BIOLOGICAL REPORT 85 (1.8) CONTAMINANT HAZARD REVIEWS
MAY 1986 REPORT NO. 8

DIOXIN HAZARDS TO FISH,
WILDLIFE, AND INVERTEBRATES:
A SYNOPTIC REVIEW

: Fish and Wildlife Service
Bs U.S. Department of the Interior
E47

MPC
Reading
Room

Other publications in the "Hazards" series.

Publication
Title number Status?

Mirex Hazards to Fish, Wildlife, and
Invertebrates: A Synoptic Review 85(1.1) Available

Cadmium Hazards to Fish, Wildlife, and
Invertebrates: A Synoptic Review S5(1.2) Available

Carbofuran Hazards to Fish, Wildlife, and
Invertebrates: A Synoptic Review 85(1.3) Available

Toxaphene Hazards to Fish, Wildlife, and
Invertebrates: A Synoptic Review 85(1.4) Available

Selenium Hazards to Fish, Wildlife, and
Invertebrates: A Synoptic Review 85(1.5) Available

Chromium Hazards to Fish, Wildlife, and
Invertebrates: A Synoptic Review 85(1.6) Available

Polychlorinated Biphenyl Hazards to Fish,
Wildlife, and Invertebrates: A
Synoptic Review 85(1.7) Available

@publications noted as available can be obtained from the Patuxent Wildlife
Research Center, U.S. Fish and Wildlife Service, Laurel, MD 20708.

OL

0 0301 0059836 3

Biological Report 85 (1.8)
May 1986 Report No. 8

DIOXIN HAZARDS TO FISH, WILDLIFE, AND INVERTERRATES:
A SYNOPTIC REVIEW

by
Ronald Eisler
Patuxent Wildlife Research Center

U.S. Fish and Wildlife Service
Laurel, MD 20708

“Woods Hole Oceanographic Institution

Fish and Wildlife Service
U.S. Department of the Interior

Contaminant Hazard Reviews

DISCLAIMER

Mention of trade names or commercial products does not constitute
endorsement or recommendation for use by the Division of Biological Services,
Research and Development, Fish and Wildlife Service, U.S. Department of the
Interior.

This report should be cited as:

Eisler, R. 1986. Dioxin hazards to fish, wildlife, and invertebrates: a
synoptic review. U.S. Fish Wild]. Serv. Biol. Rep. 85(1.8). 37 pp.

SUMMARY

Polychlorinated dibenzo- para- dioxins (PCDDs) are present as trace
impurities in some manufactured chemicals and industrial wastes. The chemical
and environmental stability of PCDDs and their tendency to accumulate in fat
have resulted in their detection within many ecosystems. In general, wherever
high levels of PCDDs have been detected, the source has been a hazardous waste
dump, an industrial discharge, or an application of PCDD-contaminated
herbicide.

There are 75 PCDD isomers; some are extremely toxic, while others are
believed to be relatively innocuous. The most toxic and most extensively
studied PCDD isomer’ is 2,3,7,8-tetrachlorodibenzo- para- dioxin
(2,3,7,8-TCDD). In the United States and elsewhere, accidental contamination
of the environment by 2,3,7,8-TCDD has resulted in deaths in many species of
wildlife and domestic animals. High residues of 2,3,7,8-TCDD in fish, i.e.,
more than 50 parts-per-trillion (ppt) wet weight, have resulted in closing
rivers to fishing. In the most seriously affected areas, hospitalization and
permanent evacuation of humans has been necessary. Laboratory studies with
birds, mammals, aquatic organisms, and other species have demonstrated that
exposure to 2,3,7,8-TCDD can result in acute and delayed mortality as well as
carcinogenic, teratogenic, mutagenic, histopathologic, immunotoxic, and
reproductive effects. These effects varied greatly among species.

No regulations governing PCDD contamination exist at present to protect
sensitive species of wildiife and aquatic organisms. However, the limited
data available suggest that 2,3,7,8-TCDD concentrations in water should not
exceed 0.01 ppt to protect aquatic life, or 10 to 12 ppt in food items of
birds and other wildlife. Additional data are needed in several areas:
background levels of PCDDs in natural systems; identification of fish and
wildlife populations at risk; relative importance of PCDD - sources;
toxicological effects of various PCDDs to aquatic biota and wildlife,
especially reproductive and immunosuppressive effects; and toxic and other
interaction effects of PCDDs with other groups of polychlorinated chemicals
having similar structure and properties, such as biphenyls, dibenzofurans, and
biphenylenes.

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CONTENTS

Page

SUMMARY). icc -¢. a osama ete hota Note eee 6s Sie OO eee iii
MABEES ea thos Sc Belem cee Proll st Risto ote Mie, be Hes! wy ens Bee ee Ue ee eee vi
AGKNOWMEDGMENIS < 02s.-c ra tatartareyiio tice ese 6i'%% wel) ou wt ele vet el. Gene eee reer vii
INTRODUCTION» osteo seme ts OCS SOR, eRe 6s So Ree ee i
ENVIRONMENTAL “CHEMESTIRN ce 0.00) ©) 6 co 0 70s ce sor chve S boe: see ol eee ee 3
BACKGROUND CONCENTRATIONS. cs 2 SOMERS ee ee OP Se 8
TOXIC AND SUBLETHAE ERFEGISOe 020 28a. be ns be ee ee ee 17
Generdlic-i- ss. a tne hele Ele se, fees os eehhs ou oe! BOW gS eee 17
Terrestrial Invertebrates fe Mie a ota 6 oe nelAwtenie ats Ste seem a eenne 17
Aguatie Ongantsms cc's, Sc 6 "se wifey o> wills: ow 5) 6) wo ols Fe eee 17
BrdS. | :s \evaeer ea ow al eet. eee OO IE Sweee ay oe eee ee 73}
COLDER ree ns ee ee a ee ere Py 23
CURRENT RECOMMENDATIONS ergs) Lbinre) <6) “6 cto 1S" ie! fe 0) \@ (Wa eves keener fo ore meer mice ae 28
EAERATURE *CLTED*¢ 2c 4 eo ate See MOr 2 ee ae ee eee 31

Number

TABLES

Levels of PCDDS in chlorinated phenols, and levels
of 2,3,7,8-TCDD in 2,4,5-T acid and ester formulations

(Hardel1 1983) Oo, 0 8% 8. 0:5) 0/0 OC... Cree els See! 1102 ©) 2.878 eS . . . .

Chemical and physical properties of 2,3,7,8-TCDD, also

known as CAS Registry No. 1746-01-6 (NIOSH 1984). .....

Concentrations of 2,3,7,8-TCDD measured in selected
organisms and nonbiological materials collected from
various locales. All values are in parts-per-trillion

(ng/kg) sfreshowetight. ceo is cenmeneennes cs. te, vo tie, aaeera

Effects of 2,3,7,8-TCDD on selected species of freshwater

ORGANS Gad o G@oomo o8-6 GO oO Oo OOO BOO OS on Oo

Acute toxicities of selected PCDD isomers to the guinea

pig and the mouse (Kociba and Schwetz 1982a,b). .......

Acute oral toxicities of 2,3,7,8-TCDD to mammals. ....

vi

Page

10

19

25
25

ACKNOWLEDGMENTS

I thank L.J. Garrett and J.E. Haber for library services; I.E. Moore
for secretarial help; Di. Stalling, C.E. Grue, and DME Swinetord stor
reviewing the manuscript; and C.H. Halvorson and J.R. Zuboy for editorial
assistance.

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INTRODUCTION

Accidental contamination of the environment by polychlorinated dibenzo-
ara- dioxins (PCDDs), especially 2,3,7,8-tetrachlorodibenzo -para- dioxin
2,3,7,8-ICDD), has been associated with poor reproduction of herring gulls
(Larus argentatus) in Lake Ontario (Stolzenburg and Sullivan 1983), with the
closure of selected rivers in Missouri to anglers due to high residues in fish
(Powell 1984), with the destruction of fish and wildlife in Vietnam during
military defoliation operations using phenoxy herbicides (Rappe 1984), and
with the death of livestock and wildlife in Missouri (Powell 1984) and Italy
(Fanelli et al. 1980b). For example, in 1976, massive kills of small animals
(predominantly rabbits and poultry) occurred within the’ first few weeks after
a chemical plant explosion in Seveso, Italy, in which 2,3,7,8-TCDD was
released; many humans were hospitalized (Fanelli et al. 1980b). Levels of
2,3,7,8-TCDD in milk from dairy cows and tissues of pigs, chickens, cattle,
goats, and sheep from Seveso were sufficiently elevated to pose a risk to
human health. Accordingly, all domestic livestock in the most’ seriously
afflicted areas were destroyed. In eastern Missouri during 1971, waste oil
contaminated with 2,3,7,8-TCDD was applied to control road dust (Powell
1984). Later, hundreds of horses kept in riding arenas became sick, and 75
died; deaths were also observed among dogs, rodents, chickens, cats, and birds
near the treated areas. Soils in Times Beach, Missouri were so _ heavily
contaminated with 2,3,7,8-TCDD that it was permanently evacuated in December
1982. The U.S. Environmental Protection Agency had earlier announced that
they would buy the dioxin-contaminated city of Times Beach; once purchase is
completed the city will no longer’ exist officially (Powell 1984).
Approximately 22 kg (48.4 pounds) of 2,3,7,8-TCDD were involved in the Times
Beach incident (Westing 1978).

PCDDs are present as trace impurities in some commercial herbicides and
chlorophenols. They can be formed as a result of photochemical and thermal
reactions in fly ash and other incineration products. Their presence in
manufactured chemicals and industrial wastes is neither intentional nor
desired. The chemical and environmental stability of PCDDs coupled with their
potential to accumulate in fat has resulted in their detection throughout the
global ecosystem. The number of chlorine atoms in PCDNs can vary between one
and eight to produce up to 75 positional isomers. Some of these isomers are
extremely toxic, while others are believed to be relatively innocuous. The
most toxic and extensively studied PCND isomer is 2,3,7,8-TCDD. In fact, it
is the most toxic synthetic compound ever tested under laboratory conditions.
This isomer is produced during the synthesis of 2,4,5-trichlorophenol, which

is used in the manufacture of the herbicide 2,4,5-trichlorophenoxyacetic acid
(2,4,5-T), and other trichlorophenoxy acids, and the germicide
hexachlorophene. There is general agreement that 2,3,7,8-TCDD is exceedingly
stable, readily incorporated into aquatic and_ terrestrial ecosystems,
extraordinarily persistent, and virtually impossible to _ destroy.
PCDD-contaminated phenoxy herbicides are not the only sources of 2,3,7,8-TCDD,
others include polychlorinated biphenyls and pentachlorophenols. The other 74
isomers enter the biosphere from a variety of sources (NRCC 1981). The fate
and effects of PCDDs--with special reference to 2,3,7,8-TCDD and its role in
poisonings of humans, aquatic organisms, wildlife, livestock, poultry, and its
contamination of vegetation, soils, and sediments--have been extensively
reviewed (Blair 1973; Cattebeni et al. 1978; Ramel 1978; Nicholson and Moore
1979; NRCC 1981; Hay 1982; Kociba and Schwetz 1982a,b; Choudhary et al. 1983;
Josephson 1983; Long et al. 1983; Stolzenburg and Sullivan 1983; NIOSH 1984;
Nriagu and Simmons 1984; Rappe 1984; Webb 1984; Kamrin and Rodgers 1985;
Stalling et al. 1985a,b; Young and Cockerham 1985).

This account summarizes available data on ecological and toxicological
aspects of PCDDs in the environment, with special reference to fish, wildlife,
and their diets. In addition, it reviews and provides recommendations for the
protection of sensitive species of wildlife and aquatic biota. This report is
part of a continuing series of synoptic reviews prepared in response to
requests for information from Resource Contaminant Specialists of the U.S.
Fish and Wildlife Service.

ENVIRONMENTAL CHEMISTRY

The PCDDs consist of 75 isomers that differ in the number and position of
attached chlorine atoms; each isomer has its own unique identity and
toxicological properties. The most toxic of the chlorinated dioxin isomers is
2,3,7,8-TCDD (Figure 1). It is one of 22 possible congeners of
tetrachlorodibenzo- p- dioxin. There is general agreement that PCDDs,
including 2,3,7,8-TCDD, are (or were, until recently) found in chlorophenols,
especially trichlorophenol and pentachlorophenol (Table 1), in certain phenoxy
pesticides (2,4,5-T; 2,4-D; Fenoprop; Silvex; Ronnel; Erbon; Agent Orange), in
hexachlorophene, and in polychlorinated biphenyls (used in electrical
transformers and capacitors, and contaminated with trichlorobenzenes). PCDDs
enter the environment through accidental release during chlorophenol
production, through aerial application of some phenoxy herbicides, and through
improper disposal of wastes into terrestrial and aquatic ecosystems (Ramel
1978; NRCC 1981; Ogilvie 1981: Choudhary et al. 1983; Josephson 1983;
Stolzenburg and Sullivan 1983; NIOSH 1984; Rappe 1984; Kamrin and Rodgers
1985). The PCDD content of technical products varies between manufacturers,
between lots and grades, and between various formulations of pesticidal
chemicals (NRCC 1981). More recently, PCDDs have been identified in effluents
from combustion products of municipal and industrial incinerators, including
fly ash and flue gas (Czuczwa and Hites 1984). These PCDDs may be associated
with small particles which have jong residence times in the atmosphere and can
become distributed over large areas. For example, in the Great Lakes
atmospheric transport of combustion products is the major source of PCDDs
(mostly octa-, hepta-, and hexa-CDDs) in sediments (Czuczwa et al. 1984).
High-temperature combustion of bituminous coal in an oxidized and chlorinated
atmosphere (produced experimentally) yielded chlorodioxins, mostly octa-,
hepta-, and hexa-CDDs and measurable quantities of tetra-CDDs (Mahle and
Whiting 1980). Other potential sources of PCDDs include fossil fuel power
plants, internal combustion engines, home fireplaces, and cigarette smoke
(Kociba and Schwetz 1982a,b), but they require verification.

In general, PCDDs exhibit a relative inertness to acids, bases,
oxidation, reduction, and heat. With increasing halogen content, they become
more environmentally and chemically stabile (NRCC 1981). PCDDs are usually
destroyed at temperatures greater than 1,000 C. They are resistant to
biological breakdown, concentrated in fat, not readily excreted, extremely
toxic to some animals, and the cumulative effects of small doses to both
animals and humans are a source of increasing concern (Stolzenburg and
Sullivan 1983). Most PCDDs are relatively insoluble in water, sparingly

o 0 ]
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Figure 1. Upper. Numbering system used for identification of
individual PCDD isomers. Lower. The isomer 2,3,7,8-tetrachlorodibenzo-
para-dioxin(2,3,7,8-TCDD).

Table 1. Levels of PCDDs in commercial chlorinated phenols, and levels
of 2,3,7,8-TCDD in 2,4,5-T acid and ester formulations (Hardell 1983).

Formulation Geographic Concentration, in mg/kg (ppm
locale PCDDs 53,/,8-ICDD
(year)
2,4,5-T Acid Sweden (1952) - 1.10
2,4,5-T Ester Sweden (1960) - 0.40
2,4,5-T Ester Finland (1962) - 0.95
2,4,5-T Ester Finland (1967) - 0.22
2,4,5-T Acid USA (1964) “ 4.8
2,4,5-T Acid USA (1969) - 6.0
Agent Orange USA (-) - 0.12
Agent Orange USA (-) ~ Sat
2,4,6-trichlorophenol Sweden (-) 3.0 -
2,4,6-trichlorophenol USA (-) 0.3 -
2,3,4,6-tetrachlorophenol England (-) 12.0 -
Pentachlorophenol USA (-) 1,900-2,625 -
Pentachlorophenol Germany (-) 6.8 -

soluble in organic solvents, and will decompose on exposure to UV light,
including sunlight (NIOSH 1984), or to hydroxy] compounds (Josephson 1983).
The isomer 2,3,7,8-TCDD is a colorless crystalline solid at room temperature
and decomposes when heated at greater than 700 C (Table 2).

Data on the biovailability of PCDDs are scarce. It is known that PCDDs
incorporated into wood as a result of chlorophenol (preservative) treatment
are bioavailable. Swine and poultry using chlorophenol-treated wooden pens or
litter have been found to be contaminated with PCDDs (NRCC 1981). Toxicities
of individual PCDD isomers can vary by a factor of 1,000 to 10,000 for isomers
as closely related as 2,3,7,8-TCDD and 1,2,3,8- TCDD or 1,2,3,7,8-penta CDD
and 1,2,4,7,8-penta CDD (Rappe 1984). Isomers with the highest biological
activity and acute toxicity have 4 to 6 chlorine atoms, and all lateral (ji.e.,
2,3,7 and 8) positions substituted with chlorine. On this basis, the most
toxic PCDD isomers are 2,3,7,8-TCDD, 1,2,3,7,8-penta CDD, 1,2,3,6,7,8-hexa
CDD, 1,2,3,7,8,9-hexa CDD, and 1,2,3,4,7,8-hexa CDD (Rappe 1984).

Although PCDDs are highly persistent, volatilization and photolysis are
major removal processes (NRCC 1981). In soils, 2,3,7,8-TCDD undergoes
photolysis rapidly on the surface in a few hours, but more deeply buried
2,3,7,8-TCDD could have a chemical half-time greater than 10 years (NRCC
1981). Microbial degradation of 2,3,7,8-TCDD in soils is slow, with
biological half-times estimated at 1.0 to 1.5 years (Ramel 1978). However,
2,3,7,8-ICDD was detected in northwestern Florida from samples of soils,

Table 2. Chemical and physical properties of 2,3,7,8-TCDD,
also known as CAS Registry No. 1746-01-6 (NIOSH 1984).
Criterion Property
Empirical formula Ga sin Ell (0
Percent by weight lea ve
Carbon 44,70
Oxygen 9595
Hydrogen S25
Chlorine 44.1
Molecular weight 322 6
Vapor pressure, mm Hg at 25 C 1.7x10
Melting point, C 305
Decomposition temperature, C >700
Solubilities, g/liter
o - dichlorobenzene 1.4
Chlorobenzene O72
Benzene 0.57
Chloroform Oc37
n - octanol 0.05
Methanol 0.01
Acetone 0.11 7
Water 2.0x10-

rodents, birds, lizards, fishes, and insects 12 years after application. This
half-time in soil was estimated at 2.9 years (Westing 1978). Uptake of
2,3,7,8-TCDD from soils by vegetation is considered negligible (Blair 1973;
Ramel 1978).

Other than 2,3,7,8-TCDD, identification difficulties with specific
isomers make quantification difficult. To date, there has been little effort
towards resolution of deficiencies in analytical methodology (NRCC 1981). A
detection level of 1 pg (10 ~12g), or lower, might be required to find
2,3,7,8-TCDD in a one gram sample. Analyses at such low levels are
complicated by interference from a multitude of other compounds, as well as by
the large number of PCDD isomers and their variations in chemical properties
(Rappe 1984). Although 2,3,7,8-TCDD is the most extensively studied PCDD
isomer, data on its fate and persistence are generally poor, interpretations
are frequently absent, and extrapolations from case to case usually
impossible. The general result is a qualitative concept of this compound's
behavior in environmental situations (NRCC 1981). The issue is further
confounded by the presence in biological and abiotic samples of chemicals of
similar structure and toxicological properties to that of 2,3,7,8-TCDD. These
isosteric compounds include: 2,3,6,7-tetrachlorobiphenylene; 2,3,7,8-chlorine
substituted dibenzofurans; and 3,3',4,4'-tetra-, 3,3',4,4',5-penta-, and

3,3',4,4',5,5'-hexachlorobipheny] (Stalling et al. 1985a,b). For example,
analytical results of fish, birds, and sediments indicated that every sample
that was positive for 2,3,7,8-TCDD also contained 2,3,/7,8-chlorine substituted
dibenzofurans (Stalling et al. 1985a,b).

BACKGROUND CONCENTRATIONS

Data are accumulating that indicate many PCDDs, in addition to
2,3,7,8-TCDD, are present in biological and abiotic samples (NRCC 1981;
O'Keefe et al. 1983; Petty et al. 1983; Stalling et al. 1983; Czuczwa et al.
1984; Lamparski et al. 1984; Kamrin and Rodgers 1985; Stalling et al. 1985a).
In general, wherever high levels of dioxins have been detected in the
environment, a local application of TCDD-contaminated herbicide, hazardous
waste site, or industrial discharge has usually been implicated as the source
(Stolzenburg and Sullivan 1983). At Eglin Air Force Base (EAFB), located in
northwestern Florida, contamination of a 208 hectare section with 2.778 kg of
2,3,7,8-TCDD (equivalent to 13 mg/ha) occurred between 1962 and 1970 as a
result of repeated, massive herbicide applications (Young and Cockerham
1985). The 2,3,7,8-TCDD isomer was present as an impurity in 76,740 kg of
2,4-D and 73,010 kg of 2,4,5-T applied to this section of EAFB during the
9-year span. Ecological surveys conducted between 1970 and 1975 showed an
apparently healthy and diverse wildlife fauna, although soil levels of 520 ppt
of 2,3,7,8-TCDD were frequently encountered, and 2,3,7,8-TCDD residues were
elevated in some species examined. The highest residues recorded in various
trophic levels were 283 ppt in whole beetle grubs, up to 1,360 ppt in whole
southern toads (Bufo terrestris), 360 ppt in viscera and 430 ppt in carcass of
a lizard, the six-Tined racerunner (Cnemidophorus sexlineatus), 18 ppt in
gonad and 85 ppt in gut contents of the spotted sunfish (Lepomis unctatus),
100 to 1,200 ppt in stomach contents of the southern meadowlark (Sturnella
magna argutula), and 300 to 2,900 ppt in liver and 130 to 200 ppt in pelt of a

eachmouse (Peromyscus polionotus) (Young and Cockerham 1985). The

significance of these elevated residues will be discussed later.

In some cases, 2,3,7,8-TCDD has constituted up to 95% of the total body
PCDD burden, as was true in lake trout, Salvelinus namaycush (O'Keefe et al.
1983), and rainbow trout, Salmo gairdneri (Petty et al. 1983) from Lake
Ontario. Concentrations of 2,3,7,8-TCDD in whole carp (Cyprinus carpio),
varied from 24% of total body PCDDs in Saginaw Bay, Michigan (Stalling et al.
1983), to 45 to 56% in the Niagara River (NRCC 1981). In herring gulls from
Saginaw Bay, 2,3,7,8-TCDD comprised 40 to 60% of the whole body PCDD content
(NRCC 1981; Petty et al. 1983), and 72 to 78% in gulls from Lakes Huron and
Ontario (Stalling et al. 1983, 1985a). In 1983, Forster's tern (Sterna
forsteri) from Green Bay, Wisconsin, contained 114 ppt of PCDDs in egg, of
which 41% was 2,3,7,8-TCDD; double-crested cormorants (Phalacrocorax auritus)
from the same area contained 25 to 214 ppt of PCDDs in whole body, of which
only 10 to 31% was 2,3,7,8-TCDD (Stalling et al. 1985a). The causes of the

observed variations are not known, but may be associated with localized inputs
from municipal sewage treatment plants (Lamparski et al. 1984) and with
atmospheric transport of incinerated domestic and industrial chemical wastes
(Czuczwa et al. 1984). For example, the PCDD composition of sewage sludge
from Milwaukee, Wisconsin, was relatively constant, as judged by analysis of
samples from 1933, 1981, and 1982 (Lamparski et al. 1984). Total PCDD content
in these samples ranged between 60,950 and 70,191 ppt, of which the great
majority was in the form of octa-CDDs (82-86%), hepta-CDDs (11.0-15.4%), and
hexa-CDDs (1.3-2.1%). However, the tetra-CDDs increased from 34 ppt in 1933,
to 138 in 1981, and to 222 in 1981; corresponding values for the 2,3,7,8-TCDD
isomer in 1933, 1981, and 1982 were 2.2, 11.0, and 16.0 ppt, respectively.
Other TCDD isomers also showed increases from 6 ppt in 1933 to 22 ppt in 1982
(1,3,7,8-TCDD), and during that same period from 2.2 ppt to 140 ppt (1,2,3,7-,
and 1,2,3,8-TCDD). It seems that chlorinated dibenzodioxins have been present
in dried sludge from this plant for at least 50 years. Their presence in this
material suggests that they may have been formed by the condensation of
chlorophenols resulting from the chlorination of naturally occurring phenolic
compounds (Lamparski et al. 1984). PCDDs were also found in sediments from
Siskiwit Lake on Isle Royale in Lake Superior, a location which can receive
only atmospheric inputs. The source of these compounds is the atmospheric
transport of dioxins formed by combustion of domestic and chemical wastes.
For example, particulates from a chemical waste incinerator in Midland,
Michigan had 260,000,000 ppt of octa-CDDs and 170,000,000 ppt of hepta-CDDs;
lower, but still elevated levels of 440,000 ppt of octa-CDDs and 310,000 ppt
of hepta-CDDs were measured in municipal trash incinerator particulates
(Czuczwa et al. 1984).

Data are limited on 2,3,7,8-TCDD concentrations in field collections of
biological and other materials (Table 3). In the Great Lakes area, fish from
the Tittabawasee and Saginaw Rivers, two tributaries of Lake Huron's Saginaw
Bay, contained up to 695 ppt of 2,3,7,8-TCDD (Stolzenburg and Sullivan 1983).
High 2,3,7,8-TCDD levels (87 to 162 ppt) were also recorded in fish from the
Niagara River, New York, and from parts of Lake Ontario; lower concentrations
(2 to 28 ppt) were noted in fish from Lakes Erie, Huron, Michigan, and
Superior (Stolzenburg and Sullivan 1983). Muscle from larger specimens of
commercial fish collected from Lake Ontario in 1980 had higher levels of
2,3,/,8-TCDD than smaller fish (Ryan et al. 1984), suggesting that
accumulation increases with age. The larger fish also contained high
concentrations (1.2 to 4.9 parts per million, fresh weight) of polychlorinated
biphenyls (Ryan et al. 1984), demonstrating a need to elucidate TCDD
interaction kinetics with other contaminants. Bottom-feeding fish, such as
carp and catfish, from rivers in Michigan during 1978, contained higher
2,3,/7,8-TCDD residues than surface feeders (Harless et al. 1982), indicating
an association with contaminated sediments. Sediments from the Spring River,
Missouri, contained 12 ppt of 2,3,7,8-TCDD immediately downstream of a now
defunct hexachlorophene facility (Kleopfer and Zirschky 1983); concentrations
in fish were measurable 111 km downstream from this disposal site (Table 3).
Fish from the Spring River (and also the Meremac River, Missouri) contained
inordinately high levels of 18 to 78 ppt of 2,3,7,8-TCDD, prompting the U.S.
Food and Drug Administration to issue a health advisory in 1982 against fish

Table 3. Concentrations of 2,3,7,8-ICDD measured in selected
organisms and nonbiological materials collected from various
locales. All values are in parts-per-trillion (ng/kg) fresh weight.

Ecosystem, taxonomic group, Concentration® Reference”
collection locale, year of (ppt )

collection, species, tissue,

and other variables

AQUATIC ORGANISMS

Amphibians

Seveso, Italy, 1978
Toad, Bufo sp., whole 200 Fanelli et al. 1980c

Molluscs

South Vietnam, during military
defoliation operations with 2,4,5-T
Various species, whole Max. 810 Ramel 1978

Fish

Massachusetts, 1983
Lake Winthrop
Muscle with skin
Brown bullhead,

Ictalurus nebulosus 25 Anon. 1984
Other fish species ND
Other bodies of water (5)
Muscle with skin, 8 spp. ND

Missouri, 1982
Spring River

Whole fish 26 Powell 1984
Fillets 18

Meremac River
Whole 78

Missouri, 1981
Spring River, whole
Distance, in km downstream from
hexachlorophene manufacturing facility

1 19 Kleopfer and Zirschky
5 37 1983
9 36

74 deel

111 0.8

10

Table 3. (Continued)

Ecosystem, taxonomic group, Concentration®
collection locale, year of (ppt )
collection, species, tissue,

and other variables

Niagara River, New York, 1981
Spottail shiner, Notropis hudsonius

Whole (4-60)
Cayuga Creek, New York, 1980
Fillets, 4 spp. (12-27)
Coho salmon, Oncorhynchus kisutch
Fillet a: ah) ee 21

Lake Ontario, 1980
Muscle fillet, skinless
White sucker,

Catostomus commersoni 3 (2-4)

Yellow perch,

Perca flavescens 3.8 (3.2-4.3)

Brown bullhead,

Ictalurus nebulosus 6.0 (3.4-8.6)

Channel catfish,

Ictalurus punctatus 15. 5 (1268-17 27)

American eel,

Anguilla rostrata 19.8 (6.4-38.5)

Rainbow smelt,

Osmerus mordax 20.0 (11.3-32.9)

Rainbow trout,

Salmo gairdneri 32

Lake trout, Salvelinus namaycush 4]
Whole

Lake trout 51

Lake Ontario, 1979
Rainbow trout

Muscle AW
Lake Ontario, 1978
Lake trout
Muscle 107
Brown trout, Salmo trutta fario
Muscle 162

Michigan Rivers, 1978
Muscle, edible
Lake trout ND
Smallmouth bass,
Micropterus dolomieui 8 (7-8)
Catostomids 11 (4-21)
Yellow perch 14 (10-20

iy

Reference>

Suns et al. 1983

O'Keefe et al.

1983

Ryan et al. 1984

OtKeefieretralls

NRCC 1981

O'Keefe et al.

O'Keefe et al.

NRCC 1981

Harless et al.

1983

1983

1983

1982

Table 3. (Continued)

Ecosystem, taxonomic group, Concentration® Reference”
collection locale, year of (ppt )

collection, species, tissue,

and other variables

Carp,
Cyprinus carpio 55 (20-153)
Channel catfish 157 (28-695)

Cayuga Creek, New York 1978
Coho salmon

Fillet 20 O'Keefe et al. 1983
Amsterdam, Netherlands
Eel, Anguilla anguilla
From sediments containing
5,000 ppt (dry weight )
Whole 1 en Heida 1983
Fat 3.9

TERRESTRIAL ORGANISMS
Higher plants

Seveso, Italy, 1976
Various species, leaves Max. 50,000,000 Ramel 1978

Annelids

Seveso, Italy, 1978
Earthworms, whole 12,000 Fanelli et al. 1980c

Reptiles

Seveso, Italy, 1978
Snakes, various spp.

Liver 2,700
Adipose tissue 16,000
Mammals

Seveso, Italy, 1978
Field mouse, Microtus arvalis

Whole 1,200 (70-49,000)
Rabbit, Lepus sp.
Liver 7,700 (2,700-13,000)

Seveso, Italy, 1976
Domestic goat, Capra sp.

12

Table 3. (Continued)

Saal. 08° 8&8 & = lS SS _

Ecosystem, taxonomic group, Concentration® Reference”
collection locale, year of (ppt )

collection, species, tissue,

and other variables

Liver 1253 Fanelli et al. 1980b
Rabbit
Liver
Precontamination 13 (0.3-55)
Postcontamination 85 (3.7-633)
Cow, Bos sp.
Milk
July 9 ND Fanelli et al. 1980a
July 28 7,900
August 2 5,100
August 10 2,500
Birds
Herring gull, Larus argentatus
Egg
Lake Ontario
1983 90 Stalling et al. 1985a
1980 (44-68) Ogilvie 1981
1971-72 (800-1,000)
1970 1,200 Nriagu and Simmons
1984
Other Great Lakes
1980 (2-14) Ogilvie 1981
Saginaw Bay
1980 (43-86)

Great Lakes area,
Green Bay and Lake Michigan
Black-crowned night-heron,

Nycticorax nycticorax
Whole

1982 2 Stalling et al. 1985a
1978 (12-59)
Double-crested cormorant,
Phalacrocorax auritus
Whole, 1983 4
Forster's tern, Sterna forsteri
Wisconsin, 198

Egg
Green Bay 47
Lake Poygan 9

13

Table 3. (Continued)

Ecosystem, taxonomic group, Concentration® Reference”
collection locale, year of (ppt )

collection, species, tissue,

and other variables

NONBIOLOGICAL MATERIALS

Soils

Seveso Italy

1978 3,500(10-12,000) Fanelli et al. 1980c
1976
Precontamination ND Fanelli et al. 1980b
Postcontamination 2,300(<0.75-51,000)
Southwest Missouri
1974 (220,000-440,000) Kimbrough 1984
1971 (31,800 ,000-33,000,000)

Pond sediments
Massachusetts, 1983
Lake Winthrop 5.9 Anon. 1984
Other ponds (5) ND
Municipal sewage sludge

Milwaukee, Wisconsin

1933 2 Lamparski et al. 1984
1981 11
1982 16

Industrial chemical and sludge samples

Trichlorophenol process

Still, bottom 111,000,000 Van Ness et al. 1980
Sump fluid

Upper layer 63

Lower layer 676,000
Sludge

Liquid 445 ,000

14

Table 3. (Concluded)

Ecosystem, taxonomic group, Concentration? Reference”
collection locale, year of (ppt )
collection, species, tissue,

and other variables

Solid 374,000
Process 79
Discharge 22,000

@Concentrations are listed as mean, (minimum-maximum), maximum=max.,
or nondetectable=ND, values recorded.

Peach reference applies to the values in the same row, and in
the rows that follow for which no other reference is indicated.

Ne)

consumption from these areas (Powell 1984). In Massachusetts, 6 ponds were
surveyed for 2,3,7,8-TCDD in 1983 after prior treatment with phenoxy
herbicides between 1958 and 1978 (Anon. 1984). Only one fish, a brown
bullhead (Ictalurus nebulosus), age 3+ years, contained measurable (25 ppt)
dioxin levels. Residues were not detectable in other species of fish sampled,
including several species of ictalurid catfish, yellow perch (Perca
flavescens), and chain pickerel (Esox niger). Negative results (less than 10
ppt 2,3,/,8-TCDD) were also documented in freshwater fish from Arkansas and
Texas following spraying of the herbicide 2,4,5-T (Shadoff et al. 1977).

In birds, the levels of 2,3,7,8-ICDD have been decreasing, according to
analysis of herring gull eggs from Lake Ontario. During the decade 1970-1980,
there was a reduction of about 50% in 2,3,7,8-TCDD levels every two years
(Ogilvie 1981; NRCC 1981; Nriagu and Simmons 1984). The reasons for the
decline are unknown, and the relevance to higher-chlorinated PCDDs has not yet
been’ determined. Until these questions are resolved and more substantative
data are acquired on dioxin residues in birds, the current predictive trends
on decline rates should be interpreted with caution.

Much of the information on 2,3,7,8-ICDD levels in wildlife and domestic
livestock are from the vicinity of Seveso, Italy (Table 3). There, on July
10, 1976, a chemical cloud containing 2,3,7,8-TCDD was released as a result of
an industrial accident. It contaminated the food (hay, grass, cut-up corn) of
dairy cows (Fanelli et al. 1980a). Grossly elevated levels (7,900 ppt) were
measured in milk from these herds at concentrations considered hazardous to
human health, i.e., more than 7,000 ppt (Fanelli et al. 1980a). Wildlife from
the most heavily-contaminated area appeared to accumulate 2,3,7,8-ICDD. Field
mice (Microtus arvalis), for example, contained very high whole body
concentrations Of 2,3,7,8-ICDD (up to 49,000 ppt) almost 2 years after the
critical contamination. The mechanisms for this phenomenon included ingestion
of contaminated soil and licking of their dioxin-contaminated pelt (Fanelli et
al... 1980c); In another study, no 2,3,7,8-TCDD was detected in livers of
mountain beavers (Aplodontia rufa) that fed for 45 to 60 days in Oregon
forests that had been sprayed with 2.2 kg of 2,4,5-T/ha (Newton and Snyder
1978). Although it was presumed that the herbicide was heavily contaminated
with dioxins, no chemical analysis of the 2,4,5-T was performed.

16

TOXIC AND SUBLETHAL EFFECTS

GENERAL

Information is lacking or scarce on the biological properties of PCDD
isomers, except 2,3,7,8-ICDD. The latter has been associated with lethal,
carcinogenic, teratogenic, reproductive, mutagenic, histopathologic, and
immunotoxic effects. There are substantial inter- and intraspecies
differences in sensitivity and toxic responses to 2,3,7,8-TCDD. Typically,
animals poisoned by 2,3,7,8-TCDD exhibit weight loss, atrophy of the thymus
gland, and eventually death. The toxicological mechanisms are imperfectly
understood.

TERRESTRIAL INVERTEBRATES

Reinecke and Nash (1984) reported that two species of earthworms
(Allolobophophora caliginosa, Lumbricus rubellus) showed no adverse effects
when held for 85 days in soils containing grossly elevated levels of 5 ppm of
2,3,7,8-TCDD, but both species died at 10 ppm. In soils containing lower
concentrations of 50 ppb of 2,3,7,8-TCDD, earthworms accumulated 5X _ soil
levels in 7 days. There was no avoidance of soils contaminated with
2,3,7,8-TCDD, suggesting indifference. No surface penetration of dioxins into
the body of earthworms was noted, and there was no biological breakdown of
2,3,7,8-TCDD during digestion as judged by the absence of mono-, di-, and
tri-CDD's in excrement. Worm-worked soils had 2,3,7,8-TCDD retention times of
80 to 400 days, suggesting that earthworms may significantly alter half-time
patterns of 2,3,7,8-TCDD in soils (Reinecke and Nash 1984).

Mutagenic responses were produced in Escherichia coli and certain strains
of Salmonella eA bacteria by 2,3,7,8-ICDD, but not by octa-CDD (Vos
1978). Further, chromosomal aberrations were induced in at least one species

of higher plant and mammal (Ramel 1978). It must be concluded at this time
that 2,3,7,8-TCDD is mutagenic or has mutagenic potential.

AQUATIC ORGANISMS

No data were available on lethal and sublethal effects of any PCDD isomer

iN7/

to aquatic organisms, except for 2,3,7,8-TCDD and freshwater biota (Table 4);
2,3,7,8-ICDD and liver microsomal enzyme activities in two marine species:
winter flounder, Pseudopleuronectes americanus, and the little skate, Raja
erinacea (Pohl et al. 1976); and 1,3,6,8-TCDD uptake and elimination by
fathead minnows and rainbow trout (Corbet et al. 1983).

Sensitive species of teleosts exhibited reduced growth and fin necrosis
at concentrations as low as 0.1 ppt of 2,3,7,8-TCDD after exposure for 24 to
96 hours. Concentrations of 1.0 ppt and higher were eventually fatal, and
exposure to lower concentrations of 0.01 ppt for 24 hours had no measurable
effect (Table 4). A typical 2,3,7,8-TCDD poisoning sequence in guppies
(Poecilia reticulatus) and coho salmon (Oncorhynchus kisutch) during a
postexposure observation period included: declining interest in feeding (5-8
days postexposure); skin discoloration and fin necrosis (30 days), with caudal
fin most severely affected; reduced resistance to fungal infestations; reduced
swimming; and, finally, death several weeks to months after exposure (Miller
et al. 1973). In general, older and larger fish die last, and smaller or
younger specimens succumb first (Norris and Miller 1974).

Histopathologic and teratogenic effects were noted in fry of rainbow
trout (Salmo gairdneri) exposed to 10 ppt of 2,3,7,8-TCDD for 96 hours as
eggs, or as yolk-sac fry (Helder 1981). Some fry showed extensive
degeneration and necrosis of the liver, and subsequently developed edema prior
to death. The remaining fry showed a high incidence of teratogenic changes,
including opercular defects, and foreshortened maxillas.

Invertebrates, plants, and amphibians were comparatively resistant to
2,3,7,8-TCDD. For example, there were no adverse effects on growth,
reproduction, or food consumption of algae, daphnids, and snails during
immersion for 32 days in solutions containing 2.4 to 4.2 ppt of 2,3,7,8-TCDD
(Yockim et al. 1978).

Accumulation of 2,3,7,8-TCDD from the aquatic environment was evident for
all species examined (Table 4). The isomer 1,3,6,8-TCDD was also accumulated
from the environment by freshwater teleosts, but accumulations were much lower
than predicted when compared to 2,3,7,8-TCDD, and elimination was 10 to 15
times more rapid than 2,3,7,8-TCDD (Corbet et al. 1983). In outdoor pond
studies, a major portion of the added 2,3,7,8-TCDD concentrated in aquatic
plants and at the sediment-water interface (Tsushimoto et al. 1982); however,
most (85-99%) of the 2,3,7,8-TCDD originally added to the ecosystem remained
in the sediments at the end of the study (Isensee and Jones 1975). Among
teleosts, body burdens of 2,3,7,8-TCDD increased with increasing concentration
in the water column and with increasing duration of exposure; on removal to
uncontaminated water, less than 50% was lost in 109 days (Miller et al.
1979). The significance of 2,3,7,8-TCDD residues in aquatic organisms is not
clear, and loss-rate kinetics are not fully documented; both areas merit
additional research.

18

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BIRDS

LD-50 values computed 37 days after a single oral dose of 2,3,7,8-TCDD
varied from 15 ug/kg body weight in Northern bobwhite (Colinus virginianus),
with 95% confidence limits of 9.2 and 24.5 ug/kg, to more than 810 ug/kg body
weight for the ringed turtle-dove (Streptopelia risoria). Mallards (Anas

latyrhynchos) were intermediate in sensitivity with an acute oral LD-50 value
of more than 108 ug/kg body weight (Hudson et al. 1984). For all 3 species,
death occurred 13 to 37 days after treatment; remission in survivors had
apparently occurred by day 30 posttreatment. Gross necropsy of ringed
turtle-doves that survived treatment showed enlarged livers, about twice
normal size. Bobwhites showed severe emaciation, high accumulations of uric
acid salts in connective tissues, and fluid accumulations in the pericardial
and abdominal cavities (Hudson et al. 1984). Some birds regurgitated within a
few minutes after treatment. Signs of intoxication that began 7 days after
treatment included excessive drinking, loss of appetite, hypoactivity,
emaciation, weakness, debility, muscular incoordination, increased reaction to
stimuli, fluffed feathers, huddled position, unkempt appearance, falling,
tremors, spasms, convulsions, and immobility (Hudson et al. 1984).

Domestic chickens were relatively sensitive to PCDDs, especially
2,3,7,8-TCDD, with an estimated 2,3,7,8-TCDD oral LD-50 range of 25 to 50
ug/kg body weight (Kociba and Schwetz 1982a,b). Chickens fed 1 or 10 ug of
2,3,7,8-TCDD, 1,2,3,7,8,9-hexa CDD, or hepta-CDDs per kg body weight daily for
21 days showed signs of chick edema disease, i.e., pericardial, subcutaneous,
and peritoneal edema; liver enlargement and necrosis with fatty degeneration;
and frequently resulted in death (NRCC 1981; Gilbertson 1983). Autopsies of
poultry killed by 2,3,7,8-TCDD in Seveso, Italy, in 1976 showed signs
characteristic of chick edema disease (Fanelli et al. 1980b). Pathological
signs of chick edema disease were also seen in herring gull chicks on the
lower Great Lakes in the early 1970's (Gilbertson 1983). Concentrations of
2,3,7,8-TCDD in eggs of the herring gull declined from about 1,000 ppt in 1971
to less than 80 ppt in 1981. This was accompanied by a decrease in the
frequency of chick edema disease (Gilbertson 1983). Decreases in levels of
other contaminants notably mirex were probably more important to the survival
of gulls in these colonies than 2,3,7,8-TCDD (Eisler 1985); however, little
data exist on the interaction of PCDDs, including 2,3,7,8-ICDD, with other
contaminants appearing concomitantly in bird tissues or their diets.

Although there presently is no evidence of biomagnification of PCDDs in
birds (Gilbertson 1983), it is speculated that piscivorous birds have a

greater potential to accumulate PCDDs than the fish that they eat (NRCC
1981).

MAMMALS

The greater toxic potential of certain PCDD isomers involves two
properties: halogen atoms occupying at least 3 of the 4 lateral ring

23

positions (2,3,7, 8 positions) and at least one of the adjacent ring positions
being nonhalogenated (Kociba and Schwetz 1982a,b). Comparative toxicity data
for selected PCDD isomers to the guinea pig (Cavia sp.) and the mouse (Mus
sp.) confirmed this generalization and demonstrated significant interspecies
differences in sensitivity (Table 5). Other PCDD isomers tested (2,8-di CDD,
octa-CDD) were relatively nontoxic to mice and guinea pigs (NRCC 1981).

Acute toxicity studies with 2,3,7,8-TCDD have shown’ marked
differences--up to 8,400X--between the single oral LD-50 dose for the guinea
pig and the hamster (Cricetus sp.) (Table 6). The acute oral LD-50 value of
0.6 ug/kg body weight for guinea pigs, suggests that 2,3,7,8-TCDD may be the
most toxic compound ever tested on small laboratory animals. The unusual
resistance of hamsters may be associated with its enhanced rate of metabolism
and excretion of 2,3,7,8-TCDD relative to other PCDD isomers examined (01son
et al. 1980b; NRCC 1981). Poisoning in mammals by 2,3,7,8-TCDD is typically
characterized by loss of body weight and delayed lethality; large interspecies
differences exist in lethal dosages and toxic effects (Vos 1978; Neal et al.
1979; Kociba and Schwetz 1982a,b; Josephson 1983; Matsumura 1983; Kimbrough
1984; Seefeld et al. 1984). For example, 2,3,7,8-TCDD produces prominent
chloracne-type skin lesions in man and monkeys, edema formation in birds, and
severe liver damage in rats, mice, and rabbits.

Intraspecies differences in sensitivity to 2,3,7,8-TCDD--up to 14
fold--were recently reported among 3 strains of mice; no reasons were given to
account for these differences. Oral LD-50 (30 day) values varied from 182 ug
2,3,7,8-TCDD per kg body weight in strain C57, the most sensitive strain
tested, and 296 for strain BD6, to 2,570 for strain DBA (Chapman and Schiller
1985). All 3 strains of mice evidenced a 25 to 34% weight loss prior to
death; however, there was no measurable decline in food consumption.

Atrophy of the thymus is a consistent finding in mammals poisoned by
2,3,7,8-TCDD, and suppression of thymus-dependent cellular immunity,
particularly in young animals, may contribute to their death. Although the
mechanisms of 2,3,7,8-TCDD toxicity are unclear, current research areas
include the role of thyroid hormones (Rozman et al. 1984), interference with
plasma membrane functions (Matsumura 1983), alterations in ligand receptors
(Vickers et al. 1985), the causes of hypophagia (reduced desire for food) and
subsequent attempts to alter or reverse the pattern of weight loss (Courtney
et al. 1978; Seefeld et al. 1984; Seefeld and Peterson 1984), and excretion
kinetics of biotransformed metabolites (Koshakji et al. 1984).

Developing mammalian fetuses are especially sensitive to 2,3,7,8-TCDD,
and maternal exposure results in increased frequencies of stillbirths. Among
live births, exposure to it produces teratogenic effects such as cystic
kidney, cleft palate, and spinal column deformities (Ramel 1978). Effects of
2,3,7,8-TCDD on reproduction are reported for rats (McNulty 1977; Murray et
al. 1979; Kociba and Schwetz 1982a,b) and monkeys (Ramel 1978; Barsotti et al.
1979; NRCC 1981; Kociba and Schwetz 1982a,b). In a 3-generation study with
rats, daily dose levels of 0.01 ug of 2,3,7,8-TCDD/kg body weight (equivalent
to 120 to 290 ppt or ng/kg in the diet), produce decreased litter size at

24

Table 5.

Acute toxicities of selected PCDD isomers to

the guinea pig and the mouse (Kociba and Schwetz 1982b).

Oral LD-50, in ug/kg body weight

PCDD isomer Guinea pig Mouse
2,8-di CDD >300 ,000 -
2,3,7-tri CDD 29,444 >3,000
2,3,7,8-TCDD 2 284
1,2,3,7,8-penta CDD 3 338
1,2,4,7,8-penta CDD ees >5 ,000
1,2,3,4,7,8-hexa CDD 73 825
1,2,3,6,7,8-hexa CDD 70-100 1,250
1,2,3,7,8,9- hexa CDD 60-100 >1,440
1,2,3,4,6,7,8-hepta CDD >600 -

Table 6. Acute oral toxicities of 2,3,7,8-TCDD to mammals.

Organism

Guinea pig
In corn oi]
In aqueous methyl]
cellulose

Rat

Rhesus monkey

Dog

Mouse

Rabbit

Hamster

®References:

LD-50, in ug/kg Reference?

body weight (ppb)

0.6 - 2 152

2.5 3
19 3
22 - 45 2
<70 4
100 - 200 2
114 - 284 2
115 4

1157 =) 15,051 2

1, Harless et al. 1982; 2, Kociba and Schwetz 1982a,b;

3, Silkworth et al. 1982; 4, Olson et al. 1980a,b.

25

birth, increased number of stillborns, and reduced survival and growth of
young in both the Fy and Fo generations. Reproduction was not affected in
rats at daily dosages of 0.001 ug/kg body weight, which are equivalent to 12
to 30 ppt or ng/kg of 2,3,7,8-TCDD in the diet. Abortion and weight loss were
reported in rhesus monkeys (Macaca mulatta) at dietary levels as low as 50 ppt
2,3,7,8-TCDD (about 0.0017 ug/kg body weight daily) after 7 to 29 months.
However, comparatively high dosages (200 ppt in diets equivalent to 0.0095
ug/kg body weight daily) could be tolerated by monkeys for short periods (3X
weekly for 3 weeks) with no adverse effects on reproduction. Higher dose
levels for extended periods (i.e., 500 ppt in diets equivalent to about 0.011
ug/kg body weight daily for 9 months) caused death (63%) or, among survivors,
abortion, chloracne, nail loss, scaly and dry skin, and progressive weakness.
Most treated monkeys remained fairly alert to external stimuli until just
prior to death. On removal from the 500 ppt 2,3,7,8-TCDD diet and transfer to
an uncontaminated diet, a severely affected monkey became pregnant and gave
birth to a well-developed infant after an uneventful gestation. This suggests
that some 2,3,7,8-TCDD damage effects are not permanent.

Androgenic deficiency in male rats given a single oral dose of 15 ug
2,3,7,8-TCDD/kg BW was evident as early as 2 days posttreatment, with
persistence up to 12 days.’ These deficiencies may account for male
reproductive pathology and dysfunction in rats treated with overtly toxic
doses of TCDD. Findings included depression in plasma testosterone
concentrations, as well as decreased weight of seminal vesicles (by 68%),
ventral prostate gland (by 48%), testes, and epididymis (Moore et al. 1985).

Accumulation of 2,3,7,8-TCDD is reported in the liver of rats during
lifetime exposure to diets containing 0.022 ug 2,3,7,8-TCDD/kg (Newton and
Snyder 1978), or when administered orally at 0.01 ug/kg body weight once a
week for 45 weeks (Cantoni et al. 1981). Liver residues of rats fed
2,3,7,8-TCDD were 0.54 ug/kg, or about 25X dietary levels; livers of rats
dosed orally contained 1.05 ug/kg, or about 2.3X the total dose received on a
unit weight basis.

Unlike toxicity, elimination rates of accumulated 2,3,7,8-TCDD were
within a relatively narrow range. The estimated retention times. of
2,3,7,8-TCDD in small laboratory mammals (rats, mice, guinea pigs, and
hamsters) extended from 10.8 to 30.2 days for 50% elimination and seemed to be
little influenced by species, concentration administered, duration of dose, or
route of administration (Blair 1973; Olson et al. 1980b; NRCC 1981; Koshakji
et al. 1984).

Histopathological effects have been reported in rabbits and horses
poisoned by 2,3,7,8-TCDD. Rabbits surviving exposure to an _ industrial
accident in Seveso, Italy, in which 2,3,7,8-TCDD was released, had edema,
hemorrhagic tracheitis, pleural hemorrhage, and dystrophic lesions of hepatic
tissue (Fanelli et al. 1980b). Horses from Missouri that died after waste
oi] contaminated with 2,3,7,8-ICDD was applied as a dust control agent in
riding arenas had liver lesions, skin hyperkeratosis, gastric ulcers, and lung
and kidney lesions (Kimbrough 1984). Since 2,3,7,8-TCDD is an extremely

26

potent porphyrogenic agent, it is probable that these animals also exhibited
porphyria, a condition characterized by fragility of the _— skin,
photosensitivity, and accumulation of porphyrins in the liver (Cantoni et al.
1981).

Teratogenic and fetotoxic effects of 2,3,7,8-TCDD are well-documented in
several species of animals (Harless et al. 1982; Kociba and Schwetz 1982a,b;
Kimbrough 1984; Weber et al. 1985). Cleft palate in young mice was associated
with daily dosages of 1.0 ug 2,3,7,8-TCDD per kg body weight in pregnant
females (no-effect level at 0.1 ug/kg), and intestinal hemorrhage was found in
sensitive strains of rats given daily dosages of 0.125 ug/kg body weight
(no-effect level at 0.03 ug/kg) (Kociba and Schwetz 1982a,b). The
2,3,7,8-TCDD isomer has been studied for carcinogenic potential in rats and
mice. There is a good correlation between carcinogenicity in both species and
long-term ingestion of higher dose levels that induce toxicity. In rats,
carcinomas in liver, pharynx, skin, lung, and thyroid were documented at daily
dosages of 0.01 to 0.1 ug of 2,3,7,8-TCDD/kg body weight; comparable values
for mice were 0.03 to 0.07 ug/kg body weight (Kociba and Schwetz 1982a,b). No
response occurred at continuous daily dose levels of 0.001 to 0.0014 ug/kg
body weight in rats and 0.001 to 0.03 in mice. Carcinogenic or cocarcinogenic
effects were also induced by 1,2,3,6,7,8-hexa CDD and 1,2,3,7,8,9-hexa CODD,
but only at higher dose levels (Rappe 1984). It appears that 2,3,7,8-TCDD has
a greater effect on growth, survival, and reproduction of animals than on
tumor formation.

Interaction effects of PCDDs with other polychlorinated compounds or
mixtures are not extensively documented. For example, certain polychlorinated
hexachlorobiphenyls (PCBs) have a _ low toxic potency to induce cleft palate
deformities in mice (Birnbaum et al. 1985). However, mixtures of 2,3,7,8-TCDD
and 2,3,4,5,3',4' hexachlorobiphenyl] resulted in a 10-fold increase in
incidence of cleft palate in mice. Thus, the toxicity of compounds such as
2,3,7,8-TCDD may be enhanced by compounds of relatively low acute toxicity
such as selected PCBs. Birnbaum et al. (1985) concluded that the widespread
environmental occurrence of such combinations suggests a need for further
evaluation of the mechanism of this interaction.

27

CURRENT RECOMMENDATIONS

At present, there are no criteria or standards promulgated for any of the
75 PCDD isomers, by any regulatory agency, for the protection of sensitive
species of wildlife and aquatic organisms. Data are scarce or missing on the
distribution and upper limits of background levels of PCDDs in natural
resources, on the identification of fish and wildlife resources potentially at
risk, on the relative importance of PCDD sources, and on the comparative
toxicities of various PCDDs to fish and wildlife, especially reproductive and
immunosuppressive toxicities (NRCC 1981). A similar situation exists for
human health protection, except for the 2,3,7,8-TCDD isomer.

For protection of human health, concentrations of 2,3,7,8-TCDD (in ppt
fresh weight) in fish muscle (and presumably other food items) considered
acceptable are 10 in New York State (Kleopfer and Zirschky 1983), 20 in Canada
(Kleopfer and Zirschky 1983), and 25 in other States within the U.S.,
according to the U.S. Food and Drug Administration (Stolzenburg and Sullivan
1983). Food items containing more than 50 ppt are considered unsafe for human
consumption, but fish fillets containing between 25 and 50 ppt of 2,3,7,8-TCDD
may be eaten once weekly by occasional consumers of fish, and twice monthly
for those who eat contaminated fish year round (Stolzenburg and Sullivan
1983). It is not known at this time whether residues of 10 to 50 ppt (or
higher) of 2,3,7,8-TCDD in fish flesh represents an unacceptable risk to the
growth, survival, reproduction, metabolism, or behavior of the teleost, or to
its predators; clearly, this is a high priority research topic.

For protection of aquatic life, it is conservatively estimated that water
levels of 2,3,7,8-TCDD should not exceed 0.01 ppt as judged by laboratory
studies with freshwater teleosts. The highest 2,3,7,8-TCDD concentration
tested to date which has no measurable adverse effect on freshwater fish is
0.01 ppt (Miller et al. 1979). The next highest concentration tested, 0.1
ppt, was associated with fin disease in guppies (Miller et al. 1979) and
eas growth of northern pike (Helder 1980) and rainbow trout (Helder
1981).

Diets containing up to 10 or 12 ppt of 2,3,7,8-TCDD may prove to be non-
hazardous to birds and other wildlife, as judged by the results of laboratory
studies with rats, monkeys, and chickens, and by the recommendations of New
York State for human health protection. Higher dietary levels of 12 to 30 ppt
of 2,3,7,8-TCDD (equivalent to about 1.0 ng/kg body weight daily) are not

28

harmful to rats, based on the results of a 3-generation study (McNulty 1977;
Murray et al. 1979). Unacceptable dietary levels of 50 ppt (equivalent to 1.7
ng/kg body weight daily) are recorded for monkeys (Ramel 1978; Barsotti et al.
1979; NRCC 1981).

In the past, the major source of 2,3,7,8-TCDD in the environment was as a
contaminant in phenoxy herbicides (such as 2,4,5-T; Silvex; 2,4-D; and Agent
Orange), in hexachlorophene, and in other chlorophenol-type compounds.
Concentrations of 2,3,7,8-TCDD in some of these products exceeded 60,000 ppb.
However, this situation has been largely corrected by new manufacturing
processes and by increasingly stringent Federal regulations (NRCC 1981;
Choudhary et al. 1983; Stolzenburg and Sullivan 1983; NIOSH 1984; Rappe
1984). For example, 2,3,7,8-TCDD level in 2,4,5-T has decreased from 60,000
ppb in 1957 to 2,000 ppb in 1965 as a result of new manufacturing processes,
and it was limited to 500 ppb in 1970 by the Canadian Federal Government. In
1970, the U.S. Department of Defense halted the spraying of Agent Orange. In
1972, the U.S. Food and Drug Administration banned the use of hexachlorophene
in nonprescription soaps and deodorants. In 1978, 7 of 14 major producers of
2,4,5-T no longer manufactured this product, and the remainder claimed that
their products contained less than 100 ppb of 2,3,7,8-TCDD. In 1979),
production of 2,4,5-T and Silvex ceased in the United States, although
stockpiles of both are still being distributed and permitted for use on rice
fields, sugarcane fields, orchards, fence rows, vacant lots, and lumber
yards. In 1982, the EPA required some industries to certify that
chlorophenol-type compounds were no longer used as slime control agents. On
October 18, 1983, EPA published its intent to cancel the registration of
pesticide products containing 2,4,5-T and Silvex, and to prohibit the
transfer, distribution, sale, or importation of any unregistered product
containing 2,4,5-T, Silvex, or their derivitives (NIOSH 1984).

At present, burning or heating of commercial and purified chlorophenates,
and pyrolysis of polychlorinated biphenyls contaminated with trichlorobenzenes
can result in the production of 2,3,7,8-TCDD and other PCDDs (NIOSH 1984),
These sources together with discharges from various municipal and industrial
incinerators of chlorinated compounds probably constitute the largest source
of PCDDs in the environment today. In 1983, the U.S. Environmental Protection
Agency proposed to monitor 2,3,7,8-TCDD in the environment (Stolzenburg and
Sullivan 1983). Specific goals of the monitoring program’ include:
determination of 2,3,7,8-TCDD concentrations in soils and biota, with emphasis
On geographic areas where PCDDS may have been manufactured, used, or
stored--and where concentrations may be in excess of 1,000 ppt; monitoring of
industrial and municipal incinerators for TCDD emissions; and establishment of
background levels for PCDDs in areas where these compounds are not expected to
occur in high levels. It seems that information is also needed on the
toxicological interactions of groups of polychlorinated chemicals (such as
certain biphenyls, biphenylenes, and dibenzofurans) known to be isosteric with

29

2,3,7,8-TCDD and which frequently coexist with 2,3,7,8-TCDD in environmental
samples. Acquisition of these data should provide the basis of a risk
assessment analysis for dioxin and fishery and wildlife resources.

30

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35

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37

50272 -101

REPORT DOCUMENTATION
PAGE

4 Title and Subtitle

1. REPORT NO. 3. Recipient’s Accession No.
Biological Report 85(1.8

5. Report Date

May 1986

Dioxin hazards to fish, wildlife, and invertebrates:
a synoptic review.

7. Author(s)
Ronald Eisler

9. Performing Organization Name and Address

8. Performing Organization Rept. No.

10. Project/Task/Work Unit No.

Patuxent Wildlife Research Center
U.S. Fish and Wildlife Service
Laurel, MD 20708

11. Contract(C) or Grant(G) No.

(C)

(G)

12. Sponsoring Organization Name and Address 13. Type of Report & Period Covered

14.

15. Supplementary Notes

-16. Abstract (Limit: 200 words)

Polychlorinated dibenzo-para-dioxins (PCDDs) are present as trace impurities in
various manufactured chemicals and in combustion products. The chemical and environmental
stability of PCDDs and their tendency to accumulate in fatty tissues have resulted in their
widespread detection throughout the global ecosystem. The most toxic and extensively
studied PLDD isomer is 2,3,7,8-tetrachlorodibenzo-para-dioxin (2,3,7,8-TCDD). Accidental
contamination of the environment by 2,3,7,8-TCDD has resulted in deaths in many species of
birds, wildlife, and domestic animals, and in the closing of rivers to fishing due to high
residues in fish, j.e., >50 parts per trillion (ppt) wet weight. Laboratory studies with
birds, mammals, aquatic organisms, and other species have conclusively demonstrated that
exposure to 2,3,/,8-TCDD can be associated with acute and delayed mortality, carcinogenic,
teratogenic, reproductive, mutagenic, histopathologic, and immunotoxic effects.

There are no regulations at present to protect sensitive species of wildlife and
aquatic organisms against any of the 75 PCDD isomers. However, the limited data available
strongly suqgest that 2,3,7,8-TCDD concentrations in water should not exceed 0.01 ppt for
the protection of aquatic life, or 10 to 12 ppt in the foods of birds and other wildlife.

17. Document Analysis a. Descriptors

MOxaGilney, Fishes
Contaminants Wildlife
Chlorohydrocarbons Natural resources

b. Identifiers/Open-Ended Terms
Dioxins

PCDD's

Metabolism
Sublethal effects

c. COSATI Field/Group

21. No. of Pages

eH

18. Availability Statement 19. Security Class (This Report)

Unclassified
20. Security Class (This Page)
Release unlimited Unclassified

{See ANSI-Z39.18) See Instructions on Reverse OPTIONAL FORM 272 (4-77)
(Formerly NTIS—35)
Department of Commerce

U.S. GOVERNMENT PRINTING OFFICE: 1987—774-207/65,067 REGION NO. 8

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Headquarters, Division of Biological
Services, Washington, DC

* astern Energy and Land Use Team
Leetown. WV

# = National Coastal Ecosystems Team
Slidell. LA

@ Western Energy and Land Use Team
Ft. Collins, CO

@ Locations of Regional Offices

REGION 1

Regional Director

U.S. Fish and Wildlife Service

Lloyd Five Hundred Building, Suite 1692
500 N.E. Multnomah Street

Portland, Oregon 97232

REGION 4

Regional Director

U.S. Fish and Wildlife Service
Richard B. Russell Building
75 Spring Street, S.W.
Atlanta, Georgia 30303

REGION 2

Regional Director

U.S. Fish and Wildlife Service
P.O. Box 1306

Albuquerque, New Mexico 87103

REGION 5

Regional Director

U.S. Fish and Wildlife Service

One Gateway Center

Newton Corner, Massachusetts 02158

REGION 7

Regional Director

U.S. Fish and Wildlife Service
1011 E. Tudor Road
Anchorage, Alaska 99503

REGION 3

Regional Director

US. Fish and Wildlife Service
Federal Building, Fort Snelling
Twin Cities, Minnesota 55111

REGION 6

Regional Director

U.S. Fish and Wildlife Service
P.O. Box 25486

Denver Federal Center
Denver, Colorado 80225

DEPARTMENT OF THE INTERIOR
U.S. FISH AND WILDLIFE SERVICE

As the Nation's principal conservation agency, the Department of the Interior has respon-
sibility for most of our nationally owned public lands and natural resources. This includes
fostering the wisest use of our land and water resources, protecting our fish and wildlife,
preserving the environmental and cultural values of our national parks and historical places,
and providing for the enjoyment of life through outdoor recreation. The Department as-
sesses 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 responsibility for
American Indian reservation communities and for people who live in island territories under
U.S. administration.