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

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the groups at weeks 11 (only haematology), 25, 51, 77 and 102 of dosing. Organ weights and gross
necropsy with extensive histopathology examination of tissues were done after terminal sacrifice.
The study complied with GLP.
Male and female rats at the intermediate and highest dose showed a slight increased survival time
and no treatment-related clinical signs were observed. Feed and water consumption was comparable
in all groups, but body-weight gain was decreased in both sexes at 2000 ppm. The final body weight
in males was 67% and in females 83% of that of the controls. In males, the effect became statistically
significant from week 68 onwards and in females from the beginning of dosing. Starting at week
11, the erythrocyte system was affected at 2000 ppm in both sexes, this being more pronounced in
females (Table 25). After 1 year, males at 750 ppm were also affected but at the end of the study,
erythrocyte parameters were no longer changed statistically significantly in any group. Statistically
significant, only body-weight adjusted kidneys weights in females at the highest dose were increased
(Table 26). However, increases of relative liver weights and decreases of relative pituitary weights
were recorded in both sexes at 2000 ppm. At terminal kill, macroscopically no treatment-related
changes were evident. Histologically, in the liver of females at 2000 ppm hepatocyte hypertrophy
and pigmentation was increased and in males more ground glass foci were recorded (Table 27).
The effects did not attain statistical significance. In both groups at the highest dose, arteritis in the
pancreas and the mesenterium was increased. In males, a dose-related increase in testes interstitial
cell hyperplasia was found in all dosed groups and the incidence of adenomas was also increased.
In both sexes at 2000 ppm, an increased severity in sternum marrow cellularity was recorded that
might be a compensatory sign of anaemia at higher doses. In females at the highest dose, a significant
decrease in the incidence of pituitary hyperplasias and tumours was found.
The NOAEL was 750 ppm, equal to 36.3 mg/kg bw per day, on the basis of body-weight
decreases and histological changes in the liver of females at 2000 ppm (Everett, 1990).
In another 24-month study of carcinogenicity, groups of 50 male and 50 female Sprague-Dawley
rats were fed diets containing dimethomorph (purity, 96.6%) at a concentration of 0, 200, 750 or
2000 ppm (equal to 0, 8.8, 33.9, 94.6 mg/kg bw per day in males and 0, 11.3, 46.3, 132.5 mg/kg bw
Table 25. Changes in erythrocyte parameters for rats fed diets containing dimethomorph for
24-months
Parameter
Dietary concentration (ppm)
Males
Females
0 200 750 2000 0 200 750 2000
Week 11
Haemoglobin (g/dl) 15.6 15.6 15.4 15.2 15.1 15.1 15.0 14.5**
Erythrocytes (10 12 /l) 7.63 7.64 7.5 7.32** 7.43 7.41 7.33 7.00***
Erythrocyte volume 0.433 0.439 0.429 0.425 0.428 0.429 0.425 0.414*
fraction (1/l)
Week 51
Haemoglobin (g/dl) 14.8 14.8 14.1** 14.3* 13.8 13.9 13.5 12.7**
Erythrocytes (10 12 /l) 7.87 7.71* 7.49*** 7.44*** 7.02 7.05 6.87 6.35***
Erythrocyte volume 0.399 0.402 0.382** 0.390 0.380 0.384 0.375 0.354**
fraction (1/l)
Week 102
Haemoglobin (g/dl) 14.7 13.3 13.8 13.9 13.6 13.5 13.3 12.6
Erythrocytes (10 12 /l) 7.54 6.71 7.08 7.15 6.63 6.37 6.28 5.86
Erythrocyte volume 0.419 0.387 0.393 0.396 0.391 0.389 0.380 0.366
fraction (1/l)
From Everett (1990)
* p < 0.05; ** p < 0.01; *** p < 0.001.
DIMETHOMORPH 273–315 JMPR 2007