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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

    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)