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

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The NOAEL was 10 mg/kg bw per day on the basis of several changes in the liver in males and
females at 100 mg/kg bw per day (Esdaile, 1991a).
In the second 4-week study, groups of seven male and seven female Fischer 344 rats received
dimethomorph Z-isomer (purity, 95.6%) at a dose of 0, 10, 100, or 750 mg/kg bw per day. During
the 4 weeks of the study, no changes in the composition of the test compound were observed. Clinical
examinations were performed twice per day, feed consumption and body-weight development
were recorded weekly. At the end of the study, haematology and clinical chemistry parameters were
investigated and organ weights (brain, heart, liver, kidneys, spleen, adrenals, testes) were recorded
and gross pathology performed. Histopathology was performed for rats in the control group and in
the group at the highest dose, for the adrenals, brain, heart, intestines, liver (also for rats at the lowest
and intermediate dose), kidneys, pituitary, spleen and stomach. The study complied with GLP.
All rats survived till study termination and body-weight gain was not affected. Minimal haematological
changes in males and females in the groups at the intermediate and the highest dose
showed no dose–response relationship and were therefore judged not to be treatment-related. Treatment-related
changes in clinical chemistry in both sexes comprised increased plasma protein concentrations
in the groups at the intermediate and highest dose, while bilirubin concentrations were
increased in males at the intermediate and highest dose and in females only at the highest dose. In the
Table 15. Organ weights a in rats given dimethomorph E-isomer by gavage for 4 weeks
Organ
Males
Organ weight (g)
Dose (mg/kg bw per day)
0 10 100 750
Spleen 0.4 0.42 0.41 0.36**
Liver 6.14 6.23 6.46* 8.14**
Adrenals 0.033 0.036 0.038* 0.044**
Females
Liver 4.05 3.97 4.18 5.81**
Adrenals 0.045 0.043 0.045 0.049
From Esdaile (1991a)
a
Organ weights were adjusted for terminal body weight.
* p ≤ 0.05; **, p ≤ 0.01.
Table 16. Macroscopic and histological changes in organs of rats given dimethomorph E-isomer
by gavage for 4 weeks
Change
Dose (mg/kg bw per day)
Males
Females
0 10 100 750 0 10 100 750
Caecal enlargement 0 0 1 7 0 0 0 7
Liver enlargement 0 0 1 7 0 0 0 7
Liver, dark discoloration 0 0 2 5 0 0 0 1
Liver, patchy midzonal cytoplasmic 0 0 2 7 0 0 4 7
lipid vacuolation
From Esdaile (1991a)
DIMETHOMORPH 273–315 JMPR 2007