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

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Groups of 22 mated Sprague-Dawley-derived CD rats were given azinphos-methyl (purity,
92.7%) at a dose of 0.4, 1.2, or 3.6 mg/kg bw per day by gavage in maize oil daily from day 6 to day
15 of gestation. All rats were observed daily for clinical signs and body weights were recorded on
days 0, 3, 6-15, 17 and 20 of gestation. Food consumption was measured twice weekly. On day 20,
the animals were killed and necropsied. No deaths or treatment-related clinical signs were observed
during the study. Food consumption during gestation was similar in control and treated females.
The group mean body weight of females at 3.6 mg/kg bw per day was slightly lower than controls
during the period before treatment, but body weight and body-weight gain were unaffected by treatment.
There were no treatment-related changes in gravid uterine weights, the number or sex of live
fetuses, or the number of resorptions. Skeletal observations revealed retarded ossification in fetuses
at 3.6 mg/kg bw per day, with reduced or absent ossification seen in the supraoccipital, pubic and
hyoid bones. An increased incidence of supernumerary ribs (14th, lumbar) was also observed at
3.6 mg/kg bw per day (4.7%; p < 0.01), and the incidence of this finding was outside the range for
historical controls in the testing laboratory (0–3.1%). In the absence of any maternal effects, the
NOAEL for maternal toxicity was 3.6 mg/kg bw per day. The NOAEL for developmental toxicity
was 1.2 mg/kg bw per day on the basis of increases in the incidence of supernumerary ribs (14th,
lumbar) and delayed ossification (pubic, hyoid, and supraoccipital bones) in fetuses at 3.6 mg/kg bw
per day (Rubin & Nyska, 1988).
Rabbits
In a teratology study in Himalayan rabbits, groups of 11 or 12 pregnant animals received
azinphos-methyl (purity, 92.4%) as a daily oral dose at 0 (control), 0.3, 1.0 or 3.0 mg/kg bw per day
from day 6 to day 18 of gestation (day of insemination was counted as day 0). Caesarean section
was carried out on day 29 of gestation. Azinphos-methyl induced no evidence of maternal toxicity at
any dose and there were no detectable effects on embryonic or fetal development (Machemer, 1975;
A nnex 1, reference 64, modified with reference to the original data).
In a further study of teratology in American Dutch rabbits, groups of 20 inseminated does
received azinphos-methyl (purity, 87.7%) as a daily oral dose at 0 (control), 1, 2.5 or 6 mg/kg bw
per day from day 6 to day 18 of gestation (day of insemination was counted as day 0). Plasma and
erythrocyte cholinesterase activities were determined on days 19 and 28 of gestation, and in brain on
day 28 of gestation. Ataxia in four does at the highest dose and tremors in two of these represented
clinical signs of reaction to treatment. At the intermediate and highest dose, plasma and erythrocyte
cholinesterase activity on day 19 of gestation was depressed compared with controls. By day 28 of
gestation there was clear evidence of recovery in plasma and erythrocyte cholinesterase activity, although
activity in brain was depressed, compared with controls, at the highest dose. Azinphos-methyl
did not affect any maternal reproductive parameters and there was no evidence of any treatmentrelated
effect on embryotoxicity, fetotoxicity or teratogenicity at any dose. The NOAEL for maternal
toxicity was 2.5 mg/kg bw per day on the basis of the inhibition of brain cholinesterase activity seen
on day 28 of gestation at 6 mg/kg bw per day (Clemens et al., 1988; Annex 1, reference 64, modified
with reference to the original data).
In a study of developmental toxicity, groups of mated New Zealand White rabbits were given
azinphos-methyl (purity, 92.7%) at a dose of 0 (vehicle control), 1.5, 4.75, or 15 mg/kg bw per day
by oral gavage in maize oil from day 7 to 19 of gestation. To ensure that at least 12 pregnant rabbits
per group were available at terminal sacrifice, the group sizes were adjusted to 16, 18, 15, and 18, at
doses of 0, 1.5, 4.75 and 15 mg/kg bw per day, respectively. Rabbits were observed daily for clinical
signs and weighed on days 0, 3, 7–19, 22, 25 and 29 of gestation. Food consumption was measured
twice per week. Cholinesterase activity in erythrocytes and plasma was measured before pairing and
again after 11 days of dosing.
AZINPHOS-METHYL 139–172 JMPR 2007