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

460
The deaths were considered to be related to gavage errors and one female was cannibalized. Clinical
signs such as general nasal soiling, reduced activity, piloerection, hunched posture and severe
emaciation were seen in the majority of rats in the group at 30 000 ppm and urogenital soiling was
seen in most males. Emaciation and general soiling was also observed in the group at 15 000 ppm.
Most rats treated by gavage showed general soiling, facial soiling, emaciation, piloerection and
reduced activity. Most males also showed urogenital soiling and reduced muscle tone, and most
females showed hunched posture. These signs were first seen from day 7 to 17 and had disappeared
by day 26. There was a dose-related decrease in body weight in all dietary groups and in males and
females for the first 4 days and this persisted throughout the study in rats at the highest dose only.
A reduction in mean body-weight gains were observed in all dietary groups and also in the group
treated by gavage compared with controls. Decreased food consumption was observed in all dietary
groups and the group treated by gavage with marked effects during the first week of treatment.
There was decrease in water consumption at 30 000 ppm in males and females and a slight reduction
in males at 10 000 ppm. No effect on water consumption was observed in the group treated by
gavage or the other dietary groups. Ophthalmoscopic examination revealed no treatment-related
effects. Statistically significant increases in erythrocyte count and haemoglobin concentration and
reductions in mean corpuscular volume (MCV) and mean cell haemoglobin (MCH) were observed
at the highest dietary concentration of 30 000 ppm and in the group treated by gavage. Statistically
significant changes were also observed in some haematological parameters in other dietary groups,
but changes were small and of doubtful toxicological significance. At 30 000 ppm, statistically significant
increases in urea, total bilirubin and gamma-glutamyl transferase (GGT) were recorded in
males and females. Also at this dose, a statistically significant decrease in total protein, albumin, total
globulin, glucose and an increase in alanine aminotransferase and carbon dioxide were recorded
in males, and reductions in alkaline phosphatase and glucose were recorded in females. At 15000
ppm, there were statistically significant increases in GGT (males and females), cholesterol (males),
alkaline phosphatase (males), phosphate (females), total bilirubin (females), and decreased glucose
and creatinine phosphokinase (CPK) (females). At 10 000 ppm, there was a statistically significant
increase in cholesterol c oncentration (males and females).
Statistically significant increases in potassium and cholesterol (males and females), a significant
increase in carbon dioxide and alanine aminotransferase (males) and a decrease in glucose (females)
were observed in the group treated by gavage. At 30 000 ppm, there were marked decreases
in absolute and relative (to brain weight) liver, kidney, heart, spleen, adrenal and gonad weights
compared with controls. However, kidney and liver weights relative to body weights of males and
females were increased, probably due to the emaciated condition of the rats. Liver and kidney weights
were affected in all treatment groups. At necropsy, an accentuated lobular pattern of the liver was
seen in all treated groups. At 30 000 ppm, multiple yellow foci in the kidneys were seen in one out
of five male and four out of five females. Histopathology revealed a treatment-related effect in the
kidneys (increase in luminal diameter, degenerative change to basophilic tubules, tubular necrosis,
increased mitotic division, karyomegaly in tubular epithelium, inflammatory infiltration), liver (accentuated
lobular pattern), oesophagus (focal acute inflammation of the muscularis in rats treated by
gavage), stomach (diffuse epithelial hyperplasia in rats treated by gavage, mucosal ulceration) and
thyroid (colloid depletion, agglomeration of colloid, follicular-cell hypertrophy, follicular epithelial
hyperplasia in rats treated by gavage). In rats given diets containing pyrimethanil, effects were predominately
recorded at 30 000 ppm, although some effects in the kidney and liver were also recorded
at 10 000 and 15000 ppm.
Dietary concentrations of 10 000 ppm and greater and the dose of 1500/1000 mg/kg bw per day
administered by gavage produced treatment-related effects on clinical signs, body weight and bodyweight
gains, food consumption, haematology, clinical chemistry, organ weights, gross pathology
and histopathology (Harvey, 1991a).
PYRIMETHANIL 445–486 JMPR 2007