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

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e xamination was performed before commencement of treatment and at termination. Body weight and
food c onsumption were measured weekly. Water consumption was measured over a 4-day period during
weeks 3–4, 7–8 and 11–12. An ophthalmoscopic examination and electrocardiography were performed
at pre-test and at the end of the study. Blood was collected from all dogs at pre-test, and after 4
and 13 weeks of t reatment for measurement of haematological and clinical parameters. Urine analysis
was performed on all dogs at termination. At the end of the study, a complete gross postmortem was
done. The adrenals, brain, kidneys, liver, pituitary, thyroid and parathyroid, lungs, heart, spleen and
t estes/ovaries were weighed. The organs specified were examined microscopically. The dosing solutions
were prepared daily for the first 7 days and then the day before use for the remaining treatment
period. Aliquots of the dosing solutions were analysed on mixing, before, during and after dosing,
and mean concentrations were reported to be 82.5–121.7% of nominal doses (study report was not
provided).
There were no treatment-related effects on mortality, organ weights, necropsy findings, histopathological,
ophthalmological, electrocardiography, urine analysis or haematological parameters. At
1000 mg/kg bw per day, there was an increased incidence of vomiting and diarrhoea in all dogs during
the first 6 days of treatment. The vomiting was observed between 0.75 h and 3.75 h after dosing.
Vomiting was also observed in one male in the control group. Vomiting was not considered to be a
toxicologically relevant effect since it may have been induced by local irritation of the gastrointestinal
tract. When the dose was reduced to 800 mg/kg bw per day, occasional to frequent vomiting was
observed in the majority of animals (about 9% of all doses). Other clinical signs observed included
salivation, cream coloration of faeces and hypoactivity. Very slight weight loss (about 4%) occurred
at the highest dose, probably due to vomiting. Food consumption was slightly decreased in the first
week of treatment. There was a marked reduction in water consumption in males (30%) and females
(19%). Clinical chemistry analysis indicated that there were statistically significant reductions in serum
phosphate concentration in males and serum total protein concentration in females after 4 weeks
of treatment. The toxicological significance of these findings is uncertain. At 80 mg/kg bw per day,
infrequent vomiting was observed in all females and three out of four males, the overall incidence of
vomiting was less than 2% of all doses was not considered to be a toxicologically relevant effect. Water
consumption was decreased (males, 9%; and females, 17%). Clinical chemistry analysis indicated
that there was a small reduction in serum phosphate concentration in males at week 4 and in females
at week 1. No treatment-related effects were reported at 6 mg/kg bw per day.
The NOAEL was 80 mg/kg bw per day and the LOAEL was 1000/800 mg/kg bw per day on the
basis of diarrhoea, salivation, hypoactivity and decreased water consumption (Harvey, 1991c).
In a 1-year study of oral toxicity, groups of four male and four female beagle dogs were given
pyrimethanil (purity, 96.3–96.9%) at a dose of 0, 2, 30 or 400/250 mg/kg bw per day by gavage in
0.5% methyl cellulose in distilled water for 12 months. The highest dose was reduced from 400 to
250 mg/kg bw per day on day 8 of the study 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.
Body weights were recorded weekly and food consumption was measured daily. Water consumption
was measured over a 4-day period during weeks of 13, 26 and 52 of treatment. An ophthalmoscopic
examination and electrocardiography were performed at pre-test and on dogs in the control group
and in the group at the highest dose at termination. Clinical examinations, including heart rate and
rectal temperature, were conducted for all dogs pre-test and at termination. Blood was collected from
all dogs at pre-test, and during 13, 26 and 52 weeks of treatment for measurement of haematological
and clinical parameters. Urine analysis was performed on all dogs during weeks 13, 26 and at termination.
At the end of the study, a complete gross postmortem was performed. The adrenals, brain,
kidneys, liver, pituitary, thyroid and parathyroid, lungs, heart, spleen and testes/ovaries were weighed.
The organs specified were examined microscopically.
PYRIMETHANIL 445–486 JMPR 2007