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    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

    ENDRIN

    Chemical name


    1,2,3,4,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-endo-
    1,4-endo-5,8,-dimethanonaphthalene;
    1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a-5,6,7,8,8a-octahydro-exo
    1,4-exo-5,8-dimethanonaphthalene

    Empirical formula

           C12H8OCl6

    Structural formula

    CHEMICAL STRUCTURE 

    BIOLOGICAL DATA

    Biochemical aspects

           Endrin fed to animals is stored unchanged in the tissues
    (Kiigemagi et al., 1958, Street et al., 1957; Terriere et al., 1958;
    Treon et al., 1955) and excreted in milk and eggs (Ely et al., 1957;
    Street et al., 1957, Terriere et al., 1958). The chief organ of
    storage is the fat, with a storage ratio of about 15 when the
    concentration in the diet is 1 ppm (Lehman, 1956). Endrin is slowly
    excreted from the tissues (Nelson et al., 1956. Zavon, 1961).

           Serum alkaline phosphatase levels in rats increased as the
    concentration of endrin in the diet was increased from 1 ppm to 100
    ppm (Nelson et al., 1956).

    Acute toxicity

                                                                    
    Animal                Route    LD50 mg/kg     References
                                   body-weight
                                                                    

    Adult rat (female)    Oral         7.3        Treon et al., 1955

    Young rat (female)    Oral        16.8        Treon et al., 1955

    Adult rat (male)      Oral       40-43.4      Speck & Maaske, 1958
                                                  Treon et al., 1955

    (cont'd)
                                                                    
    Animal                Route    LD50 mg/kg     References
                                   body-weight
                                                                    

    Young rat (male)      Oral        28.8        Treon et al., 1955

    Rabbit (female)       Oral        7-10        Treon et al., 1955

    Guinea-pig            Oral    approx. 16-36   Treon et al., 1955

    Monkey                Oral      approx. 3     Treon et al., 1955
                                                                    


           Man. In one incident 59 people became ill from the ingestion of
    bread containing 150 ppm of endrin, but there were no fatalities
    (Davies & Lewis, 1956). The maximum amount consumed was estimated to
    have been 1 mg/kg (Zavon, 1961).

    Short-term studies

           Rat. Adult rats, 5 males and 5 females per group, were given
    diets containing 1, 5, 25, 50 and 100 ppm of endrin for 16 weeks. Only
    2 rats on 50 ppm and 3 on 25 ppm survived. Three male rats died in the
    group on 5 ppm. There was loss of weight and hypersensitivity to
    tactile stimuli in all groups ingesting endrin (Nelson et al., 1956).

           Dog. In a series of experiments, dogs were fed diets containing
    from 1 to 50 ppm endrin. Two of 4 fed a diet containing 8 ppm and the
    one dog on 5 ppm died. The 2 surviving dogs on 8 ppm were kept on the
    diet for about 6 months and then killed; increased organ/body-weight
    ratios for the liver, kidney and brain were found, and
    histopathological examination showed slight degeneration of kidney
    tissue. Three dogs on 4 ppm of endrin survived (Treon et al., 1955).

           In an experiment of about 19 months' duration, groups of 4
    beagles (2 males and 2 females) were placed on diets containing 1 and
    3 ppm of endrin. All dogs on 3 ppm had increased organ/body-weight
    ratios for the kidney and heart. At 1 ppm the females showed
    questionable tubular vacuolation in the kidneys (Treon et al., 1955).

           Cattle and sheep. Cattle and sheep were not affected by 5 ppm
    of endrin in their diet for 112 days (Radeleff, 1956).

           Fowl. Seven-day-old chicks were unaffected by a ration
    containing endrin at levels of 1.5 and 3 ppm. When the concentration
    of endrin was either 6 or 12 ppm the chicks became highly excitable,
    failed to gain as much weight as the controls and the survival rates
    for the 12 weeks were 85% and 5% respectively (controls 100%) (Sherman
    & Rosenberg, 1954).

    Long-term studies

           Rat. In a 2-year experiment, groups of rats of 20 males and 20
    females each were given diets containing 1, 5, 25, 50 and 100 ppm of
    endrin. Concentrations of 50 and 100 ppm were lethal within a few
    weeks. The concentration of 25 ppm increased the mortality rate of the
    females. Non-survivors at the 3 higher levels exhibited diffuse
    degeneration of the brain, liver, kidneys and adrenal glands. The
    survivors in the 2 higher levels showed degenerative changes in the
    liver only, while those fed at the lower levels had normal viscera.
    The level of 5 ppm caused an increase in liver/body-weight ratio in
    males and an increase in kidney/body-weight ratio in females. There
    was no effect at the 1 ppm level (Treon et al., 1955).

    Comments on experimental studies reported

           Studies of 2 years' duration in rats and 19 months' duration in
    dogs have been published. Other studies of shorter duration have been
    published on the toxicity of endrin to rats, fowl, sheep and cattle.

           In one experiment, the no-effect level in rats was 1 ppm. In
    another study this dose level caused an increase in the serum alkaline
    phosphatase level. A questionable effect occurred in female dogs on 1
    ppm of endrin.

    EVALUATION

    Level causing no significant toxicological effect

           In neither the dog nor the rat has a no-effect level been
    demonstrated.

    Acceptable daily intake for man

           From the data presented, an acceptable daily intake for man
    cannot be estimated. Until further evidence is forthcoming, every
    effort should be made to see that the intake of endrin for man is kept
    at the lowest possible level.

    Further work required

           Additional long-term studies including reproduction studies.
    Determination of a no-effect level in more than one species.

    REFERENCES

    Devise, G. M. & Lewis, I. (1956) Brit. med. J., ii, 393

    Ely, R. E., Moore, L. A., Carter, R. H. & App, B. E. (1957) J. econ.
    Ent., 20, 348

    Kiigemagi, U., Sprowls, R. G. & Terriere, L. C. (1958) J. Agr. Food
    Chem., 6, 518

    Lehman, A. J. (1956) Quart. Bull. Assoc. Food and Drug Officials
    U.S., 20, 95

    Nelson, S. C., Bahler, T. L., Hartwell, W. V., Greenwood, D. A. &
    Harris, L. E. (1956) J. Agr. Food Chem., 4, 696

    Radeleff, R. D. (1956) Mosquito News, 16, 79

    Sherman, M. & Rosenberg, M. M. (1954) J. econ. Ent., 47, 1082

    Speck, L. B. & Maaske, C. A. (1958) A.M.A. Arch. industr. Hlth,
    18, 268

    Street, J. C., Butcher, J. E., Raleigh, R. J. & Clanton, D. C. (1957)
    Proc. Western Sec. Amer. Soc. for Anim. Production, XLVI, 1

    Terriere, L. C., Kiigemagi, U. & England, D. C. (1958) J. Agr. Food
    Chem., 6, 516

    Treon, J. F., Cleveland, F. P. & Cappel, J. (1955) J. Agr. Food.
    Chem., 3, 842

    Zavon, M. R. (1961) Unpublished data from the Kettering Laboratory,
    University of Cincinnati, Cincinnati, Ohio
    


    See Also:
       Toxicological Abbreviations
       Endrin (EHC 130, 1992)
       Endrin (HSG 60, 1991)
       Endrin (ICSC)
       Endrin (AGP:1970/M/12/1)
       Endrin (WHO Pesticide Residues Series 4)
       Endrin (WHO Pesticide Residues Series 5)
       Endrin (IARC Summary & Evaluation, Volume 5, 1974)