Endosulfan (EHC 40, 1984)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 40

ENDOSULFAN

This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.

Published under the joint sponsorship of
the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization

Draft prepared by Professor D. Beritc-Stahuljak and Professor
F. Valic (University of Azgreb, Croatia) using texts made
available by Dr R. Millischer (ATOCHEM, Paris, France),
Dr. S. Magda (Kali-Chemie, Hanover, Germany), Mr D.J. Tinston
(ICI Central Toxicology Laboratory, United Kingdom), Dr. H.J.
Trochimowicz (E.I. Du Pont de Nemours, Newark, Delaware, USA)
and Dr G.M. Rusch (Engineered Materials Sector, Allied-Signal Inc.,
Morristown, New Jersey, USA).

World Health Orgnization
Geneva, 1984

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chemicals.

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR ENDOSULFAN

1. SUMMARY AND RECOMMENDATIONS

1.1. Identity, analytical methods, and sources of exposure
1.1.2. Environmental concentrations and exposures
1.1.3. Kinetics and metabolism
1.1.4. Studies on experimental animals
1.1.5. Effects on man
1.1.6. Effects on the environment
1.2. Recommendations

2. IDENTITY, ANALYTICAL METHODS AND SOURCES OF EXPOSURE

2.1. Identity
2.2. Properties and analytical methods
2.2.1. Physical and chemical properties
2.2.2. Analytical methods

3. USES, ENVIRONMENTAL SOURCES, TRANSPORT AND DISTRIBUTION

3.1. Uses
3.2. Transport and distribution
3.3. Levels of exposure

4. KINETICS AND METABOLISM

4.1. Animal studies
4.2. Human studies

5. STUDIES ON EXPERIMENTAL ANIMALS

5.1. Short-term exposures
5.1.1. Single exposure
5.1.2. Repeated exposure
5.2. Long-term exposures
5.3. Reproduction studies
5.4. Mutagenicity
5.5. Teratogenicity
5.6. Carcinogenicity
5.7. Factors influencing toxicity

6. EFFECTS ON MAN

6.1. Poisoning incidents
6.2. Occupational exposure
6.3. Treatment of poisoning

7. EFFECTS ON THE ENVIRONMENT

7.1. Toxicity for aquatic organisms
7.2. Toxicity for terrestrial organisms
7.2.1. Plants
7.2.2. Honey bees
7.2.3. Birds
7.3. Toxicity for microorganisms
7.4. Bioaccumulation

8. PREVIOUS EVALUATIONS OF ENDOSULFAN BY INTERNATIONAL BODIES

9. EVALUATION OF HEALTH RISKS FOR MAN AND EFFECTS ON THE ENVIRONMENT

9.1. Evaluation of health risks for man
9.2. Evaluation of overall environmental effects
9.3. Conclusions

REFERENCES

TASK GROUP MEETING ON ENVIRONMENTAL HEALTH CRITERIA FOR
ORGANOCHLORINE PESTICIDES OTHER THAN DDT (ENDOSULFAN,
QUINTOZENE, TECNAZENE, TETRADIFON)

Members

Dr E. Astolfi, Faculty of Medicine of Buenos Aires, Buenos
Aires, Argentina

Dr I. Desi, Department of Environmental Hygienic Toxicology,
National Institute of Hygiene, Budapest, Hungary
(Vice-Chairman)

Dr R. Drew, Department of Clinical Pharmacology, Flinders
University of South Australia, Bedford Park, South
Australia

Dr S.K. Kashyap, National Institute of Occupational Health,
Ahmedabad, India

Dr A.N. Mohammed, University of Calabar, Calabar, Nigeria

Dr O.E. Paynter, Office of Pesticide Programs, US
Environmental Protection Agency, Washington DC, USA

Dr W.O. Phoon, Department of Social Medicine and Public
Health, Faculty of Medicine, University of Singapore,
Outram Hill, Singapore (Chairman)

Dr D. Wassermann, Department of Occupational Health, The
Hebrew University, Hadassah Medical School, Jerusalem,
Israel

Representatives of Other Organizations

Dr H. Kaufmann, International Group of National Associations
of Agrochemical Manufacturers (GIFAP)

Dr V.E.F. Solman, International Union for Conservation of
Nature and Natural Resources (IUCN), Ottawa, Ontario,
Canada

Secretariat

Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood
Experimental Station, Abbots Ripton, Huntingdon, United
Kingdom (Temporary Adviser)

Dr M. Gilbert, International Register for Potentially Toxic
Chemicals, United Nations Environment Programme, Geneva,
Switzerland

Dr K.W. Jager, Division of Environmental Health, International
Programme on Chemical Safety, World Health Organization,
Geneva, Switzerland (Secretary)

Secretariat (contd.)

Dr D.C. Villeneuve, Health Protection Branch, Department of
National Health and Welfare, Tunney's Pasture, Ottawa,
Ontario, Canada (Temporary Adviser) (Rapporteur)

Mr J.D. Wilbourn, Unit of Carcinogen Identification and
Evaluation, International Agency for Research on Cancer,
Lyons, France

NOTE TO READERS OF THE CRITERIA DOCUMENTS

While every effort has been made to present information in the
criteria documents as accurately as possible without unduly
delaying their publication, mistakes might have occurred and are
likely to occur in the future. In the interest of all users of the
environmental health criteria documents, readers are kindly
requested to communicate any errors found to the Manager of the
International Programme on Chemical Safety, World Health
Organization, Geneva, Switzerland, in order that they may be
included in corrigenda, which will appear in subsequent volumes.

In addition, experts in any particular field dealt with in the
criteria documents are kindly requested to make available to the
WHO Secretariat any important published information that may have
inadvertently been omitted and which may change the evaluation of
health risks from exposure to the environmental agent under
examination, so that the information may be considered in the event
of updating and re-evaluation of the conclusions contained in the
criteria documents.

* * *

A detailed data profile and a legal file can be obtained from
the International Register of Potentially Toxic Chemicals, Palais
des Nations, 1211 Geneva 10, Switzerland (Telephone no. 988400 -
985850).

ENVIRONMENTAL HEALTH CRITERIA FOR ENDOSULFAN

Following the recommendations of the United Nations Conference
on the Human Environment held in Stockholm in 1972, and in response
to a number of World Health Resolutions (WHA23.60, WHA24.47,
WHA25.58, WHA26.68), and the recommendation of the Governing
Council of the United Nations Environment Programme, (UNEP/GC/10, 3
July 1973), a programme on the integrated assessment of the health
effects of environmental pollution was initiated in 1973. The
programme, known as the WHO Environmental Health Criteria
Programme, has been implemented with the support of the Environment
Fund of the United Nations Environment Programme. In 1980, the
Environmental Health Criteria Programme was incorporated into the
International Programme on Chemical Safety (IPCS). The result of
the Environmental Health Criteria Programme is a series of criteria
documents.

A WHO Task Group on Environmental Health Criteria for
Organochlorine Pesticides other than DDT (Endosulfan, Quintozene,
Tecnazene, Tetradifon) was held at the Health Protection Branch,
Department of National Health and Welfare Ottawa from 28 May - 1
June, 1984. The meeting was opened by Dr E. Somers, Director-
General, Environmental Health Directorate, and Dr K.W. Jager
welcomed the participants on behalf of the three co-sponsoring
organizations of the IPCS (UNEP/ILO/WHO). The Task Group reviewed
and revised the draft criteria document and made an evaluation of
the health risks of exposure to endosulfan.

The drafts of this document were prepared by Dr D.C. Villeneuve
of Canada and Dr S. Dobson of the United Kingdom.

The efforts of all who helped in the preparation and
finalization of the document are gratefully acknowledged.

* * *

Partial financial support for the publication of this criteria
document was kindly provided by the United States Department of
Health and Human Services, through a contract from the National
Institute of Environmental Health Sciences, Research Triangle Park,
North Carolina, USA - a WHO Collaborating Centre for Environmental
Health Effects.

1. SUMMARY AND RECOMMENDATIONS

1.1. SUMMARY

1.1.1. Identity, analytical methods, and sources of exposure

Technical endosulfan (6,7,8,9,10, 10-hexachloro-1,5,5a,6,9,9a,
hexahydro 6,9-methano-2,4,3-benzodioxathiepin, 3-oxide) is a brown
crystalline substance consisting of alpha- and beta-isomers in the
ratio of approximately 70:30. It is used in a formulated form as a
broad-spectrum contact and stomach insecticide mainly in agriculture
and, in some countries, in public health.

The method of choice for its determination is gas chromatography
combined with electron capture detection. In considering residue
levels, the sum of the alpha- and beta-isomers plus the endosulfan
sulfate metabolite, which is similar in toxicity to the parent
compound, have to be considered.

The main source of exposure of the general population is food,
but residues have generally been found to be well below the FAO/WHO
maximum residue limits. Because of its use in tobacco farming,
smoking may be an additional source of endosulfan exposure.

1.1.2. Environmental concentrations and exposures

Both endosulfan isomers are fairly resistant to photo-
degradation, but the metabolites endosulfan sulfate and endosulfan
diol are susceptible to photolysis. Its half-life in water is
estimated to be 4 days, but anaerobic conditions and/or a low pH
will lengthen the half-life. In water, it is mainly degraded to
endosulfan diol. Fish are extremely sensitive to endosulfan and
fish kills have been reported as a result of the discharge of
endosulfan into rivers. Agricultural run-off has not caused such a
problem.

In soil, the alpha-isomer disappears more rapidly than the beta-
isomer. Endosulfan sulfate is the major degradation product in
soil. These compounds are not prone to leaching.

Biodegradation in soil and water is dependent on climatic
conditions and on the type of microorganisms present.

1.1.3. Kinetics and metabolism

Endosulfan can be absorbed following ingestion, inhalation, and
skin contact. Following oral or parenteral dosing, it is rapidly
excreted via faeces and urine. Following acute over-exposure, high
endosulfan concentrations can temporarily be found in the liver;
the concentration in plasma decreases rapidly. The major
metabolities are endosulfan sulfate and endosulfan diol.

1.1.4. Studies on experimental animals

Endosulfan is moderately to highly toxic according to the scale
of Hodge & Sterner (1956). The oral LD₅₀ in the rat ranges from 18
to 355 mg/kg body weight. WHO (1984) classified endosulfan in
Class II: technical products moderately hazardous. One of its
metabolites, endosulfan sulfate, has the same order of toxicity as
endosulfan.

Signs of acute intoxication include neurological manifestations,
such as hyperactivity, muscular twitching, and convulsions, some-
times followed by death.

In rats, induction of hepatic mixed-function oxidases was
observed after administration of endosulfan for 7 days at 2.5 mg/kg
body weight per day. At higher doses (100 mg/kg in the diet for
104 weeks), testicular atrophy and renal tubular damage with
interstitial nephritis were observed. The long-term, no-observed-
adverse-effect level in rats was 30 mg/kg of diet (1.5 mg/kg body
weight) and 0.75 mg/kg body weight in dogs. Protein-deficient rats
are more sensitive to acute toxic effects of endosulfan.

Adequate data were not available on effects on reproduction, or
teratogenic or embryotoxic effects. Negative or conflicting
results were obtained in short-term tests for genetic activity.
Carcinogenicity studies on mice and rats were difficult to evaluate
because of inadequate reporting or early death in males; however,
there was no indication of carcinogenic activity in females.

1.1.5. Effects on man

Several cases of accidental and suicidal poisoning have been
reported. In fatal cases, death occurred within a few hours of
ingestion. Signs of poisoning included vomiting, restlessness,
irritability, convulsions, pulmonary oedema, and cyanosis. EEG
changes have been reported in occupationally overexposed persons.
Cases of poisoning in production workers have been reported, but
occurred only when safe handling procedures were neglected.

1.1.6. Effects on the environment

Endosulfan is not readily bioaccumulated and it is not
persistent in biological tissues. It is hazardous as an acute
poison for some aquatic species, particularly fish, even at
application rates recommended for wetland areas. It is moderately
toxic for honey bees. It is moderately to highly toxic for birds
in a laboratory setting, but no poisonings have been reported under
field conditions.

1.2. Recommendations

1. Precautions should be taken to avoid contamination
of surface and drinking-water supplies during
spraying. Where necessary, residue levels of
endosulfan in drinking-water should be reduced by
proper water treatment.

2. In countries where endosulfan is used for tsetse
fly control, exposed populations should be monitored
for potential adverse health effects.

3. Research is required to determine whether biological
monitoring can be used as an early warning of
endosulfan exposure.

4. Further research is required to investigate possible
reproductive, teratological, and embryotoxic effects.

5. An adequate carcinogenicity study should be
carried out.

2. IDENTITY, ANALYTICAL METHODS AND SOURCES OF EXPOSURE

2.1. Identity

Molecular formula: C₉H₆Cl₆O₃S

CAS chemical name: 6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a
-hexahydro-6,9-methano-2,4,3-benzo-
dioxa-thiepin-3-oxide

Common trade names: Benzoepin, Beosit, Chlorthiepin,
Cyclodan, FMC 5462, Insectophene,
Kop-thiodan, HOE 2671, Malix,
NCI-C00566, NIA 5462, Thifor,
Thimul, Thiodan, Thiofor, Thiomul,
Thionex, Thiosulfan, Tionel, Tiovel.
Formulations under other trade names
may also exist.

CAS registry number: 115-29-7

Relative molecular mass: 406.9

Endosulfan was developed and introduced in the mid 1950s
(Maier-Bode, 1968). Technical endosulfan is obtained through the
Diels-Alder addition of hexachlorocylopentadiene and cis-butene-
1,4-diol, followed by reaction of the addition-product with thionyl
chloride (Canada, National Research Council, 1975). Technical
endosulfan consists of a mixture of alpha- and beta-isomers in the
approximate ratio of 70:30.

2.2. Properties and Analytical Methods

2.2.1. Physical and chemical properties

Technical endosulfan is usually sold in the form of brown
crystalline flakes with a terpene odour (Maier-Bode, 1968). It has
a melting point of 79 - 100°C (Canada, National Research Council,
1975) and a vapour pressure of 1 x 10^-5 mm Hg at 25°C. Its
solubility in water is low: 60 - 150 µg/litre (Canada, National
Research Council, 1975), and increases with decreasing pH
(Shuttleworth, 1971). Solubility in other solvents varies from 5 -
65% (Maier-Bode, 1968; Canada, National Research Council, 1975).

Endosulfan is available as a wettable powder, granules,
emulsifiable concentrates, dusts, and as ultra-low-volume (ULV)
formulations.

2.2.2. Analytical methods

Methods for the clean-up and determination of endolsulfan have
been summarized by Maier-Bode (1968), Canada, National Research
Council (1975), and Goebel et al., (1982), but the sensitivities
and recoveries for the various methods are not always given.
Although colorimetric techniques, thin-layer chromatography, and
bio-assays have been used for the determination of endosulfan, the
most recent method involves a combination of gas chromatography
with electron capture detection (GC-EC).

The sensitivity of assays in water ranged from 0.01 - 2.0
g/litre with recoveries generally greater than 90% (Wegman &
Greve, 1978; 1980; Frank et al., 1979a). In soil and sediment,
assays were not as sensitive, ranging from 0.001 to 0.1 mg/kg with
recoveries between 80 - 110% but usually less than 90% (Miles &
Harris, 1973; Frank et al., 1976; Carey et al., 1979). Biological
samples such as animal and plant tissues, milk, etc., normally
require more extensive clean-up procedures (i.e., column methods).
Sensitivities from 0.2 to 10 µg/kg were usual with most recoveries
greater than 90% (Cheng & Braun, 1977; Chopra & Mahfouz, 1977;
Frank et al., 1979a; Zanini et al., 1980). Samples with a high
sugar content gave erroneous results, but methods have been
developed to overcome the problem (Shuttleworth, 1971). Clean-up
methods employing high-pressure liquid chromatography (HPLC) have
been used, which reduce the time involved in the preparation of
such samples (Demeter & Heyndrickx, 1979).

It should be noted that detection limits for the alpha- and
beta-isomers of endosulfan usually differ, the alpha-isomer being
easiest to detect (Goebel et al., 1982). At low concentrations,
the identification of endosulfan residues can be hampered by a
variety of other pesticides or plant components. Endosulfan
residues in environmental samples can only be considered to be
valid if alpha- and beta-together with endosulfan sulphate are
found simultaneously. Validation can be achieved by methods
summarized by Goebel et al. (1982).

3. USES, ENVIRONMENTAL SOURCES, TRANSPORT AND DISTRIBUTION

3.1. Uses

Endosulfan is a contact and stomach poison that has been used
to control insects such as the Colorado potato beetle, flea beetle,
cabbageworm, peach tree borer, and tarnished plant bug, as well as
several species of aphid and leafhopper (Canada, National Research
Council, 1975). It is used in countries throughout the world to
control pests on fruit, vegetables, tea, and on non-food crops such
as tobacco and cotton (FAO/WHO, 1968). Depending on the type of
crop and the area in which it is grown, application rates usually
range between 0.45 kg ai and 1.4 kg/ha, but both smaller and larger
doses have occasionally been used. Minimum time intervals between
the last application and harvesting are prescribed in most
countries and vary between 0 and 42 days, depending on the crop,
type of formulation used, the mode of application, tolerances, and
agronomic needs (Hoechst, 1977).

In addition to its agricultural use, and its use in the control
of the tsetse fly, endosulfan is used as a wood preservative and
for the control of home garden pests (Canada, National Research
Council, 1975). A list of uses together with respective quantities
used in some countries appear in Table 1.

Figures for world production are not available but, after DDT
was banned, the use of endosulfan in Canada increased quite rapidly
until the mid 1970s (Canada, National Research Council, 1975). At
present, world production might be in the order of 10 000 tonnes
per year.

An estimated several tens of thousands of drums containing
chemical waste including endosulfan, which have been found in and
along the North Sea, are a potential source of pollution (Greve,
1971b).

3.2. Transport and Distribution

Air

Endosulfan is most frequently applied using air-blast equipment
or boom sprayers with a resulting potential for local drift and air
pollution. Keil et al. (1972) included 4-metre guard rows between
treated and control plots. The day after treatment, endosulfan
levels of 0.091 - 0.529 mg/kg were found in the control plots,
indicating a considerable drift of the insecticide between the
plots. Eighteen days after treatment, an endosulfan level of 0.037
mg/kg was still detectable in the control plots. Endosulfan was
also found in the water and sediments of streams adjacent to
sprayed crops (Canada, National Research Council, 1975).

Table 1. Usage data for endosulfan from selected countries^a
----------------------------------------------------------------------
Area Quantity Year Uses
----------------------------------------------------------------------
Colombia 21 834 kg 1982 agricultural insecticide recommended
15 918 kg 1981 in the growth of cotton, rice, corn,
16 868 kg 1980 cabbage, sorghum

Malaysia insecticide

Sweden 2000 kg 1981 horticultural use against insects
and mites

Tanzania 2130 tonne 1980-83 applied to various crops to control
chewing, mining, and sucking pests

Thailand 63 420 kg 1982 insecticide
114 800 kg 1981
99 550 kg 1980
27 587 kg 1979
24 519 kg 1978
18 482 kg 1977
1540 kg 1976

United 27.58 tonne 1975-79 insecticide and acaricide
Kingdom per year

USA 511-704 tonne 1980 insecticide on various crops;
454 tonne 1971 insecticide on potatoes, tobacco,
and fruits
----------------------------------------------------------------------
^a From: IRPTC, personal communication, 1984.

Residues of alpha- and beta-endosulfan have been detected in
ambient air samples in the USA (Alabama, Arkansa, Illinois, Kansas,
Kentucky, Louisiana, Maine, Montana, New Mexico, North Carolina,
Ohio, Oklahoma, Oregon, Pennsylvania, South Dakota, Tennessee),
though not frequently (Kutz et al., 1976). Between 1970 and 1972,
alpha-endosulfan was found in 2.11% of samples tested in the USA at
a mean concentration of 111.9 ng/m³ and a maximum of 2256 ng/m³.
During the same period, beta-endosulfan was present in 0.32% of the
samples at a mean of 22.0 ng/m³ and a maximum concentration of 54.5
ng/m³. This information suggests that the alpha-isomer is more
persistent in air. Both alpha- and beta-endosulfan have been
detected at levels up to 12 ng/litre in precipitation in the Great
Lakes area of Canada and the USA (Strachan et al., 1980).

Water

Endosulfan contamination does not appear to be widespread in
the aquatic environment but has been found in agricultural run-off
and rivers in industrialized areas where it is manufactured or
formulated. Estimates for the aquatic half-life of both isomers of
endosulfan range from 4 days in river water subjected to municipal
and industrial runoff (Eichelberger & Lichtenberg, 1971) to 7 days

(Greve, 1971a) in normal water (pH 7, with normal oxygen
saturation). However, the half-life was profoundly affected by pH
and oxygen content; a drop in either of these two parameters
inhibited endosulfan degradation. Under anaerobic conditions at pH
7, the half-life increased to approximately 5 weeks, and at pH 5.5,
the half-life was nearly 5 months (Greve, 1971a). More than 80% of
the endosulfan present can be removed from water by filtration and
almost all by treatment with activated charcoal (Greve, 1971a).

Studies of endosulfan in agricultural run-off, in the USA,
indicate that, if rain follows within 4 days of application (0.35
kg/ha), residues can average 16 µg/litre run-off (Epstein & Grant,
1968).

A widespread fish kill was observed in 1969, when an estimated
quantity of 30 kg of endosulfan was discharged into the section of
the Rhine river that runs through the Federal Republic of Germany
(Sievers et al., 1972). Annual monitoring of endosulfan (drinking
water, ground water, rain water, surface water) since 1969 in the
Netherlands has revealed that maximum levels have dropped
approximately 3 orders of magnitude, with maximum concentrations in
1977 of 0.03 µg/litre (Wegman & Greve, 1980).

Endosulfan was found only once in rivers draining orchard areas
in Ontario, during 2-week sampling periods in 1973 at levels
ranging from 0.47 to 0.083 µg/litre (Frank, unpublished data,
1973). Studies on water samples from Lake Erie, Ontario, and the
St. Lawrence River showed that approximately 15% of the samples
contained endosulfan at levels ranging from 0.005 to 0.060 µg/litre
(Natural Research council, 1975). In recent work in Western
Canada, endosulfan was found (0.011 µg/litre) in one out of 1400
surface water samples, indicating that water contamination by this
insecticide was not widespread (Gummer, 1980).

No alpha- or beta-endosulfan or endosulfan sulfate residues
were detected (method sensitivity, 10 µg/litre) in well waters
located near treated fields in Wisconsin and Florida, USA, 282 and
100 days, respectively, after the last endosulfan application. The
treated fields in Wisconsin received seven foliar applications of
endosulfan at 0.56 kg/ha (2 in 1966 and 5 in 1969), while the
fields in Florida were treated with 10 - 16 foliar applications of
endosulfan at 1.12 kg/ha over a 5-year period (Niagara Chemical
Division, 1971).

Soil

Early work by Byers et al. (1965) indicated that the alpha-
isomer dissipated more rapidly in the soil than the beta-isomer.
The authors suggested that the latter was more strongly adsorbed on
soil than the former. The results of field studies have since
confirmed that the alpha-isomer has a shorter half-life (60 days)
than the beta-isomer (900 days) (Steward & Cairns, 1974).

It was also suggested that endosulfan sulfate (the major
degradation product in soil) accumulated at a rate comparable
to the rate of loss of alpha- and beta-endosulfan. Endosulfan
sulfate tended to be more stable than either of the 2
endosulfan isomers, but none of the 3 compounds was prone to
leaching in soil (Stewart & Cairns, 1974).

The degradation of endosulfan, which was substantially reduced
when the compound was incorporated into soil, halted during winter
months (Niagara Chemical Division, 1966, Stewart & Cairns, 1974).
A survey of agricultural soils in North America showed that
endosulfan residue levels were typically below 1 mg/kg, with a few
exceptions (4.78 mg/kg, 4.93 mg/kg) (Frank et al., 1976; Harris et
al., 1977). A study from Italy revealed endosulfan soil residues
ranging from 0.23 to 3.88 mg/kg (Sanna et al., 1979). Endosulfan
has been detected in the sediments of drainage ditches (Miles &
Harris, 1971; Niagara Chemical Division, 1971), rivers (Miles,
1976), and lakes (Canada, National Research Council, 1975).
Concentrations ranged from trace amounts to 0.64 mg/kg dry weight
(Miles et al., 1971).

Degradation of endosulfan appears to be different in sediments
and in soil. Martens (1977) studied soil samples under a variety
of conditions, including flooding, and demonstrated that the
percentage of endosulfan diol was increased in the flooded soil
samples and that a lower percentage of the sulfate was observed.
Carbon dioxide production was measured in all samples and was
highest under aerobic condition (Martens, 1977).

Abiotic degradation and bioaccummulation

Both alpha- and beta-endosulfan are fairly resistant to
photodegradation (Schumacher et al., 1971; Schuphan et al., 1972),
but the 2 dominant break-down products, endosulfan sulfate and
endosulfan diol, are susceptible to photolysis (Fig. 1) (Schuphan
et al., 1972). Technical endosulfan is sensitive to moisture,
acids, and alkali and will undergo slow hydrolyses producing sulfur
dioxide (S0₂) and endosulfan alcohol via the intermediate
endosulfan sulfate (FAO/WHO, 1968; Martens, 1977).

In soil and on plant surfaces, endosulfan sulfate is the
primary degradation product of endosulfan (Cassil & Drummond, 1965;
Martens, 1977) with lesser amounts of endosulfan diol and
endosulfan lactone being produced. Although sunlight may be
involved in the initiation of sulfate production, Archer et al.
(1972) felt that thermolysis was the principle formation mechanism.

In aquatic environments (water and sediment), endosulfan diol
was present together with smaller amounts of the sulfate and other
compounds (Eichelberger & Lichtenberg, 1971; Martens, 1977).

Martens (1972) demonstrated the production of endosulfan and
endosulfan diol by fungi, but the role that these and other
microorganisms play in environmental degradation is not clear.

As a result of the higher solubility in water of endosulfan
compared with most other organochlorine pesticides, it does not
have the affinity for lipids that most related compounds have.
Consequently, biomagnification and accumulation of endosulfan in
food chains is less likely to occur. The typical response for most
organisms exposed to endosulfan at below lethal levels, is to
accumulate the compound up to a plateau, but clear the residues
fairly rapidly once the source of contamination is removed. The
higher the exposure level, the longer it takes to reach a plateau
and the higher the plateau is. This response was demonstrated in
mussels (Roberts, 1972), fish (Schoettger & Bier, 1970; Oeser &
Knauf, 1973), and algae (Oeser & Knauf, 1973). An estimate of the
half-life of endosulfan in fish was 3 days (Oeser & Knauf, 1973).
Similar results have been found in mammals; summaries of data have
been made by Maier-Bode (1968), Goebel et al. (1982), and US EPA
(1982). Endosulfan sulfate was generally the only compound
detected in tissues of animals exposed to endosulfan. In cattle
(FAO/WHO, 1967), the concentration factors were small (0.5 in milk,
0.05 in muscle tissue, and 0.15 in fat), and residues cleared quite
rapidly when endosulfan was removed from the diet. Other diet
studies have produced similar results in sheep (Maier-Bode, 1968)
and dogs (FMC Corp., unpublished data, 1963). No reports of
endosulfan residues in human adipose tissue or breast milk were
available.

In plants sprayed with endosulfan, initial residues on fruits
and vegetables can vary from about 1 to 100 mg/kg; after 1 week,
residues generally decrease to 20% or less of the initial amount
(Canada, National Research Council, 1975).

3.3. Levels of Exposure

Air

Human exposure during endosulfan spraying for tsetse fly
control using a helicopter in the Ivory Coast was assessed by means
of exposure pads worn over or under light overalls (Copplestone et
al., 1979). Three male volunteers were positioned within a village
and three more in the area deliberately being sprayed. The men
walked in the area during spraying and for 1 h afterwards. The
application rate of the compound is not stated. Five cm square
sections of 7 pads, 6 worn over and 1 worn under clothing, were
analysed from each volunteer and the total exposure to endosulfan
calculated assuming that all endosulfan measured on the pads was
absorbed into the body, irrespective of clothing. An addition of
10% was made to the calculation as an estimate of respiratory
absorption. Calculated values were compared with the dermal LD₅₀
for rat of 74 mg/kg body weight. The men outside the village
received 0.27% and those in the village 0.007% of the rat LD₅₀.
The exposure calculated was an overestimate as it assumed that
clothing offered no protection. The authors showed that the cotton
overalls reduced the dose of endosulfan by the pads by a factor of
at least 20.

Endosulfan has been shown to be released from a wood
preservative into a room atmosphere over a 1-year period of
observation (Zimmerli et al., 1979).

It is well-known that the respiratory route is a potential
route of exposure to endosulfan (Oudbier et al., 1974; Wolfe,
1976), and a TLV has been established at 0.1 mg/m³ (ACGIH, 1982).

Food

In the USA, endosulfan has been reported to be present in the
market basket survey since 1967. Between the 1967 and the 1974-75
studies, the level of contamination decreased, but the proportion
of food samples containing endosulfan increased. Endosulfan
(alpha-, beta-isomer and the sulfate derivative) was present in 3
out of 360 food samples in the 1967-68 survey, at a concentration
range of 0.008 - 0.134 mg/kg and was found in 1 sample of each of 3
food groups: garden fruits, leafy vegetables, and oils and fats
(Corneliussen, 1969). The 1968-69 survey revealed that endosulfan
was present in 16 out of 360 food samples with a range from 0.01 to
0.042 mg/kg. It was present in 7 out of 20 food samples, but only
in 2 food groups, leafy vegetables and garden fruits (Johnson &
Manske, 1977). Similar results for the above food groups were
found in Canada (Canada, National Research Council, 1975).

Endosulfan sulfate was also present in cow's milk from tobacco
farming areas at levels of up to 0.010 mg/litre (Frank et al.,
1970, 1979). Beck et al. (1966) reported that endosulfan could not
be detected in the milk of cows that had been fed forage containing
endosulfan at 0.41, 0.70, or 2.35 mg/kg for 21 days.

No endosulfan residues have been reported in market basket
surveys from other countries and there are no reports of the daily
human intake of endosulfan exceeding the FAO/WHO temporary ADI of
0.008 mg/kg body weight (FAO/WHO, 1982).

In general, endosulfan residues in food are well below the
tolerance levels established for various food types by the FAO/WHO
(1975a) (Table 2). These residue tolerances refer to the total
residue of alpha- and beta-endosulfan and endosulfan sulfate.

Table 2. Endosulfan tolerances in food^a
--------------------------------------------------
Food FAO/WHO tolerance^b
--------------------------------------------------
Tea (dry, manufactured) 30 mg/kg
Fruits and vegetables 2 mg/kg
(other than exceptions noted)
Carrots, potatoes, sweet 0.2 mg/kg
potatoes, bulb onions
Cottonseed 1.0 mg/kg
Cottonseed oil (crude) 0.4 mg/kg
Rice (in husk) 0.1 mg/kg
Milk and milk products 0.5 mg/kg
(fat basis)
Fat and meat 0.2 mg/kg
--------------------------------------------------
^a From: FAO/WHO (1975a).
^b Calculated as the total of alpha- and beta-endosulphan plus
endosulfan sulfate.

High endosulfan residues have been found in tobacco leaves in
both Canada and the USA. Pyrolysis studies on tobacco indicate
that the alpha- and beta-isomers, the sulfate derivative, and a
variety of other products are present in contaminated tobacco smoke
(Chopra et al., 1978). Levels as high as 30.9 and 20 µg/m³ were
detected in Canada and the USA, respectively (Dorough, 1973; Cheng
& Braun, 1977). Residues seem to consist primarily of endosulfan
sulfate followed by the beta-isomer, then the alpha-isomer (Cheng
& Braun, 1977).

Relative importance of different sources

With good agricultural practice, endosulfan residues in food
should not be significant. Its use in tobacco farming has been
discouraged (Cheng & Braun, 1977) but, if not regulated, could
provide a significant route of exposure. As a rule, endosulfan
concentrations in air and water are very low and localized, and
accordingly of no significance as far as risk for general
population is concerned.

No reports of endosulfan in breast milk have appeared in the
literature. However, since endosulfan is used as a wood
preservative and garden pesticide in some countries, direct
exposure of infants and children remains a possibility.

Occupational exposure

Only 2 reports on occupational exposure were found; both
involved workers who filled sacks with endosulfan powder. A total
of 11 people were poisoned, all of whom experienced difficulties in
concentration, vertigo, followed by epileptiform convulsions or
stupor (FAO/WHO, 1975b). No further information on workers exposed
during the production or spraying of endosulfan was available.

4. KINETICS AND METABOLISM

4.1. Animal Studies

Five days after a single oral administration (by gavage) of
¹⁴C-labelled alpha-endosulfan in corn oil at 2 mg/kg body weight to
female albino rats, totals of 75% and 13% of the dose were
eliminated in the faeces and urine, respectively. With the same
dose of ¹⁴C-labelled beta-endosulfan, and under the same
conditions, the values were 68% and 18.5%, respectively. When
radio-labelled endosulfan was fed to rats at 5 mg/kg diet for 14
days, 56% was eliminated in the faeces and 8% in the urine.
Maximum residues of endosulfan, which occurred in the kidney and
liver, were 3 and 1 mg/kg, respectively. Metabolism studies using
alpha- and beta-endosulfan did not reveal any appreciable
differences in the fate of the 2 isomers in the rat (Dorough et
al., 1978). Endosulfan was metabolized in rats to endosulfan diol,
endosulfan hydroxyethers, endosulfan lactone, endosulfan sulfate,
and some unidentified polar metabolites (Dorough et al., 1978).
Similar metabolites of endosulfan were identified in mice (Deema et
al., 1966; Schuphan et al., 1968).

Sheep given daily doses of endosulfan at 15 mg/kg body weight
for 28 days, eliminated 20% of the dose in the faeces as the
unchanged compound; only a small amount of endosulfan diol was
detected in the urine. Endosulfan sulfate (0.1 mg/kg) was found in
perirenal and mesenteric adipose tissues (Gorbach, 1965).

In rabbits, after a single intravenous (iv) injection of
endosulfan at 2.0 mg/kg, the concentration in plasma declined
rapidly. Thirty-seven percent of the dose was excreted in the
urine as alpha-endosulfan and 11% as beta-isomer in the first 5
days (Gupta & Ehrnebo, 1979).

The distribution pattern of endosulfan in the plasma and brain
was studied when rats were administered daily doses of 5 or 10
mg/kg body weight in peanut oil by gavage (approximately 1/20 and
1/10 LD₅₀) (2 alpha-:1 beta-isomer ratio) for 15 days (Gupta,
1978). On day 16, the rats that were dosed with 5 mg/kg had the
following concentrations of the alpha-isomer in the brain:
cerebrum, 3.76 mg/kg, cerebellum, 2.04 mg/kg; remaining parts of
the brain, 2.66 mg/kg. The concentrations of the beta-isomer were
0.06 mg/kg in the cerebrum and 0.02 mg/kg in the cerebellum; no
beta-isomer was detected in the other parts of the brain (Gupta,
1978). When the rats were fed the higher dose level the same
pattern of isomers and metobolite was found, the only difference
being that the concentrations were higher than in rats receiving
the lower dose. Distribution of endosulfan was also investigated
in the cat brain. Following a single iv administration of 3 mg/kg
body weight, groups of animals were sacrificed at selected time
intervals and analysed for endosulfan content. The cerebrum had
the highest concentration followed by the spinal cord, cerebellum,
and the brain stem (Khanna et al., 1979).

4.2. Human Studies

Some human data were obtained following the analysis of a case
of suicide in which an unknown amount of endosulfan was ingested
(Demeter et al., 1977) in combination with alcohol. The individual
died within 6 h after ingestion of the chemical. The tissue
distribution of endosulfan is given in Table 3. It could not be
concluded that death was due solely to the effects of endosulfan.

Table 3. Tissue distribution of endosulfan
---------------------------------------------------
Tissue alpha-endosulfan beta-endosulfan
(mg/kg) (mg/kg)
---------------------------------------------------
Liver 12.4 5.2
Kidney 2.48 1.8
Blood 0.06 0.015
Urine 1.78 0.87
Stomach content 2610 1900
Small intestinal 190 99
content
---------------------------------------------------

5. STUDIES ON EXPERIMENTAL ANIMALS

The toxicity and the residue data on endosulfan have been
reviewed by the Joint Meeting on Pesticide Residues (JMPR) in 1965,
1967, 1968, 1971, 1974, and 1982 (FAO/WHO, 1965, 1968, 1969, 1972,
1975a, 1983). For their conclusion, refer to section 8. We refer
to these reports, which contain more detailed information on the
toxicity studies and residue data than the present report.
Moreover, several unpublished studies have been evaluated and
reported there.

5.1. Short-Term Exposures

5.1.1. Single exposure

The LD₅₀ of endosulfan varied widely depending on the route
of administration, species, vehicle, and sex of the animal. The
available acute toxicity data are summarized in Table 4. The
clinical signs of toxicity include hyperactivity, tremors, and
convulsions, followed by death (Boyd, 1972; Gosselin et al., 1976;
Gupta, 1976).

Limited short-term studies on the dog showed that as little as
30 mg/kg body weight could be fatal (Canada, National Research
Council, 1975), and 2.5 mg/kg body weight per day for 3 days
induced toxic symptoms (FAO/WHO, 1968). The 2 stereoisomers have
comparable LD₅₀ values for the rat (Lindquest & Dahm, 1957).

Male rats given a single oral dose of endosulfan at 40 mg/kg
body weight displayed acute neurotoxic manifestations and showed a
significant increase in blood glucose, blood ascorbic acid, and
blood and brain glutathione (Garg et al., 1980). There have been
no published data on skin irritation or sensitization.

5.1.2. Repeated exposures

Endosulfan sulfate was fed to rats in the diet for 3 months at
levels as high as 500 mg/kg (Canada, National Research Council,
1975); no effects were detected other than increased liver or
kidney weight.

The same compound was administered to dogs for 3 months at
levels ranging from 0.75 to 2.5 mg/kg body weight per day. The
lowest dose did not have any effect, but the highest dose was not
tolerated and the 1.5 mg/kg dose induced occasional signs of
toxicity. It was concluded that endosulfan sulfate appeared to
have the same order of toxicity as endosulfan (Canada, National
Research Council, 1975).

Table 4. Acute toxicity of endosulfan in different animal species
------------------------------------------------------------------
Species Sex Route Vehicle LD₅₀ Reference
(mg/kg
body
weight)
------------------------------------------------------------------
Rat NS oral olive oil 64 Truhaut et al.
(1974)

Rat NS oral 95% alcohol 40 - 50 FAO/WHO (1968)

Rat M oral peanut oil 43 Gaines (1969)

Rat M oral cottonseed 121 Boyd (1972d)
oil

Rat F oral peanut oil 18 Gaines (1969)

Rat NS oral NS 355 Boyd & Dobos
(1969)

Rat NS ip 95% alcohol 8 FAO/WHO (1965)

Rat N dermal xylene 130 Gaines (1969)

Rat F dermal xylene 74 Gaines (1969)

Rat NS dermal cottonseed 681 Gupta & Gupta
oil (1979)

Rat NS inhalation NS 350 Gupta & Gupta
(mg/m³)^a (1979)

Mouse F ip 95% alcohol 7.5 Gupta (1976)

Mouse F ip alcohol & 13.5 Gupta (1976)
peanut oil

Mouse M ip 95% alcohol 6.9 Gupta (1976)

Mouse M ip alcohol & 12.6 Gupta (1976)
peanut oil

Rabbit NS dermal cottonseed 147 Gupta & Gupta
oil (1979)

Rabbit NS percutan- cottonseed 360 Gupta & Gupta
aneous oil (1979)

Rabbit NS dermal oil solvent 359 Martin (1968)
------------------------------------------------------------------

Table 4. (contd.)
------------------------------------------------------------------
Species Sex Route Vehicle LD₅₀ Reference
(mg/kg
body
weight)
------------------------------------------------------------------
Rabbit NS dermal chloroform 187 Gupta &
Chandra (1975)

Guinea- NS dermal cottonseed 1000 Gupta & Gupta
pig oil (1979)

Hamster NS oral olive oil 118 Truhaut et
al. (1974)
------------------------------------------------------------------
^a Value represents the LC₅₀ in mg/m³ for a 4-h exposure period.
NS = Not stated.
M = Male.
F = Female.

When rats were treated with daily oral doses of endosulfan at
1.6 - 3.2 mg/kg body weight, for 12 weeks, no effects were observed
on growth-rate (FAO/WHO, 1967). Administration of dietary levels
of endosulfan ranging from 2 to 200 mg/kg to male rats for 2 weeks,
resulted in changes in mixed-function oxidase activity (Den
Tonkelaar et al., 1974). Endosulfan at the highest level (200
mg/kg, approximately 10 mg/kg body weight per day) was found to
induce mixed-function oxidases activity (aniline hydroxylase and
aminopyrine demethylase).

Endosulfan was administered to female rats at daily oral doses
of 1.0, 2.5, or 5.0 mg/kg body weight for 7 or 15 days (Gupta &
Gupta, 1977). No changes were observed in body, ovary, or adrenal
weights. Liver weight increased and pentobarbital sleeping time
decreased at the 2 highest dose levels and both time intervals.
The results of subsequent studies (Agarwal et al., 1978) showed
that the 2 highest levels resulted in induction of aminopyrine
demethylase and aniline hydroxylase activities as well as a dose-
related increase in amino-transferase activity and spontaneous
lipid peroxidation.

Male rats were dosed by oral intubation with endosulfan at
levels of 5 or 10 mg/kg body weight per day for 15 days (Gupta,
1978). A reduction in body weight gain was observed at the higher
dose, and 3 out of 12 animals died during testing.

In a separate study (Garg et al., 1980), male rats were dosed
orally with endosulfan at 0.625, 5.0, or 20 mg/kg body weight, 6
days per week, for 7 weeks. Animals receiving the highest dose
showed a slight increase in blood glucose and a decrease in plasma
calcium levels.

Endosulfan was administered orally to 4 dogs for 3 days at 2.5
mg/kg body weight (FAO/WHO, 1967). Vomiting was observed in one
dog and vomiting, tremors, convulsions, rapid respiration, and
mydriasis in the 3 remaining animals. Three other groups of dogs,
2 males and 2 females per group, were administered endosulfan
orally at levels of 0.075, 0.25, or 0.75 mg/kg body weight for 6
days a week over a 1-year period (FAO/WHO, 1968). No signs of
toxicity were observed. At autopsy, gross and microscopic
examination of the tissues did not reveal any differences between
treated and control animals.

When endosulfan was administered to cats (Misra et al., 1980)
at levels of 2, 3, or 4 mg/kg body weight, muscular twitching
was observed in all treatment groups, followed by convulsions. At
the 2 higher dose levels, there was a marked rise in blood glucose
levels after 15 and 30 min with a gradual fall up to 4 h.
Adrenalectomy prevented this rise. Cats were fasted for 1 - 2 h
before this study and were then injected with a single intravenous
dose of endosulfan (2, 3, or 4 mg/kg) through a cannula inserted
into the femoral vein. Blood was drawn from the femoral vein after
0, 15, and 30 min, and 1, 2, and 4 h.

Endosulfan is able to inhibit sodium-, potassium-, and
magnesium-dependent ATPase enzymes in rainbow trout brain (Davis &
Wedemeyer, 1971).

5.2. Long-Term Exposures

Groups of 25 male and 25 female rats received technical grade
endosulfan at 10, 30, and 100 mg/kg diet for 104 weeks (FAO/WHO,
1968). Survival of the female rats in the 10 and 30 mg/kg groups
was lower than that in the female control group, during the second
year of exposure. In the 100 mg/kg female group, survival was
significantly lower after 26 weeks and abnormalities were observed
in weight gain and haematological parameters. At autopsy, the
relative weight of the testes in the 10 mg/kg male group was
significantly lower than in the control group. Significant
histopathological findings were apparent only in the 100 mg/kg male
group. In these animals, the kidneys were enlarged and there were
signs of renal tubular damage with interstitial nephritis.
Hydropic changes were seen in liver cells. The tumor incidence in
all test groups was within the range of the control group.

In a study reported by the Commission of European Communities
(CEC, 1981), male and female dogs were dosed with endosulfan (by
capsule), 6 days a week for 10 months. The dose levels ranged from
0.075 to 0.75 mg/kg body weight. No gross or microscopic evidence
of toxicity was noted.

The Joint Meeting on Pesticide Residues (JMPR) reviewed the
toxicity data on endosulfan in its 1982 meeting (FAO/WHO, 1983) and
concluded that the following levels did not cause any toxicological
effects:

rat: 30 mg/kg diet, equivalent to 1.5 mg/kg body weight;
and

dog: 0.75 mg/kg body weight per day (administered by
capsules)

5.3. Reproduction Studies

Adequate data are not available.

5.4. Mutagenicity

Endosulfan was not mutagenic in E. coli or S. typhimurium
(Fahrig, 1974; Moriya et al., 1982). It did not induce mitotic
conversion in Saccharomyces cerevisae (Fahrig, 1974). However, in
one study, technical grade endosulfan was reported to induce reverse
mutations, cross overs, and mitotic gene conversions in Saccharomyces
cerevisiae (Yadav et al., 1982).

Endosulfan did not induce chromosomal abberations in bone
marrow cells or spermatogonia of male rats treated with 5 daily
oral doses of 11 - 55 mg/kg body weight (Dikshith & Datta, 1978).

An increased number of micronuclei induced in the bone marrow
erythrocytes of mice treated with endosulfan in the drinking-water
(43.3 mg/litre) for 2 consecutive days was not statistically
significant (Usha Rani et al., 1980). Negative results were
observed in a dominant lethal test in mice (Canada, National
Research Council, 1975).

5.5. Teratogenicity

Adequate data are not available.

5.6. Carcinogenicity

The carcinogenicity of technical grade endosulfan was tested
using Osborne-Mendel rats and B6C3F1 mice (NCI Tech. Series, 1978).
The time-weighted average high and low endosulfan concentrations in
the diet for male rats were 952 and 408 mg/kg; for female rats 445
and 223 mg/kg; for male mice 6.9 and 3.5 mg/kg; and for female mice
3.9 and 2.0 mg/kg. Testing of high-dose male rats was terminated
during week 82 and low dose male rats during week 74.

Female rats were administered endosulfan for 78 weeks followed
by a 33-week observation period. Mice were administered the
chemical for 78 weeks and observed for an additional 14 weeks. A
high early mortality rate in male rats and mice precluded any
conclusions concerning carcinogenicity. Under the conditions of
the assay, it was concluded that endosulfan was not carcinogenic
for female Osborne-Mendel rats or female B6C3F1 mice.

In a large scale screening study, 2 strains of male and female
hybrid mice [(C57BL/6 x C3H/Anf)F₁] and [(C57BL/6 x AKR)F₁] were
given 2.15 or 3.0 mg/kg body weight endosulfan by oral intubution
on days 7 - 28 of age followed by the feeding of diets containing
concentrations of 3 or 6 mg/kg diet for 78 weeks (Innes et al.,
1969). Although no conclusion could be drawn about its
carcinogenic potential, endosulfan was reported as being one of the
compounds requiring further study.

5.7. Factors Influencing Toxicity

Rats subjected to protein-deficient diets were more susceptible
to the acute toxic effects of endosulfan (Boyd, 1972). The LD₅₀
for rats on normal lab chow was reported to be 121 mg/kg body
weight, compared with 5 mg/kg for rats on a protein-deficient diet.

6. EFFECTS ON MAN

6.1. Poisoning Incidents

A report from Bulgaria described the circumstances, clinical
symptoms, and morphological changes in 5 cases associated with
endosulfan poisoning (Terziev et al., 1974). These cases comprised
2 suicides and 3 accidental poisonings. Death generally followed a
few hours after ingestion. The clinical symptoms included
vomiting, agitation, convulsions, cyanosis, dyspnoea, foaming at
the mouth, and noisy breathing.

Another report lists the findings on 2 cases (apparently
suicides) of men who died after ingesting endosulfan (Demeter &
Heyndrickx, 1978). Again, death was noted to occur within a few
hours of ingestion, and significant post-mortem findings included
congested and oedematous lungs and cyanosis. Tissue analysis for
residues indicated the possible synergistic effect of endosulfan
and alcohol in one patient (Demeter et al., 1977) and endosulfan,
alcohol, and dimethoate, an organophosphorous insecticide, in the
second.

6.2. Occupational Exposure

Three cases of poisoning in workers employed in a chemical
factory have been reported (Israeli et al., 1969; Tiberin et al.,
1970). Poisoning occurred when the men filled bags with
insecticide without wearing protective clothing and masks.
Symptoms developed after 3 weeks, 1 month, and 18 months,
respectively, following daily exposure, and consisted of headaches,
restlessness, irritability, vertigo, stupor, disorientation, and
epileptiform convulsive seizures.

Electroencephalogram changes were noted. Endosulfan has been
shown to persist on the hands of pest control operators for up to
31 days after exposure. No clinical symptoms were observed (Kazen
et al., 1974).

6.3. Treatment of Poisoning

In case of overexposure, medical advice should be sought
immediately.

If the pesticide has been ingested, gastric lavage should be
performed with 2 - 4 litres of tap water followed by saline
purgatives (30 g sodium sulfate in 250 ml of water). Barbiturates
or diazepam should be given intraveneously in sufficient dosage to
control restlessness or convulsions. Mechanical respiratory
assistance with oxygen may be required. Calcium gluconate (10% in
10 ml) should be injected 4-hourly. Contraindications are oily
purgatives, epinephrine, and other adrenergic drugs and central
stimulants of all types (FAO/WHO, 1975b).

7. EFFECTS ON THE ENVIRONMENT

7.1. Toxicity for Aquatic Organisms

The most representative studies on the toxicity of endosulfan
for aquatic organisms are summarized in Table 5. A more
comprehensive table, listing different conditions and exposure
times, is available on request from IRPTC, Geneva, Switzerland.

Ramachandran et al. (1981) looked at the effects of a low
concentration of endosulfan (50 µg/litre) on photosynthesis and
respiration in some common seaweeds. The red alga Gracilaria
verrucosa showed the highest tolerance to endosulfan. Photo-
synthesis was 96.2% of control levels and respiration was
stimulated to 112.32%. The 3 other algal species Gratiloupia,
Enteromorpha intestinalis, and Cheatomorpha linum showed photo-
synthetic rates of 80.4, 83.6, and 84.6% of control levels and
respiration rate of 107.38, 86.97, and 93.6%, respectively. The
respiration to photosynthesis ratio was lower than control levels
for all 4 species.

The toxic effects of endosulfan, determined for 1 freshwater
and 2 seawater species of crustacea, are summarized in Table 5.
McLeese & Metcalfe (1980) studied the effects of including sediment
in test vessels. For the shrimp Crangon, 96-h LC₅₀ values for
endosulfan increased from 0.2 µg/litre to 6.9 µg/litre with the
inclusion of sediment. The mortality rate estimate of Butler
(1963) for the brown shrimp included animals immobilized by the
material and showing no clear signs of life. Twenty-four- and 48-h
LC₅₀ values for the freshwater scud Gammarus lacustris were 9.2
and 6.4 µg/litre, respectively (Sanders, 1969).

McLeese et al. (1982) tested the toxicity of endosulfan for the
ragworm Nereis virens with and without sediment in the test
vessels. The LC₅₀ for endosulfan in 288-h tests were 100 µg/litre
with sea water and 340 µg/kg with sediment. Symptoms of stress in
the worms included eversion of the proboscis, lost equilibrium, and
immobilization. Stressed worms in sediment tests emerged from the
sediment and subsequently did not burrow, even after the sediment
was changed.

Table 5. Toxicity of endosulfan for aquatic organisms
---------------------------------------------------------------------------------------------------------
Organism Size/ Grade Temp pH Stat/ Sal Effect Parameter Conc. Reference
age (°C) flow (⁰/00) (µg/litre)
---------------------------------------------------------------------------------------------------------
eastern oyster 28 22 decrease 96-h EC₅₀ 65 Butler (1963)
(Crassostrea in shell
virginical) growth

polychaete worm adult 9-10 stat death 12-day LC₅₀ 100 McLeese et al.
(Nereis nereis) (1982)

adult 9-10 stat death 12-day LC₅₀ 340^a McLeese et al.
(1982)

Cladoceran 10 7.4 45^b death 96-h LC₅₀ 52.9 Schoettger
(Daphnia magna) 38^c (1970)

shrimp adult 20 stat death 96-h LC₅₀ 0.2 McLeese &
Metcalfe (1980)

(Crangon adult 10 stat death 96-h LC₅₀ 6.9^a McLeese &
septemspinosa) Metcalfe (1980)

blue crab juv. 30 stat death or 24-h EC₅₀ 55 Butler (1963)
(Callinectes loss of 48-h EC₅₀ 35 Butler (1963)
sapidus) equilib-
rium

freshwater mite adult tech 25- 7.8- stat immobil- 48-h EC₅₀ 2.8 Nair (1981)
(Hydrachna 31 8 isation
trilobata)

stonefly nymph 15.5 7.1 stat death 96-h LC₅₀ 2.3 Sanders & Cope
(Pteronarcys (1968)
californica)

rainbow trout 1.3g tech death 96-h LC₅₀ 1.4 Johnson &
(Salmo gairdneri) 96% Finley (1980)

fathead minnow 0.7g tech death 96-h/LC₅₀ 1.5 Johnson &
96% Finley (1980)
---------------------------------------------------------------------------------------------------------

Table 5. (contd.)
---------------------------------------------------------------------------------------------------------
Organism Size/ Grade Temp pH Stat/ Sal Effect Parameter Conc. Reference
age (°C) flow (⁰/00) (µg/litre)
---------------------------------------------------------------------------------------------------------
channel catfish 1.7g tech death 96-h LC₅₀ 1.5 Johnson &
(Ictalurus 96% Finley (1980)
punctatus

catfish 6-10g 35% 18.2 6.9- stat death 96-h LC₅₀ 0.67 Verma et al.
(Mystusvittatus) 80- EC 7.4 (1980)
100mm

6-10g 35% 18.2 6.9- stat death 96-h LC₀ 0.06 Verma et al.
80- EC 7.4 (1980)
100mm

6-10g 35% 18.2 6.9- stat death 96-h LC₅₀ 3.50 Verma et al.
80- EC 7.4 (1980)
100mm 8.4 flow 152^b death 96-h LC₅₀ 2.2 Rao & Murty
330^c (1982)

catfish 8.4 flow 152^b death 96-h LC₅₀ 1.1 Rao & Murty
(Heteropneustes 330^c (1982)
fossilis)
41.8± 35% 7.8 stat 120^c death 96-h/LC₅₀ 14.7 Singh & Narain
4.7g (1982)
197± EC
8mm

11.3± 35% 7.8 stat 120^c death 96-h/LC₅₀ 7.3 Singh & Narain
1.6g (1982)
102± EC
5mm

catfish 8.4 flow 152^b death 96-h LC₅₀ 1.9 Rao & Murty (1982)
(Mystuscavasius) 330^c

catfish 40-55g 35% 18.2 6.9- stat death 96-h LC₅₀ 22 Verma et al.
(Ophiocephalus 90- EC 7.4 (1981)
punctatus) 100mm
---------------------------------------------------------------------------------------------------------
^a Sediment present in test vessel.
^b Hardness mg CO₃/litre.
^c Alkalinity mg HCO₃-/litre.
Nair (1981) tested endosulfan toxicity with a range of
concentrations from 2.6 and 2.9 µg/litre on the freshwater mite
Hydrachna trilobata viets and reported a 48-h LC₅₀ value of
2.8 µg/litre. The small difference between the no-effect and
lethal dosages of endosulfan is typical for many different aquatic
organisms. A 96-h LC₅₀ of 1890 µg/litre was reported by Holcombe
et al. (1983) for adult freshwater snails Aplexa hypnorum. Roberts
(1972) reported that endosulfan at a concentration of 1000 µg/litre
delayed the onset of spawning and prolonged the spawning period for
the common mussel Mytilus edulis. At a lower dose of 100 µg/litre,
a slight reduction in the length of the spawning period was
considered by the author to reflect the experimental tank
conditions rather than the endosulfan treatment.

Endosulfan has a high acute toxicity for fish. There have been
studies on many species of teleosts with 96-h LC₅₀ values ranging
from 0.67 µg/litre to 4.8 µg/litre. Where commercial preparations
of endosulfan have been used, it is not always clear how the dose
is presented. Where LC₅₀ values exceed 4.8, it seems clear that
the values given are for a preparation that usually contains only
35% endosulfan.

Singh & Narain (1982) looked at variations in LC₅₀ values
in 96-h tests on the catfish Heteropneustes fossilis in
relation to season, and size and weight of the fish. Tolerances of
the fish to the Thiodan preparation (35% endosulfan) showed a
significant seasonal variation. Fish were more tolerant to
endosulfan during the colder months of the year. The toxicity of
endosulfan was directly proportional to the length and weight of
fish; LC₅₀ values increased from 5 to 4.7 µg/litre with an increase
in fish weight from 4.8 to 41.8 g and an increase in length from
6.2 to 19.7 cm. The relative toxicity of technical endosulfan,
endosulfan isomers, and formulations, was investigated in the
freshwater fish Labeo rohita by Rao et al. (1980), and in Channa
punctata, a catfish, by Devi et al. (1981). In Labeo rohita,
endosulfan-A was 3.33 times and endosulfan-B 0.16 times more toxic
than technical endosulfan; the alpha-isomer was 30 times and the
beta-isomer 0.7 times more toxic than technical material in Channa
punctata. Rao & Murty (1982) demonstrated in 3 species of catfish
that the relative toxicity between species could not be determined
using LC₅₀ values alone. The slopes of endosulfan toxicity curves
were different for different species. The same authors (Rao &
Murty, 1980), reported that endosulfan metabolites were eliminated
mainly with faeces and urine, the principal sites of detoxification
of endosulfan being the liver and kidney. Using the freshwater
catfish Saccobranchus fossilis, Verma et al. (1982a) calculated the
safe levels of 2 preparations of endosulfan to be 0.14 µg/litre
(Thiotox) and 0.23 µg/litre (Thiodan). Verma et al. (1980) looked
for synergism and antagonism between endosulfan, dichlorvos and
carbofuran on the test fish Mystus vittatus and Ophiocephalus
punctatus, but did not find any evidence of either.

Histopathological, biochemical, and physiological changes in
fish after exposure to endosulfan have been reported in a large
number of studies. Gopal et al. (1981a) measured blood glucose
levels in catfish during 96-h of exposure to endosulfan at 10
µg/litre. A marked rise, at 4 h, of 66.4% over control levels
increased to a peak of 101.6% at 48 h compared with control levels
and then declined to match control levels at 72 h. At the end of
the study, after 95 h, the glucose level was not significantly
different from controls. Singh & Srivastava (1981) exposed Indian
catfish to a high sublethal concentration of endosulfan of 1.5
µg/litre (representing 75% of the 96-h LC₅₀ for the species). The
average mortality rate for all fish groups was 5% over the 96-h
experimental period. Muscle glycogen was depressed for most of the
experimental period. Liver glycogen was the least affected of all
the variables measured. Blood glucose was significantly elevated
at 3, 6, 48, and 96 h of exposure, but not at 12 h. Blood pyruvate
was elevated at 6 and 48 h only, whereas blood lactate was
significantly elevated for the first 6 h of exposure and
significantly depressed for the remainder of the observation
period. Endosulfan was shown by Sastry & Siddiqui (1982) to reduce
intestinal uptake of glucose by the fish Channa punctatus at doses
of 1 mg/litre and above. Using endosulfan concentrations of
between 0.17 and 2.3 µg/litre on 3 species of Indian catfish, Verma
et al. (1983) found elevation of blood glucose ranging from 67.31%
to 98.36%. The concentrations of endosulfan used represent 25% of
the 96-h LC₅₀ for each species. Murty & Devi (1982) demonstrated
that changes in tissue protein, glycogen, and lipid levels in the
fish Channa punctatus were greater with exposure to the alpha- than
to the beta-isomer of endosulfan.

A clear dose-related reduction in both oxygen consumption and
total nitrogen excretion was shown by Rao et al. (1981) in the fish
Macrognathus aculeatum with endosulfan concentrations ranging from
1 to 15 µg/litre. Verma et al. measured the activity of 3
phosphatases in the liver, brain, and gills of Saccobranchus
fossilis after 30 days exposure to endosulfan at concentrations
from 0.63 µg/litre. The depression in the activity of these
enzymes was increased by the addition of ascorbic acid to the food
of the fish. Dalela et al. (1979) reported that acute (5 h of
exposure) and short-term exposure (up to 32 days) of the fish
Channa gachua to endosulfan at respectively 11.76 and 3.5 µg/litre
produced histological changes in the gills. On acute exposure to
11.76 µg/litre, there was separation of the respiratory gill
epithelium from the basement membrane, pronounced hyperaemia,
necrosis, fusion of adjacent gill lamellae, erosion at the distal
end of gill filaments, and loss of cell membrane. With exposure to
a sub-lethal dose of 3.5 µg endosulfan/litre, damage to the gill
was not as severe after 8 days, but was found to be progressively
more pronounced with increasing exposure time.

A detailed field study was conducted in relation to tsetse fly
control operations in the Okavango delta region of Botswana. Fox &
Matthiessen (1982) reported that in laboratory studies, 24-h LC₅₀
values for Okavango fish ranged from 1.2 to 7.4 µg/litre, depending
on species. Field concentrations of endosulfan after spraying at
9.5 g/ha ranged between 0.2 and 4.2 µg/litre. The authors

determined pre-spraying population densities and, thereby, the
apparent mortality rate in a variety of fish species after
spraying. Estimated mortality rates ranged from 0.2 to 4.3% for
individual species with an overall estimate of 0.9%. Matthiessen &
Roberts (1982) reported pathological changes in the liver and brain
of fish exposed to endosulfan spray, and Matthiessen (1981)
reported a significant elevation in blood cell counts during
spraying.

7.2. Toxicity for Terrestrial Organisms

The toxicity of endosulfan for terrestrial organisms is
summarized in Table 6.

7.2.1. Plants

Some phytotoxic effects of endosulfan have been reported.
Gentile et al. (1978) reported that 24% endosulfan reduced the
germination of cucumber pollen to 54.6% of control levels at a
concentration of 1000 mg ai/litre, half the recommended
concentration for field use. At the same concentration,
pollentube length was only 8.1% of controls. Morey & Singh (1980)
examined the effects of endosulfan on several species of Cucurbitae
and found that it was phytotoxic to all but one species and
moderately phytotoxic to the latter. Concentrations ranged from
0.035 to 0.14%. Phytotoxicity was estimated by necrotic spots on
leaves. Agarwal & Beg (1982a) studied the effects of endosulfan on
the germination and seedling growth of Cicer arietinum. They found
reduced viability and delayed germination with endosulfan
treatment. Inhibition, at lower concentrations of 0.01, 0.1, and 1
mg/litre in an agar bed used as the germination medium, was
reversed as germination progressed, whereas at 10 mg/litre
inhibition persisted. Endosulfan affected all major stages of
germination and seedling growth. The results of a simple in vitro
experiment suggested that endosulfan changed the permeability of
root membranes. Gupta & Gupta (1977) examined 4 concentrations of
endosulfan between 0.35 g/kg and 3 g/kg for effects on Green Gram,
Vigna radiata. Toxic effects were dose-dependent. At 0.35 g/kg
and 0.7 g/kg, no adverse effects were observed in any of the
parameters studied, but, at higher concentrations of 1.5 g/kg and 3
g/kg, symptoms of toxicity were visible. These included coiling of
the radical, inhibition of root growth, stunting of shoots, and
burning of the tips and margins of leaves. Plants were dwarfed and
chlorotic, having damaged pollen grains and low productivity.
Agarwal & Beg (1982b) reported that exposure of germinating Cicer
arietinum seeds to endosulfan resulted in a fall in the pectin,
hemicellulose, and cellulose contents of cell walls at all stages
of germination compared with untreated controls. It must be stated
that these were very isolated phytotoxic effects. In normal usage,
endosulfan has not been shown to be significantly toxic to plants.

Table 6. Toxicity of endosulfan for terrestrial organisms
---------------------------------------------------------------------------------------------------------
Organism Size/ Grade Temp Route Parameter Concentration Reference
age (°C) (mg/kg)^a
---------------------------------------------------------------------------------------------------------
braconoid parasite adult technical 24 contact 24-h LC₅₀ 494 mg/litre Hagley et al.
(Apanteles ornigis) (1981)

ladybird beetle adult technical contact 72-h LC₈₃ 200 mg/litre Makar & Jadhav
(1981)

(Menochilus 1-day-old technical contact 72-h LC₇₈ 200 mg/litre Makar & Jadhav
sexmaculatus) larva (1981)
3rd instar

honey bee, worker 95% contact LD₅₀ 7.1 g/bee Stevenson et
(Apis mellifera) oral LD₅₀ 6.9 g/bee al. (1978)

mallard 36 h 96% oral acute LD₅₀ 27.8 Hudson et al.
( Anas (22.8-33.8) (1972)
platyrhynchos)
7 day 96% oral acute LD₅₀ 6.47 Hudson et al.
(5.19-9.05) (1972)
30 day 96% oral acute LD₅₀ 7.89 Hudson et al.
(5.77-10.8) (1972)
3-4 month 96% oral acute LD₅₀ 33 (23.8-45.8) Tucker &
Crabtree (1970)
6 month 96% oral acute LD₅₀ 34.4 Hudson et al.
(1972)
16 day 96% diet 5-day LC₅₀ 1053 Hill et al.
(781-1540) (1975)
young 35%^b diet < 10-day LC₅₀ 1000 DeWitt et al.
(1963)
adult 35%^b diet < 10-day LC₅₀ > 5000 DeWitt et al.
(1963)
adult 35%^b diet < 100-day LC₅₀ 1000 DeWitt et al.
(1963)
---------------------------------------------------------------------------------------------------------

Table 6. (contd.)
---------------------------------------------------------------------------------------------------------
Organism Size/ Grade Temp Route Parameter Concentration Reference
age (°C) (mg/kg)^a
---------------------------------------------------------------------------------------------------------
ringnecked pheasant 10 day 96% diet 5-day LC₅₀ 1275 Hill et al.
(Phasianus (1098-1482) (1975)
colchicus) young 35%^b diet < 10-day LC₅₀ 500 DeWitt et al.
(1963)
young 35%^b diet < 100-day LC₅₀ > 300 DeWitt et al.
(1963)
adult 35%^b diet < 100-day LC₅₀ 1000 DeWitt et al.
(1963)

Japanese quail 14-day 96% diet 5-day LC₅₀ 1250 Hill et al.
(Coturnix coturnix (1975)
japonica)

bobwhite quail 9-day 96% diet 5-day LC₅₀ 805 (690-939) Hill et al.
(Colinus (1975)
virginianus) young 35%^b diet < 10-day LC₅₀ 300 DeWitt et al.
(1963)
young 35%^b diet < 100-day LC₅₀ 100 DeWitt et al.
(1963)
adult 35%^b diet < 100-day LC₅₀ > 250 DeWitt et al.
(1963)

cowbird 35%^b diet 10-day LC₅₀ 1000 DeWitt et al.
(1963)
---------------------------------------------------------------------------------------------------------
^a Concentrations are mg/kg body weight for oral dosing and mg/kg diet for dietary dosing.
^b Preparation used is "thiodan", which is a 35% formulation of endosulfan.

7.2.2. Honey bees

Endosulfan is considered of moderate or low toxicity for honey
bees. Stevenson et al. (1978) reported a contact LD₅₀ of 7.1 µg/bee
and an oral LD₅₀ of 6.9 µg/bee for endosulfan. Endosulfan has never
been implicated in episodes of poisoning of bees investigated in
Great Britain (Stevenson et al., 1978).

7.2.3. Birds

The toxicity of endosulfan for birds is summarized in Table 6.
Hudson et al. (1972) examined the effects of age of mallard ducks
on their sensitivity to endosulfan. The acute oral LD₅₀s for ducks
at 36 h, 7 days, 30 days, and 6 months of age were 27.8, 6.47,
7.89, and 34.4 mg/kg body weight, respectively.

Field studies on birds in the Okavango delta of Botswana
related to endosulfan sprays for tsetse fly control failed to show
any change in bird numbers or species diversity (Douthwaite, 1980).
Douthwaite (1982) looked specifically at kingfishers that fed on
fish killed or incapacitated by the spray. The feeding rates of
kingfishers were greatly increased by the availability of
debilitated fish, but these rates fell when spraying ended. The
kingfisher population in the study area survived and numbers at a
communal roost were steady.

7.3. Toxicity for Microorganisms

Endosulfan is toxic for a wide variety of microorganisms.
Srivastava & Misra (1981) found a dose-related increase in oxygen
consumption by the yeast Rhodotorula gracilis at concentrations of
endosulfan between 10 and 200 mg/litre medium. Further increases
in dose up to 400 mg/litre did not show any increased effects.
The authors suggested that endosulfan affects membrane components.
Butler (1963) reported that endosulfan (thiodan) at a concentration
of 1 mg/litre, decreased productivity in a natural phytoplankton
community by 86.6% during a 4-h exposure. The bacterial
insecticide, Bacillus thuringiensis, was reported by Kahlon et al.
(1981) to show reduced viable count and spore count on incubation
with solutions of endosulfan at 0.5 or 1 µg/litre. Endosulfan was
the most effective inhibitor of sporulation of the 3 insecticides
tested. Tarar & Salpekar (1980) reported that endosulfan was the
most toxic of 6 organochlorines for soil algae. Of algal species
present in the soil (18 species present in the control soil), 17
were eliminated by endosulfan concentrations of 2 g/kg. Only 1
species survived endosulfan at 4 and 6 g/kg. This species,
Chlorococcum humicolo, was unaffected by any of the organochlorines
with which the soil was treated. El Beit et al. (1981) examined
the microbial metabolism of pesticides and effects of the
pesticides on the growth of bacterial and actinomycete colonies.
Endosulfan either as the alpha- or beta-isomer applied at 4000
mg/litre prevented the growth of any bacterial or actinomycete
colonies from any soil type tested. Alpha-endosulfan seemed to be
broken down by both bacteria and fungi whereas the beta-isomer was
degraded more by bacteria than by fungi. Results suggest that

while both isomers can be degraded by microbial organisms, the
degradation materials released counteract the growth of the
microorganisms.

7.4. Bioaccumulation

In aquatic ecosystems, endosulfan residues tend to reach a
plateau level in tissues. Schoettger (1970) exposed western white
suckers to water containing ¹⁴C-labelled endosulfan at 29 µg/litre
for 12 h. In the tissues concentrating the most endosulfan, a
plateau level of the compound was reached within 12 h. A plateau
was maintained over a prolonged period in studies on goldfish
exposed to endosulfan solutions at 7 µg/litre. Residue levels in
muscle were 2.54 mg/kg after 5 days and 1.09 mg/kg after 20 days
(Schoettger, 1970). Accumulation appeared to be transitory,
because endosulfan disappeared rapidly in mussels (Roberts, 1972)
and goldfish after the source was removed (Schoettger, 1970).
Oeser & Knauf (1973) calculated the half-life for the elimination
of endosulfan from goldfish to be 2 - 3 days. This followed a 5-
day exposure to 1 µg of the pesticide/litre, during which time
residues reached a mean level of 0.35 mg/kg. Little accumulation
of endosulfan seems to have been reported in the field. The mean
residue level in fish living in endosulfan-contaminated natural
surface water was 0.4 mg/kg (Gorbach & Knauf, 1971).

Roberts (1972) reported concentration factors of 17, 11, and
8.1 after exposing mussels to 0.1, 0.5, and 1.0 mg endosulfan/litre,
respectively, for 112 days. Although the mussels assimilated more
pesticide at higher dose levels, the greatest concentration factors
were achieved with the lowest dose of 0.1 mg/litre, a maximum BCF
of 22.5 being reached after 70 days. Roberts (1972) found that the
major storage site for endosulfan in scallops was the digestive
gland. He suggested this would also be the case for mussels and
other bivalves.

In a study by Ernst (1977) on the uptake and elimination of
endosulfan, a somewhat higher BCF value of 600 was measured in
mussels, with an initial concentration of endosulfan in the water
of 2.05 µg/litre. The concentration factor is based on a steady
state concentration of 0.14 µg endosulfan/litre water. If the BCF
is calculated on the initial concentration, a BCF of 41, a more
typical value for aquatic organisms, is obtained. Bioaccumulation
data are summarized in Table 7.

Table 7. Bioaccumulation of endosulfan
-----------------------------------------------------------------------------------------
Organism Grade Temp Organ Exposure Concen- Dose References
(°C) time tration (µg/
factor litre)
BCF
-----------------------------------------------------------------------------------------
green alga WB^c initial 2500 Oeser et al.
(Chlorella sp.) BCF (1971)

mussel WB 112 day 17 100 Roberts (1972)
(Mytilus edulis) WB 112 day 11 500 Roberts (1972)
WB 112 day 8.1 1000 Roberts (1972)
alpha- WB 600^a 0.14^a Ernst (1977)
isomer (41)^b (2.05)^b

goldfish liver 11-20 day 781 7 Schoettger (1970)
(Carassius auratus) muscle 5-20 day 314 7 Schoettger (1970)

western white 19 muscle 12 h 65 20 Schoettger (1970)
sucker 19 muscle 9 h 55 20 Schoettger (1970)
(Catostomus 19 liver 12 h 550 20 Schoettger (1970)
commersoni) 19 liver 9 h 695 20 Schoettger (1970)
-----------------------------------------------------------------------------------------
^a Higher BCF based on steady state concentration of endosulfan.
^b Values in () based on original concentration of endosulfan (static test).
^c WB = whole body.

Koeman et al. (1974) measured residues in animal species in
Java, following BIMAS programmes for the control of paddy-stem
borer that had continued over several years. No residues were
found (detection limit 0.03 mg/kg); animals used included fish,
molluscs, crabs, and shrimps. Matthiessen et al. (1982) studied
the accumulation of endosulfan in fish and their predators
following aerial spraying to control the tsetse fly in Botswana.
Residue levels in fish predators, birds, and crocodiles, were
similar to those in their prey. Risk to predators was consequently
deemed to be low. Although endosulfan residues in insects were not
measured, low residues in insectivorous birds suggested rapid
degradation and little accumulation. According to Matthiessen et
al. (1982), lean fish have a lower survival rate than fat ones at
subacute concentrations of endosulfan in the water.

There do not seem to be any accumulation data available for
wild mammals.

8. PREVIOUS EVALUATIONS OF ENDOSULFAN BY INTERNATIONAL BODIES

The Joint Meeting on Pesticide Residues (JMPR) have reviewed
residues and toxicity data on endosulfan on several occasions in
the past: 1965, 1967, 1968, 1971, 1974, and 1982 (FAO/WHO, 1965,
1968, 1969, 1972, 1975a, 1983).

In 1982, the estimate of a temporary acceptable daily intake
for man was made at 0 - 0.008 mg/kg body weight (total of alpha-
and beta-endosulfan and endosulfan sulfate). This was based on
no-observed-adverse-effect levels of:

rat: 30 mg/kg diet, equivalent to 1.5 mg/kg body weight;
and

dog: 0.75 mg/kg body weight per day (administered by
capsules).

The FAO/WHO (1975b) in its series of "Data sheets on chemical
pesticides" issued one on Endosulfan. Based on a brief review of
use, exposure, and toxicity, practical advice is given on
labelling, safe-handling, transport, storage, disposal,
decontamination, selection, training, and medical supervision of
workers, and first aid and medical treatment.

WHO (1984), classified endosulfan in the list of technical
products being moderately hazardous.

Regulatory standards established by national bodies in 12
different countries (Argentina, Brazil, Czechoslovakia, Federal
Republic of Germany, India, Japan, Kenya, Mexico, Sweden, the
United Kingdom, the USA, and the USSR) and the EEC can be found in
the IRPTC (International Register of Potentially Toxic Chemicals)
Legal file (IRPTC, 1983).

9. EVALUATION OF HEALTH RISKS FOR MAN AND EFFECTS ON THE ENVIRONMENT

9.1. Evaluation of Health Risks for Man

Endosulfan toxicity

Endosulfan is moderately to highly toxic according to the scale
of Hodge & Sterner (1956). The oral LD₅₀ in the rat ranges from 18
- 355 mg/kg body weight, depending on such parameters as sex,
strain, and vehicle used.

WHO (1984) classified endosulfan in the category of technical
products that are moderately hazardous.

Endosulfan can be absorbed following ingestion, inhalation, and
skin contact. It is readily metabolized and excreted and does not
accumulate in the body.

On acute intoxication, neurological manifestations may occur,
such as irritability, restlessness, muscular twitchings, and
convulsions. Lung oedema and cyanosis may precede death.

Endosulfan was negative or produced conflicting results in
short-term tests for genetic activity. It showed no carcinogenic
activity in mice or rats but studies were limited by inadequate
reporting or survival.

Several cases of suicidal and occupational poisoning have been
reported, the latter resulting, in most cases, from neglect of
safety precautions.

Exposure to endosulfan

Food is the main source of exposure of the general population
to endosulfan. Endosulfan residues in food (the sum of its alpha-
and beta-isomers and endosulfan sulfate) have been found to be
generally well below FAO/WHO maximum residue limits.

In occupationally-exposed persons, both skin contact and
inhalation can be important routes of absorption when adequate
safety precautions are not taken.

Hazard assessment

The main hazard associated with endosulfan is acute
intoxication through overexposure. Such situations may be due to
intentional or accidental overexposure or to gross negligence in
occupational situations.

In all other exposure situations, especially as far as the
general population is concerned, the toxicity profile and the
present exposure pattern do not indicate any appreciable hazard.

9.2. Evaluation of Overall Environmental Effects

Degradation of endosulfan in soil and water by photolysis,
chemical reactions, and biotransformation is governed by a wide
range of climatic factors and the type of microorganisms present.

Endosulfan does not appear to be a problem with regard to
persistence. It is not readily bioaccumulated. In aquatic
organisms, loss soon balances uptake and a fairly low plateau level
of residues is achieved.

Endosulfan is hazardous in acute overexposure for some aquatic
species, especially fish. There has been large-scale field
experience with endosulfan without any long-term adverse effects on
the environment.

Careful application to avoid overexposure of non-target
organisms does not eliminate kills in local fish populations when
endosulfan is applied to wetland areas at recommended rates.
Because there is little or no biomagnification, endosulfan, when
applied at recommended rates, is not hazardous to terrestial
animals. Toxicity for bees is low to moderate.

The reported toxicity of endosulfan for microorganisms in the
laboratory is low; it is unlikely to have an appreciable effect in
the field.

9.3. Conclusions

1. The general population does not appear to be at risk
from endosulfan residues in food. Exposure of the
general population via air and drinking-water is
generally low.

2. Occupational exposure has resulted in some incidents
of poisoning. These appear however, only to have
occurred when adequate safety precautions were not
taken.

3. In terms of the general environment, endosulfan is
highly toxic for some aquatic species, particularly
fish. Endosulfan is moderately toxic for honey bees.

4. Endosulfan does not accumulate in food chains and is
excreted from the body rapidly.

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    See Also:
       Toxicological Abbreviations
       Endosulfan (HSG 17, 1988)
       Endosulfan (PIM 576)
       Endosulfan (FAO Meeting Report PL/1965/10/1)
       Endosulfan (FAO/PL:1967/M/11/1)
       Endosulfan (FAO/PL:1968/M/9/1)
       Endosulfan (WHO Pesticide Residues Series 1)
       Endosulfan (WHO Pesticide Residues Series 4)
       Endosulfan (WHO Pesticide Residues Series 5)
       Endosulfan (Pesticide residues in food: 1982 evaluations)
       Endosulfan (Pesticide residues in food: 1989 evaluations Part II Toxicology)
       Endosulfan (JMPR Evaluations 1998 Part II Toxicological)