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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

    PHENYLMERCURIC ACETATE

    Chemical name

           Phenylmercuric acetate

    Synonym

           PMA

    Empirical formula

           C8H8O2Hg

    Structural formula

    CHEMICAL STRUCTURE 

    BIOLOGICAL DATA

    Biochemical aspects

           In rats, phenylmercuric acetate is readily absorbed from the
    gastro-intestinal tract (Fitzhugh et al., 1950; Princkett et al.,
    1950). The major route of elimination of mercury after oral,
    intramuscular or intravenous administration of PMA is by way of the
    bile and excretion into the alimentary tract (Berlin & Ullberg, 1963;
    Princkett et al., 1950).

           PMA given orally and intramuscularly to 87 chicks,
    intramuscularly to 12 rats, and intravenously to 4 dogs, was absorbed
    apparently unchanged. After about 96 hours no PMA could be detected in
    the tissues, but inorganic mercury accumulated in the liver and kidney
    (Miller et al., 1960). These findings were confirmed by studies with
    radioactive PMA (Berlin & Ullberg, 1963). Excretion by the kidneys was
    in the form of inorganic mercury and not as PMA (Berlin, 1963; Miller
    et al., 1960). One explanation of this may be that PMA is
    protein-bound in the blood.

    Acute toxicity
                                                                                
    Animal       Route             LD50 mg/kg         References
                                   body-weight
                                                                            

    Rat     Intraperitoneal            10             Swensson, 1952
                              (approx. lethal dose)

    Mouse        Oral                  70             Goldberg et al., 1950

    Chick        Oral                  60             Miller et al., 1960
                              (approx. lethal dose)
                                                                            
    
    Short-term studies

           Rat. Rats were given intraperitoneal injections of PMA at
    dosages of 1-2.5 mg/kg body-weight every other day for 4 weeks. The
    animals showed gradually increasing apathy, loss of weight, and
    finally neurological symptoms (ataxia and paresis), especially at the
    higher dosages. Histopathological examination revealed damage to the
    granular layer and the Purkinje cells of the cerebellum, and to the
    spinal cord (Swensson, 1952).

           Rabbit. A rabbit was fed with a diet containing PMA for 130
    days, the total amount of mercury consumed during the experimental
    period being 770 mg. The animal showed marked growth depression and
    died after 130 days. Chemical analysis revealed large amounts of
    mercury in the organs - 29 mg/kg organ-weight in the kidney, 0.52
    mg/kg in the liver and 5.18 mg/kg in the gastro-intestinal tract
    - whereas a control rabbit showed only 0.06 mg/kg in the kidney and
    traces in the liver. Another rabbit fed a diet containing PMA for 100
    days received a total amount of 6.9 mg of mercury. There was no
    abnormality in appearance or growth. The contents of mercury in the
    organs were 0.455 mg/kg in the kidney and 0.042 mg/kg in the liver
    (Kluge et al., 1938).

           Guinea-pig. A guinea-pig was fed a diet containing PMA for 670
    days and consumed a total of 20.4 mg during the whole experimental
    period. No ill-effects were observed in general appearance or growth.
    The mercury content of the kidney was 4.76 mg/kg organ-weight, whereas
    that of a control animal was 0.3 mg/kg (Kluge et al., 1938).

    Long-term studies

           Rat. Groups, each of 10-12 male and 10-12 female rats, were fed
    diets containing 0.1, 0.5, 2.5, 10, 40 and 160 ppm of PMA for 2 years.
    The growth was significantly retarded at 40 ppm and upward, and also
    retarded in males at 10 ppm. The average survival period was reduced
    at 160 ppm, while other dosage levels did not affect the mortality

    rates. Gross pathological examination revealed enlargement and
    granularity of the kidney, and moderate paleness of the viscera
    suggestive of anaemia at 0.5 ppm and upward. Microscopic studies
    demonstrated severe damage of the tubules of the kidney at 10 ppm in
    females at one year, and there was detectable kidney damage at 0.5 ppm
    in both sexes at 2 years. In males, marked changes in the renal
    tubules were observed at 160 ppm at one year, and moderate to slight
    at 40 ppm in both sexes. There were also some changes in the bone
    marrow and caeca at high dosage levels. Accumulation of mercury
    occurred in the organs and the storage of mercury in the kidney and
    liver in the group at 0.1 ppm PMA was higher than that in the control
    group (Fitzhugh et al., 1950).

    Comments on experimental studies reported

           It is clear from the biochemical studies that PMA may give rise
    to mercury accumulation in the tissues and the long-term study in the
    rat failed to demonstrate a no-effect level.

    EVALUATION

    Level causing no significant toxicological effect in rat

           A no-effect level has not been demonstrated.

    Estimate of acceptable daily intake for man

           The level of 0.1 ppm, equivalent to 0.005 mg/kg body-weight per
    day, produced a slight effect in the rat. Even if this figure were to
    be adopted as a maximum no-effect level and the customary safety
    factor applied this would give an acceptable daily intake for man of
    0.00005 mg/kg body-weight. This is tantamount to zero. It is
    undesirable that for the general population there should be any
    increase in the natural intake of mercury. The same considerations
    apply to other phenylmercury salts.

    REFERENCES

    Berlin, M. (1963) Arch. environm. Hlth, 6, 626

    Berlin, M. & Ullberg, S. (1963) Arch. environm. Hlth, 6, 602

    Fitzhugh, O. G. Nelson, A. A. Laug, E. P. & Kunze, F. M. (1950)
    A.M.A. Arch. industr. Hyg., 2, 433

    Goldberg, A. A., Shapero, M. & Wilder, E. (1950) J. Pharm. (Lond.),
    2, 20

    Kluge, H., Tschubel, H. & Zitek, A. (1938) Z. Untersuch.
    Lebensmitt., 76, 322

    Miller, V. L., Klavano, P. A. & Csonka, E. (1960) Toxicol. appl.
    Pharmacol., 2, 344

    Princkett, C. S., Laug, E. P. & Kunze, F. M. (1950) Proc. Soc. exp.
    Biol. (N.Y.), 73, 585

    Swensson, A. (1952) Acta med. scand., 143, 365
    


    See Also:
       Toxicological Abbreviations
       Phenylmercuric acetate (ICSC)