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 formulaBIOLOGICAL 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)