Contribution from the Bureau of Bape na CARL L. ALSBERG, Chief

Washington, D. C. Vv November 12, 1920

TOXICITY OF BARIUM CARBONATE TO RATS.

By Ericu W. Scuwartze, Junior Pharmacologist, Pharmacological Laboratory.

CONTENTS. Page. Page. Purpose Of Investigation. 2-4 Sc ocak ee ss 1 | Results of experimental work on other barium PISVAIOUSINVESTISAtIONS 2. ee oeeee sts ul GOTT) OUTTA S Seer Oe as ae gay Dean aM eaane a 9 iE Xperunentaly proceG@uUres: se yee 3 | Toxicity of barium carbonate to animals Results of experimental work..............-. 4 oGherpbhan rats sey oe hia eee 9 Minimum efficient concentration of barium Wonehisions: 0) ee). Um ouch eee eRe eae 9 (CPT) OO} Or MSE ae ene er loca eT a GHileBibliogran hy seeseene eee oss ocak ee ena 10

PURPOSE OF INVESTIGATION.

A series of experiments on the toxicity of various substances to rats and their suitability for poisoning these animals was undertaken, in 1918, at the request of the Bureau of Biological Survey of the United States Department of Agriculture, for the purpose cf obtain- ing toxicological data for use in connection with the rat-extermina- tion work in the zone of occupation of the American Expeditionary Forces. Although this incentive ceased with the signing of the armis- tice, the studies have been continued because of their importance to agricultural economics as well as to the public health,

PREVIOUS INVESTIGATIONS.

The literature contains no references to. work dealing with the toxicity of barium carbonate to rats, in spite of the fact that many articles give directions for its use as a rat poison and discuss its tox- icity to other animals. The earliest communication which is of in- terest here is one by Crampe (5),+ who recommended 20 per cent barium carbonate in bait for poisoning field mice. Lantz’s (9) ba- rium carbonate formula also calls for 20 per cent of this substance. Recently White (20) has reported good results from poisoning Mus rattus by the use of 25 per cent of barium carbonate. This concen- tration, however, was ultimately diluted, as water was added to the barium carbonate bait mixture. White set out individual baits containing 3 grains (200 mg.) of barium carbonate. If entirely con-

1 The figures in parentheses refer to the bibliography at the end of this bulletin. 10939°—20—Bull. 915

BULLETIN 915,

U. S. DEPARTMENT OF AGRICULTURE.

sumed, one such bait for a rat of average size would amount to 600

or 800 mg. of the poison per kilo.

Storer (19) reported that calcium

carbonate (whiting) protected rats and mice against barium carbon- ate as well as lead carbonate poisoning. There is, however, some uncertainty about these experiments, in the absence of definite quantitative poison and food-intake data.

An illustration of an old popular conception of the ideal rat poison which was held by some investigators is found in the following trans-

lation by Boelter (4) from Raebiger (15):

‘‘T have come to the con-

clusion that preparations which are really nonpoisonous are unable to kill rats, and poisons, call them what you like, if they kill rats will

also kill domestic animals.’’

Raebiger’s resuits are in harmony with

all known facts, and demonstrate the fallacy of the conception of a poison specific for rats.

As the toxicity of barium salts to other animals is of interest both to the user of barium rat baits and to the laboratory worker, a a few citations (Tables 1 and 2) on this point are quoted.

TABLE |1.—Tovzicity to various animals of barium chlorid administered subcutaneously.

9 ; T j- Animal. Salt. sublethal -tethatdosen| = o «belt Citation. oe: per kilo. | Mg. per kilo. RG es eee ee ees Boo ks iBaClas24|Roan eet Sone EKO os caqg| Wey oss - Table 4 (p. 4). DD) ORES ee Seles do. 4008) See GOs poses Soe el eae Sete Bary (8). Aa Dib eeeeaa Sear icioee lies domssias| 20 and 46 AMO Wis acca! Deasesnosec 0. DO ay See ees Se ee ell ae dozte— se! 40 to 50 50 up Marya Maurel (10). IDDeS Reese se coseosedleae Gotwen aa tee 8 eee AAO seas escdsodade Kissner (8). DOS a Ee eicete yee cial ee GOs eA. es. Sastre 10 to 15 Jeet pete tae Ss Aloy and Cournet (1). ID) ORE ee ees GOSH ed | eee etc 15 and 17 WADE eet een Schedel (17). DORE eae See EES 2 Ee do. | Gand 19._._- 15020" A ee Ge SSE Wont Bary (3). DOE ease ee eee seal ose do. 4.5 to 14.3 Onlandi4e aes | e2eee eer eee | Pilliet and Malbec (14). Cater ne see eee do. le eee ee 18 to 60- EAA see vate ote Bary (38). - Chickents= qm eee alee dos25= 40 @?)) 2 50 and 80 Bes eee Do. PIS COMM as Sh ees Se SISO Nee do. (DeceeSce ee SOMID tac ease ees Maurel (10). WO aseset sscocbelssaeene|oos OOS eeerdlees saaeecceure CORE ere ee Ml aoe cee | Bary (8). TABLE 2.— Toxicity to various animals of barium salts administered per os. Animal. | Weight. | Barium salt.| “bseute | Dose per Result. Citation. Kilo Grams. Grams. : SUR ete See Sales Fo ar ae ard Ba CV seis: Wie le Te ae ete 0.355 to 0.533 | Fatal. . .| Table 5 (p. 4). Rabbitt ITS Lic Pera ee Ba(Co H; Oa OPMOE Sossa5L a (Vere aes ee GOS see Crawford (6). DOs 4 |PIGS0 SSE et ets ae 5005s eee OOree eae: fhe dose 42s Do. WOseS00 ese 13440} Peer es 6 ae ieee ws ik ee OCS eee eee GO neces eee | Bary (3 ye Sheep? s2-5.1s eee ate eel ee does A OO} Sees gee | i Se Survived......-. Dieckerhoff (7). DOSE AE aati ees aren do.. GLO00 BSS eS eas Ma tale ae ee - Do. Cattleree eC ae 25st + selma do. 40: 000 -2= | Set ee Survived.......- Do. TEVORS Oe sel erase es | eee do. SOOO ts eae eee eee Surv. wed, thera- Do. 12.000. peut MVR) Fa rae oe ees ager [ee Oa aos 1a OOO RE Eee (IBS SE socase Fatal, Tathlocnl Reynolds (16). ° effects in stomach from two boli. DOS see. SS VOMs WO ssese do. 720 to .900 OOD ee arse ee Mataltsntecces.5 Aloy and Cour- 10.000. net (1). PIP COM eee see Se s|oo ace GO ee SOO See Lae Survived 2......;| Maurel (10). ChickenBeiee ea: oa iBAcOz-eteee gS Be i wl Peer ek a Fatal. -| White (20). MAT ees | ere sare BaCliee see SiGe eee | Ree ee eer Fatalin 10 hours | Stern (18). Doe err ee eae. do. . 3 1Q) aera oe elle taco ek ee ee ee Pabals sss eee Am. Med. Assoc. (2).

1 Dose per 1,000 pounds of horse weight.

2 Yomited. 3 A. P. Chadbourne (personal communication) found that the lowest fatal dose of barium chlorid for

man was that reported by Stern. Approximately 8.6 grams were fatal in 10 hours.

In view of the prox-

imity of the fatal and therapeutic doses reported (2), the fatal dose ther ein given would seem to be rather

small.

TOXICITY OF BARIUM CARBONATE TO RATS. 3

Unfortunately, in some cases, exact lethal and sublethal doses are not known, since the amounts administered have not been based upon body weight. In other instances it has -been necessary to calculate some of the figures from the authors’ data. It would appear, however, that rabbits, chickens, and pigeons are about equally susceptible to barium administered subcutaneously, while cats and dogs are approximately three times as sensitive. Owing to differences in the physiology of the stomachs of the different species, and presumably to the differences in the average size between species, the toxicity of barium by mouth varies markedly, the purely species characteristic becoming more or less masked. For practical pur- poses, however, it may be assumed that the lethal dose of barium per os per kilo tends to decrease relatively as the size of the animal increases.

EXPERIMENTAL PROCEDURE.

In the experiments here reported the brown rat (Rattus norvegicus) was used as often as practicable. The domesticated white strain was employed for obtaining accurate food-intake data and for testing the relative efficiency of different percentages of barium carbonate in the bait. The melanotic strain was used in only a few toxicity ex- periments for purposes of comparison. The substitution of the white rat for the brown strain would seem fair, since the toxicity of barium to these two strains was found to be the same. The feeding experi- ments were confined, as far as possible, to the laboratory phase, although at times it was necessary to consider in some detail the practical aspects. In the experiments in which the stomach tube was used, the animals were first anesthetized with ether. The lethal doses are regarded, not as the minimum amounts which might be fatal, but those amounts which will kill a large proportion of the rats.

The barium chlorid administered was the ordinary crystalized salt (BaCl,-2H,0). The carbonate, which was of high purity and free from soluble chlorid, was always used in the form of fine powder, hav- ing been passed through a 100-mesh sieve. The molecular weight and barium content of these preparations are given in Table 3, since their relative toxicity is determined on the basis of their barium content.

TaBiE 3.— Molecular weight and barium content of barium chlorid and barium carbonate.

Serta Convelsion

olecular a actor of

Salt. weight. Barium. barium into salt.

Per cent.

BaCl,-2H,0O.. 244. 32 56. 2 1.778

BaCOge-2 sa 197. 37 69. 6 1. 437

Bae ae eee UIBY Ee | Dehn ug case ake

1 Atomic weight.

RESULTS OF EXPERIMENTAL WORK.

The results from the subcutaneous and oral administration of barium chlorid are summarized in Tables 4 and 5, respectively.

BULLETIN 915, U. S. DEPARTMENT OF AGRICULTURE.

TaBLe 4.—Tozicity of barium chlorid to brown rats (injected subcutaneously on the

abdomen). Barium nada aa Fatalities. in 0.65 — per Ba- see ero cent rium : solii- our. | hour. ber. tion. Mg.per | Még.per Per cent.| kilo. kiko. Die Oa 0. 45 20 35 0 0 0 Teles -45 25 45 0 0 3 a eee -45 35 62 1 1 0 isis ase -45 50 89 1 nO 3 Hebeaen -45 75 13 1 | 0 0 (sta ees -45 100 178 8 | 0 0

COR RISE WO

TABLE 5.—Toxicity of barwum chlorid to brown rats (injected by stomach tube after pre- liminary light etherization).

The subcutaneous lethal dose was from 45 to 89 mg. per kilo, and

the.ora!l lethal dose from 355 to 533 mg. per kilo.

From this it

would appear that barium chlorid is about six or seven times more toxic subcutaneously than per os.

The data obtained from the administration of barium carbonate in starch paste suspension by a stomach tube to etherized rats are

given in Table

TABLE 6.—Tozxicity of barium carbonate, 100 fine, suspended in starch paste (wnjected by tube after preliminary light etherization).

¥ Barium pee carbon- Kind of rats. of ate in suspen- rats. Sori PChs IBrOWME eee ceaae 16 10 ID Of Sas eee e 7 10 Wihites< sess soee 6 10 IBTOWNE: sees eee 7 20 Blackie eee ae 7 20 Whites oie 7 20 LBILOMNNe Serncoosoes 7 10 Doss eee 16 10 DOR oa eae ae 17 10

Barium. |!

Mg. per kilo. 350

400 400

525

700

830 to 1, 400 1, 400

Fatalities. Barium car- Aver- bonate. | 16th | 24th |; 4... |Num-|70tl| “age hour.) hour ber ee per | cent. Mg. per kilo. ae 500 3 0 0 3 19 19 630 5 0 1 6 86 \ 85 630 2 0 3 5 84 750 4 1 val 6 86 750 2 2 2 6 86 99 750 3 1 3 7 | 100 1,000 5 2 0 7; 100 1, 200 to 2, 000 14 ORS Sad. 15 94 92 2 15 0 0] 15] 88

TOXICITY OF BARIUM CARBONATE TO RATS. 5

From 630 to 750 mg. per kilo was found to be the least amount which could be considered efficient. On increasing the amount administered, however, there were still a few survivals, although the increased potency of the larger doses was clearly indicated by the relative increase of fatalities occurring within the first 16 hours. The occasional survival of an animal from a large dose would indicate that a 100 per cent mortality could not be expected.

Since it is possible for liquid to be forced through the pyloris under some conditions, these data have been checked against the results of feeding experiments (Table 7).

TABLE 7.—IJntake by hungry white rats of food containing 5 or 10 per cent barium carbonate.

2 Amount Barium Barium ; T W eight of of food carbonate | carbonate Result. 2 eaten. in food, eaten. fg. per Grams Grams. Per cent. kilo. 295 0.55 90 Lived 159 20 10 125 (6) 185 25 10 135 Do 184 - 50 5 140 Do 167 220 10 150 Do 286 .90 5 155 Do. 174 -30 10 170 Do. 198 OO) 16 175 O. 292 1.40 5 240 Dead within 48 hours 310 116 2595) 5 250 Lived. 215 30) 10 255 Do. 192 1.00 | 5 260 Do 245 1.40 5 285 Do 330 2hAb 5 375 Do. 206 1.55 5 375 Dead within 24 hours. 155 -65 10 420 Lived. 291 2.50 5 430 Do. 250 2.25 5 450 Dead within 40 hours. 175 85 10 485 Dead within 48 hours. 343 3.50 5 510 Lived. 148 1.60 5 540 Do. 166 1.85 5 555 Do. 188 1.05 10 555 Do. 193 2.40 5 620 Dead within 16 hours. 169 1.00 10 625 Dead within 72 hours. 270 3.60 5 655 Dead within 40 hours. 264 3.50 5 655 Do. 215 1.45 10 665 Dead within 48 hours. 280 4.10 5 730 Dead within 40 hours. 320 4.70 5 735 Do. 170 2.60 5 765 Do. 252 3.90 5 775 Lived. 366 5.70 5 780 Dead within 40 hours. 175 1.40 10 800 Dead within 24 hours. 215 1.75 10 815 Dead within 48 hours. 205 1.70 10 830 Dead within 24 hours. 167 1.40 10 840 Do. 167 1.45 10 870 Do. 150 115835) 10 900 Do. 144 3.60 5 1,270 Dead within 20 hours.

eee eee ee

The results of these two sets of experiments, given in the order of the barium carbonate intake per kilo, are in general agreement, the efficient lethal dose of barium carbonate being 630 mg. per kilo, or, more conservatively, 750 mg. On the basis of the barium content, this preparation of barium carbonate was from 57 to 75 per cent as potent as barium chlorid. In other words, approximately two- thirds of the carbonate was utilized in poisoning the animal. This does not mean, however, that every preparation of barium carbonate

6 BULLETIN 915, U. S. DEPARTMENT OF AGRICULTURE.

possesses an equally favorable ratio of toxicity, since both fineness and physical texture undoubtedly influence the relative ease of disintegration and rate of solution.

MINIMUM EFFICIENT CONCENTRATION OF BARIUM CARBONATE.

Since the experiments already discussed have dealt with the toxicological consideration of barium, there remained to be deter- mined the minimum concentration of barium carbonate in the poisoned bait which would give a high percentage of relatively quick fatalities. For these tests white rats were starved 12 to 24 hours before being fed the poison, to insure an empty stomach and a sharp appetite. The rat is a nocturnal animal and under ordinary circumstances probably would not be deprived of food for longer than 12 hours. A series of 14 rats, therefore, were starved for 12 hours and fed at 9 p. m. with the poisoned bait. As there was no marked difference between the results of this series and those of the experiments carried on in the daytime, with respect to both the average food mtake and the percentage of fatalities from the con- centration of barium carbonate used, it was concluded that the daytime experiments were valid.

It was occasionally observed for group tests that the average food intake varied somewhat, although the experiments were tried under as closely similar conditions as possible. For this reason the experi- ments were performed at widely separated intervals to minimize accidental influences and to make the general averages as represen- tative as possible. Sometimes the same rats were used over again, in which instances no evidence was obtained of their having derived any benefit from their previous experience. Because of the fact that the rats used in these tests had been living upon the concentrated type of experimental diet and had accordingly adjusted their appetite or daily food intake, the averages expressed for this type of food might be slightly less than those which would have been secured by the use of a more bulky type of food. Such a possibility, however, is of minor importance, since it would favor the probability of fatal poisoning because of the larger amount of food which might be consumed.

Several series of starved rats were for an hour offered different types of diet, such as grain, dog biscuit, and soft, mealy food. The last-named food, which consisted approximately of 70 per cent peanut meal, 10 per cent milk powder, and 20 per cent lard, was usually consumed much faster, more of it was eaten before the appetite was satisfied, and less was scattered or wasted. In addi- tion, the rapid consumption of food would occasionally seem very important, smce a few rats fairly soon gave evidence of discomfort, due presumably to the relatively quick solution of the barium car- bonate by the acid of the stomach, with consequent irritation.

TOXICITY OF BARIUM CARBONATE TO RATS. i

The results obtained from feeding both poisoned and unpoisoned food are summarized in Tables 8 and 9. The rats were divided arbitrarily into weight groups, and the food intake calculated on the per rat and the per kilo basis. The probable errors are given for individual observations as well as for each group.

TABLE 8.—IJntake of control food (rats divided into weight groups).

TaBLE 9.—Intake of food containing barium carbonate, all percentages (rats divided into ; weight groups).

MAOICOMOOEM eas sete 22 | 3,791 172 | 56.6 2.57 | 40.65 | +0.15 14.9 | +3.88 | +0.86 ZOOKO24 ORR EEE eee PAS Nb, 7083 220 | 68.5 2504) | e1 3 oN 20826 12.0 | +5.92 | +1.12 PHOLLOW IO: Eas ae 17 | 4,614 271 | 44.65 2.62) £1.0-) +£0.25 9.7 | 43.72 | +0.90 SOOMIPE Se eases anes 14 | 4,795 SIO T Bbes 2.56.| +£0.79 | +0:21 7.5 | +2.30} +0.62 Motallise eee es 79 | 18,903 239 | 205.55 DEO eee Nerec cathy, a ec LOS 85; yea ee eee

Slightly greater variations occurred in the control series, and would seem to indicate the need of caution in too strict a mathemat- ical interpretation. The data indicate, however, that on the average the food intake was approximately one one-hundredth of the rat’s weight, both for the control and the barium-carbonate-fed series, from which it was concluded that the barium carbonate added to the diet was perfectly palatable. Just why the food intake per rat for all of the groups is approximately the same, when the stomachs of larger rats have greater capacity, is not at. present clear. The greater food intake per kilo for the smaller rats is, under these cir- cumstances, without significance.

For practical purposes, however, the individual food intake is the most important (Table 7), since the rats which eat scantily are the ones which necessarily determine the percentage to be placed in the diet, because they must also ingest a lethal dose. With this object

8 BULLETIN 915, U. S. DEPARTMENT OF AGRICULTURE.

in view, different percentages of barium carbonate were fed. The results of these experiments are summarized in Table 10.

TaBLe 10.—E ficiency of different percentages of barium carbonate in the diet.

1920. Per : Per

cent ceni LIND) Og AMES sae eat 5 | 114 | Individual, in very large 6 0 2 (iS Fess dean) eevee cages. 1919. Mia 12 Ae eae ce aes 5 10 | Individual, in very small 5 0 i 1 Suleoees cages. Rep elb cg syste 5 Os ae GOR a aN epg a het Ae 6} (2) 1 2 sh ere an Mar? Since ee ie am 5 1) |v ee (Cope ee oar nme ies 6 | (?) 1 3 OFeess 4 Boy 29) KGS i ea ite A 5 A ah Fen Se ER TURE NO 2 D3 leotsse | 5 12 4 48 1919. ee eee AJybh aXe U7 Seite ae te ates 10 3 | Individual, in very small 2} () 1 0 On reem ee cages. 1920. DTD Rae OI rey 10 10 | Group,in very large cages. 5 4 1 Oueeers May See ae Sani ee 10 UO) Woeses CG Ko eae esa ace aN 5} () 1 1 Shea ANKE ee heat 10 RSA NG a ol Sees ea a NER SN Pfeil eats 11 2 3 70 1920. ye Be Ree erie ccs ACW A DOR Bees, aes Soe es 20 15 | Group, in very large cages. 0 13 2 (0) OUR: TMS Ona Rae es eo legen Sens 20 11 | Individual, in very large (@) 5 3 Done ase cages. Moya Ame ise ge 20 PASS) age aed ae Ne ce Sy ae a oe Oe cies oie 20 3 2 96 1 Fed at night. 2 No observation made.

About 50 per cent of the rats succumbed when fed 5 per cent barium carbonate. Most of the fatalities occurred after the twenty- fourth hour. On a diet containing 10 per cent, about 70 per cent of the rats died, the majority succumbing within the first 24 hours. Twenty per cent barium carbonate was even more efficient, only 5— per cent surviving and a great majority of fatalities occurring within the first 16 hours.

As already stated, the average food intake at a meal for the aver- age hungry rat is one one-hundredth of the body weight, and from 630 to 750 mg. of barium carbonate per kilo may be regarded as the fairly certain fatal dose. When 5 per cent barium carbonate is fed in the bait it would be necessary for all rats to eat 12.5 to 15 grams per kilo, or one-eightieth to one sixth-seventh of their body weight. Some of the rats will do this and die, and a few of those which eat slightly less will succumb. This explains why about 50 per cent of the rats which were fed this diet died. When a 10 per cent barium carbonate bait is fed, a rat must eat one one-hundred-and-sixtieth to one one-hundred-and-thirty-third of its body weight, or 63 to 75 per cent of a meal of averagesize. A 70 per cent mortality on this concen-

BPAY ce:

TOXICITY OF BARIUM CARBONATE TO RATS. 9

carbonate in the bait, it is necessary for the rats to consume only one three-hundred-and-twentieth to one two-hundred-and-sixty-sixth of their body weight, or 31 to 37 per cent of the average food intake, in order to ingest a lethal dose of barium carbonate. As a few will fail to do this and many eat much more, this concentration 1s efficient, as well as quickly fatal.

RESULTS OF EXPERIMENTAL WORK ON OTHER BARIUM COMPOUNDS.

Barium chromate was found to be nontoxic in doses as high as 2,000 mg. per kilo.

Barium soap, chiefly palmitate, was fairly toxic. Although not enough experiments were performed to definitely fix the lethal dose,

it would seem to be approximately equal to that of barium carbonate. .

Its ease of hydrolysis apparently would favor the mobilization of the barium, upon which basis it would be more desirable than the car- bonate. This fact, however, precludes its use in rat bait, since the hydrolysis occurring from a small amount of moisture would impart a disagreeable taste.

TOXICITY OF BARIUM CARBONATE TO ANIMALS OTHER THAN RATS.

Apparently rats are about as susceptible to barium administered subcutaneously as rabbits, chickens, and pigeons, and approximately one-third as sensitive as cats and dogs. When the barium is ad- ministered by mouth, however, the rat is comparatively the least susceptible of all the mammals cited, although the absolute amount is less, because of the small size of the rat.

If 20 per cent barium carbonate is used, it will be possible, on the basis of the recorded doses of barium chlorid, for adult animals to eat without fatal effects the following amounts of this rat bait: Sheep, one-half ounce; horses, 14 ounces; and cattle, 5 ounces. Pre- sumably, one and a half times this amount could be borne, since barium carbonate is less toxic than the soluble chlorid. The lethal dose of barium carbonate for chickens (20) is 20 grains, or one-fifth ounce, of rat bait containing 20 per cent of this poison. The danger to man, particularly children, is so very great that an amount of bait set for one or two rats might prove fatal.

CONCLUSIONS.

The lethal dose of barium compounds for rats is as follows: Barium chlorid, subcutaneously, 45 to 89 mg. per kilo; barium chlorid, by stomach tube, 350 to 535 mg. per kilo; barium carbonate, per os, 630 to 750 mg. per kilo. On the basis of the barium content, the carbonate is about two-thirds as active as the chlorid per os.

10 BULLETIN 915, U. S. DEPARTMENT OF AGRICULTURE.

The average intake of food, both poisoned and unpoisoned, by hungry white rats used in these tests was one one-hundredth of their body weight.

Twenty per cent of barium carbonate in the rat bait was found to be an efficient concentration. With this percentage a rat is required to eat only one-third or three-eighths of a meal of average size, or one three-hundred-and-twentieth to one two-hundred-and-sixty-sixth of its own weight, in order to secure the ingestion of a lethal amount. With this concentration, many of the rats die within the first 24 hours, the chief factor being the consumption of an amount larger than the minimum efficient lethal dose.

From the results of both the pharmidcologicn) and the feeding tests, it would not seem advisable to always expect 100 per cent

mortality from the administration of barium carbonate, in proper

amounts, to rats. BIBLIOGRAPHY.

(1) Atoy, J., and Cournet, A. Recherches toxicologiques sur le chlorure de baryum. J. pharm. chimie (1918), 17: 76. (2) AMERICAN MeEpIcaL ASSOCIATION. Rept. Council Pharm. Chem. Council Reports (1911): 53. (83) Bary, ALEXANDER. Beitrige zur Baryumwirkung. Inaugural Dissertation. Dorpat, 1888. (4) Bortter, W. R. The rat problem, p. 121. London, 1909. (5) Crampse, Hueco. . Bewiahrte Mittel gegen Feldmiuse. Deut Landw. Presse (1878), 5: 530; Jahresb. Agr. Chem. (1878) 7: 347. (6) CRAWFORD, ALBERT C. Barium, a cause of the loco-weed disease. U.S. Dept. Agr., B. P. I. Bull. 129 (1908). : (7) DIECKERHOFT, W, Ueber die Wirkung des Chlorbaryum bei Pierden, Rindern und Schafen. Berl. tierarztl. Wochschrift. (1895): 265. (8) KissnER, G. Ueber Baryum-Vergiftungen u. deren Einfluss auf d. Glykogengehalt der Leber. Diss. Schotten (Hessen), 1896. : (9) Lantz, D. E. The house rat: The most destructive animal in the world. U. 8. Dept. Agr. Yearbook (1917): 235. (10) Mauret, E. Fixation des doses minima mortelles, toxiques et thérapeutiques, de chlorure de baryum donné par la voie sous-cutanée a la grenouille, au pigeon et au lapin. Compt. rend. soc. biol. (1912), 72: 182.

(11) Influence de la voie d’administration sur les doses minima mortelles et sur les doses thérapeutiques de chlorure de baryum. Conia rend. soc. biol. (1912), 72: 250. (12)

De l’influence de la voie d’administration sur la production de la diarrhée par le chlorure de baryum. Compt. rend. soc. biol. (1912), 72: 299.

TOXICITY OF BARIUM CARBONATE TO RATS. 11

(13) Mavuret, E. Nouvelles recherches sur la dose minima mortelle de chlorure de baryum donné au lapin par la voile hypodermique. Compt. rend. soc. biol. (1912), 72. 360: (14) Pruuret, A., and Mausec, A. Note sur les lesions histologiques du rein produites par les sels de baryte sur les animaux. Compt. rend. soc. biol. (1892), 44: 957. (15) RAEBIGER. Masznahmen zur Bekaémpfung der Ratten, Méuse und Schneckenplage. Berlin, 1907. (16) Reynoups, M. H. A study of certain cathartics. Univ. Minn. Agr. Exp. Sta. 15th Ann. Rept. (1907): XxI. (17) ScuEpet, H. Beitrige zur Wirkung des Chlorbariums, besonders als Herzmittel. Mit einem Vortwort von R. Kobert. Diss. Stuttgart, 1903. (18) Stern, E. Vergiftung mit Chlorbaryum. Zeit. Medizinalbeamte (1896), 9: 381. (19) StormrR, F. H. Experiments on feeding mice with painter’s-putty and with other mixtures of pigments and oil. Bull. Bussey Inst. (1884), 2, pt. iv: 264. (20) Wurtz, F. Norman. Rat destruction. British Med. J. (Nov. 15, 1919): 629.

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