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

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after completion of the feeding trial, and at post-treatment observation periods using an unspecified
method. Two birds per group were killed at the conclusion of dosing and the remaining birds were
killed 1 day after the completion of the post-treatment observation period. One bird at 9.4 mg/kg bw
day died during the post-treatment observation period as a result of suspected pneumonia, but no details
of necropsy were provided. The group mean body weight of birds at 75 mg/kg bw per day was
reduced to about 13% of that of the controls by day 14 on study and remained unchanged up until the
conclusion of the treatment period. The hens, however, regained weight thereafter and body weights
were comparable to those of the controls during the post-treatment observation period. Food consumption
was unaffected by treatment. No signs of neurotoxicity or any behavioural changes were noted
in any of the treated birds. No intergroup differences in blood cholinesterase activity was seen before
treatment or at day 1 of the post-observation period. However, at day 1 after treatment, dose-related
depressions in blood cholinesterase activity of about 15% and 27% were observed in birds at 37.5 and
75.0 mg/kg bw per day respectively relative to the controls (Kimmerle, 1964).
In a follow up study with essentially the same experimental protocol as described in an earlier
study (Kimmerle, 1964), the administered dietary concentrations of azinphos-methyl (purity unspecified)
were increased to 900, 1200, 1500, or 1800 ppm (equivalent to approximately 112.5, 150, 187
and 225 mg/kg bw per day respectively). One bird at 150 mg/kg bw per day died during the last week
of the 4-week treatment period. The cause of the death was not specified and necropsy details were
not provided. Food consumption in treatment groups was reduced by about 27%, 43%, 40% and 44%
(at 112.5, 150.0, 187.0 and 225.0 mg/kg bw per day, respectively) relative to the controls during the
treatment period. All birds including the controls lost body weight during the treatment period. Hens
in the control group and hens at 112.5 and 150.0 mg/kg bw per day were about 15%, 23% and 21%
respectively lighter relative to the corresponding pre-treatment body weights at the conclusion of the
4-week treatment period. The groups receiving the test substance at 187.0 and 225.0 mg/kg bw per
day showed a body-weight loss of about 27% at the same observation time. The body-weight data
appeared to be consistent with the observations on food consumption. The birds had not achieved
their pre-treatment body weights by the completion of the recovery period, though there was some
recovery of body weights in all groups. Blood cholinesterase activity was unaffected by treatment.
No signs of neurotoxicity or any behavioural changes related to treatment were noted. Similarly, no
histopathological findings were made (Grundman, 1965; Kimmerle, 1965).
Rats
In a study to investigate acute neurotoxicity, groups of 18 male and 18 female fasted Fischer
344 CDF/BR rats were given azinphos-methyl (purity, 92.8%) at a dose of 0 (vehicle), 2, 6
or 12 mg/kg bw for males, and 0, 1, 3 or 6 mg/kg bw for females by oral gavage in 0.5% (w/v)
methylcellulose and 0.4% (w/v) Tween 80. Of the treated rats, six males and six females in satellite
groups were used for determinations of cholinesterase activity and the remainder were involved in
testing for changes in n eurobehaviour.
Five males (one in the main study and four in the satellite group) and fifteen females (nine in
the main study and all in the satellite group) in the group at the highest dose died. Treatment-related
clinical signs in males were muscle fasciculations (2 out of 12 and 8 out of 11 at 6 and 12 mg/kg bw
respectively), tremors (1 out of 11 at 12 mg/kg bw), uncoordinated gait (1 out of 11 at 12 mg/kg bw),
oral stain (3 out of 12 and 10 out of 11 at 6 and 12 mg/kg bw, respectively), and urine stain (1 out
of 12, 2 out of 12 and 10 out of 11 at 2, 6 and 12 mg/kg bw, respectively) and red nasal stain (2 out
of 12, 2 out of 12 and 7 out of 11 at 2, 6 and 12 mg/kg bw, respectively). One of the three surviving
females at 6 mg/kg bw had oral and urine staining for about 2 days after treatment. All clinical signs
that did not involve staining were only observed about 30 min after treatment on the day of dosing.
Staining was typically observed from between 1 to 3 days after dosing. There were no treatment
r elated d ifferences in group mean body weights of the surviving animals.
AZINPHOS-METHYL 139–172 JMPR 2007