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

    MANEB

    Chemical name

           Manganese ethylene-1,2-bisdithiocarbamate

    Synonyms

           Manzate, MEB, MnEBD

    Empirical formula

           C4H6N2S4Mn

    Structural formula

    

    BIOLOGICAL DATA

    Biochemical aspects

           No evidence.

    Acute toxicity

                                                                                    
    Animal         Route    LD50 mg/kg    References
                            body-weight
                                                                                

    Rat            Oral        7500       United Kingdom Ministry of Agriculture

    Guinea-pig     Oral        7500       United Kingdom Ministry of Agriculture
                                                                                
    
    Short-term studies

           Dog. Groups, each of 2 dogs, were fed maneb orally at the rate
    of 2.0. 20, 75 and 200 mg/kg body-weight daily for one year. At the
    two highest dose levels the animals showed marked and persistent
    anorexia and weight loss and those given 200 mg/kg body-weight were
    killed in extremis at 3-7 months. At 20 mg/kg body-weight similar

    symptoms were observed, but were less severe. Toxic signs included
    tremors, general malaise, weakness, gastro-intestinal disturbances,
    depression of the reflexes in the hind limbs, posterior
    incoordination, hypotonus, progressing at 200 mg/kg body-weight to
    flaccid paraplegia. There was also evidence of impairment of kidney
    function at 75 and 200 mg/kg body-weight. Microscopic examination
    post-mortem revealed damage to the spinal cord, peripheral nerves and
    muscles in those animals given 200 mg/kg body-weight, but no effect on
    the thyroid gland (Clayton et al., 1957).

    Long-term studies

           Rat. Groups of rats, each of 25 males and 25 females, were fed
    diets containing 25, 250, 1250 and 2500 ppm of maneb for 2 years. At
    1250 ppm there was some depression of growth rate and at 2500 ppm
    there was growth depression, impaired food consumption and increased
    mortality rate. At the end of 2 years those animals receiving 1250 ppm
    had an increased liver/body-weight ratio and those receiving 2500 ppm
    showed, in addition, thyroid hyperplasia and nodular goitre (Clayton
    et al., 1957).

    Comments on the experimental studies reported

           For maneb, as for most of the dithiocarbamates, short- and
    long-term studies in animals have been reported, but for all of them
    biochemical data are inadequate.

    EVALUATION

           The chemical nature of the residues of the dithiocarbamates in 
    or on the plant has not been ascertained. The compounds themselves 
    have effects on the thyroid, nervous system and blood in animals. In 
    the absence of information about their mode of action an acceptable 
    intake for man cannot be estimated.

    Further work required

           Determination and evaluation of toxicity of the residues
    occurring in the plant. Extension of the long-term experiments,
    including reproduction studies which should concern at least 2
    species. Special attention should be given to neurological changes
    goitrogenicity and occurrence of anaemia.

    REFERENCES

    Clayton, J. W., Hood, D. B., Barnes, J. R. & Borgmann, A. R. (1957)
    Amer. industr. Hyg. Ass. Quart.

    United Kingdom Ministry of Agriculture, Fisheries and Food
    (Unpublished data)
    

    See Also:
       Toxicological Abbreviations
       Maneb (ICSC)
       Maneb (FAO/PL:1967/M/11/1)
       Maneb (Pesticide residues in food: 1993 evaluations Part II Toxicology)
       Maneb (IARC Summary & Evaluation, Volume 12, 1976)