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

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per day or 800 mg/kg bw per day. The female dog also vomited within 1–3 h after dosing and liquefied
faeces were recorded between 1 h and 6 h after dosing during the first phase of the study. Vomiting
also occurred on one occasion in a female treated at 1200 mg/kg bw per day during the second phase
of the study; liquefied and white soft faeces were also recorded. Slight decreases in body weight and
food consumption were noted at 1200 mg/kg bw per day and greater. There were no treatment-related
effects on haematological and clinical chemistry parameters, electrocardiograms, organ weights and
necropsy findings. The study author concluded that the maximum tolerated dose was between 640 and
1000 mg/kg bw per day (Harvey, 1992a).
In a 28-day study of oral toxicity, groups of two male and two female beagle dogs were given
pyrimethanil (purity, 99.0%) at a dose of 0, 100, 500, or 1000 mg/kg bw per day by gavage in 1%
methyl cellulose in distilled water. The highest dose of 1000 mg/kg bw per day was reduced to 800
mg/kg bw per day on day 7 owing to persistent vomiting. The dogs were inspected twice per day
for morbidity or mortality, with clinical signs being checked daily. A detailed physical examination
was performed before commencement of treatment and at week 4 before the end of treatment. Body
weight and food consumption were measured each week. An ophthalmoscopic examinations and
electrocardiography were performed pre-test and at the end of the study. Blood was collected from
all animals at pre-test, and after 15 and 28 days of treatment for measurement of haematological
and clinical parameters. Urine analysis was performed on all animals at termination. At the end of
the study, a complete gross postmortem was done. The adrenals, brain, kidneys, liver, thyroid and
p arathyroid, heart, and gonads were weighed. The organs specified were examined microscopically.
All dosing solutions were prepared daily. The dosing solutions were analysed for concentrations
and homogeneity on the first day of each week. However, the results of analysis of the s uspension
concentrations and homogeneity were not provided in the study report.
No deaths occurred during the study. There were no treatment-related findings on urine analysis,
electrocardiography, ophthalmoscopic examinations and haematological parameters. Frequent
vomiting, 2 to 4 h after dosing, was recorded in all animals treated with 1000 mg/kg bw per day. This
occurred less frequently when the dose was reduced to 800 mg/kg bw. Vomiting also occurred in one
male and one female at 500 mg/kg bw per day. No other treatment-related symptoms were recorded.
No treatment-related changes were noted on detailed clinical examination conducted at the end of
treatment. Slight decreases in body-weight gain (24% decrease compared with controls) were observed
in females at 1000 mg/kg bw per day. After reduction of the highest dose, overall body weights
were slightly reduced (4%) in females. There was no effect on body weights in the groups at 100 and
500 mg/kg bw per day. No treatment-related effect was observed on food consumption in males at
any dose. Slight decreases in food consumption was noted in females at 500 and 1000/800 mg/kg bw
per day in the first 3 weeks and were comparable to controls during the last week of the treatment.
There was a trend towards slight increases in plasma cholesterol concentration in the treatment groups
compared with controls; however, the increase in cholesterol concentration was not considered to be
treatment-related in the absence of any other histopathological findings. No treatment-related effects
were noted on organ weights, necropsy findings or histopathological examinations.
The NOAEL was 500 mg/kg bw per day and the LOAEL was 1000 mg/kg bw per day on the
basis of vomiting, decreased body-weight gain and slight decreases in food consumption in females
(Harvey & Davies, 1990).
In a 90-day study of oral toxicity, groups of four male and four female beagle dogs were given
pyrimethanil (purity, 97.9%) at a dose of 0, 6, 80 or 1000/800 mg/kg bw per day by gavage in
0.5% methyl cellulose in distilled water for 13 weeks. The highest dose was reduced from 1000 to
800 mg/kg bw per day on day 7 owing to persistent vomiting seen in all dogs. The dogs were inspected
twice per day for morbidity or mortality, with clinical signs being checked daily. A detailed physical
PYRIMETHANIL 445–486 JMPR 2007