FAO Meeting Report No. PL/1965/10/1
    WHO/Food Add./27.65

    EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD

    The content of this document is the result of the deliberations of the
    Joint Meeting of the FAO Committee on Pesticides in Agriculture and
    the WHO Expert Committee on Pesticide Residues, which met in Rome,
    15-22 March 19651

    Food and Agriculture Organization of the United Nations
    World Health Organization
    1965

                
    1 Report of the second joint meeting of the FAO Committee on
    Pesticides in Agriculture and the WHO Expert Committee on Pesticide
    Residues, FAO Meeting Report No. PL/1965/10; WHO/Food Add./26.65

    ENDOSULFAN

    Chemical name

           6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-
    2,4,3- benzo(e) dioxathiepin-3-oxide, or 1,2,3,4,7,7,-
    hexachlorobicyclo-(2,2,1)hepten-5,6-bisoxymethylene sulfite
    chlorthiepin.

    Synonym

           Thiodan

    Empirical formula

           C9H6O3Cl6S

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

           Endosulfan is rapidly absorbed from the intestinal tract and
    about 30% of a lethal dose is eliminated during 24 hours in the rat
    (Czech, 1958).

    Acute toxicity (technical grade) 
    
                                                                          
    Animal       Route          LD50 mg/kg     References
                                body-weight
                                                                          

    Rat          Oral         40-50 and 110*   Hazleton Laboratories, 1957
    Rat     Intraperitoneal          8         Czech, 1958
                                                                          

    * Dependent on the vehicle used.
    
    Short-term studies

           Rat. Rats tolerated daily 1.6-3.2 mg/kg body-weight orally for
    12 weeks without any influence on growth-rate (Czech, 1958).

           Dog. Endosulfan technical grade was administered daily in
    gelatin capsules to 4 dogs for 5 days in a dose of 2.5 mg/kg
    body-weight. Vomiting was observed in one dog and vomiting, tremors,
    convulsions, rapid respiration, and mydriasis in 3 dogs (Hazleton
    Laboratories, 1959a).

           Three groups of dogs each consisting of 2 males and 2 females
    were given endosulfan orally in gelatin capsules 6 days a week for one
    year in doses corresponding to 0.075, 0.25 and 0.75 mg/kg body-weight.
    No signs of toxicity were observed. At autopsy gross and microscopic
    examination of the tissues showed no difference between treated and
    control animals (Hazleton Laboratories, 1959a).

    Long-term studies

           Rat. Groups of 25 male and 25 female rats received 10, 30 and
    100 ppm of endosulfan technical grade in the diet for 104 weeks.
    Survival of the female rats in the 10- and 30-ppm group, was lower
    than that of the female control group during the second year. In the
    100-ppm female group, survival was significantly lower after 26 weeks
    and abnormalities were observed in weight gain and on haematological
    examinations. At autopsy the relative weight of the testes in the
    10-ppm male group was significantly lower than in the control group.
    Consistent histopathological findings were apparent only in the
    100-ppm male group. In these the kidneys were enlarged and there were
    signs of renal tubular damage with interstitial nephritis. Hydropic
    cells were seen in the liver. The tumour incidence was within normal
    range in all test groups (Hazleton Laboratories, 1959b).

    Comments on experimental studies reported

           The animal and biochemical studies are insufficient.

    EVALUATION

           The toxicological data are inadequate to estimate an acceptable
    intake for man.

    Further work required

           Investigation on the chemical nature and toxicity of the residue
    occurring in the plant. Further long-term studies in rats and other
    species, including reproduction studies. Determination of a no-effect
    level in two species.

    REFERENCES

    Czech, M. (1958) Medizin u. Chemie., 6, 574

    Hazleton Laboratories, Falls Church, Virginia, United States of
    America. Unpublished report of 11 January 1957

    Hazleton Laboratories, Falls Church, Virginia, United States of
    America. Unpublished report of 12 May 1959a

    Hazleton Laboratories, Falls Church, Virginia, United States of
    America. Unpublished report of 22 May 1959b
    

    See Also:
       Toxicological Abbreviations
       Endosulfan (EHC 40, 1984)
       Endosulfan (HSG 17, 1988)
       Endosulfan (PIM 576)
       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)