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for males and females at 2500 or 10 000 ppm. Histopathology revealed changes in the liver of mice
at 10 000 ppm and 2500 ppm. The changes consisted of multifocal coagulative necrosis of hepatic
parenchyma, together with centrilobular cytoplasmic swelling, nuclear enlargement, coarsely dispersed
chromatin and multinucleate hepatocytes (Table 11). Decreases in kidney and spleen weights
were also noted at dietary concentrations of 2500 ppm and greater (Table 11).
The NOAEL was 100 ppm (reportedly equal to 19.6 mg/kg bw per day), on the basis of liver
pathology (coagulative necrosis) in males at dietary concentrations of 500 ppm and greater. This
study did not claim GLP compliance (Weir et al., 1984).
Groups of 20 male and 20 female ICR mice weer given diets containing procymidone (purity,
96.9%) at a concentration of 0, 50, 150 or 500 ppm for 26 weeks. The mice were observed twice per
day for clinical signs of toxicity and mortality and body weights were determined weekly. Food and
water consumption were determined on three consecutive days each week. At the end of the treatment
period, an ophthalmological examination was conducted and blood was taken for measurement of
biochemical and haematological parameters. All surviving mice were necropsied immediately after
blood was taken, organs were weighed and tissues were examined microscopically.
Achieved intakes are presented in Table 12. There were 11 deaths during the study; these
occurred in all groups and there was no indication of a relationship to treatment. No treatment-related
effects were detected on behaviour, appearance, survival, body weights, food and water intakes, ophthalmological
examination, or macroscopic pathology. There was a statistically significant decrease
in the leukocyte count in males at 150 and 500 ppm (Table 12), the deficit being primarily in lymphocytes.
Since no comparable change was found in other studies in mice, these effects were considered
to be unrelated to treatment. There was also a statistically significant increase in creatinine concentration
and cholinesterase activity in male mice at 500 ppm and a reduction in cholinesterase activity in
female mice of that group; these are considered to be sporadic findings unrelated to treatment. Organ
weights were similar across all groups; an increase in pituitary weight in all groups of males was
without a dose–response relationship, not reproduced in females and was considered to be a chance
Table 11. Findings in mice (n = 12) fed diets containing procymidone for 13 weeks
Finding a
Dietary concentration (ppm)
0 100 500 2500 10000
M F M F M F M F M F
Creatinine (mg/dl) 1.2 0.9 1.0 0.7 0.7* 0.6 0.6* 0.6 0.5* 0.8
Cholesterol (mg/dl) 139 116 139 139 158 141 158 128 154 164*
BUN (mg/dl) 41 29 31 25 24* 26 29* 27 23* 22
ALT (U/l) 268 229 353 260 256 125 531 216 795* 327
Liver weight (g) 1.7 1.5 1.7 1.5 1.7 1.7 2.0* 2.0* 2.4* 2.3*
Relative liver weight (%) 6.6 6.4 6.3 6.6 6.8 7.2* 8.2* 8.7* 10.1* 10.5*
Relative kidney weight (%) 2.4 2.1 2.3 2.0 2.3 2.0 2.2 1.9 1.9* 1.7*
Relative spleen weight (%) 0.33 0.45 0.35 0.43 0.32 0.47 0.35 0.40 0.31 0.39*
Centrilobular hepatocyte 0 0 1 0 6 0 11 7 12 12
swelling
Liver, coagulative necrosis 0 0 0 0 1 1 5 0 10 7
From Weir et al. (1984)
ALT, alanine aminotransferase; BUN, blood urea nitrogen; F, females; M, males.
a
Values are means for each group of 12 mice.
* p < 0.05.
PROCYMIDONE 349–401 JMPR 2007