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

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2.2 Short-term studies of toxicity
Mice
Groups of 10 male and 10 female Crl:CD-1(ICR)BR mice were given diets containing zoxamide
(purity, 94.2%) at a concentration of 0, 70, 700, 2500 or 7000 ppm (equal to 0, 12, 123, 436
and 1212 mg/kg bw per day respectively in males, and 0, 17, 174, 574, 1666 mg/kg bw per day in
females) for 90 days. All mice were observed daily for signs of ill health or reaction to treatment.
Physical examinations were performed each week. Body weight and feed consumption were determined
each week. At the end of the study period, all surviving mice were bled for haematology and
clinical chemistry investigations, killed and necropsied. Selected organ weights were recorded and
tissues were collected for histopathological evaluation. The study was certified to be compliant with
GLP and satisfied the essential criteria of OECD guideline 408.
No treatment-related deaths or clinical signs of toxicity were observed. There were no treatment-related
effects on body weight or body-weight change in males at any dose. After 4 weeks of
treatment, there was a persistent and apparently treatment-related but statistically non-significant
decrease in body weight and cumulative body-weight gain in females at 7000 ppm compared with
concurrent controls (Table 6). In males, a number of statistically significant decreases in mean body
weight and cumulative body-weight gain were observed in the groups at 700 ppm and 2500 ppm
throughout the treatment period, but these decreases were not considered to be treatment-related
Table 6. Body weights, body-weight gain and liver weight in mice fed diets containing zoxamide
for 90 days
Parameter
Dietary concentration (ppm)
0 70 700 2500 7000
Males
Body weight (g):
Week 0 30.8 30.4 30.2 29.2 29.8
Week 4 34.6 33.7 33.2* 32.0 32.8
Week 8 37.9 36.3 35.8* 34.3* 35.4
Week 13 (mean ± SD) 41.1 ± 4.9 38.5 ± 2.2 38.0 ± 1.9* 36.7 ± 3.5 38.3 ± 3.9
Cumulative body-weight gain, week 13
(g, mean ± SD)
12.3 ± 4.2 9.5 ± 1.9 9.1 ± 1.1* 8.9 ± 2.7 10.0 ± 2.7
Absolute liver weight (g, mean ± SD) 2.1 ± 0.24 2.0 ± 0.20 1.9 ± 0.13 2.1 ± 0.25 2.2 ± 0.21
Relative liver weight (%, mean ± SD) 5.2 ± 0.41 5.2 ± 0.39 5.2 ± 0.25 5.8 ± 0.49* 5.8 ± 0.55*
Females
Body weight (g):
Week 0 23.3 23.3 22.2 22.8 20.9
Week 4 26.8 26.8 25.6 25.1 23.6
Week 8 28.1 28.9 27.3 26.8 25.0
Week 13 (mean ± SD) 30.6 ± 4.8 31.1 ± 3.2 29.3 ± 3.8 28.7 ± 3.3 25.8 ± 2.1
Cumulative body-weight gain, week 13
(g, mean ± SD)
7.4 ± 3.1 7.7 ± 2.4 7.0 ± 2.6 5.9 ± 2.0 4.9 ± 1.7*
Absolute liver weight (g, mean ± SD) 1.5 ± 0.16 1.6 ± 0.16 1.7 ± 0.21 1.6 ± 0.24 1.5 ± 0.17
Relative liver weight (%, mean ± SD) 5.2 ± 0.51 5.3 ± 0.26 5.7 ± 0.52 5.7 ± 0.57 6.0 ± 0.51*
From Shuey et al. (1996)
SD, standard deviation.
* Significant difference from controls (p < 0.05).
ZOXAMIDE 487–522 JMPR 2007