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

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groups at the highest dose, females had increased cholesterol and males increased calcium and phosphate
concentrations. Body-weight adjusted liver weights were increased in both sexes at 100 and
750 mg/kg bw (Table 17). As with the E-isomer, caecal and liver enlargements, liver discoloration
and hepatocyte lipid vacuolation were observed, all effects starting at 100 mg/kg bw (Table 18).
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, 1991b).
For E- and Z-isomers of dimethomorph, no obvious differences in toxicity profile or potency
were evident.
In a 13-week feeding study , groups of 10 male and 10 female Sprague-Dawley rats were fed
diets containing dimethomorph (purity, 98.7) at a concentration of 0, 40, 200, or 1000 ppm (equal to
0, 2.9, 14.2, 73 mg/kg bw per day in males and 0, 3.2, 15.8, 82 mg/kg bw per day in females). Additionally,
recovery groups of 10 male and 10 female rats were fed diets containing dimethomorph at
a concentration of 0 or 1000 ppm for 13 weeks and were then given control feed for an additional 4
weeks to evaluate the reversibility of any effects induced during treatment with dimethomorph. Daily
cage-side observations, daily/weekly detailed clinical examinations were performed and ophthalmology
at the end of the study in the control group and in the group at the highest dose. Body weights and
feed consumption were recorded weekly and at the end of the study, haematology, clinical chemistry
and urine-analysis parameters were analysed, and a gross necropsy with extensive histopathological
examination of tissues and organ weights was conducted. The study complied with GLP.
There were no mortalities in the study and body-weight gain and feed consumption were
comparable within all groups and sexes. Minimal changes in haematology parameters were noted in
males and most of them were reversible in the recovery group (Table 19). Mildly decreased activity
of alanine aminotransferase in males and minimally increased calcium and decreased chloride
Table 17. Liver weights a in rats given dimethomorph Z-isomer by gavage for 4 weeks
Sex
Liver weight (g)
Dose (mg/kg bw per day)
0 10 100 750
Males 6.59 6.65 7.2** 7.97**
Females 4.27 4.21 4.87** 5.81**
From Esdaile (1991b)
a
Adjusted for terminal body weight.
** p ≤ 0.01.
Table 18. Macroscopic and histological changes in organs of rats given dimethomorph Z-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 6 0 0 0 1
Liver enlargements 0 1 2 7 0 0 3 7
Liver, dark discoloration 0 0 1 4 0 1 3 7
Liver, patchy midzonal cytoplasmic 0 0 3 7 0 0 4 7
lipid vacuolation
From Esdaile (1991b)
DIMETHOMORPH 273–315 JMPR 2007