Pesticide residues in food — 2007: Toxicological ... - ipcs inchem

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measures to prevent worker exposure “did not exist” in the plant. Whole-blood cholinesterase activity
for 15 operators was assayed randomly over a period of 4 months. The concentration of azinphosmethyl
in the operator’s breathing zone ranged from 0.5 to 1.0 mg/m 3 . This concentration was found
to be well above the tentative limit of 0.3 mg/m 3 , set by the Division of Occupational Health of New
South Wales Department of Public Health at that time. The concentration of azinphos-methyl found
on drum tops was about 2.3 mg/cm 2 . During the processing season (unspecified), 13 operators (details
not provided) were removed from contact as their cholinesterase activity fell to below 60 units
or 60% of the pre-exposure level. Two operators showed signs of organophosphate poisoning (onset,
types and duration unspecified), and one of them had to be hospitalized. The cholinesterase levels
of these two persons were 25 and 30 units respectively, and that of the remaining 13 persons ranged
from 32 to 110 units. A line graph presented showed the recovery of whole-blood cholinesterase
activity to about 80−90 units in about 15 days after completely removing these workers from the
formulating plant. However, a comparable recovery of the enzyme activity in workers who remained
in the plant doing other jobs was noticed only after about 35 days (Simpson, 1965).
Published reports from the pesticide incident monitoring system in the United States of A merica
(USA) and additional data from the state of California in the USA have been reviewed. Between 1982
and 1988, a small number of incidents were reported annually (involving 5–12 persons each year)
that have been definitely, probably or possibly associated with exposure to azinphos-methyl either
alone or in combination with other pesticides. In addition, two incidents occurred in 1987, one involving
26 people, the other involving 32 people. The first involved spray drift in adverse weather
conditions. The second involved workers who experienced symptoms including headache, nausea,
weakness and vomiting upon entry to a field to pick peaches 3 days after methomyl was applied to
the crop and about 6 weeks after an application of azinphos-methyl (United States Environment
P rotection Agency, 1981; Mahler, 1991; Annex 1, reference 64).
Biochemical aspects
Comments
After oral administration of radiolabelled azinphos-methyl, the radiolabel was rapidly and completely
(90–100% of the administered dose) absorbed from the mammalian intestinal tract, widely
distributed throughout the organs, and eliminated in the urine (60–70% of the administered dose) and
faeces via bile (25–35% of the administered dose) within 48 h. The maximum concentration in blood
was reached within 2–3 h after administration. Azinphos-methyl was rapidly cleared from the blood
and tissues, and consequently there is negligible potential for accumulation. In rats, the initial steps of
metabolism involved the formation of the highly reactive oxon metabolite and mercaptomethylbenzazimide
by cytochrome P450. Glutathionyl methylbenzazimide and desmethyl isoazinphos-methyl
were formed via glutathione transferase. Subsequent hydrolysis of glutathionyl methyl-benzazimide
resulted in the formation of cysteinyl-methylbenzazimide, which was then oxidized to form its
c orresponding sulfoxide and sulfone.
Toxicological data
Azinphos-methyl was highly acutely toxic (LD 50
range, 4.4–26 mg/kg bw) when administered
orally in an aqueous or non-aqueous vehicle to rats, and its profile of clinical signs was similar to
those of other cholinesterase-inhibiting organophosphorus pesticides. Clinical signs observed in experimental
animals after acute exposure were salivation, lacrimation, vomiting, diarrhoea, anorexia,
reduced locomotor activity, piloerection, staggering gait and muscular tremors. These signs were
generally evident within 5–20 min after dosing. There was very little difference in the sensitivity of
male and female rats to the acute effects of azinphos-methyl.
AZINPHOS-METHYL 139–172 JMPR 2007