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    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.

    Figure 1

          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


See Also:
        Endosulfan (EHC 40, 1984)
        Endosulfan (PIM 576)