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
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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.
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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
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Zollinger, H. V. (1953) Virchows Arch. path. Anat., 323, 694