530R86102
Xl / // F ~n F
ATE
U ALITY
ADVISORY
ENDOSULFAN SULFATE
Criteria and Standards Division
i Water Regulations and Standards
United States
EInviranmental Protection Rgency
MRRCH 1 9 8 G
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WATER QUALITY ADVISORY
Number 4 .
ENDOSULFAN SULFATE
Criteria and Standards Division
Office of Water Regulations and Standards
United States Environmental Protection Agency
The advisory concentration for Endosulfan Sulfate in ambient water
for the protection of freshwater aquatic life is estimated to be 0.056
ug/L. The advisory concentration for the protection of saltwater
aquatic organisms is estimated to be 0.0087 ug/L. Care should be
taken in the application of this advisory, with consideration of its
derivation, as stated in the attached support document.
A value given to protect aquatic life can be derived from no
observed effect levels (NOEL), the lowest concentration found in the
data which has been observed to cause acute or chronic toxicity or
other experimental data which may be applicable. When there is no
valid experimental evidence, a value may be derived from a model which
uses structure-activity relationships (SAR) as its basis. The advisory
concentrations should be used with caution, since they are derived
from minimal experimental evidence, or in the case of SAR derived
values, no data on the specific chemical.
The advisory concentration for Endosulfan Sulfate in ambient water
for the protection of human health is estimated to be 74 ug/L, based
on data and information which are available to U.S. EPA. Care should
be taken in the application of this advisory, with consideration of
its derivation, as stated in the attached support document.
An advisory concentration can be derived from a number of sources:
The Office of Drinking Water Health Effects Advisories; Acceptable
Daily Intake(ADI) values from EPA; Office of Pesticides and Toxic
Substances risk assessments; Carcinogen Assessment Group(CAG) cancer
risk estimates; risk estimates derived from the open literature; or
other sources which will be given in the support document. The
advisory concentrations derived from these sources will vary in
confidence and usefulness, based on the amount and quality of data
used as well as the assumptions behind the original estimates. The
user is advised to read the background information carefully to
determine the strengths or deficiencies of the values given in the
advisory.
U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevar.d, 12th Floor
Chicago, IL 60604-3590
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HUMAN HEALTH AND AQUATIC LIFE
LITERATURE SEARCH AND DATA BASE
EVALUATION FOR
ENDOSULFAN SULFATE
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF WATER REGULATIONS AND STANDARDS
CRITERIA AND STANDARDS DIVISION
WASHINGTON, D.C.
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TABLE OF CONTENTS
INTRODUCTION 1
SCOPE OF SEARCH 2
SUMMARY OF FINDINGS 3
Aquatic Toxicity 3
Endosulfan 3
Endosulfan Sulfate 3
Health Effects 7
Endosulfan 1
Endosulfan Sulfate 11
CRITERIA EVALUATION AND RECOMMENDATIONS 12
Aquatic Toxicity 12
Human Health 12
REFERENCES 16
LIST OF TABLES
Table 1. Summary of Aquatic Toxicity Literature
Review of Endosulfan 4
Table 2. Summary of Human Health Effects Literature
Review of Endosulfan 8
Table 3. Data Requirements for Calculation of Aquatic Life
Interim CriteriaEndosulfan Sulfate 13
Table 4. Data Requirements for Calculation of Human Health
Interim CriteriaEndosulfan Sulfate 14
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HUMAN HEALTH AND AQUATIC LIFE
LITERATURE SEARCH AND DATA BASE
EVALUATION FOR
ENDOSULFAN SULFATE
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF WATER REGULATIONS AND STANDARDS
CRITERIA AND STANDARDS DIVISION
WASHINGTON, D.C.
INTRODUCTION
Endosulfan is an organochlorine of the cyclodiene group with the
chemical name 6,7,8,9,10,10-hexachloro-l,5,5a,6,9,9a-hexahydro-6,9-
methano-2,4,3-benzo-dioxathiepin-3-oxide. The most commonly used
trademark of endosulfan is Thiodan. The principle producers of
endosulfan are Excel Industries, Ltd., India; FMC Corp., USA;
Hinduston Insecticides Ltd., India; Hoechst AG, West Germany; Hooker
Chemical and Plastics Corp., USA., I. Pi. Ci. S. p. A., Italy.,
Maichteshim-Agan, Israel; and Velsicol Chemical Corp., USA.
Endosulfan sulfate is a metabolite of both the A and B endosulfan
isomers of the parent compound endosulfan. Endosulfan sulfate has
been found in tissues of both fish and rats as well as in soils where
it is reported to be more persistent than the parent compound (McEwen
and Stephenson, 1979).
Production of endosulfan in the United States was 3 million pounds
in 1974 (U.S. EPA, 1980). -The pesticide is used in agriculture for
control of a number of insect species and mites on deciduous, citrus
and fruit trees, vegetables, forage crops, grains, tobacco, coffee,
tea, and forest trees (McEwen and Stephenson, 1979). Endosulfan is a
brown, crystalline solid with a terpene-like odor and the following
physiochemical characteristics:
Molecular weight 406.95
Vapor pressure 9 x 10-3 mm Hg at 8C°C
Solubility in water 60-150 ppm
Melting point 70-100P°C.
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Endosulfan has a low water solubility and is relatively short-
lived in water systems (McEwen and Stephenson, 1979). Endosulfan
sulfate is an oxidation product of endosulfan with the chemical name
6,7,8,9,10,10-hexachloro-l,5,5a,6,9,9a-hexahydro-6-9-methano-2,4,3-
benzodioxathiepin-3,3 dioxide. Endosulfan sulfate reaches maximum
concentrations on plant surfaces and in soils 10 to 12 days after
application of the parent compound (Cassil and Drummond, 1965).
Fourteen days after application, endosulfan sulfate comprised about 50
percent of total endosulfan residues on leaves of sugar beets (Goebel
et al., 1982). Endosulfan sulfate levels in soil were 2 to 7 times
greater than the parent compound 2 to 15 months after application of
0.5 kg active ingredient of endosulfan per hectare to sugar beet
fields (Goebel et al., 1982). Additionally, levels of the sulfate
metabolite in water were up to 3 times greater than endosulfan shortly
after heavy application of parent compound to adjacent rice fields
(Goebel et al., 1982).
Although certain soil bacteria metabolize endosulfan to endosulfan
sulfate, fungi are the major microbial producers of the metabolite in
soils (Rup and Saxena, 1982). Endosulfan sulfate forms in both the
presence and absence of ultraviolet radiation; its production is
positively correlated with temperature (Cassil and Drummond, 1965.,
Goebel et al., 1982). The metabolite has a molecular weight of 422.9,
a melting point of 181°C, and less volatility than the parent com-
pound, resulting in greater persistence time (Goebel et al., 1982).
Endosulfan sulfate is also a metabolic byproduct in animals
which is excreted rapidly and is reportedly similar in toxicity to
the parent compound in rats (Cassil and Drummond, 1965; McEwen and
Stephenson, 1979., Das and Garg, 1981, Matthiessen et al., 1982).
The EPA published an Ambient Water Quality Criteria Document for
endosulfan which set criterion levels for aquatic life and human
health effects for endosulfan only (EPA, 1980). Endosulfan sulfate
was mentioned throughout the document but was not included in criteria
development. The investigation presented here evaluates data compiled
subsequent to the development of the endosulfan criteria and evaluates
endosulfan sulfate data with respect to requirements for criteria
development.
SCOPE OF SEARCH
Sources were identified though a computerized literature search of
TOXLINE, TOXBACK, NTIS and Toxicology Data Base focusing primarily on
dose-response studies published from 1965 to the present. Quality
assurance/quality control measures used during the study were eva-
luated for the use of positive and negative controls, replication, and
chemical analysis of test concentrations. Other information, such as
bioaccumulation/bioconcentration, food chain, ecological, and health
effects data were obtained where available.
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Studies were evaluated with respect to guidelines established by
the U.S. EPA in "Guidelines and Methodology Used in Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Quality
Criteria Documents" (FR 45:79347, November 28, 1980) and the "Guide-
lines for Deriving Numerical National Water Quality Criteria for the
Protection of Aquatic Life and Their Uses" (Stephan et al., 1985).
Data on the toxicity of endosulfan sulfate to aquatic organisms
and a review of human health effects are presented. Interim criteria
are estimated based on the summarized data and recommendations are
made for additional studies.
SUMMARY OF FINDINGS
Aquatic Toxicity
Endosulfan
Few studies on the aquatic toxicity of endosulfan have been
reported using species native to the U.S. since the publication of the
ambient water quality criteria for endosulfan in 1980 (U.S. EPA,
1980). Acute toxicity values reported since 1980 for invertebrates
ranged from 2.3 ppb for the stonefly Pteronarcys sp. to 9500 ppb for
the fresh water fairy shrimp Artemia salina (Table 1). Acute values
for Daphnia magna and Daphnia p_u_lex ranged from 130 to 740 ppb, which
fall within the range of acute values (62-740 ppb) for cladocera
reported in the 1980 water quality criteria for endosulfan (U.S. EPA,
1980). The mean value for acute toxicity for Daphnia magna was 435
ppb and the mean chronic value was 18 ppb. Therefore, the acute-
chronic ratio was 21, which also falls within those ratios (4.9-38)
reported in the 1980 criteria document. Acute values for inverte-
brates published since 1980 include 5.8 ppb for the amphipod (Gammarus
lacustris); 2.3 ppb for the stonefly (Pteronarcys sp.); and 60-70 ppb
for the damsel fly (Ischnura sp.). Although these values are in close
agreement with acute values reported in the 1980 criteria document,
the authors of these studies did not report quality assurance or
control procedures. The range of acute values for the remaining fresh
water invertebrate species was from 10 ppb for the snail (Ancylus sp.)
to 9500 ppb for the fairy shrimp (Artemia salina). These values were
also reported without mention of quality assurance methods.
The acute values for fishes exposed to endosulfan ranged from 1.1
ppb for rainbow trout (Sa_lmo gairdneri) to 11 ppb for carp (Cyprinus
carpio). Although these values are in close agreement with acute
values for the same species in the 1980 water quality criteria,
detailed quality control methods were not mentioned in these studies.
Endosulfan Sulfate
No reports of acute endosulfan sulfate toxicity to aquatic
organisms were found. One study, however, reported exposing a green
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alga, Chlorella vulgaris, and bluegreen alga, Phormidium sp., to
endosulfan sulfate for 120 hours and 14 days, respectively (Goebel et
al., 1982). Levels of endosulfan sulfate less than 10 ppm had no
effect on photosynthetic efficiency of Chlorella while levels greater
than 2 ppm caused decreased cell division. A 20 ppm endosulfan sul-
fate exposure produced a color change in Phormidium, while 1.25 ppm
had no effect. It is uncertain from this report whether these algae
were exposed to the metabolite directly or indirectly as a result of
exposure to the parent compound.
Endosulfan sulfate residues have been reported in fish tissues
that were exposed to endosulfan. After 28 days of exposure to
endosulfan and significant bioconcentration was observed in the
striped mullet (Mu^gJ.1. cephalus); endosulfan sulfate comprised nearly
all of the endosulfan residues detected (Schimmel et al., 1977).
Similarly, endosulfan sulfate accounted for nearly all residues of
endosulfan in three species of marine fishes exposed to endosulfan for
4 days (Schimmel et al., 1977). In contrast, however, nearly all of
the endosulfan residues detected in fathead minnows (Pimephales
promelas) were the A and B isomers, indicating an inability by this
species to completely metabolize endosulfan (U.S. EPA, 1980). The
excretion of endosulfan sulfate and endosulfan by fishes is rapid, and
is complete 2-14 days after dosing (Gorbach, 1972; Schimmel et al.,
1977) .
Endosulfan sulfate has been detected in waters and sediments
contaminated with the parent compound. Endosulfan sulfate levels in
water were 0.06 to 0.19 ppb, while endosulfan levels were 0.1 to 0.13
ppb after application of parent compound to nearby rice fields in Java
(Gorbach et al., 1971). Following a fish kill in Sincoe, Ontario,
bottom sediments of the affected pond had endosulfan sulfate levels of
1.1 to 1.2 ppb and endosulfan levels of 0.9 to 1.0 ppb while neither
compound was detected in the water (Frank, 1972). After application
of endosulfan (6 times in 3 months) to nearby vegetation at the rate
of 58.5 g/hectare in Botswana, the ratio of endosulfan sulfate to
endosulfan in fish tissues increased with time from about 1 to over 6
in waters with levels of 0.2 to 4.2 ppb endosulfan (Matthiessen et
al., 1982).
Health Effects
Endosulfan
Acute toxicity (LD50) values for endosulfan to rats ranged from 8
mg/kg by intraperitoneal injection to 781 mg/kg for dermal exposure
(Table 2). After a single oral dose of 40 ppm and repeated oral doses
of 20 ppm, increases in blood glucose were reported at both levels
with a decrease in plasma calcium reported at the higher dosage (Garg
and Kunwar, 1980). LD50 values for mice ranged from 6.9 to 13.5 mg/kg
by intraperitoneal injection and 147 to 359 mg/kg for rabbits by
dermal and percutaneous exposure. An LC50 for guinea pigs was 1,000
mg/kg from dermal exposure and 30 mg/kg for dogs from oral exposure.
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Chronic effects for rats included a reduction in weight gain from oral
exposure to 0.5 ppm for 9 weeks (Das and Garg, 1981) and increased
female mortality and decreased male testicular weight at 5 ppm for 2
years of oral exposure (Gupta and Gupta, 1979). Two years of dietary
exposure for dogs at levels of 3 ppm resulted in no observed toxic
effects (Goebel et al., 1982). OPP has judged the NOEL for dogs to be
30ppm, based on two long term (1 and 2 years) studies.
Teratogenic effects were observed at levels of 5 and 10 mg/kg
endosulfan after intraperitoneal injection to pregnant rats during
embryogenesis (Gupta and Gupta, 1979). On the other hand, no effects
on female rats or offspring were observed at dietary levels of 1.5 ppm
during the 15th-16th day of pregnancy or at 50 ppm in a three genera-
tion study (Goebel et al., 1982).
Effects of endosulfan on mutagenicity were contradictory.
Although mortality occurred at 22-55 ppm after 5 days of exposure by
intubation in rats, no inhibition of mitosis or chromosome damage was
evident in cells of bone marrow and seminiferous tubules (Dikshith and
Datta, 1978). Additionally, 48 hours of oral exposure to rats at 43.3
ppm caused no increase in clastogenesis (chromosonal breakage) in bone
marrow cells (Usha Rani et al., 1980). No evidence of mutagenicity
was found in Salmonella sp. by microsomal assays (Quinto et al., 1981)
However, a significant increase in mutation, gene conversion, and
chromosonal breakage occurred at 1 percent endosulfan (weight/volume)
in solution for the fungus Sacchavomyces cerevasia (Yadav et al.,
1982). Furthermore, after 24 hours exposure of 100 and 200 ppm in the
diet of the fruit fly Drosophila melanogaster, an increase was found
in the percent of sex-linked recessive lethal genes in first instar
larvae and 2-day old adults (Velazquez et al., 1984).
Exposure to endosulfan in the diet of rats (223 and 952 ppm) and
mice (2 and 3.9 ppm) for up to 106 weeks resulted in high mortality of
male rats while no carcinogenicity was evidenced in female rats and
mice (NCI, 1978). However, subsequent histopathological examinations
indicated significant increases in sarcomas and carcinomas (primarily
in endocrine organs) of female rats at both low and high doses
(Reuber, 1981). Although no significant increase in carcinomas
occurred in male rats, a high incidence of sarcomas was found, but was
not significantly greater than controls (Reuber, 1981). Because of
extremely high and variable doses of endosulfan and high incidences of
neoplasms in control rats, the carcinogenicity of endosulfan to rats
is uncertain from this study (Reuber, 1981).
Endosulfan Sulfate
Although the toxicity of endosulfan sulfate to mammals has been
reported to be similar to the parent compound, B endosulfan and endo-
sulfan sulfate had LD50 values of 76 mg/kg while B endosulfan exhi-
bited an LD50 of 240 mg/kg (Goebel et al., 1982). Endosulfan sulfate
was less effective than the parent compound in altering mitochondrial
11
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enzymes in rat liver homogenates (Dubey et al., 1984). Additionally,
endosulfan sulfate showed negative results for mutagenicity in Ames
tests (Quinto et al., 1981).
The majority of data from the literature with respect to endosul-
fan sulfate and mammals deals with tissue levels of the metabolite
after oral exposure to endosulfan. Endosulfan sulfate was the most
common metabolite in the organs, tissues, and feces of rats (Whitacre,
1970) and accounted for 15-80 percent of total endosulfan residues in
adipose tissues of rats fed 0.5 and 100 ppm of parent compound for 9
to 18 weeks (Das and Garg, 1981). Endosulfan sulfate was the major
form of endosulfan in liver, small intestine, visceral fat, and feces
of mice fed endosulfan at 10 ppm for 28 days (Deema et al., 1966).
CRITERIA EVALUATION AND RECOMMENDATIONS
Aquatic Toxicity
Until required studies are conducted, a AWQ criterion for
endosulfan sulfate cannot be calculated. The current freshwater and
salt water aquatic life criteria (24-hour average) for endosulfan are
0.056 ppb and .0087 respectively (U.S. EPA, 1980). Only two studies
were found since the publication of the criterion which provide
additional data appropriate for criteria calculations. The mean acute
values for Daphnia magna and Crangona septemspinosa fall within the
ranges reported for these and similar species in the 1980 criteria.
It is unlikely that the incorporation of these acute values would
alter the current criteria.
Endosulfan sulfate has been detected at significant levels in
tissues of fishes and in the waters and sediments adjacent to areas of
endosulfan application. No data on the acute or chronic toxicity of
endosulfan sulfate to aquatic organisms were found in this investiga-
tion. Because of the lack of these data, neither recommendation for
an interim criterion nor comparison with the existing endosulfan
criterion can be made. Data elements required for criteria develop-
ment formulae as defined by EPA (Stephan et al., 1985) are listed in
Table 3. This advisory recommends the use of endosulfan criteria
values in the absence of other data.
Human Health
The current criterion level for endosulfan is 74 ug/L for
ingestion water (U.S. EPA, 1980). This criterion was based upon a
no-observed-effect level (NOEL) of 0.4 ppm for mice fed endosulfan for
78 weeks (U.S. EPA, 1980). Because no acceptable data were found
(Table 4) reporting a NOEL less than 0.4 ppm for mammals, no revision
of the 1980 criterion for endosulfan is warranted. Although acute
toxicity values for endosulfan sulfate are similar to endosulfan for
rats, no long-term studies of toxicity for endosulfan sulfate have
been published. Because studies required by EPA (FR 45:79347) for
12
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TABLE 3. DATA REQUIREMENTS FOR CALCULATION OF AQUATIC LIFE
INTERIM CRITERIAENDOSULFAN SULFATE
Criterion Requirements
Aquatic Toxicity
Available Data
Acceptability
of Available Data
Acute Test Results from tests on:
A salmonid (class Osteichthyes) NO
A warm water species NO
commercially or recreationally
important (class Osteichthyes)
Another family in the phylum NO
Chordata (fish, amphibian, etc.)
A planktonic crustacean NO
(cladoceran, copepod, etc.)
Benthic crustacean (ostracod, NO
isopod, scud, crayfish, etc.)
Insect (mayfly, dragonfly, NO
damselfly, stonefly, mosquito, etc.)
Phylum other than Arthropoda/ NO
Chordata (Rotifera, Annelida,
Mollusca)
Another family of insect NO
Acute-chronic ratios with species from
three different families:
One fish NO
One invertebrate NO
Acutely sensitive freshwater NO
animal species
Acceptable test results from a test with:
Freshwater algae NO
A vascular plant NO
Bioaccumulation factor with a fresh- NO
water species (if a maximum permissible
tissue concentration is available)
13
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TABLE 4. DATA REQUIREMENTS FOR CALCULATION OF HUMAN
HEALTH INTERIM CRITERIA--ENDOSULFAN SULFATE
Criterion Requirements Acceptability
Human Health Effects Available Data of Available Data
Non-Threshold:
Carcinogen NO
Tumor incidence tests (Incidence of NO
tumor formation significantly more
than the control for at least one
dose level), or
Data set which give the highest NO
estimate of carcinogenetic risk, or
Lifetime average exposure tests, or NO
Human epidemiology studies NO
(if available, not required)
Threshold:
Non-carcinogens
No observed adverse effect level NO
(at least 90-day), or
Lowest observed effect level NO
Lowest observed adverse effect NO
level
Acceptable Daily Intake:
Daily water consumption YES YES
(EPA assumption)
Daily fish consumption YES YES
(EPA assumption)
Bioconcentration factor NO
Non-fish dietary intake YES YES
(EPA assumption)
Daily intake by inhalation NO
Threshold Limit Value:
(Based on 8-hour time-weighted NO
average concentrations in air)
Inhalation Studies:
Available pharmacokinetic data NO
Measurements of absorption efficiency NO
Comparative excretion data NO
14
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calculation of a water quality criterion for endosulfan sulfate are
currently lacking (Table 4), no recommendation of an interim criterion
nor comparison with the existing criterion for endosulfan can be made.
This advisory is recommending that concentrations of endosulfan sul-
fate not exceed the criterion for endosulfan, 74 ug/L, in the absence
of other data.
15
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REFERENCES
Cassil, C. C., and P. E. Drummond. 1965. A plant surface oxidation
product of endosulfan. J. Econ. Entomol. 58:356.
Das, N., and A. Garg. 1981. Effect of endosulfan in female rats
growing on low and high protein cereal diet. Pestic. Biochem.
Physiol. 15:90-98.
Deema, 0., E. Thompson, and G. W. Ware. 1966. Metabolism, storage
and excretion of 14C endosulfan in the mouse. J. Econ. Entomol.
59:546.
Dikshith, T.S.S., and K. K. Datta. 1978. Endosulfan: Lack of
cytogenetic effects in male rats. Bull. Environ. Contam. Toxicol.
20:826.
Borough, H. W., I. Huhtanen, T. C. Marshall, and H. E. Bryant. 1978.
Fate of endosulfan in rats and toxicological considerations of apolar
metabolites. Pesticide Biochemistry and Physiology. 8:241-252.
Dubey, R. K., V. Beg Mirza, and J. Singh. 1984. Effects of endosul-
fan and its metabolites on rat liver mitochondrial respiration and
enzyme activities in vitro. Biochem. Pharmacology. 33:3405-3410.
Federal Register. 1980. Guidelines and methodology used in prepara-
tion of health effect assessment chapters of the consent decree water
quality criteria documents. November 28, 1980. 45:79347-79356.
Frank, R. 1972. A fish kill near Simcoe, Ontario. Unpublished
report. Ontario Ministry of Agriculture and Food, Guelph, Ontario.
In: National Research Council of Canada, 1975. (As cited in U.S.
EPA, 1980)
Garg, A. and K. Kunwar. 1980. Endosulfan intoxication-blood glucose,
plasma electrolytes, Ca levels and hexokinase in rats. Indian J.
Biochem. Biophys. 17:113.
Goebel, H., S. Gorbach, W. Knauf, R. Rimpau, H. Huttenbach. 1982.
Properties, effects, residues, and analytics of the insecticide
endosulfan. Vol. 28. In: Residue reviews, residues of pesticides
and other contaminants in the total environment. Springer-Verlag, New
York, NY.
Gorbach, S. G. 1972. Terminal residues of endosulfan. Proc. 2nd
Int. Congr. Pestic. Chem. 6:283. (As cited in U.S. EPA, 1980)
Gorbach, S., R. Haarting, W. Knauf, and H. Werner. 1971. Residue
analyses in the water system if East Java (River Brantas, ponds,
seawater) after continued large-scale application of Thiodan in rice.
Bull. Environ. Contam. Toxicol. 6:40.
16
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U.S. Environmental Protection Agency
Region 5, Library (PL-12J)
77 West Jackson Boulevard. 12th Floor
Chicago, IL 60504-3590
-------
Gupta, P. K. and R. C. Gupta. 1979. Pharmacology, toxicology, and
degradation of endosulfan. A review. Toxicology. 13:115-130.
Johnson, W. W., and A. T. Finley. 1980. Handbook of acute toxicity
of chemicals to fish and aquatic invertebrates. Res. Bull. 137, U.S.
Dept. Int. Fish. Wildl. Serv., Washington, DC.
Matthiessen, P., P. J. Fox, R. J. Douthwaite, and A. B. Wood. 1982.
Accumulation of endosulfan residues in fish and their predators after
aerial spraying for the tsetse fly in Botswana. Pestic. Sci. 13:39-
48.
McEwen, F. L., and G. R. Stephenson. 1979. pp. 177-179. In: The
use and significance of pesticides in the environment. John Wiley and
Sons, Inc., New York.
National Cancer Institute (NCI). 1978. Bioassay of endosulfan for
possible carcinogenicity. Natl. Cancer Inst. Div. Cancer Cause and
Prevention. Bethesda, Maryland. DHEW Pub. No. (NIH) 78-1312. (As
cited in U.S. EPA, 1980)
Nebeker, A. V. 1982. Evaluation of a Daphnia magna renewal life-
cycle test method with silver and endosulfan. Water Res. 16:739-744.
Quinto, I., G. Martire, G. Vricella, F. Riccardi, A. Perfumo, R.
Giulivo, and F. DeLorenzo. 1981. Screening of 24 pesticides by
Salmonella/microsone assay: Mutagenicity of benazolin, metoxuron and
paraoxon. Mutat. Res. 85:265.
Reuber, M. D. 1981. The role of toxicity in the carcinogenicity of
endosulfan. Sci. Total Environ. 20:23-47.
Rup, L. and D. M. Saxena. 1982. Accumulation, metabolism and effects
of organochlorine insecticides on microorganisms. Microbiological
Reviews. 46:95-127.
Schimmel, S. C., J. M. Patrick, and A. J. Wilson. 1977. Acute toxi-
city and bioconcentration of endosulfan by estuarine anhnals. ASTM
Spec. Tech. Publ. 634:241-252.
Stephan, C. E., 0. I. Mount, D. J. Hansen, J. H. Gentile, G. A.
Chapman, and W. A. Brungs. 1985. Guidelines for deriving numerical
national water quality criteria for the protection of aquatic
organisms and their uses. U.S. Environmental Protection Agency,
Office of Research and Development, Environmental Research
Laboratories, Duluth, MN.
United States Environmental Protection Agency (U.S. EPA). 1980.
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PB81-117574.
17
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