WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
VBC/75.15
ORIGINAL: ENGLISH
DATA SHEETS ON PESTICIDES No. 15
1975
ENDOSULFAN
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
ENDOSULFAN
Part 1 - General information
CLASSIFICATION
Primary use: insecticide
Secondary uses: acaracide
Chemical group: organochlorine
compound
Data sheet No. 15
Date issued: December 1975
1.1 COMMON NAME: Endosulfan (ISO)
Identity: 6,7,8,9,10,10-Hexachloro-1,5,5a,6,9,9a-hexahydro-
6,9-methano-2,4,3-benzodioxathiepin-3-oxide, also known as (alpha) ß -
1,2,3,4,7,7, - hexachlorobicyclo 2,2,1 hepten-2-biosoxymethylon-5,6
sulphite; technical endosulfan contains two stereoisomers, endosulfans
A and B. The proportion of the two isomers is variously reported as
from 4:1 to 7:3. The technical material is a 90-95% pure mixture of
the two isomers.
Synonyms Local synonyms
Thiodan
OMS 204 (endosulfan A)
OMS 205 (endosulfan B)
1.2 SYNOPSIS: a toxic organochlorine pesticide of moderate mammalian
toxicity which does not accumulate in the tissues of man or animals to
any significant extent.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics: A mixture of two isomers mp 106°C and
212°C, respectively. The technical product is a brownish crystalline
solid mp 80-90°C.
1.3.2 Solubility: Water at 20°C; practically insoluble; alcohol, 5%;
soluble in most organic solvents.
1.3.3 Stability: Hydrolysed slowly by water, more rapidly by acids and
bases. Decomposition is catalysed by iron, which it corrodes.
Compatible with neutral pesticides.
1.3.4 Vapour pressure: 1 x 10-5 mm/Hg at 25°C
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
Emulsifiable concentrates, 17.5, 25 and 35%; wettable powders,
17.5, 35 and 50%; dusts, 1, 3, 4 and 5%; granules, 5%. There are FAO
specifications for emulsifiable concentrates, dispersible powders and
dusts.
1.4.2 Pests mainly controlled
Effective against a wide range of insects by contact and stomach
action, notably various beetles, caterpillars and aphids. Particularly
active against Colorado beetle and woolly apple aphid, but of low
toxicity to bees.
1.4.3 Use pattern
Used as a pre-harvest insecticide on a wide range of berry and tree
fruits, nuts, vegetables, field and grain crops, including rice, and
ornamentals. Also has important uses on non-food crops such as cotton
and tobacco, and on tea. It is applied when insects first appear, with
repeated applications as necessary. Minimum intervals between the last
treatment and harvest varying from 15 to 42 days are observed. Not
used in veterinary practice.
1.4.4 Unintended effects
Not generally phytotoxic. Not recommended for use on Concord grapes.
Treated crops should not be used as food for livestock.
1.5 PUBLIC HEALTH PROGRAMMES
1.6 HOUSEHOLD USE
Not recommended for household use.
ENDOSULFAN
Part 2 - Toxicology and risks
Common name: endosulfan
Data sheet No. 15
Date issued: December 1975
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route: Undiluted endosulfan is slowly and incompletely
absorbed in the gastrointestinal tract of warm-blooded animals.
Absorption is more rapid in the presence of alcohols, oils and
emulsifiers. These substances also accelerate the absorption of
endosulfan through the skin.
2.1.2 Mode of action: Central nervous system stimulant producing
convulsions.
2.1.3 Excretion products: Endosulfan is rapidly metabolized and
excreted in the urine and faeces largely as oxidation products
("endosulfan sulfate") or alcohol and ether derivatives resulting from
the cleavage of the cyclic sulfite group. There is little storage
although the sulfate may be detected in body fat during the first 27
days following administration of endosulfan.
2.1.4 Toxicity, single dose
Oral: LD50 rat 40-50 mg/kg, 110 mg/kg dependent on vehicle
used.
Dermal: LD50 rat 130-681 mg/kg
LD50 rabbit 147-359 mg/kg; endosulfan B; LD50 rat 240 mg/kg
Endosulfan A; LD50 rat 76 mg/kg; endosulfan B; LD50 rat
240 mg/kg.
Most susceptible species: Not known
2.1.5 Toxicity, repeated doses
Oral: Rats tolerated daily 1.6-3.2 mg/kg orally for 12 weeks without
any influence on growth rate. Toxic signs (vomiting, tremors,
convulsions, etc.) were seen in three out of four dogs (LD50 (oral)
dog 76 mg/kg) given 2.5 mg/kg daily for three days. However, there
were no signs of toxicity at a dose level of 0.75 mg/kg or less given
six days a week for one year. Growth and histopathological
examinations of tissues revealed no abnormalities at this dose when
compared to controls.
Dermal: No information.
Inhalation: The inhalation LD50 is 350 mg/m3 for male rats
and 80 mg/m3 for female rats when exposed for four hours.
Cumulation of compound: Endosulfan is not cumulative in body
tissues to any significant extent.
2.1.6 Dietary studies
Short-term: In 20 months' feeding trials on dogs with dietary
levels of 3, 10 and 30 ppm (0.075, 0.25 or 0.75 mg/kg/day) there
was no evidence of intoxication.
Long-term: When rats were fed 10 or 30 ppm
(0.5 or 1.5 mg/kg/day) of endosulfan for two years, there were
no significant macroscopic changes detectable in the organs.
At 100 ppm (5 mg/kg/day) for two years, histological changes in
the kidney and liver were apparent. Survival was also reduced
at loo ppm (5 mg/kg/day) after 26 weeks and in the females at
10 and 30 ppm (0.5 and 1-5 mg/kg/day) in the second year.
2.1.7 Supplementary studies
Carcinogenicity
Rat: There was no increase in tumour incidence in rats fed up
to 100 ppm (5 mg/kg/day) for two years when compared to
controls.
Reproduction
Rat: In rats fed 2 or 50 ppm (0.1 or 2.5 mg/kg/day) of
endosulfan through three generations, no adverse effects were
noted among either the parental animals or their progeny in all
generations.
2.1.8 Modifications of toxicity
The acute toxicity of endosulfan was increased by a factor of 4.3
when rats were fed a low (3.5%) protein diet.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
See 2.1.1
2.2.2 Dangerous doses:
Single: Not known.
Repeated: Not known.
2.2.3 Observations of occupationally exposed workers
In one American country, nine workers displayed convulsions while
bagging endosulfan. It was known that in six of these cases, there was
no known history of convulsions.
In an Asian country, three workers were poisoned while filling sacks
with endosulfan powder. Symptoms appeared one-half to 24 hours after
contact and were initially restlessness, headache, increased
irritability and "comic feelings". Later vertigo, stupour,
dis-orientation and 1-3 hours later, epileptiform convulsions occurred.
Electroencephalographic changes were observed.
2.2.4 Observations on exposure of the general population
Total diet studies in one country reveal that endosulfan was only
found in 1.2% of raw agricultural produce the average level not
exceeding 0.005 ppm.
In two countries where they were sought, no residues of endosulfan
were found in human fat.
2.2.5 Observations of volunteers
No information.
2.2.6 Reported mishaps
Reported incidences of poisoning by endosulfan have all been
occupational in origin and there have been no food poisoning outbreaks
reported.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
The entries in these sections are intended to draw attention to
special risks and to give warnings of any needs for special
precautions.
2.3.1 Fish
Highly toxic to fish.
2.3.2 Birds
Toxic to some species.
2.3.3 Other species
Relatively harmless to bees and mammals.
ENDOSULFAN
Part 3 - For regulatory authorities
Common name: endosulfan
Data sheet No. 15
Date issued: December 1975
RECOMMENDATIONS ON REGULATION OF COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories, see introduction)
Liquid formulations over 5%, category 3, all others category 4.
Solid formulations over 20% category 4, all other formulations,
category 5.
3.2 TRANSPORTATION AND STORAGE
All formulations
Should be transported or stored in clearly labelled impermeable
containers, under lock and key, secure from access by unauthorized
persons and children. No food or drink should be stored in the same
compartment.
3.3 HANDLING
All formulations, categories 3 and 4
Full protective clothing (see part 4) should be provided for all
handling of the compound. Adequate washing facilities should be
available at all times during handling and should be close to the site
of handling. Eating, drinking and smoking should be prohibited during
handling and before washing after handling.
Formulations, category 5
No facilities other than those needed for the handling of any
chemical need to be required.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS
All formulations
Containers may be decontaminated (for method, see paragraph 4.3 on
part 4). Decontaminated containers should not be used for food and
drink. Containers that are not decontaminated should be burned or
should be crushed and buried below topsoil. Care must be taken to
avoid subsequent contamination of water sources.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
All formulations categories 3 and 4
Pre-employment and periodic medical examination of workers advisable
but often not practical. Workers suffering from active hepatic or
renal disease should be excluded from contact. Special account should
be taken of the workers' mental ability to comprehend and follow
instructions. Training of workers in techniques to avoid contact
essential.
All formulations category 5
Warning of workers to minimize contact essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations
Pilots and loaders should have special training in application
methods and recognition of early Symptoms of poisoning. Use of flagmen
not recommended. Flagmen, if used, should wear overalls and be located
well away from the dropping zone.
3.7 LABELLING
All formulations categories 3 and 4
Minimum cautionary statement
"Endosulfan is a toxic substance and may cause convulsions. It
is poisonous if swallowed. It may be absorbed through the skin
or inhaled as dusts or mists. Avoid skin contact, wear
protective gloves and clean protective clothing while using the
material. Wash thoroughly with soap and water after using.
Keep the material out of reach of children and well away from
foodstuffs, animal feed and their containers.
Formulations category 5
"This formulation contains endosulfan, a toxic substance. It is
poisonous if swallowed and may cause convulsions. Keep the
material out of reach of children and well away from foodstuffs,
animal feed and their containers."
3.8 RESIDUES IN FOOD
Maximum residue limits have been recommended by the Joint FAO/WHO
Meeting on Pesticide Residues. As these are subject to change at
annual reviews, the latest data will be found in the 1975 Joint FAO/WHO
Meeting on Pesticide Residues.
ENDOSULFAN
Part 4 - Prevention of poisoning in man and emergency aid
Common name: endosulfan
Data sheet No. 15
Date issued: December 1975
4.1 PRECAUTIONS IN USE
4.1.1 General
Endosulfan is an organochlorine pesticide of moderate toxicity which
penetrates the intact skin and is also absorbed by inhalation and from
the gastrointestinal tract. Most formulations should be handled by
trained personnel wearing protective clothing.
4.1.2 Manufacture and formulation
T.L.V.
(A.C.G.I.H.) 0.1 mg/m3
Closed systems and forced ventilation may be required to reduce as
much as possible the exposure of workers to the chemical.
4.1.3 Mixers and applicators
When opening the container and when mixing, protective impermeable
boots, clean overalls, gloves and respirator should be worn. Mixing,
if not mechanical, should always be carried out with a paddle of
appropriate length. When spraying tall crops or during aerial applica-
tion, a face mask should be worn as well as an impermeable hood,
clothing, boots and gloves. The applicator should avoid working in a
spray mist and avoid contact with the mouth.
Particular care is needed when equipment is being washed after use.
All protective clothing should be washed immediately after use,
including the insides of gloves. Splashes must be washed immediately
from the skin or eyes with large quantities of water. Before eating,
drinking or smoking, hands and other exposed skin should be washed.
4.1.4 Other associated workers (including flagmen in aerial operations)
Persons exposed to endosulfan and associated with its application
should wear protective clothing and observe the precautions described
above in 4.1.3 under "mixers and applicators."
4.1.5 Other populations likely to be affected
With good agricultural practice subject to 4.2 below, other
populations should not be exposed to hazardous amounts of endosulfan.
4.2 ENTRY OF PERSON INTO TREATED AREAS
Unprotected persons should be kept out of treated areas for at least
one day, and for several days, if practicable.
4.3 SAFE DISPOSAL OF CONTAINERS AND SPILLAGE
Residues in containers should be emptied in a diluted form into a
deep pit taking care to avoid ground waters. The empty container may
be decontaminated by rinsing two or three times with water and
scrubbing the sides. An additional rinse should be carried out with 5%
sodium hydroxide solution which should remain in the container
overnight. Impermeable gauntlets should be worn during this work and a
soakage pit should be provided for the rinsings. Decontaminated
containers should not be used for food and drink.
Spillage of endosulfan and its formulations should be removed by
washing with 5% sodium hydroxide solution and then rinsing with large
quantities of water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Early symptoms of poisoning are headache, dizziness, nausea,
vomiting, weakness of the legs, loss of appetite and possibly insomnia
and temporary deafness. Later, convulsions may occur.
4.4.2 Treatment before Person is seen by a physician, if these symptoms
appear following exposure
The person should stop work immediately, remove contaminated clothing
and wash the affected skin with soap, if available, and flush the area
with large quantities of water. If swallowed, vomiting should be
induced, if the person is conscious.
ENDOSULFAN
Part 5 - For medical and laboratory personnel
Common name: endosulfan
Data sheet No. 15
Date issued: December 1975
5.1 MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING
5.1.1 General information
An organochlorine pesticide of moderate toxicity which may be
absorbed through the intact skin as well as by inhalation and from the
gastrointestinal tract. Its mode of action is as a central nervous
system stimulant leading to convulsions. It is rapidly metabolized and
its metabolites are excreted in the urine and faeces. It does not
persist in the tissues to any significant extent.
5.1.2 Symptoms and signs
Mild symptoms of poisoning involve headache, dizziness, nausea,
vomiting, weakness of the legs, loss of appetite, and possibly insomnia
and temporary deafness. More serious symptoms are convulsions.
5.1.3 Laboratory
Blood levels of endosulfan associated with poisoning are not known.
After exposure, the electroencephalogram may show abnormalities.
5.1.4 Treatment
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 (preferably
phenobarbitone or pentobarbitone) or diazepam should be given I.M. or
I.V. 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.
5.1.5 Prognosis
If the convulsions are survived the chances of complete recovery are
probably good. However, in very severe cases, there may be a
possibility of permanent brain damage secondary to continued anoxia
resulting from prolonged convulsions.
5.1.6 Reference of previously reported cases
The following reference gives methods of treatment used in episodes
of poisoning:
Ely, T. S., Macfarlane, J. W., Galan, W. P. & Hine, C. H. (1967)
J. occup. Med., 9, 35-37
5.2 SURVEILLANCE METHODS
There are no readily available surveillance methods.
5.3 LABORATORY METHODS
5.3.1 Detection and analysis
Residues of endosulfan may be determined by multi-residue gas-
chromatographic methods. Suitable procedures for endosulfan A and B
and endosulfan sulfate are given by the United States Food & Drug
Administration (1971). Endosulfan is also determined by the method of
Abbott et al. (1969), Graham et al. (1964). Gas-chromatographic
methods of confirming identity are described by Chau (1969), Greve et
Wit (1972) and the Deutsche Forschungsgemeinschaft (1972).
5.3.2 Other tests in cases of poisoning
None.
REFERENCES
U.S. Food & Drug Administration.
Pesticide Analytical Manual, Vol. I, 1971, Sections 211, 212
Abbott, D. C., Holmes, D. C. & Tatton, J.O'G.
Pesticide Residues in the Total Diet in England and Wales,
1966-1967 II. - organochlorine Pesticide Residues in the Total
Diet. J.Sci. Fd Agric., 1969, 20 245
Chau, A. S. Y.
Derivative formation for the confirmation of endosulfan by gas
chromatography. J. Assoc. Off. Anal. Chem., 1969, 52, 1240
Greve, P. A. & Wit, S. L.
Rapid identification method for endosulfan from glc peak shifts
under the influence of alkali. J. agric. Ed Chem., 1971, 19, 372
Deutsche Forschungsgemeinschaft (1972) Rückstandsanalytic von
Pflanzenschutzmitteln Endosulfan 50-1
Graham, J. R. et al. in Zwig G. (Ed) "Analytical methods for
Pesticides, Plant Growth Regulators and Food Additives, Vol II,
Academic Press, New York and London, 1964