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

502
Table 10. Organ weight and histopathological findings in dogs receiving zoxamide
Finding
Dietary concentration (ppm)
0 1500 7500 30 000
Mean organ weights (mean ± SD)
Males
Absolute liver weight (g) 304 ± 14 319 ± 33 310 ± 116 371 ± 45*
Relative liver weight (%) 2.66 ± 0.24 2.80 ± 0.22 2.80 ± 0.87 4.14 ± 0.06*
Females
Absolute liver weight (g) 244 ± 49 269 ± 39 300 ± 48 329 ± 45*
Relative liver weight (%) 2.68 ± 0.20 3.11 ± 0.40 3.44 ± 0.30* 4.37 ± 0.31*
Histopathology (No. affected/No.
examined)
Males
Liver hypertrophy 0/4 0/4 0/4 4/4
Thyroid hypertrophy 0/4 0/4 0/4 1/4
Females
Liver hypertrophy 0/4 0/4 0/4 4/4
Thyroid hypertrophy 0/4 0/4 0/4 1/4
From Ferguson et al. (1997)
* Significant difference from controls (p < 0.05).
weight, cumulative body-weight gain, and feed consumption in both sexes at 30 000 ppm; it was not
until week 7 that all the females returned to their pre-test body weight. Females at 7500 ppm had
reduced body-weight gain in the early stages of the study and this early deficit persisted (Table 11).
Haematology and urine analysis parameters did not reveal any treatment-related differences. Clinical
chemistry parameters showed treatment-related decreases in albumin and increases in alkaline phosphatase
activity in both sexes at 30 000 ppm (Table 11). Ophthalmology at termination did not reveal
any treatment-related ocular changes.
Organ weights showed a treatment-related increase in absolute and relative liver weights in
both sexes at 30 000 ppm and in females at 7500 ppm (Table 12). A dose-related increase in absolute
and relative thyroid weights was also evident (Table 12). No treatment-related gross findings were
made at necropsy. Treatment-related microscopic changes were observed in the livers of some animals
from the group at 30 000 ppm and consisted of diffuse hepatocellular hypertrophy in two males
and one female; another female had multifocal haemorrhage and necrosis; a third female had congestion
and mononuclear cell infiltration, a finding also seen in a male without hypertrophy (Table 12).
None of the animals in this study had thyroid cell hyperplasia.
The NOAEL was 1500 ppm, equal to 48 mg/kg bw per day, on the basis of reduction in bodyweight
gain in females at 7500 ppm, equal to 255 mg/kg bw per day (Ferguson et al., 1998b).
2.3 Long-term studies of toxicity and carcinogenicity
Mice
In a long-term study of toxicity/carcinogenicity, groups of 60 male and 60 female Crl:CD-1
(ICR) BR (VAF/+) mice were given diets containing zoxamide (purity, 92.3%) at a concentration
of 0, 350, 1750, or 7000 ppm (equal to 0, 51.1, 251 or 1021 mg/kg bw per day and 0, 60.4, 326 or
1289 mg/kg bw per day in males and females respectively) for 18 months. All mice were observed
ZOXAMIDE 487–522 JMPR 2007