22(6) : 1 1 1 9-1 1 24- Strobel , G.A. 1966. The fixation of hydrocyanic acid by a psychrophilic Basidiomycete. J. Biol. Chem., 241:2618-2621. Strobel , G.A. 1967. 4-Amino-4-cyanobutyric acid as an intermediate in glutamate biosynthesis. J. Biol. Chem. 242:3265-3269. Stutzenberger, F.J., and J.N. Parle. 1972. Binding of benz imidazole compounds to conidia of Pithomyces chartarum. J. Gen. Microbiol., 73:85-94. Subba Rao, N.V., and A.G. Pollard. 1951. Photo-decomposition of rotenone in spray deposits. III. Kinetics of the photo-decomposition. J. Sci. Food Agric, 2:462-472. Suffling, R., D.W. Smith, and G. Sirons. 1974. Lateral loss of picloram and 2,4-D from c forest podsol during rainstorms. Weed Res., 14:301-304. Sugiura, K., M. Hattori, M. Baba, and M. Goto. 1975a. Accumulation and excretion of PCB's in the mouse. Chemosphere, 4(3) : 181 -187- Sugiura, K., S. Sato, and M. Goto. 1975b. Adsorption-diffusion mechanism of BHC-residues. A consid- eration based on bacteria experiments as models. Chemosphere, 4(3):189-194. Sumida, S., Y. Hisada, A. Kometani , and J. Miyamoto. 1973a. Biotransformation of 3-(3' ,5' -dichlorophenyl )5,5- dimethyl oxazolidine-2,4-dione. Part 1. Metabolism in the rats. Agric. Biol. Chem., 37(9) :2127-2136. Sumida, S., R. Yoshihara, and J. Miyamoto. 1973b. Degradation of 3-(3,5-dichlorophenyl )-5,5-dimethyl oxazolidine-2,4-dione by plants, soil and light. Agric. Biol. Chem., 37(12) :2781-2790. Summers, A.O., and E. Lewis. 1972. Volatilization of mercuric chloride by mercury-resistant plasmid-bearing strains of Escherichia coli , Staphylococcus aureus, and Pseudomonas aeruginosa. J. Bacterid., 113(2) : 1 070-1 072. 366 Summers, A.O., and S. Silver. 1972. Mercury resistance in plasmid-bearing strain of Escherichia coli. J. Bacterid., 112(3):1228-1236. Summers, A.O., and L.I. Sugarman. 1974. Cell -free mercury ( ID-reducing activity in plasmid- bearing strain of Escherichia coli. J. Bacterid., 119(1): 242-249. Sundstrom, G., and B. Jansson. 1975. The metabolism of 2,2' ,3,5' ,6-pentachlorobiphenyl in rats, mice and quails. Chemosphere, 4(6) :361 -370. Sundstrom, G., B. Jansson, and S. Jensen. 1975. Structure of phenolic metabolites of p,p'-DDE in rat, wild seal and guillemot. Nature, 255:627-628. Sundstrom, G., and C.A. Wachmeister. 1975. Structure of a major metabolite of 2,2' ,4,5,5' -pentachloro- bi phenyl in mice. Chemosphere, 4(1): 7-1 1 - Sutherland, D.J., M. Siewierski, A.H. Marei, and K. Helrich. 1970. The effect on mosquitoes of sublethal exposure to insecticides II. DDT metabolism. Mosq. News, 30(1):8-11. Suzuki, M., Y. Yamato, and T. Watanabe. 1974. Photodieldrin residues in field soils. Bull. Environ. Contam. Toxicol., 12(3) : 275-280. Suzuki, T., K. Furukawa, and K. Tonomura. 1968. Studies on the removal of inorganic mercurial compounds in waste by the cell -reused method of mercury-resistant bacterium. J. Ferment. Technol . , 46(12) :1048-1055. Suzuki, T. , and J. Miyamoto. 1973. Metabolism of tetramethrin in houseflies and rats In vitro. Pestic. Biochem. Physiol., 4:86-97. Suzuki, T., and M. Uchiyama. 1975. Pathway of nitro reduction of parathion by spinach homogenate. J. Agric. Food Chem. , 23(2) :281-285. Syversen, T.L.M. 1974a. Biotransformation of Hg-203 labeled methyl mercuric chloride in rat brain measured by specific determination of Hg2+. Acta Pharmacol. Toxicol., 35:277-283. Syversen, T.L.M. 1974b. Distribution of mercury in enzymatically characterized subcellular fractions from the developing rat brain after injections of methyl mercuric chloride and diethyl mercury. Biochem. Pharmacol., 23:2999-3007. Tadjer, G.S., and M.N. Egyed. 1974. Detection of cyolane in alfalfa pellets and rumen content of a cow. Bull. Environ. Contam. Toxicol., 12(2) : 1 73-1 76 . Takase, I., and H. Nakamura. 1974. The fate of ethyl thiometon (0,0-diethyl S-[2-(ethyl thio) ethyl ]phosphorodithioate) in paddy soil. J. Agric. Chem. Soc. Jap., 48(1 ):29-34. 367 Takase, I., K.E. Tan, and K. Ishuzuka. 1973. Metabolic transformation and accumulation of 0-ethyl S,S- diphenyl phosphorodithiolate (Hinosan) in rice plants. Agric. Biol. Chem. , 37(7) : 1 563-1571 . Takase, I., H. Tsuda, and Y. Yoshimoto. 1972. The fate of disyston active ingredient in soil. Pflanzenschutz-Nachr. , 25(1 ) :43-63. Talekar, N.S., and E.P. Lichtenstein. 1973. Influence of mineral nutrients on the penetration, trans- location, and metabolism of [1<+C]dyfonate in pea plants. J. Agric. Food Chem., 21 (5):851-855. Tanabe, M. , R.L. Dehn, and R.R. Bramshall. 1974. The photochemistry of imidan in diethyl ether. J. Agric. Food Chem., 22(l):54-56. Temizer, A. 1970. Metabolisme de L'Aldrine Chez la Mouche de L'Oignon. Phytiatr.-Phytopharm. , 19(1) :9-18. Terranova, A.C. 1969. The residual fate of N,N,N' ,N'-tetramethyl-£-piperidino- phosphonic diamide after injection, tarsal contact, and topical application to the boll weevil. J. Econ. Etomol . , 62(1 ) :821 -823. Tewfik, M.S., and Y.A. Hamdi. 1975. Metabolism of fluorodifen by soil microorganisms. Soil Biol. Biochem., 7:79-82. Thomas, K.P., and D.G. Rowlands. 1975. The uptake and degradation of pirimiphos-methyl by Cheshire cheese. J. Stored Prod. Res., 11:53-56. Thomason, I.J., and M.V. McKenry. 1974. Part I. Movement and fate as affected by various conditions in several soils. Hilgardia, 42(11 ) :393-421. Thompson, A.R. 1971. Stonefly metabolism and the effects of DDT. Diss. Abstr. , 32B(4):2373. Thompson, A.R., and W.W. Sans. 1973. Effects of soil insecticides in southwestern Ontario on non-target invertebrates: Earthworms in pasture. Environ. Entomol., 3(2) :305-308. Thompson, L. , Jr. 1972. Metabolism of chloro s-triazine herbicides by Panicum and Setaria. Weed Sci., 20(6): 584-587. Thorn, G.D. 1973. Uptake and metabolism of chloroneb by Phaseolus vulgaris. Pestic. Biochem. Physiol., 3(2):137-140. Tiedje, J.M. 1969. Metabolism of 2,4-dichlorophenoxyacetic acid by enzymes of an Arthrobacter sp. Diss. Abstr., 29B(11 ) :4298-4299. 368 Tiedje, J.M,. and M.L. Hagedorn. 1975. Degradation of alachlor by a soil fungus, Chaetomium globosum. J. Agric. Food Chem., 23(1):77-81. Tillman, R.W., M.R. Siegle, and J.W. Long. 1973. Mechanism of action and fate of the fungicide chlorothalonil (2,4,5,6-tetrachloroisophthaloni trile) in biological systems. Pestic. Biochem. Physiol., 3(2) : 160-167. Tisdale, M.J., and K.A. Lord. 1973. Uptake and distrubution of thiabendazole by seed potatoes. Pestic. Sci. , 4:121-130. Tocco, D.J., R.P. Buhs, H.D. Brown, A.R. Matzuk, H.E. Mertel, R.E. Harman, and N.R. Trenner. 1964. The metabolic fate of thiabendazole in sheep. J. Med. Chem., 7:399-405. Tomlin, A.D. 1972. The toxicity, penetration and metabolism of gardona in gypsy moth larvae. Diss. Abstr. , 33B(4):1410. Tomoyeda, M. , H. Horitsu, and T. Azuma. 1973. Isolation of phenyl mercuric-, and mercuric acetate-tolerant microorganism and the incorporation of their compounds into cells of the microorganism (Studies on recovery of heavy metal compounds by microorganism Part II). J. Agric. Chem. Soc. Jap., 47(1 ) :51 -55. Torgeson, D.C., and H. Mee. 1967. Microbial degradation of bromacil. Proc. Northeast. Weed Contr. Conf. , 21:584. Torstensson, N.T.L., J. Stark, and B. Goransson. 1975. The effect of repeated applications of 2,4-D and MCPA on their breakdown in soil. Weed Res., 15:159-164. Townsend, M.G., E.M. Odam, and J.M.J. Page. 1975. Studies of the microsomal drug metabolism system in warfarin-resistant and -susceptible rats. Biochem. Pharmacol., 24:729-735. Tripathi, R.K., and R.D. O'Brien. 1973. Insensitivity of acetylcholinesterase as a factor in resistance of houseflies to the organophosphate rabon. Pestic. Biochem. Physiol., 3(4) :495-498. Tseng, Y.-C. L., and R.E. Menzer. 1974. Effect of hepatic enzyme inducers on the In vivo and in vitro metabolism of dicrotophos, dimethoate, and phosphamidon in mice. Pestic. Biochem. Physiol., 4:425-437. Tucker, D.P., and R.L. Phillips. 1969. Movement and degradation of herbicides in Florida citrus soils. Proc. Fl a. State Hortic. Soc, 81:72-75. Turner, J.C. 1969. Cyanide detoxi cation in the opossum (Trichosurus vulpecula). N. Z. J. Sci., 12:569-575. 369 Uchiyama, M. , H. Abe, R. Sato, M. Shimura, and T. Watanabe. 1973. Fate of 3-allyloxy-l ,2-benzisothiazole 1,1 -dioxide (oryzemate). Agric. Biol. Chem. , 37(4) :737-745. Udagawa, T., T. Miyata, and T. Saito. 1974. Metabolism of continuous three weeks administered ll4C-pyridafenthion, 0,0-diethyl-0-(3-oxo-2-phenyl -2H-pyridazine- 6-yl )phosphorothioate, in mouse. Botyu-Kagaku, 39:15-18. Ueda, K., L.C. Gaughan, J.E. Casida. 1974. Photodecomposition of resmethrin and related pyrethroids. J. Agric. Food Chem., 22(2) :21 2-220. Ueda, K., L.C. Gaughan, and J.E. Casida. 1975a. Metabolism of (+)-trans- and (+)-cis-resmethrin in rats. J. Agric. Food Chem., 23(1 ):106-115. Ueda, K., L.C. Gaughan, and J.E. Casida. 1975b. Metabolism of four resmethrin isomers by liver microsomes. Pestic. Biochem. Physiol., 5:280-294. Ueyama, I., and I. Takase. 1975. Metabolic behavior of 0-ethyl S,S-diphenyl phosphoro- dithiolate (edifenphos) in female goat. Agric. Biol. Chem., 39(9) :1 719-1727. Ueyama, I., Y. Uesugi , C. Tomizawa, and T. Murai. 1973. Metabolic fate of 0-ethyl S,S-diphenyl phosphorodithiolate (Hinosan) in rice plant. Agric. Biol. Chem., 37(7) : 1543-1 551 . Unlu, M.Y., M. Heyrand, and S. Keckes. 1972. Mercury as a hydrospheric pollutant. I. Accumulation and excretion of 203HgCl2 in Tapes decussatus L. p. 292. In M. Ruivo (ed.) Marine pollution and sea life. FTshing News (BoolTs), London. Valenta, J.R., C.J. DiCuollo, L.R. Fare, J. A. Miller, and J.F. Pagano. 1974. Microbial transformation of methyl 5(6) -butyl -2-benzimid- azolecarbamate. Appl . Microbiol., 28(6) :995-998. Valentine, J. P., and S.W. Bingham. 1974. Influence of several algae on 2,4-D residues in water. Weed Sci., 22:358-363. VanAlfen, N.K., and T. Kosuge. 1974. Microbial metabolism of the fungicide 2,6-dichloro-4- nitroaniline. J. Agric. Food Chem. , 22(2) :221-224. Van Dijk, H. 1974. Degradation of 1 ,3-dichloropropenes in the soil. Agro-Ecosystems, 1:193-204. Van Miller, J. P., I.C. Hsu, and J.R. Allen. 1975. Distribution and metabolism of 3H-2,5,2' ,5' -tetrachloro- biphenyl in rats. Proc. Soc. Exper. Biol. Med., 148:682-687. Varela-Alvarez, H.J., D. Sink, and L.L. Wilson. 1973. Certain physiological factors affecting organochlorine pesticide metabolism in ovine females. J. Agric. Food Chem., 21(3):407-409. 370 Voerman, S., and A.F.H. Besemer. 1975. Persistence of dieldrin, lindane, and DDT in a light sandy soil and their uptake by grass. Bull. Environ. Contam. Toxicol., 13(4) :501 -505. Vonk, J.W., and A.K. Sijpesteijn. 1973. Studies on the methylation of mercuric chloride by pure cultures of bacteria and fungi. Antonie van Leeuwenhoek J. Microbiol. Serol . , 39(3) :505-513. Walker, C.H., A.C.C. Craven, and M. Kurukgy. 1975. The metabolism of organochlorine compounds by microsomal enzymes of the shag (Phalacrocorax aristotelis). Environ. Physiol. Biochem., 5:58-64. Walker, C.H., and G.A. El Zorgani. 1973. Metabolism of a dieldrin analogue - secondary oxidation by liver microsomes. Life Sci., 13:585-593. Walker, C.H., and G.A. El Zorgani. 1974. The comparative metabolism and excretion of HCE, a biodegradable analogue of dieldrin, by vertebrate species. Arch. Environ. Contam. Toxicol., 2(2): 97-1 16- Walker, W.W. 1972. Degradation of malathion by indigenous soil microorganisms. Diss. Abstr., 33B(4):1347. Wall cave, L, and R. Gingell. 1974. Species differences in the acute toxicity and tissue distribution of DDT in mice and hamsters. Toxicol. Appl. Pharmacol., 28(3) :384-394. Wallnofer, P.R., G. Engelhardt, S. Safe, and 0. Hutzinger. 1973a. Microbial hydroxylation of 4-chlorobiphenyl and 4,4'- dichlorobiphenyl . Chemosphere, 2:69-72. Wallnofer, P.R., M. Koniger, S. Safe, and 0. Hutzinger. 1972. The metabolism of the systemic fungicide carboxin (vitavax) by Rhizopus japonicus. Int. J. Environ. Anal. Chem. , 2:37-43. Wallnofer, P.R., S. Safe, and 0. Hutzinger. 1973b. Microbial hydroxylation of the herbicide M-(3,4-dichloro- phenyl )methacryl amide (dicryl). J. Agric. Food CHem. , 21(3): 502-504. Wallnofer, P.R., S. Safe, and 0. Hutzinger. 1973c. Microbial demethylation and debutynylation of four phenylurea herbicides. Pestic. Biochem. Physiol., 3(3) :253-258. Ward, P.F.V., and N.S. Huskisson. 1972. The metabolism of fluoroacetate in lettuce. Biochem. J., 130:575-587. Ware, G.W., W.P. Cahill, and B.J Estesen. 1975. Volatization of DDT and related materials from dry and irrigated soils. Environ. Contam. Toxicol., 14(l):88-96. Ware, G.W., D.M. Whitacre, and J.B. Dobie. 1973. Apparent increase of DDT residues in wafered hay. Bull. Environ. Contam. Toxicol., 9(3): 173-1 78. 371 Waring, R.H. 1973. The metabolism of vitavax by rats and rabbits. Xenobiotica, 3(2):65-71. Wathana, S. 1971. Absorption, translocation, and metabolism of 4-(2,4- dichlorophenoxy) butyric acid in soybean and cocklebur. Diss. Abstr., 31B(12)(Part I):7029. Watson, M., B. Pharoah, J. Wyllie, and W.W. Benson. 1975. Metabolism of low oral doses of DDT and DDE by tame mule deer fawns. Bull. Environ. Contam. Toxicol., 13(3) : 31 6-323. Watts, R.R., R.W. Storherr, and J.H. Onley. 1974. Effects of cooking on ethylenebisdithiocarbamate degradation to ethylene thiourea. Bull. Environ. Contam. Toxicol., 12(2): 224-226. Wauchope, R.D., and R. Haque. 1973. Effects of pH, light and temperature on carbaryl in aqueous media. Bull. Environ. Contam. Toxicol., 9-( 5) : 257-260. Webb, R.G., and A.C. McCall. 1972. Identities of polychlorinated biphenyl isomers in aroclors. J. Assoc. Off. Anal. Chem. , 55(4) :746-752. Weisgerber, I., D. Bieniek, J. Kohl i , and W. Klein. 1975a. Isolation and identification of three unreported photo- dieldrin-1I+C metabolites in soil. J. Agric. Food Chem., 23(5): 873-877. Weisgerber, I., J. Kohl i , R. Kaul , W. Klein, and F. Korte. 1974. Fate of aldrin-11+C in maize, wheat, and soils under outdoor conditions. J. Agric. Food Chem. , 22(4) :609-612. Weisgerber, I., W. Tomberg, W. Klein, and F. Korte. 1975b. Beitrage Zur Okologischen Chemie. XCV. Isolierung und Strukturaufklarung Einiger Hydrophiler Isodrin-11+C-Metaboliten aus Weisskohl. Chemosphere, 4(2):99-104. Welling, W. , A.W. deVries, and S. Voerman. 1974. Oxidative cleavage of a carboxyester bond as a mechanism of resistance to malaoxon in houseflies. Pestic. Biochem. Physiol., 4:31-43. Wells, M.R., J.L. Ludke, and J.D. Yarbrough. 1973. Epoxidation and fate of [11+C]aldrin in insecticide- resistant and susceptible populations of mosquitofish (Gambusia affinis). J. Agric. Food Chem. , 21 (3) :428-429. Werner, R.A. 1974. Distribution and toxicity of root-absorbed lt+C-orthene and its metabolites in loblolly pine seedlings. J. Econ. Entomol., 67(5): 588- 591. West, H.D., J.R. Lawson, I.H. Miller, and G.R. Mathura. 1956. The fate of diphenyl in the rat. Arch. Biochem. Biophys., 60:14-20. 372 Westmacott, D., and S.J.L. Wright. 1975. Studies on the breakdown of p-chlorophenyl methyl carbamate. II. In cultures of a soil Arthrobacter sp. Pestic. Sci., 6:61-68. Wheeler, L., and A. Strother. 1973. In vitro metabolism of 11+C-pesticidal carbamates by fetal and maternal- brain, liver, and placenta of the rat. Drug Metab. Dispos., 2(6) :533-538. Whitacre, D.M. 1970. Endosulfan metabolism in temperature-stressed rats. Diss. Abstr., 30B(9):4435-4436. White, E.R., E.A. Bose, J.M. Ogawa, B.T. Manji, and W.W. Kilgore. 1973. Thermal and base-catalyzed hydrolysis products of the systemic fungicide, benomyl . J. Agric. FoodChem., 21 (4) : 61 6-61 8. White, J.F., and A. Rothstein. 1973. The interaction of methyl mercury with erythrocytes. Toxicol. Appl . Pharmacol., 26:370-384. Whitten, C.J., and D.L. Bull. 1974a. Fate of 3,3-dimethyl -1 -(methyl thio)-2-butanone 0-(methyl- carbamoyl )oxime (Diamond Shamrock DS-15647) in cotton plants and soil. J. Agric. FoodChem., 22(2) :234-238. Whitten, C.J., and D.L. Bull. 1974b. Comparative toxicity, absorption, and metabolism of chlorpyrifos and its dimethyl homologue in methyl parathion- resistant and -susceptible tobacco budworms. Pest. Biochem. Physiol., 5:266-274. Wichman, J.R., and W.R. Byrnes. 1975. Uptake, distribution, and degradation of simazine by black walnut and yellowpoplar seedlings. Weed Sci., 23(6) :448-453. Wiedmann, J.L., and G.G. Ecke. 1975. Synthesis and isolation of 1 -hydroxy- 2-p ropy 1-3' -chloro- carbanilate from soybean plants treated with isopropyl-3- chlorocarbanilate. Abstracts, 170th ACS Meeting, PEST 20. Wiese, M.V., and J.M. Vargas, Jr. 1973. Interconversion of chloroneb and 2,5-dichloro-4-methoxyphenol by soil microorganisms. Pest. Biochem. Physiol., 3(2) : 21 4-222. Willis, D.E., and R.F. Addison. 1974. Hydroxylation of bi phenyl vn vitro by tissue preparations of some marine organisms. Comp. Gen. Pharmacol., 5:77-81. Wilson, D.M., and P.C. Oloffs. 1973. Residues in alfalfa following soil treatment with high purity chlordane (Velsicol HCS-3260). Bull. Environ. Contam. Toxicol., 9(6):337-344. Wimmer, J. 1974. Untersuchungen Uber die Wanderung und Auswaschung von Quecksilber im Boden. Die Bodenkultur. , 25(4) :369-379. Winterlin, W. , J.B. Bailey, L. Langbehn, and C. Mourar. 1975. Degradation of parathion applied to peach leaves. Pestic. Monit. J., 8(4):263-269. 373 Winterlin, W. , C. Mourer, and J.B. Bailey. 1974. Degradation of four organophosphate insecticides in grape tissues. Pestic. Monit. J., 8(1): 59-65. Wolcott, R.M. 1971. Studies on the mechanism of metabolism of dialkyl aryl phosphorothionate insecticides. Diss. Abstr. , 31 B ( 1 0) : 5806. Wolf, D.C., and J. P. Martin. 1974. Microbial degradation of 2-carbon-14 bromacil and terbacil. Soil Sci. Soc. Am. Proc. , 38(6) :921 -925. Wolfe, H.R., D.C. Staiff, J.F. Armstrong, and S.W. Comer. 1973. Persistence of parathion in soil. Bull. Environ. Contain. Toxicol., 10(1 ):1 -9. Wolfe, N.L., R.G. Zepp, J. A. Gordon, and G.L. Baughman. 1975a. Kinetic investigation of malathion degradation in water. Bull. Environ. Contam. Toxicol., 13(6): 707-71 3. Wolfe, N.L., R.G. Zepp, J. A. Gordon, and G.L. Baughman. 1973. Chemistry of methyl mercurials in aqueous solution. Chemosphere, 2(4) : 1 47-152- Wolfe, N.L., R.G. Zepp, J. A. Gordon, and R.C. Fincher. 1975b. N-Mitrosoatrazine: Formation and degradation. Abstracts, 170th ACS Meeting, PEST 23. Wong, P.T.S., and K.L.E. Kaiser. 1975. Bacterial degradation of polychlorinated biphenyls. II. Rate studies. Bull. Environ. Contam. Toxicol., 13(2) :249-256. Wood, J.M. 1971. Environmental pollution by mercury. Adv. Environ. Sci. Technol., 2:39-56. Wood, J.M. 1974. Biological cycles for toxic elements in the environment. Science, 183:1049-1051. Woodham, D.W., C.A. Bond, E.H. Ahrens, and J.G. Medley. 1975. The cumulation and disappearance of mirex residues. III. In eggs and tissues of hens fed two concentrations of the insecticide in their diet. Bull. Environ. Contam. Toxicol., 14(1 ) :98-104. Woodham, D.W., J.C. Hatchett, and C.A. Bond. 1974. Comparison of dimethoate and dimethoxon residues in citrus leaves and grapefruit following foliar treatment with dimethoate wetable powder with and without surfactant. J. Agric. Food Chem. , 22(2):239-242. Woodrow, J.E., J.N. Seiber, D.G. Crosby, K.W. Moilanen, C. Mourer, C.J. Soderquist, and W.L. Winterlin. 1975. Breakdown of parathion in the air and on leaves and soil of a treated orchard. Abstracts, 170th ACS Meeting, PEST 125. Woods, R.J., and S. Akhtar. 1974. Radiation-induced dechlorination of chloral hydrate and 1 ,1 ,1 -trichloro-2,2-bis(£-chlorophenyl )ethane (DDT). J. Am. Chem. Soc, 22:1132-1133. 374 Woolson, E.A., and P.C. Kearney. 1973. Persistencae and reactions of 14C-cacodylic acid in soils. Environ. Sci. Technol., 7(1) :47-50. Wright, F.C., J.S. Palmer, and J.C. Riner. 1973. Retention of mercury in tissues of cattle and sheep given oral doses of a mercurial fungicide, Ceresan M. J. Agric. Food Chem., 21(4):614-615. Wustner, D.A., and T.R. Fukuto. 1974. Affinity and phosphonylation constants for the inhibition of cholinesterases by the optical isomers of 0-2-butyl S-2(di- methylammonium)ethyl ethylphosphonothioate hydrogen oxalate. Pest. Biochem. Physiol., 4:365-376. Yaklich, R.W. 1970. The metabolism of the herbicide N,N-dimethyl -2, 2-diphenyl- acetamide by corn root. Diss. Abstr. , 31 B(6) :3215-3216. Yaklich, R.W., S.J. Karczmarczyk, and R.M. Devlin. 1974. Metabolism of 11+C-San-6706 and 14C-Norflurazon in cranberry plants. Weed Sci., 22(6):595-599. Yamaguchi, I., H. Shibata, H. Seto, and T. Misato. 1975. Isolation and purification of blasticidin S deaminase from Aspergillus terreus. J. Antibiot., 28(1):7-14. Yamamoto, H., C. Tomizawa, Y. Uesugi, and T. Murai. 1973. Absorption, translocation and metabolism of 0,0-diisopropyl S-benzyl phosphorothiolate (Kitazin P) in rice plant. Agric. Biol. Chem., 37(7) :1553-1 561 - Yamamoto, H., and H. Yoshimura. 1973. Metabolic studies on polychlorinated biphenyls. III. Complete structure and acute toxicity of the metabolites of 2,4,3' ,4'-tetrachlorobiphenyl. Chem. Pharm. Bull., 21(10): 2237-2242. Yang, R.S.H. 1971. Comparative studies on the vn vitro metabolism of diazinon and diazoxon in the rat and the housefly. Diss. Abstr., 31 B( 1 0) : 5858. Yang, R.S.H. , W.C. Dauterman, and E. Hodgson. 1969. Enzymatic degradation of diazinon by rat liver microsomes. Life Sci., 8(Part l):667-672. Yaron, B., B. Heuer, and Y. Birk. 1974. Kinetics of azinphosmethyl losses in the soil environment. J. Agric. Food Chem., 22(3) :439-441 . Yoshimura, H. , and M. Oshima. 1971. Studies on the tissue distribution and elimination of several components of KC-400 (chlorobiphenyls) in mice. Fukuoka Acta Med., 62(1 ) :5-l 1 . Yoshimura, H., and H. Yamamoto. 1973. Metabolic studies on polychlorinated biphenyls. I. Metabolic fate of 3,4,3' ,4' -tetrachlorobiphenyl in rats. Chem. Pharm. Bull., 21 (5) :1 168-1 169. 375 Yoshimura, H., and H. Yamamoto. 1975. A novel route of excretion of 2,4,3' ,4'-teterachlorobiphenyl in rats. Bull. Environ. Contam. Toxicol., 13(6) :6fal-688. Yoshimura, H., H. Yamamoto, J. Nagai, Y. Yae, H. Uzawa, Y. Ito, A. Notomi , S. Minakami, A. Ito, K. Kato, and H. Tsuji. 1971. Studies on the tissue distribution and the urinary and fecal excretion of 3H-Kanechlor (chlorobiphenyls) in rats. Fukuoka Acta Med., 62(1):12-19. Yoshimura, H., H. Yamamoto, and S. Saeki. 1973. Metabolic studies on polychlorinated biphenyls. II. Metabolic fate of 2,4,3' ,4'-tetrachlorobiphenyl in rats. Chem. Pharm. Bull., 21 (10):2231-2236. Yu, C.-C, G.M. Booth, D.J. Hansen, and J.R. Larsen. 1974a. Fate of carbofuran in a model ecosystem. J. Agric. Food Chem., 22(3):431-434. Yu, C.-C, G.M. Booth, D.J. Hansen, and J.R. Larsen. 1974b. Fate of bux insecticide in a model' ecosystem. Environ. Entomol., 3(6) :975-977. Yu, C.-C, G.M. Booth, and J.R. Larsen. 1975a. Fate of triazine herbicide cyanazine in a model ecosystem. J. Agric. Food Chem. , 23(5) : 1014-1015. Yu, C.-C, D.J. Hansen, and G.M. Booth. 1975b. Fate of dicamba in a model ecosystem. Bull. Environ. Contam. Toxicol., 1 3( 3) : 280-283. Yule, W.N. 1973. Intensive studies of DDT residues in forest soil. Bull. Environ. Contam. Toxicol., 9:57-64. Yule, W.N. 1974. The persistence and fate of fenitrothion insecticide in a forest environment. II. Accumulation of residues in balsam fir foliage. Bull. Environ. Contam. Toxicol., 12(2):249-252. Yule, W.N., and J.R. Duffy 1972. The persistence and fate of fenitrothion insecticide in a forest environment. Bull. Environ. Contam. Toxicol., 8:10-18. Zayed, S.M.A., I.M.I. Fakhr, and M.R.E. Bahig. 1973. Metabolism of organophosphorus insecticides-XII. Biochem. Pharmacol., 22:285-292. Zemskaya, V.A., Y.V. Rakitin, L.M. Chernikova, and Z.V. Kalibernaya. 1971. Kinetics of the process of 2,4-D bonding by proteins in maize leaf tissues. Fiziol. Rast. , 18(4) :738-745. Zepp, R.G., N.L. Wolfe, G.L. Baughman, and J. A. Gordon. 1974. Dynamics of 2,4-D esters in the aquatic environment: Hydrolysis and photodegradation. Abstracts, 168th ACS Meeting, Atlantic City, NJ, Sept. 9-13, PEST 68. Zepp, R.G., N.L. Wolfe, R.C Fincher, and J. A. Gordon. 1975. Chemical and light-induced decomposition of methoxychlor. Abstracts, 170th ACS Meeting, PEST 129. 376 Zepp, R.G., N.L. Wolfe, and J. A. Gordon. 1973. Photodecomposition of phenyl mercury compounds in sunlight. Chemosphere, 2(3):93-99. Zettler, J.L. 1974. Esterases in malathion-susceptible and a malathion resistant strain of Plodia interpunctella. J. Ga. Entomol. Soc, 9(4): 207-213. Zinck, M.E., and R.F. Addison. 1974. The fate of 2-, 3-, and 4-chlorobiphenyl following intra- venous administration to the thorny skate (Raja radiata) and the winter skate (Raja ocellata). Arch. Environ. Contam. Toxicol., 2(l):52-fal. Zoro, J. A., J.M. Hunter, G. Eglinton, and G.C. Ware. 1974. Degradation of p_,£'-DDT in reducing environments. Nature, 247(5438):235-237. Zulalian, J., D.A. Champagne, R.S. Wayne, and R.C. Blinn. 1975. Absorption, excretion, and metabolism of 1,3-bis (D_-chlorobenzyl ideneamino)guanidine hydrochloride (Robenz robenidine hydrochloride) in the chicken. J. Agric. Food Chem., 23(4):724-730. Zulalian, J., ana P.E. Gatterdam. 1973. Absorption, excretion, and metabolism of robenz, robenidine hydrochloride [1 ,3-bis(p_-chlorobenzylideneamino)guanidine hydro- chloride], in the rat. J. Agric. Food Chem. , 21 (5) :794-797. 377 Bibliography - Addendum Chapman, A.H., and J.W. Price. 1972. Degradation of tri phenyl tin acetate by ultra-violet light. Int. Pest. Contr., 14(1):11-12. Kapoor, I. P., R.L. Metcalf, A.S. Hirwe, P.-Y. Lu, J.R. Coats, and R.F. Nystrom. 1972. Comparative metabolism of DDT, methylchlor, and ethoxychlor in mouse, insects, and in a model ecosystem. J. Agric. Food. Chem. , 20(l):l-6. Kearney, P.C., E.A. Woolson, and C.P. Ellington, Jr. 1972. Persistence and metabolism of chlorodioxins in soils. Environ. Sci. Technol., 6:1017-1019. 378 Appendix I Effect of Temperature on Carbamate Insecticides Heat of Molarity of Ki K2 Activation Compound C NaOH (Min-r ) l-min^md-1 Qio (kCal mol"1) Carbaryl 3 0.009 2.18 x 10-2 2.42 x 10 13 6.22 x io-2 6.91 x 10 23 1.84 x io-1 2.04 x IO2 2.9 16.9 33 4.84 x IO"1 5.37 x IO2 Baygon 5 0.01 7.30 x IO"2 7.37 10 1.12 x IO"1 1.12 x 10 20 3.04 x io-1 3.04 x 10 2.49 15.8 30 7.59 x IO"1 7.59 x 10 40 1.16 1.16 x IO2 Pyrolan 5 0.1 2.00 x IO"3 2.00 x IO"2 10 3.20 x io-3 3.20 x IO"2 20 7.00 x io-3 7.00 x IO"1 222 13.7 30 1.49 x IO"2 1.49 x IO"1 40 2.99 x IO"2 2.99 x IO"1 Dimetilan 10 0.5 1.65 x IO"4 3.40 x IO"3 20 1.65 x IO"3 3.40 x IO"3 1.91 14.0 30 3.25 x io-3 6.50 x IO"3 40 7.14 x io-3 1.43 x 10 (Aly and El-Dib, 1971) 379 Appendix II In Vivo Inhibition of Liver Arylamidase Dose (mq/kq i.p.) Percent Inhibition Compound Ma le Female Parathion 0.05 9.2 + 7.58 22.6 ± 1.69 0.2 19.0 + 6.57 33.1 ± 7.42 0.4 64.9 + 4.40 81.5 ± 2.01 0.8 97.9 + 0.87 98.9 ±0.52 Paraoxon 0.05 39.3 ± 7.05 0.2 26.5 + 8.51 67.3 ± 3.78 0.4 67.7 + 4.07 86.0 ± 1.90 0.8 97.0 + 0.69 98.8 ± 0.48 EPN 0.4 20.3 + 2.27 22.5 ± 6.70 1.0 53.2 + 2.77 57.3 ± 5.95 4.0 95.9 + 1.12 98.1 ± 0.32 Folex 1 41.8 + 7.61 50.2 ± 3.82 5 83.3 + 1.04 88.6 ± 0.96 10 96.0 + 0.89 96.0 ± 0.45 20 98.5 + 0.22 98.2 ± 0.50 Sumithion 0.5 28.0 + 0.78 36.8 ± 3.55 2 42.8 + 2.98 50.6 ± 5.95 10 59.5 + 5.17 66.0 ± 2.75 50 61.7 + 1.59 68.8 ± 2.62 100 67.7 + 1.26 81.4 ± 1.75 Malathion 2 22.4 + 2.71 0 ± 7.72 10 50.1 + 4.35 49.4 ± 5.65 50 70.2 + 1.71 73.6 ± 7.44 100 84.4 + 1.78 84.2 ± 1.29 TOTP 1 36.8 + 5.09 31.0 ± 2.20 5 83.5 + 4.18 57.5 ± 1.90 10 98.3 + 0.39 77.1 ± 1.42 20 100.0 + 0.00 98.0 ± 0.43 (Satch, 1973) 380 Appendix III Effect of Substitution in Parathion Analogs Hydrolysis Uoh min'1) Inhibition (kj M^min"1) Substituent [pH .5) Fly ACh E Bovine I \Ch E H 6.14 X 10-" 1.14 X I06 2.44 X I05 3-F 1.34 X TO"3 2.88 X I06 2.32 X I05 3-C1 1.69 X 10-3 7.17 X I06 1.90 X I05 3-Br 1.74 X 10-3 2.02 X I07 2.53 X I05 3-1 1.49 X IO-3 4.51 X I07 6.61 X I05 3-CF3 3.12 X 10-3 2.69 X I07 5.94 X 10" 3-CH3 4.15 X 10-" 1.26 X I06 3.79 X 10" 2-F 2.27 X TO"3 1.21 X I07 3.36 X I05 2-C1 2.67 X TO"3 7.82 X I06 1.87 X I05 2-CF3 3.84 X 10-3 3.56 X O5 1.27 X I03 2-CH3 4.61 X 10"" 1.78 X I05 1.43 X I03 2.5-C12 3.42 X 10-3 3.22 X I06 7.94 X I03 3,5-Cl2 2.26 X TO"3 8.59 X I06 8.34 X 10" 2,5-(CH3)2 2.56 X 10-" 1.48 X I05 2.8 X I02 3,5-(CH3)2 2.20 X 10-" 1.49 X I05 6.2 X I02 (Metcalf and Metcalf, 1973) 381 As the Nation's principal conservation agency, the Department of the Interi >r has responsibility for most of our nationally owned public lands and natural resjurces. This includes fostering the wisest use of our land and water resources, protecting our fish and wildlife, preserv- ing the environmental and cultural values of our national parks and historic al places, and providing for the enjoyment of life through out- door recreation. The Department assesses our energy and mineral resources and works to assure that their development is in the best interests of all our people. The Department also has a major responsi- bility for American Indian reservation communities and for people who live in island territories under U.S. administration. UNITED STATES DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE SERVICE EDITORIAL OFFICE AYLESWORTH HALL. CSU FORT COLLINS. COLORADO 80523 POSTAGE AND FEES PAID U.S. DEPARTMENT OF THE INTERIOR INT 423 NOTE: Mailing lists arc computerized. Please return address label with change of address.