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 LEAD ARSENATE Chemical names Diplumbic hydrogen arsenate; dilead arsenate; dilead orthoarsenate; lead hydrogen arsenate; acid lead arsenate. Formula PbHAsO4 BIOLOGICAL DATA Biochemical aspects Both lead and arsenic occur naturally, though not lead as arsenate, and are ingested in small quantities in the diet. The 2 elements may be absorbed from the alimentary tract, but apparently play no part in the natural biological processes of the body. Normally a balance is attained between uptake and excretion, though when the uptake is increased retention and storage may occur. Lead is retained chiefly in the skeletal tissues and arsenic in the skin, hair and nails, but also in the liver, kidney, lung and spleen. In excess, both elements interfere with the function of nervous tissue, probably by different biochemical mechanisms, and lead is damaging to the kidney. Arsenic has an affinity for -SH groups entering into biochemical processes (Calvery, 1938; UK Food Standards Committee, 1955). Acute toxicity Animal Route LD50 mg/kg Reference body-weight Rat Oral 100 Borbély, 1958 Rabbit Oral 125 " " Hen Oral approximately " " 450 Short-term studies Rat. Nine matched pairs of male weanling rats and 5 matched pairs of female weanling rats were given an adequate diet containing 0.73 mg of lead and 0.1 mg of arsenic per kg. The experiment was continued until each animal had consumed 1 kg of the diet - an average period of 77 days. The treated animals of each pair received a dietary addition of lead arsenate, adjusted so that the total lead intake was increased to 3.53 mg for the period of the experiment. The total lead arsenate was therefore about 4.7 mg per animal over 77 days. During this time the growth rate of the treated males was significantly impaired, but not that of the females. Lead storage was slightly increased in all the treated animals. There was no effect on the mortality rate and there were no recognizable histapathological changes (Laug & Morris, 1938). Man. One man was given lead arsenate daily for 50 days, the total amount of this compound consumed being about 2 g. No ill effects could be detected (Cardiff, 1940). Two men are reported to have ingested 100 mg of lead arsenate daily for 10 days without untoward symptoms being noted (Fairhall & Neal, 1938). A mixed population, including children, consumed apples sprayed with lead arsenate so that the average daily intake of the compound was about 9 mg. They suffered no ill effect and the only changes reported were marginal increases in the levels of lead in the blood, and of lead and arsenic in the urine, over those found in an ordinary urban community (Neal et al., 1941). Long-term studies Rat. A group of 49 rats was fed a diet to which lead arsenate had been added so that the intake of this compound was about 10 mg daily and the experiment extended for 2 years in all. The treated animals showed an increased mortality rate in comparison with the control animals, an increased tissue storage of both lead and arsenic and, histologically, kidney damage and splenic haemosiderosis (Fairhall & Miller, 1941). Comments Though the 2 elements, lead and arsenic, can be manifestly toxic to man it is clear that both can be ingested in small quantities in the food without ill effect, even over a life-span. Despite the extensive investigations reported in the literature, the maximum ill-effect level of these 2 elements for man is still the subject of controversy. There is no reason to believe that the compound lead arsenate is endowed with any particular toxicity over and above that attributable to its 2 component elements. For man, there are numerous reports of poisoning from lead arsenate. At the same time, there are accounts of people ingesting this substance over relatively long periods as a food contaminant, apparently without hazard. For man, then, a maximum no-effect level has by no means been established. The long-term animal work with the compound is limited to one experiment with rats, and is thus quite inadequate to be of any assistance (Fairhall & Miller, 1941). There is some reason to suspect carcinogenicity. The production of renal tumours in rats with other lead salts has been demonstrated (Boyland et al., 1962; van Esch et al., 1962; Zollinger, 1953). In man the role of arsenic in this respect has been critically reviewed (Wld Hlth Org. techn. Rep. Ser., 1961, 220) and more recently a high incidence of skin carcinomas was described in an area of Taiwan in which the drinking-water contained 0.8 to 2.5 ppm of arsenic (Shu Yeh, 1963). The lack of a thorough statistical investigation in populations exposed to arsenicals has been emphasized (Clayson, 1962). On the other hand no experimental data have been published demonstrating that any form of arsenic is carcinogenic for animals. In some studies, early suspicions arose that arsenic trioxide might be a co-carcinogen for mice, but this could not be confirmed using larger groups of animals (Baroni et al., 1963; Boyland, 1960). EVALUATION At this stage the available data are quite insufficient to propose a maximum acceptable daily intake of lead arsenate for man. Until further evidence is forthcoming every effort should be made to see that the intake of lead arsenate for man is kept at the lowest possible level. Further work required Long-term studies in more than one species. REFERENCES Baroni, C., van Esch, G. J. & Saffiotti, U. (1963) Arch. environm. Hlth, 7, 668 Borbély, F. (1958) Schweiz. Z. Obst-und Weinbau, 67, 333 Boyland, E. (1960) Progr. exp. Tumor Res. (Basel), 1, 162 Boyland, E., Dukes, C. E., Grover, P. L. & Mitchley, B. C. V. (1962) Brit. J. Cancer, 16, 283 Calvery, H. O. (1938) J. Amer. med. Ass., 111, 1722 Cardiff, I. R. (1940) J. industr. Hyg., 22, 333 Clayson, D. (1962) Chemical carcinogenesis, J. A. Churchill, ed., London van Esch, G. J., van Genderen, H. & Vink, H. H. (1962) Brit. J. Cancer, 16, 289 Fairhall, L. T. & Miller, J. W. (1941) Publ. Hlth Rep. (Wash.), 56, 1610 Fairhall, L. T. & Neal, P. A. (1938) Publ. Hlth Rep. (Wash.), 52, 1231 Laug, E. P. & Morris, H. P. (1938) J. Pharmacol. exp. Ther., 64, 388 Neal, P. A. et al. (1941) US Publ. Hlth Serv. Bull., 267 Shu Yeh (1963) Nat. Cancer Inst. Mongr., 10, 81 United Kingdom Food Standards Committee (1955) Report on Arsenic, London, H.M. Stationery Office World Health Organization (1961) Wld Hlth Org. techn. Rep. Ser., 220 Zollinger, H. V. (1953) Virchows Arch. path. Anat., 323, 694
See Also: Toxicological Abbreviations Lead arsenate (ICSC) Lead arsenate (FAO/PL:1968/M/9/1)