. . FINAL DRAFT
United States .- > Y ' - rp»n rru rnoo
, v ., x Environmental Protection * f' '><-c ECAO-CIN-bOyj
vu A Agency March, 1991
CT>
Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR ENDOSULFAN
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: DO NOT CITE OR QUOTE HEADQUARTERS LIBRARY
ENVIRONMENTAL PROTECTION AGENCY
** WASHINGTON, D.C. 20460
o_ NOTICE
LU
This document Is a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It 1s being circulated for comments
on its technical accuracy and policy implications.
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ORD CLEARANCE FORM
[1 EPA Report No. 2. Series 3. Lab/Office Draft No. 4. Cc
EPA/600/8 ECAO-Cin- G093 Q ,
Final Document Title:
1th and Environmental Effects Document for Endosulfan
SB. Final Document Title, if changed:
6. Authcirts), Affiliation, and Address (identify
fPA nuthors with Lab/Office)
10. OU/Obj./PPA/Project/Deliverable Output No.
D109 Y105
11. Technical Information (Program) Manager
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Document Manager ' '
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Braneti A-362(CinM*»*3/87)
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DISCLAIMER
This report Is an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
Health and Environmental Effects Documents (HEEDs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
Is Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for 1n this document
and the dates searched are Included 1n "Appendix: Literature Searched."
Literature search material 1s current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates {front
cover) reflect the date the document 1s sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfOs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD Is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time interval I.e., for an Interval that
does not constitute a significant portion of the Ufespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfOs is the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, RfDs are not estimated. Instead,
a carcinogenic potency factor, or q-j* (U.S. EPA, 1980a), is provided.
These potency estimates are derived for both oral and inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxlclty and carcino-
genicity are derived. The RQ is used to determine the quantity of a hazard-
ous substance for which notification is required in the event of
as specified under the Comprehensive Environmental Response,
and Liability Act (CERCLA). These two RQs (chronic toxicity
genlcHy) represent two of six scores developed (the remaining
ignitabilUy, reactivity, aquatic toxlclty, and acute mammalian toxlclty}.
Chemical-specific RQs reflect the lowest of these six primary criteria. The
methodology for chronic toxlclty and cancer based RQs are defined in U.S.
EPA, 1984 and 1986, respectively.
a release
Compensation
and carcino-
four reflect
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EXECUTIVE SUMMARY
Endosulfan 1s the common name for l,4,5,6,7,7-hexachloro-8,9,10 trlnor-
born-5-en-2,3,yleled1methylsulph1te. Two Isomers of this compound exist and
are commonly referred to as either a-endosulfan and B-endosulfan or
endosulfan I or endosulfan II. The two endosulfan Isomers can Interconvert
with one another. Technical grade endosulfan 1s a brown crystalline solid
with an odor of sulphur dioxide (Worthing and Walker, 1987). The pure endo-
sulfan Isomers are colorless solids at room temperature {Wlndholz, 1983).
They are slightly soluble In water (Worthing and Walker, 1987) and soluble
In most common organic solvents (Wlndholz, 1983). Endosulfan Is stable In
mineral acids, but It rapidly hydrolyzes In alkaline solutions (Worthing and
Walker, 1987). The sole U.S. producer of endosulfan Is SureCo, Inc., In
Fort Valley, GA (SRI, 1989). It Is produced by the D1els-Alder reaction of
hexachlorocyclopentadlene with butenedlol, followed by a condensation with
thlonyl chloride. Commercial endosulfan Is a mixture of the alpha (64-67%)
and beta (29-32%) Isomers, endosulfan sulfate and endosulfan dlol.
Endosulfan 1s a wide-range, nonsystemlc contact and stomach Insecticide
effective against numerous Insects and certain mites on cereals, coffee,
cotton, fruit, oilseeds, potatoes, tea, vegetables and numerous other crops
(Worthing and Walker, 1987).
In soil, the major removal processes of endosulfan are probably
biological degradation and, 1n basic soils, hydrolysis. Blodegradatlon has.
occurred In soil under aerobic (Martens, 1976, 1977; Miles and Hoy, 1979)
and anaerobic conditions (Martens, 1977). Losses of endosulfan in soil from
hydrolysis were 8% at pH 6.3, 28% at pH 7 and 90% at pH 8 after 10 days
(Martens, 1976). Endosulfan 1s expected to adsorb strongly to soils.
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Volatilization of endosulfan from the soil surface to the atmosphere Is not
expected to be significant.
If released to water, endosulfan 1s expected to adsorb to sediment and
suspended organic matter, moderately bloconcentrate 1n fish and aquatic
organisms and undergo destructive removal by hydrolysis. The rate constants
for hydrolysis of a-endosulfan and B-endosulfan have been experimentally
determined (Ellington et al., 1988), and the calculated half-lives for each
Isomer are 5.1x10= and 5.6xl05 days at pH 6, 9.0 and 7.8 days at pH 7
and 4.2 and 2.8 days at pH 8, respectively. Limited data are available on
the blodegradatlon of endosulfan In water, and Us fate by this process
cannot be determined. Volatilization of endosulfan from water to the
atmosphere 1s expected to be a significant process, with an estimated
volatilization half-life from a model river of between 3 and 7 days.
Data regarding the fate of endosulfan In the atmosphere are limited.
Direct photochemical degradation In the air Is not expected to occur to any
significant extent. Endosulfan has been detected In rainwater; therefore,
removal from the atmosphere by rain washout may occur. Endosulfan 1s
expected to exist primarily In the vapor phase In the atmosphere.
The general population may be exposed to endosulfan through Inhalation
and 1ngest1on of contaminated food. The U.S. Food and Drug Administration's
market basket survey, conducted from 1968-1984, found that the average dally
Intake (normalized for body weight) for adult males 16-19 years old ranged
from trace to 22 ng/kg bw (both a- and B-lsomer combined) from all food
groups. Endosulfan was commonly found In the potato, leafy vegetable,
garden fruit, fruit, o^l, fat and shortening food groups. The average dally
Intake of endosulfan for Infants and toddlers ranged from not detected to
15.5 ng/kg bw and not detected to 15.6 ng/kg bw, respectively (both Isomers
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combined). The average yearly Intake of endosulfan, determined during a
Canadian market basket survey performed 1n Ontario during 1985, was 140.1
Mg/year for A-endosulfan and 690.4 Mg/year for 8-endosulfan.
In the National Pesticide Monitoring Program conducted In 1970-1972,
endosulfan was only found In the first year In 6/16 of the states monitored.
In 1970, 6.6% of the samples tested positive for A-endosulfan, and 1%
tested positive for 8-endosulfan.
Occupational exposure to endosulfan 1s expected to occur for those
Involved 1n the production, formulation or application of this Insecticide.
A farmer applying this Insecticide to his fields Inhaled between 4490 and
36,570 ng/m1nute during mixing, and between 68 and 155 ng/mlnute during
spraying (Oudbler et al., 1974).
The acute toxlclty of technical grade endosulfan has been assessed with
at least 17 freshwater fish and Invertebrate and 14 saltwater fish and
Invertebrate natively-reproducing species using currently acceptable
bloassay techniques (Butler, 1963, 1964; Holcombe et al., 1983; Korn and
Earnest, 1974; Johnson and Flnley, 1980; Joshl and Rege, 1980; Joshl et al.,
1981; Kleiner et al., 1984; Lemke, 1980; LI and Chen, 1981; Macek et al.,
1969, 1976; Mayer and Ellersleck, 1986; Naqvl and Hawkins, 1988; Naqvl et
al., 1987; Nebeker, 1982; Nebeker et al., 1983; Pesch and Hoffman, 1985;
Pickering and Henderson, 1966; Sanders, 1969, 1972; Sanders and Cope, 1968;
Schlmmel, 1981; Schlmmel et al., 1977; Schoettger, 1970a; U.S. EPA, 1979,
1980c; Verma et al., 1981). Acute toxldty values for freshwater fauna
ranged from a 96-hour LC-- of 0.17 Mg/P for S. galrdnerl to a 48-hour
EC5Q of 750 Mg/P for 0. magna {Lemke, 1980), with fishes and benthlc
Invertebrate species being generally less sensitive than planktonlc Inverte-
brates. Acute toxlclty for saltwater fauna ranged from 0.04 Mg/P with
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pink shrimp, P. duorarum (Schlmmel et al., 1977), to 730 Mg/P with the
benthlc marine worm, N. arenaceodentata (Pesch and Hoffman, 1985).
Additional acute toxic responses to endosulfan (with nonnatlvely-reprodudng
species, with unreported forms or emulslflable endosulfan formulations or
for other toxic endpolnts) provide supporting evidence of the degree and
type of toxic effects that may result among exposed aquatic fauna (Deoray
and Wagh, 1987; Devi et al., 1981; Ferrando et al., 1987; Gopal et al.,
1981, 1985; Haider and Inbaraj, 1986, 1988; Joshl et al., 1981; Matthlessen
and Logan, 1984; Huley and Mane, 1986, 1987; Nebeker, 1982; Paul and Raut,
1987; Rao and Murty, 1980b, 1982; Rao et al., 1981; Roberts, 1975a; Singh
and Naraln. 1982; Swarup et al., 1981).
Acute tests of endosulfan conducted with the same species In the same
laboratory by both static nominal and flowthrough measured techniques showed
good agreement In most cases. Conflicting data have been reported regarding
effects of water hardness (as CaCCL) on endosulfan toxlclty (Pickering and
Henderson, 1966; Paul and Raut, 1987). There appears to be a positive
correlation between endosulfan toxldty and pH and temperature (Almar et
al., 1988; Ferrando et al., 1987; Macek et al., 1969; Paul and Raut, 1987).
Chronic toxlclty data are available for one freshwater Invertebrate and
three fishes, and for one saltwater Invertebrate and one fish (Breteler et
al., 1982; Joshl et al., 1981; Macek et al., 1976; Nebeker et al., 1983;
U.S. EPA, 1980b). Chronic values ranged from 0.2-108 Mg/P among fresh-
water forms, and for marine fauna were 0.40 and 0.69 Mg/P for M. bah1a
and C. varleqatus, respectively. Fish and M. bahla were more sensitive than
D. magna. Additional chronic toxlclty data regarding sublethal effects or
other lethal endpolnts support the above range of toxlclty (Dalela et al.,
1978; Gopal et al., 1982; Haider and Inbaraj, 1988; KhUlare and Wagh,
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1987; Kleiner et al., 1984; Mlshra et al.. 1986; Najml et a!., 1986; Pandey,
1988; Pesch and Hoffman, 1985; Rao and Nagabhushanam, 1987; Sastry and
Slddlqul, 1982; Shukla and Pandey, 1986; Vasantha and Parveen, 1988).
New significant data to Influence values for the Acute-Chronic Ratio or
the Final Chronic Value were not located In the available literature;
therefore, deferral Is recommended to the extant Freshwater Criteria and
Saltwater Criteria derived by the U.S. EPA (1980c) for the protection of
aquatic life from endosulfan (Section 7.2.}.
B1oconcentrat1on data were not located In the available literature for
freshwater species, and data derived from saltwater values are Inconclusive.
Highly disparate values were reported for C. varleqatus {U.S. EPA, 1980c)
and M. cephalus {Schlmmel et al., 1977). Data derived with Hytllus edulls
do not Include analyses of endosulfan sulfate, the predominant form In
tissues of other exposed species (Roberts, 1972). Available data, however,
suggest that endosulfan residues are quickly metabolized or purged to
nondetectable concentrations when fish are removed from endosulfan-polluted
waters.
Exposure of seven species of blue-green algae to 5-20 mg/P of endo-
sulfan (purity not reported) Induced retarded growth and decreased nitrogen
fixation (Shlvaprakash and Shetty, 1986). C_. vulgaMs was not sensitive to
exposures <10,000 Mg/P HC-endosulfan (technical grade) (Gohrbach and
Knauf, 1971). Growth Inhibition was noted at 2000 Mg/P with exposure
of Chlorella to an emulslflable concentrate (Knauf and Schulze, 1973). A
LOEC of 1 Mg/mp of endosulfan was reported for the freshwater algae,
Anabaena sp. and Auloslra sp. (Tandon et al., 1988), and a maximum
acceptable toxicant concentration of <47 Mg/P for the marine red algae,
Champ1a sp. (Thursby et al., 1985).
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Endosulfan had a 48-hour LCcn of 24 yg/cm2 In the earthworm, £.
foetlda (Roberts and Dorough, 1984). Direct contact L05Q values ranged
from 1.53-14.94 wg/g In PhllUplne plant and leaf-hoppers and from
7.33-96.07 ug/g In their arthropod predators (Fabellar and Helnrlchs,
1986). Endosulfan was not as toxic to Colorado potato beetle strains
previously exposed to similar pesticides, having direct contact LD_0
values of 207-251 yg/g. It produced a relatively mild Increase 1n
mortality of spotted tentlform leafmlner eggs exposed by spray (Hayden and
HowHt, 1986) and produced no mortality at all 1n green lace-wing eggs,
larvae or adults exposed to 0.0754 solution (Krlshnamoorthy, 1985).
Dose-related Increases In mortality were seen 1n larval and adult Orosophlla
exposed to 25-100 ppm (Creus et al., 1983). Endosulfan was less toxic to
very young ducklings (LDC = 27.8 mg/kg) and full grown ducks (LDC
50
50
34.4 mg/kg) than to ducklings of Intermediate ages (LD.n = 6.47-7.89
mg/kg) (Hudson et al., 1972).
Soil algae populations declined 1n a dose-related manner upon exposure
to endosulfan at 50-100 ppm. C. arJeUmim plants exposed to 0-10 ppm had a
concentration-related decrease In root and shoot growth (Agarwal and Beg,
1982). Exposure to 1000 ppm reduced pollen germination and length of the
pollen tube In cucumbers (Gentile et al., 1978). Concentration-related
growth Inhibition was reported 1n V. radlata exposed to >1500 ppm endosulfan
(Gupta and Gupta, 1980).
Oral exposure studies with rats Indicate that -80% of the endosulfan
dose 1s absorbed In 48 hours from the gastrointestinal tract (Dorough et
al., 1978). The highest levels occurred In male reproductive tissues and
kidneys after repeated oral exposures (Ansarl et al., 1984). Endosulfan
does not accumulate In fat but Is distributed to the brain (Gupta, 1978;
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Khanna et al., 1979). Data reviewed 1n Chapter 6 Indicate that the kidneys,
male reproductive tissues and CNS appear to be the main targets of
endosulfan toxlclty. Endosulfan Is excreted primarily In the feces from
bile. Single and repeated-dose oral studies with rats Indicate that fecal
and urinary excretion of endosulfan and metabolites Is ~60-7Q and 10-20%,
respectively (Dorough et al., 1978). The major excretory products are
unidentified polar metabolites. Nonpolar metabolites of endosulfan In
orally treated rats Include endosulfan dlol, endosulfan a-hydroxy ether
and endosulfan lactone. Appreciable quantities of endosulfan or metabolites
1n the feces and tissues are In an unidentified bound (unextractable) form
{Dorough et al., 1978).
Effects on kidneys, testes and Immunologlc and central nervous systems
In animals have been attributed to subchronlc and chronic oral exposure to
endosulfan. Rats treated with 7.5 but not 2.5 mg/kg/day doses of endosulfan
for 60 days experienced Increased liver and lung weights, slightly decreased
testes weight, hyperactlvlty, tremors, clonlcotonlc convulsions and death
(Ansarl et al., 1984). Immunosuppresslve effects occurred In rats adminis-
tered diets containing 10 and 20 ppm endosulfan, but not 5 ppm, for 8-22
weeks (Banerjee and Hussaln, 1986); these Included decreased antigen
(tetanus toxold 1nject1on)-1nduced serum globulin (computed as ratios to
albumin) and IgG levels, decreased antibody tUres, decreased leucocyte
migration Inhibition (blood leukocytes), decreased macrophage migration
inhibition (peritoneal macrophages), and decreased spleen weights. Similar
Immunosuppresslve effects occurred In rats administered diets containing >3Q
ppm endosulfan, but not 10 ppm, for 6 weeks (Banerjee and Hussaln, 1987).
Decreased testes weight, degenerative testlcular alterations (e.g., tubules
devoid of spermatogenlc elements) and mortality occurred 1n rats orally
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exposed to 10 mg/kg/day but not 5 mg/kg/day doses of endosulfan for 15 days
(Gupta and Chandra, 1977). Rats that were orally administered endosulfan
for 58 days showed reduced activity of alkaline phosphatase In the ventral
prostate at >Q.625 mg/kg/day, decreased weights of reproductive tissues
("ventral prostate", decreased epldldymls, seminal vesicle and coagulating
gland) at >2.5 mg/kg/day, and decreased number and motlllty of spermatozoa
1n the vas deferens at >2.5 mg/kg/day (Gupta and SMvastava, 1980).
Although similar findings were reported by Gupta et al. (1981) and Ansarl
and Gupta (1981), reproductive performance was not evaluated In any of these
studies.
A review of the neurologic effects of endosulfan by Gupta and Gupta
(1979) describe the prominent symptoms of poisoning 1n rats and mice as
hyperactlvlty, tremors and convulsions of clonlc nature followed by death,
as well as decreased respiration, dyspnea and salivation. Neurotoxlc
effects reported 1n rabbits dosed with 225 mg/kg endosulfan by dermal
application Include hyperesponslveness to sudden sound and tactile stimuli,
fine tremors (whole body), moderate tremors, and episodes of clonlc
convulsions. In dogs administered an oral dose of 200-500 mg/kg of
endosulfan Increased salivation, vomiting, and tonic and clonlc cramps were
reported. Sheep grazing on strawberry fields sprayed with 35% endosulfan
(two sheep Ingesting a maximal dose estimated at 5 mg/kg) exhibited an
unsteady gait followed by an Inability to stand up. Srlkanth and Seth
(1990) reported that endosulfan Induces amlnopyrIne-n-demethylase and
aniline hydroxylase activities In the brain of rats and that endosulfan
potentiates malathlon neurotoxlclty In these rats. Agrawal et al. (1983)
determined that long-term endosulfan exposure (3 mg/kg l.p.) caused
aggressive behavior (foot-shock-induced fighting behavior) 1n 8-week-old
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male albino rats which was Inhibited by a serotonin blocker. Zaldl et al.
{1985} determined that repeated administration of the 1.0 mg/kg dose
produced significant Increases In labeled serotonin receptor binding as well
as foot-shock-induced fighting behavior, effects seen even 8 days after
cessation of treatment. Seth et al. (1986) described the effects of
endosulfan on various neurotransmltter receptors In pre- and postnatally
exposed pups and adult rats. Repeated administration of endosulfan during
geatatlon produced a significant decrease In the affinity and maximum number
of strlatal dopamlnerglc receptors of rat pups without affecting the binding
characteristics of other receptors. Endosulfan-dosed neonatal rats did not
exhibit a dopamlne receptor effect. However, there was an Increase In
serotonin and benzodlazeplne receptors resulting 1n a serotonerglc mediated
aggressive behavior. In comparison to adult rats the developing animals
exhibited a greater sensitivity and a differential response towards
endosulfan. Furthermore, these changes In adults were reversible whereas 1n
neonates these differences persisted even 8 days after cessation of
treatment. Anand et al. (1985) reported that rats exposed to 3 mg/kg
endosulfan by l.p. Injection demonstrated significant alterations 1n
neurological behavior.
An NCI (1978) bloassay was conducted 1n which endosulfan was adminis-
tered In diets to male rats at TWA concentrations of 408 ppm for 78 weeks or
952 ppm for 63 weeks (observed for 3 or 10 additional weeks, respectively),
female rats at TWA concentrations of 223 or 445 ppm For 78 weeks (observed
for 33 additional weeks), male mice at TWA concentrations of 3.5 or 6.9 ppm
for 78 weeks (observed for 14 additional weeks) and female mice at TWA
concentrations of 2 or 3.9 ppm for 78 weeks (observed for 14 additional
weeks). Toxic effects attributable to treatment occurred in rats at all
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concentrations; these Included marked early mortality in males, high
Incidences of toxic nephropathy In both sexes and testlcular atrophy.
Survival was markedly reduced In mice that were treated with endosulfan by
gavage at doses of 1 or 2.15 mg/kg/day on days 7-28 of age, followed by
treatment In the diet at concentrations of 3 or 6 ppm, respectively, for
73-76 weeks (BRL, 1968). Dogs treated with endosulfan 1n capsules at doses
<0.75 mg/kg, 6 days/week for 1 year showed no treatment-related effects on
growth, organ weights, biochemical and hematologlcal Indices, urine
chemistry or gross or hlstologlcal appearance of tissues (Keller, 1959a).
Available evidence Indicates that endosulfan Is maternally toxic,
fetotoxlc and teratogenlc. Effects In rats treated with 5 or 10 mg/kg/day
oral doses of endosulfan during gestation Included maternal deaths,
resorptlons and fetuses with skeletal abnormalities (Gupta et al., 1978).
Maternal effects (reduced body weight and signs of CMS stimulation) and
fetal effects (unspecified skeletal, visceral and external anomalies,
reduced size and weight) occurred In rats orally treated with 6 mg/kg/day
but not 2 mg/kg/day doses of endosulfan (Raltech Scientific Services, 1960).
Reproductive and fetal developmental effects were not observed In rats fed
3-75 ppm dietary endosulfan 1n a 2-generatlon study (Huntlngton Research
Center, 1984), but toxic alterations occurred In the kidneys of F,. males
at all levels. Fetotoxlc and developmental effects were not observed In
rabbits orally treated with 0.3-1.8 mg/kg/day doses of endosulfan during
gestation, but maternal toxlclty (Including death) occurred at 1.8 mg/kg/day.
Raltech Scientific Services (1980), summarized by the U.S. EPA (1982),
yielded fetal effects Including unspecified skeletal, visceral and external
anomalies with reduced size and weight at 6 mg/kg bw/day. Data necessary
for a full evaluation are unavailable. Gupta et al. (1978) demonstrates
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fetal anomalies (teratogenlc effects) at 5 mg/kg bw/day. Fetal skeletal
malformations Included a missing fifth sternebrae, flth metacarpus or an
extra rib. Studies detailing teratogenlc effects of endosulfan are
considered unreliable (U.S. EPA, 1982).
Signs of acute oral endosulfan Intoxication In animals Include hyper-
activity, depression, salivation, lacrlmatlon, labored respiration, tremors
and tonlcoclonlc convulsions (U.S. EPA, 1982; WHO, 1984). Oral LD^s of
9-121, 85 and 118 mg/kg have been reported for rats, mice and hamsters,
respectively. Estimated oral doses of 250-2500 mg/kg were lethal for humans
(Tsa1 et al., 1988); manifestations of poisoning Included gastrointestinal
Irritation, CNS Irritability manifested as seizures, respiratory depression
and cardiovascular collapse. Symptoms of occupational exposure (respiratory
and dermal) to endosulfan are similar to those of oral poisoning (Israeli et
al., 1969; Tlberln et al., 1970). Four-hour LC5Q values of 350 and 80
mg/m3 were determined for male and female rats, respectively (Ely et al.,
1967).
There Is limited evidence describing endosulfan cardnogenlclty. In NCI
(1978), Increased Incidences of tumors were not observed In male rats fed
diets containing >408 ppm, female rats fed >223 for 78 weeks, male mice fed
>3.5 for 78 weeks or female mice fed >2 ppm for 78 weeks. High early
mortality precluded evaluation of cardnogenlclty In the male rats and male
mice In this study. Tumor Incidences were not Increased In rats fed diets
containing 0, 10, 30 or 100 ppm endosulfan for 2 years (Keller, 1959b), but
lack of additional Information precludes evaluation of these data.
Treatment-related Increased Incidences of tumors did not occur In mice of
either sex that were treated with endosulfan by gavage at doses of 1 or 2.15
mg/kg/day on days 7-28 of age, followed by endosulfan administered in the
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diet at concentrations of 3 or 6 ppm, respectively, for 73-76 weeks (BRL,
1968; Innes et al., 1969). Relatively small numbers of animals (10-18/
group) and high mortality In both sexes of B6C3F1 mice (both doses) and
B6AKF1 mice (high dose) may have precluded detection or development of
tumors 1n this study. Tumor Incidences did not Increase In B6C3F1 or B6AKF1
mice of either sex 18 months following a single 2.15 mg/kg subcutaneous
Injection of endosulfan (BRL, 1968).
Endosulfan Induced mutation, gene conversion and chromosome aberrations
1n S. cerevlsae (Yadav et al., 1982), mutation 1n L5178Y mouse lymphoma
cells In vitro (McGregor et al., 1988), sex-linked recessive lethal mutation
and sex-chromosome loss In PxosoRhljA (Velazquez et al., 1984), chromosome
aberrations In bone marrow cells of Syrian hamsters treated by Intraperlto-
neal Injection (Dzwonkowska and Hubner, 1986) and sister chromatld exchange
1n human lymphold cells In vitro (Sobtl et al., 1983). Lack of mutagenldty
In bacteria (Fahrlg, 1974; Dorough et al., 1978; MoMya et al., 1983;
Pednekar et al., 1987), dominant lethality In mice (Arnold, 1972), chromo-
some aberrations In orally treated rats (Dlkshlth and Datta, 1978; Dlkshlth
et al., 1978) or mlcronucle! 1n orally treated mice (Usha Rani et al., 1980)
Indicate that the evidence for mutagenldty and clastogenlclty of endosulfan
should be regarded as Inconclusive.
Data were not sufficient to derive RfD values for Inhalation exposure.
An RfD of 0.0002 mg/kg/day for subchronlc oral exposure to endosulfan was
based on the LOAEL of 0.15 mg/kg/day associated with kidney toxlclty in the
2-generation rat study by Huntlngton Research Center (1984). An RfD of
0.00005 mg/kg/day for chronic oral exposure was based on the same data. An
RQ of 10 for chronic (noncancer) toxlclty was based on Increased mortality
In mice (BRL, 1968).
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Cardnogenlclty data In humans were not available In the literature.
Endosulfan was assigned to U.S. EPA Group D: not classifiable as to
carclnogenlcHy to humans. Data were not sufficient to derive slope factors
for Inhalation or oral exposure. A cancer-based RQ was not derived.
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TABLE OF CONTENTS
Page
1. INTRODUCTION 1-1
1.1. STRUCTURE AND CAS NUMBER 1-1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1-1
1.3. PRODUCTION DATA 1-3
1.4. USE DATA 1-3
1.5. SUMMARY 1-3
2. ENVIRONMENTAL FATE AND TRANSPORT 2-1
2.1. AIR 2-1
2.2. WATER 2-1
2.3. SOIL 2-4
2.4. SUMMARY 2-6
3. EXPOSURE 3-1
3.1. WATER 3-1
3.2. FOOD 3-1
3.3. INHALATION 3-3
3.4. DERMAL 3-6
3.5. OTHER 3-6
3.6. SUMMARY 3-7
4. ENVIRONMENTAL TOXICOLOGY 4-1
4.1. AQUATIC TOXICOLOGY 4-1
4.1.1. Acute Toxic Effects on Fauna 4-1
4.1.2. Chronic Effects on Fauna 4-23
4.1.3. Effects on Flora 4-26
4.1.4. Effects on Bacteria 4-27
4.2. TERRESTRIAL TOXICOLOGY 4-28
4.2.1. Effects on Fauna 4-28
4.2.2. Effects on Flora 4-30
4.3. FIELD STUDIES 4-30
4.4. AQUATIC RISK ASSESSMENT 4-31
4.5. SUMMARY 4-36
5. PHARMACOKINETICS 5-1
5.1. ABSORP1ION 5-1
5.2. DISTRIBUTION 5-1
5.3. METABOLISM 5-4
5.4. EXCRETION 5-7
5.5. SUMMARY 5-11
xv11
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TABLE OF CONTENTS (cont.)
Page
6. EFFECTS 6-1
6.1. SYSTEMIC TOXICITY 6-1
6.1.1. Inhalation Exposure 6-1
6.1.2. Oral Exposure 6-1
6.1.3. Other Relevant Information 6-8
6.2. CARCINOGENICITY 6-16
6.2.1. Inhalation 6-16
6.2.2. Oral 6-16
6.2.3. Other Relevant Information 6-18
6.3. MUTAGENICITY 6-18
6.4. DEVELOPMENTAL TOXICITY 6-21
6.5. OTHER REPRODUCTIVE EFFECTS 6-22
6.6. SUMMARY 6-25
7. EXISTING GUIDELINES AND STANDARDS 7-1
7.1. HUMAN 7-1
7.2. AQUATIC 7-1
8. RISK ASSESSMENT 8-1
8.1. CARCINOGENICITY 8-1
8.1.1. Inhalation 8-1
8.1.2. Oral 8-1
8.1.3. Other Routes 8-2
8.1.4. Weight of Evidence 8-2
8.1.5. Quantitative Risk Estimates 8-3
8.2. SYSTEMIC TOXICITY 8-3
8.2.1. Inhalation Exposure 8-3
8.2.2. Oral Exposure 8-3
9. REPORTABLE QUANTITIES 9-1
9.1. BASED ON SYSTEMIC TOXICITY 9-1
9.2. BASED ON CARCINOGENICITY 9-5
10. REFERENCES 10-1
APPENDIX A: LITERATURE SEARCHED A-l
APPENDIX B: SUMMARY TABLE FOR ENDOSULFAN B-l
APPENDIX C: DOSE/DURATION RESPONSE GRAPH(S) FOR EXPOSURE TO
ENDOSULFAN C-l
XV111
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4»
LIST OF TABLES
No. Title Page
1-1 Selected Chemical and Physical Properties of the
Isomerlc Endosulfans 1-2
2-1 Calculated Half-Lives for the Hydrolysis of Endosulfan. ... 2-3
3-1 Levels of Endosulfan In Surface Water and Sediment 3-2
3-2 Summary of Endosulfan Intake from FDA's Market Basket
Survey 3-4
3-3 Average Dally Intake of Endosulfan for Toddlers and Infants . 3-5
4-1 Acute ToxIcUy of Endosulfan to Natively-Reproducing
Aquatic Fauna 4-2
4-2 Acute Lethality of Endosulfan to Nonnatlve Fauna 4-18
4-3 Additional Sublethal Effects of Endosulfan on Aquatic Fauna . 4-21
4-4 Chronic Values for Endosulfan 4-24
4-5 Genus Species/Mean Acute Values for Endosulfan 4-32
5-1 Distribution Patterns of A- and B-Isoraers of Endosulfan
In Tissues of Rat After Oral Administration for 60 Days . . . 5-3
5-2 Distribution of Endosulfan 1n a Human Following Acute
Ingestlon 5-5
5-3 Extraction Characteristics of Residues 1n Excreta and
Tissues of Rats Treated with [HC]Endosulfan 5-8
6-1 Acute Oral Lethality of Endosulfan In Animals 6-9
6-2 Genotoxlclty Testing of Endosulfan 6-19
9-1 Oral ToxIcUy Summary for Endosulfan 9-2
9-2 Oral Composite Scores for Endosulfan 9-4
9-3 Endosulfan: Minimum Effective Dose (MED) and Reportable
Quantity (RQ) 9-6
xtx
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LIST OF FIGURES
4-2
Title Page
Organization Chart for Listing GHAVs, GMCVs and BCFs
Required to Derive a Numerical Water Quality Criteria by
the Method of U.S. EPA/OWRS (1986) for the Protection of
Freshwater Aquatic Life from Exposure to Endosulfan 4-34
Organization Chart for Listing GHAVs, GHCVs and BCFs
Required to Derive a Numerical Water Quality Criteria by
the Method of U.S. EPA/OWRS (1986) for the Protection of
Saltwater Aquatic Life from Exposure to Endosulfan
5-1
Metabolism of Endosulfan 1n Animals
4-35
5-6
-------
LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AEL Adverse effect level
BCF Bloconcentratlon factor
CAS Chemical Abstract Service
CBI Confidential business Information
CNS Central nervous system
CS Composite score
DMSO Dimethyl sulfoxlde
DNA Oeoxyrlbonuclelc add
ECso Concentration effective to 50% of recipients
(and all other subscripted dose levels)
FEL Frank effect level
GMAV Genus mean acute value
GMCV Genus mean chronic value
Ig ImmunoglobulIn
Koc Soil sorptlon coefficient
Kow Octanol/water coefficient
LC5Q Concentration lethal to 50% of recipients
(and all other subscripted dose levels)
1050 Dose lethal to 50% of recipients
LM1 Leucocyte migration Inhibition
LOAEL Lowest-observed-adverse-effect level
LOEC Lowest-observed-effect concentration
MATC Maximum acceptable toxicant concentration
MEO Minimum effective dose
MMI Macrophage migration Inhibition
xx1
-------
NOAEL
NOEL
ppb
ppm
ppt
RfO
RfDso
RNA
RQ
RVd
RVe
TWA
LIST OF ABBREVIATIONS (cont.)
No-observed-adverse-effect level
No-observed-effect level
Parts per billion
parts per million
Parts per trillion
Reference dose
Subchronlc oral reference dose
Rlbonuclelc acid
Reportable quantity
Dose-rating value
Effect-rating value
Time-weighted average
xx11
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Endosulfan Is the common name for 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-
hexahydro-6,9-methano-2,4,3-benzod1oxath1ep1n-3-ox1de or 1,4,5,6,7,7-hexa-
chloro-8,9,10 tr1norborn-5-en-2,3-yleled1methylsulph1te. It Is also known
by the trade names Thlodan, BeosU and Cyclodan (Royal Society of Chemistry,
1983}. Two Isomers of endosulfan exist and can Interconvert with one
another. These are normally referred to as either a-endosulfan and
B-endosulfan, or endosulfan I and endosulfan II (Chemllne. 1989). The
structure, CAS Registry number, empirical formula and molecular weight of
each Isomer, as well as the commercial mixture of Isomers, are given below.
B-endosulfan
33213-65-9
mixture
15-29-7
a-endosulfan
CAS Registry No.: 959-98-8
Empirical formula: CQH,C1,00S
3D 00
Molecular weight: 406.95
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Technical grade endosulfan 1s a brown crystalline solid with an odor of
sulphur dioxide (Worthing and Walker, 1987). The pure Isomers of endosulfan
are colorless solids at room temperature. They are soluble In most organic
solvents and stable In mineral acids, but they hydrolyze rapidly 1n the
presence of alkalies (Wlndholz, 1983). Selected chemical and physical
properties of the endosulfan Isomers are listed 1n Table 1-1.
0253d
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1.3. PRODUCTION DATA
According to SRI (1989), SureCo, Inc., 1n Fort Valley, GA, 1s the sole
producer of endosulfan In the United States. Data on U.S. production volume
were not located In the available literature cited 1n Appendix A.
This Insecticide 1s synthesized by the dels-Alder reaction of hexa-
chlorocyclopentadlene with butenedlol, followed by a condensation with
thlonyl chloride. Commercial endosulfan 1s a mixture of the alpha (64-67%)
and beta (29-32%) Isomers, endosulfan sulfate and endosulfan dlol (Worthing
and Walker, 1987).
1.4. USE DATA
Endosulfan 1s a wide-range, nonsystemlc contact and stomach Insecticide
effective against numerous Insects and certain mites on cereals, coffee,
cotton, fruit, oilseeds, potatoes, tea, vegetables and numerous other crops
(Worthing and Walker, 1987).
1.5. SUMMARY
Endosulfan Is the common name for 1,4,5,6,7,7-hexachloro-8,9,lO-tr1nor-
born-5-en-2,3,yleled1methylsulph1te. Two Isomers of this compound exist and
are commonly referred to as either a-endosulfan and S-endosulfan or endo-
sulfan I or endosulfan II. The two endosulfan Isomers can Interconvert with
one another. Technical grade endosulfan 1s a brown crystalline solid with
an odor of sulphur dioxide (Worthing and Walker, 1987). The pure endosulfan
Isomers are colorless solids at room temperature (Wlndholz, 1983). They are
slightly soluble In water (Worthing and Walker, 1987) and soluble in most
common organic solvents (Wlndholz, 1983). Endosulfan Is stable in mineral
acids, but 1t rapidly hydrolyzes 1n alkaline solutions (Worthing and Walker,
1987). The sole U.S. producer of endosulfan Is SureCo, Inc., in Fort
Valley, GA (SRI, 1989). It is produced by the D1els-Alder reaction of
0253d 1-3 10/02/89
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hexachlorocyclopentadlene with butenedlol, followed by a condensation with
thlonyl chloride. Commercial endosulfan Is a mixture of the alpha (64-67%)
and beta (29-32%) Isomers, endosulfan sulfate and endosulfan dlol.
Endosulfan Is a wide-range, nonsystemlc contact and stomach Insecticide
effective against numerous Insects and certain mites on cereals, coffee,
cotton, fruit, oilseeds, potatoes, tea, vegetables and numerous other crops
(Worthing and Walker, 1987).
0253d
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10/02/89
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corresponding values for B-endosulfan are 7.4x10 3 8,/mol-hour, 3.7xlO~3
8./hour and 1.5x10* 8,/mol-hour. At neutral pH, the author calculated
hydrolysis half-lives of 218 hours (9.1 days) for the a-1somer and 187
hours (7.8 days) for the B-lsomer (Ellington et al., 1988). Calculated
half-lives for the hydrolysis of endosulfan at the environmentally .signifi-
cant pH range (25°C), derived from the above rate constants, are given 1n
Table 2-1.
Data regarding the blodegradatlon of endosulfan In water were limited.
In a screening test using a settled domestic wastewater sludge Inocolum,
a-endosulfan at an Initial concentration of 5 or 10 mg/i underwent 0%
degradation after a 7-day test under aerobic conditions. No degradation
ensued through the second and third subcultures. Results for B-endosulfan
were Identical (Tabak et al., 1981). Greve and WH (1971) reported that
endosulfan can be degraded In aerobic waters at pH 7, with a half-life of ~1
week. The loss of endosulfan from a sediment/water sample was slower than
In pure water (Walker et al., 1988), Indicating that blodegradatlon In water
may not be significant.
Endosulfan Is expected to adsorb significantly to sediment and suspended
matter In water. In a study of the environmental fate of Insecticides that
entered the Rhine River after a fire at a chemical warehouse, endosulfan was
listed as the only nonmercury compound that was sorptlve enough to remain In
the sediment (Cape! et al., 1988). This Is consistent with the estimated
K of 2.89xl03 (Section 2.3.), which suggests that adsorption 1s
expected to be a significant fate process.
Endosulfan Is expected to moderately bloconcentrate In fish and aquatic
organisms. An experimental BCF of 602 has been determined for endosulfan In
mussels, Mytllus edulls (Hawker and Connell, 1986). A BCF of 480 can be
0254d 2-2 11/06/89
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TABLE 2-1
Calculated Half-Lives for the Hydrolysis of Endosulfan
PH
Half-life (days)
5.0
6.0
8.0
9.0
5.1x10*
S.lxlO5
9.0
0.42 (10 hours)
5.6x10*
5.6xl05
7.8
0.28 (6.7 hours)
0254d
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10/03/89
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calculated for a-endosulfan using the experimental K of 3.83 (Hansch
and Leo, 1985) and the regression equation log BCF = 0.76 log KQW - 0.23
(Bysshe, 1982). A Henry's Law constant for a-endosulfan of l.OxlO'5
atm-mVmol can be calculated based on the water solubility at 20°C {0.51
mg/l) (Bowman and Sans, 1983) and a vapor pressure of 0.998xlO~5 mm Hg
at 25°C (Suntlo et al., 1988). A calculated Henry's Law constant of
2.94xlO~5 atm-mVmol at 20°C has been reported In the literature for
endosulfan, although no Isomer was specified (Suntlo et al.. 1988). Based
on these values, the volatilization half-life of endosulfan from a model
river 1 m deep, flowing at 1 m/sec with a wind velocity of 3 m/sec 1s -3-7
days (Thomas, 1982). Therefore, volatilization from water to the atmosphere
1s expected to be a significant fate process.
2.3. SOIL
The major pathways for removal of endosulfan from soil are probably
mlcroblal degradation and hydrolysis In alkaline soils. Of 28 fungi, 49
bacteria and 10 actlnomycetes Isolated from soil, pure cultures of 16, 15
and 3 of these species, respectively, degraded endosulfan under aerobic
laboratory conditions. Metabolites from the biological breakdown of endo-
sulfan were endosulfan sulfate, endosulfan dlol and endosulfan hydroxyether,
along with two unidentified products (Martens, 1976). Endosulfan at an
Initial concentration of 10 ppm was blodegraded under aerobic, anaerobic and
flooded conditions 1n seven different soils from Germany. England and
Thailand (Martens, 1977). Endosulfan and Us known blodegradatlon products
underwent aerobic blodegradatlon when Incubated with a mixed culture
obtained from a sandy loam at pH 6.5, and the half-lives were as follows:
a-endosulfan, 1.1 weeks; B-endosulfan, 2.2 weeks; endosulfan ether, 6
weeks; endosulfan a-hydroxy ether, 8 weeks; endosulfan sulfate, 11 weeks;
0254d 2-4 10/03/89
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endosulfan dlol, 14 weeks; and endosulfan lactone, 5.5 hours {probably not a
result of biological processes) (Miles and Hoy, 1979). Degradation of
endosulfan In soil can also occur by hydrolysis. In a soil blodegradatlon
study, losses of endosulfan from hydrolysis were 2% at pH 5.5, 8% at pH 6.3,
28% at pH 7 and 90% at pH 8 after 10 days (Martens, 1976).
The persistence of endosulfan has been measured In field studies,
although the exact mechanisms of removal cannot be determined. Endosulfan
applied to a field at a rate of 2 Ib/acre on two occasions In Hay, 1963, was
found In the soil during August of the same year at concentrations of 0.12
and 0.14 ppm, or -14% of the original amount applied (Byers et a!., 1965).
In soil samples taken from eight orchard and vegetable plots In Colorado
where 0.25-1.25 ppm endosulfan had been applied 2-7 years earlier, only one
sample tested positive for residues of this compound (Hulllns et a!., 1971).
The persistence of endosulfan In soils from India was determined by measur-
ing the residue after 17.6 ppm was applied to a wet soil, and 19.7, 89.6 and
8.0 ppm were applied to dry soils. After 60 days, 3.2, 1.8, 1.1 and 0.9%
remained In the fields, respectively (Rao and Murty, 1980a). The authors
concluded that the persistence of endosulfan In soils Is shorter than that
of other organochlorlne pesticides, and that Us persistence In dry soils Is
directly related to the Initial rate of application.
Endosulfan Is expected to adsorb strongly to soils. In the laboratory,
endosulfan applied at concentrations <43.2 vq/g to a sandy clay loam
column did not leach >17 cm (6.7 Inches) from the top over a period of 300
days when pure water was used as an eluent simulating 0.25 cmVday of rain
(El Belt et al., 1981). Similar results were obtained In Identical experi-
ments using a Gezlra soil and another sandy clay loam (El Belt et al., 1981,
1983). Endosulfan applied to soil plots In India (0.2-0.5% organic carbon)
0254d 2-5 11/06/89
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was not found at a depth >4 Inches after 100 days when the Initial appli-
cation rate was between 8.0 and 89.6 ppm (Rao and Murty, 1980a}. These
results are consistent with a K of 2.89xl03 for a-endosulfan
oc
obtained from the regression equation log K = 0.544 log K * 1.377
(Lyman, 1982) using a K of 3.83 (Hansch and Leo, 1985). A K between
2000 and 5000 suggests slight mobility In soil (Swann et al., 1983).
Volatilization of endosulfan from soil 1s not expected to be
significant. In an experiment that measured the volatility of endosulfan
from plant surfaces, loss of a-endosulfan was greater than that of B-endo-
sulfan under controlled conditions. After 10 days, 86% (a-) and 99% (8-)
of the amount applied to bean plant leaves remained (Beard and Ware, 1969).
In addition, the strong adsorption of endosulfan to soil Is expected to
reduce the rate of volatilization from the soil surface to a negligible
level.
2.4. SUMMARY
In soil, the major removal processes of endosulfan are probably
biological degradation and, In basic soils, hydrolysis. Blodegradatlon has
occurred In soil under aerobic (Martens, 1976, 1977; Miles and Hoy, 1979)
and anaerobic conditions (Martens, 1977). Losses of endosulfan In soil from
hydrolysis were 8% at pH 6.3, 28% at pH 7 and 90% at pH 8 after 10 days
(Martens, 1976). Endosulfan Is expected to adsorb strongly to soils.
Volatilization of endosulfan from the soil surface to the atmosphere Is not
expected to be significant.
If released to water, endosulfan Is expected to adsorb to sediment and
suspended organic matter, bloconcentrate moderately In fish and aquatic
organisms and undergo destructive removal by hydrolysis. The rate constants
for hydrolysis of a-endosulfan and 8-endosulfan have been experimentally
0254d 2-6 01/22/91
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determined (Ellington et al., 1988), and the calculated half-lives for each
Isomer are S.lxlO5 and 5.6xl05 days at pH 6, 9.0 and 7.8 days at pH 7
and 4.2 and 2.8 days at pH 8, respectively. Limited data are available on
the blodegradatlon of endosulfan 1n water, and Us fate by this process
cannot be determined. Volatilization of endosulfan from water to the
atmosphere Is also expected to be a significant process, with an estimated
volatilization half-life from a model river of between 3 and 7 days.
Data regarding the fate of endosulfan In the atmosphere are limited.
Direct photochemical degradation In the air Is not expected to occur to any
significant extent. Endosulfan has been detected 1n rainwater; therefore,
removal from the atmosphere by rain washout may occur. Endosulfan Is
expected to exist primarily 1n the vapor phase In the atmosphere.
0254d 2-7 10/03/89
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3. EXPOSURE
Endosulfan may enter the atmosphere during application to control animal
and plant pests In agricultural and residential settings, from manufacturing
and formulating procedures and through commercial application. Pesticides
may enter air during application of dusts and aerosols In target areas and
may drift Into the atmosphere of nontarget areas (Kutz et al., 1976). Spray
application Is probably the major source of atmospheric contamination by
pesticides (Lewis and Lee, 1976).
3.1. WATER
The levels of endosulfan detected 1n surface water are reported In Table
3-1. Endosulfan has also been detected In well water samples obtained from
54 private and municipal wells 1n California, although the concentrations
were not quantified (Maddy et al., 1982). In 36 and 52X of 50 rainfalls on
the Canadian side of the Great Lakes 1n 1976, a-endosulfan and B-endo-
sulfan were found at mean (maximum) concentrations of 1.5 and 4.9 ng/s, (15
and 45 ng/l), respectively (Strachan and Huneault, 1979). Another study
In the Great Lakes ecosystem found both the a- and B-endosulfan Isomers In
rainwater samples at a concentration ranging from 1-10 and 1-12 ngA,
respectively (Elsenrelch et al., 1981).
3.2. FOOD
The market basket survey conducted by the U.S. Food and Drug Administra-
tion, which analyzed samples collected In retail food outlets throughout the
United States, routinely found endosulfan residues 1n the following food
groups: potatoes, leafy vegetables, garden fruits, fruits, oils, fats and
shortenings (Cornellussen, 1972; Ouggan and Cornellussen, 1972; Hanske and
Cornellussen, 1974; Hanske and Johnson, 1975, 1977; Johnson and Manske,
0255d
3-1
10/02/89
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1976, 1977; Johnson et al., 1981a,b, 1984a,b; Podrebarac, 1984a,b; Gartrell
et al., 1985a,b,c, 1986a,b; Gunderson, 1988). Values for the average dally
Intake of endosulfan from all food groups 1n these studies for 16- to
19-year-old males can be found In Table 3-2. Corresponding data for Infants
and toddlers are reported In Table 3-3.
The estimated annual dietary Intake of endosulfan from the Ingestlon of
fresh food grown In Ontario, Canada, In 1985 obtained from quantitative data
on residues In fruits, leafy vegetables, milk and eggs/meat, was 140.1
yg/year for a-endosulfan and 690.36 pg/year for 0-endosulfan (Davles,
1988). Endosulfan has also been found 1n vegetable oil (4 ppb), and the oil
of groundnut (8 ppm), sesame {22 ppm) and mustard seeds (832 ppm) purchased
In Lucknow, India (Olkshlth et al., 1989).
3.3. INHALATION
According to Kutz et al. (1976), Inhalation Is an Important route of
exposure to pesticides for the general population. A farmer routinely
applying endosulfan to his fields Inhaled 4490-36,570 ng/m1nute of endo-
sulfan during mixing and 68-155 ng/mlnute during spraying (Oudbler et al.,
1974).
a-Endosulfan was found 1n the air of Columbia, SC, at an average
concentration of 0.078 ng/m3, but not In the air of Boston, MA (Bldleman,
1981). Data collected at urban and rural sites 1n 14 states during 1970 and
at 16 sites during 1971-1972 Indicate that neither a-endosulfan nor
B-endosulfan was detected 1n samples taken during the latter two years. For
1970, 6.61% of the samples tested positive for a-endosulfan and 1.02%
tested positive for 0-endosulfan, with mean concentrations for the positive
samples of 111.9 and 22.0 ng/m3, respectively. The maximum values
detected were 2256.5 ng/m3 (a-) and 54.5 ng/m3 (8-). Endosulfan was
0255d
3-3
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TABLE 3-2
Summary of Endosulfan Intake from FDA's Market Basket Survey3'^
Fiscal Year
1968
1969
1976
1977
1978
1979
1977-1980
1980
1980-1982
1981-1982
1982-19846
Intake (ng/kg
a
id
Traced
3
2.6
2.5
3
NR
3
NR
9
2.7
bw/day]
B
NR
NR
3
3.1
3.4
2
NR
8
NR
13
5.0
I ntake
a
NR
NR
NR
NR
NR
NR
0.216
NR
0.596
NR
NR
( tig/da y)c
B
NR
NR
NR
NR
NR
NR
0.549
NR
0.898
NR
NR
aSources: Cornellussen, 1972; Ouggan and Cornellussen, 1972; Manske and
Cornellussen, 1974; Manske and Johnson, 1975, 1977; Johnson and Manske,
1976, 1977; Johnson et al., 1981a,b, 1984a,b; Podrebarac, 1984; Gartrell
et al., 1985a,b,c, 1986a,b; Gunderson, 1988
bFor adult males aged 16-19 years
cBody weight taken to be 69.1 kg
dlsomer not specified
eFor males aged 14-16 years
NR = Not reported
0255d
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10/02/89
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TABLE 3-3
Average Dally Intake of Endosulfan for Toddlers and Infants*
Fiscal Year
1975
1976
1977
1978
1979
1980
1981-1982
a
NO
11
ND
ND
1
ND
ND
Intake
Infant
B
ND
4.5
ND
0.2
5
1
3
(nq/kg bw/day)
Toddler
a
ND
7.8
0.4
5.0
6
1
6
3
ND
7.8
1.2
5.5
3.7
2
11
*Sources: Johnson et al., 1981a, 1984a; Gartrell et a!., 1985a, 1986a;
Podrebarac, 1984a
ND = Not detected
0255d 3-5 10/02/89
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found In air samples from 6/16 states monitored In this study (Kutz et al.,
1976). Endosulfan has also been detected In the air over the Great Lakes
{E1senre1ch et al., 1981).
In the relatively small city of Delft In the densely populated western
Netherlands, atmospheric concentrations for a-endosulfan for 1979-1981 had
mean and maximum values of 168 and 1130 pg/m3. The estimated dally and
yearly Intake based on this data and on an Inhalation rate of 20 mVday
was given as 3.4 ng/day and 1.2 jig/year (Gu1cher1t and Schultlng, 1985).
3.4. DERMAL
Data regarding dermal exposure to endosulfan were limited. Endosulfan
may persist on the hands of workers spraying this Insecticide for <32 days
after use (Kazen et al., 1974).
3.5. OTHER
a-Endosulfan was detected at a concentration of 0.01 ppm in 0.07% (1
sample) of 1506 samples taken from 35 states as part of the National Soil
Monitoring Program during fiscal year 1970. In a similar study performed
the following year, of 1486 samples from 37 states, o-endosulfan was found
In 0.1% (2 sites) of the samples at concentrations of 0.05 and 0.23 ppm.
For B-endosulfan, corresponding values were 0.27% positive (4 sites) and
0.2% positive (3 sites), with maximum concentrations of 0.07 and 1.24 ppm,
respectively (Carey et al., 1978; Crockett et al., 1974). Endosulfan
(a- and B-lsomer or endosulfan sulfate) was found In 13 high organic
content soils taken from 28 vegetable farms during 1S76 In southwestern
Ontario, Canada, at concentrations ranging from 0.03-1.79 ppm (Miles and
Harris, 1978). Soil pesticide levels were measured at 51 locations through-
out the United States that represented areas of regular, limited and no
pesticide use In 1965-1967. Endosulfan was not found In the latter two
0255d
3-6
10/02/89
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areas but was found In regular-use areas In the following crops and concen-
trations: vegetable and/or cotton, 32% positive at 0.01-1.22 ppm; tree
fruits, 30% at 0.02-4.63 ppm; and small grains and root crops, 9% at
0.07-0.92 ppm (Stevens et al., 1970). Endosulfan was found In 31 soil
samples taken from apple orchards In Ontario, Canada during 1975 at a
concentration range from not detected to 2.63 ppm (mean = 0.26 ppm) at a
depth of 0-15 cm, and not detected to 1.01 ppm (mean = 0.06 ppm) at a depth
of 15-30 cm (Frank et al., 1976).
Endosulfan was qualitatively detected 1n Connecticut bee apiaries and
brood comb (Anderson and Wojtas, 1986). It was found In the eggs of Chinook
salmon returning from Lake Michigan 1n fall 1982, at a concentration of
0.6-27.8 yg/kg (median, 6.61) (Glesy, 1988; Glesy et al., 1986).
3.6. SUMMARY
The general population may be exposed to endosulfan through Inhalation
and 1ngest1on of contaminated food. The U.S. Food and Drug Administration's
market basket survey, conducted from 1968-1984, found that the average dally
Intake (normalized for body weight) for adult males 16-19 years old ranged
from trace to 22 ng/kg bw (both a- and B-lsomer combined) from all food
groups. Endosulfan was commonly found In the potato, leafy vegetable,
garden fruit, fruit, oil, fat and shortening food groups. The average dally
Intake of endosulfan for Infants and toddlers ranged from not detected to
15.5 ng/kg bw and not detected to 15.6 ng/kg bw, respectively (both Isomers
combined). The average yearly Intake of endosulfan, determined during a
Canadian market basket survey performed In Ontario during 1985, was 140.1
pg/year for o-endosulfan and 690.4 pg/year for 8-endosulfan.
In the National Pesticide Monitoring Program conducted In 1970-1972,
endosulfan was only found In the first year 1n 6/16 of the states monitored.
0255d 3-7 10/02/89
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In 1970, 6.6% of the samples tested positive for a-endosulfan, and 1%
tested positive for B-endosulfan.
Occupational exposure to endosulfan 1s expected to occur for those
Involved 1n the production, formulation or application of this Insecticide.
A farmer applying this Insecticide to his fields Inhaled between 4490 and
36,570 ng/mlnute during mixing, and between 68 and 155 ng/mlnute during
spraying (Oudbler et al., 1974).
0255d 3-8 10/02/89
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4. ENVIRONMENTAL TOXICOLOGY
4.1. AQUATIC TOXICOLOGY
4.1.1. Acute Toxic Effects on Fauna. Acute median toxic responses from
endosulfan exposure have been assessed with >7 freshwater Invertebrates, 10
freshwater fishes, 8 saltwater Invertebrates and 6 saltwater fishes (Table
4-1). Data presented In this table are from studies assaying technical
grade endosulfan using natively-reproducing species. Saltwater species were
generally more sensitive to endosulfan than freshwater forms. The most
sensitive species was the pink shrimp, Penaeus duorarum (LC5Q = 0.04
Median response concentrations for freshwater forms ranged from
a 96-hour LC5Q of 0.16 jig/s, for rainbow trout, Sal mo qa1rdner1. to a
48-hour EC5Q for the water flea, Daphnla magna. Fishes and most benthlc
Invertebrates were two or three orders of magnitude more sensitive to
endosulfan than was the planktonlc D. magna. In saltwater forms, a simi-
larly disparate sensitivity among species was apparent. In this case, the
benthlc Invertebrates, Neanthes arenaceodentata and Crassostrea Virginia.
were the highly resistant forms. Differences In sensitivities among
organisms raise questions regarding the validity of the data, especially In
the case of D_. magna , since It 1s usually among the most sensitive of test
species. In this case, however, the data for D_. magna were gathered by six
laboratories that conducted round-robin tests (Nebeker, 1982). These data
showed good agreement. Data obtained with N. arenaceodentata were similarly
obtained and also showed good agreement. C_. vlrglnlca data may be less
reliable, since they were provided by only one laboratory and derived by
older methods (Butler, 1963, 1964).
0256d 4-1 11/07/89
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