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

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in females). This study was conducted in parallel with a similar long-term study of toxicity (Everett,
1990). Rats were daily observed for mortalities, clinical signs and palpable masses; body weights, feed
and water consumption were recorded weekly. Haematology data were collected from the groups at
weeks 52, 78 and 103 of dosing. Gross necropsy with extensive histopathology examination of tissues
was done after terminal sacrifice. The study complied with GLP.
From the Kaplan-Meier survival curves, no significant differences between groups with regard
to time to death and total number of pre-term deaths are evident. In females at the highest dose, feed
intake was decreased by 7%, but not in other groups; terminal body weights in males at 2000 ppm
were 14% lower and in females 9%, 23% and 38% lower at 200, 750 and 2000 ppm, respectively. In
the first 12 weeks, five females at the highest dose had severely swollen hind limbs and were killed
pre-term. The reason for this effect remains unclear. Haematology was not affected in any group. On
gross pathology, at 2000 ppm increased incidences of enlarged adrenals and lymph node cysts in males
were recorded and, in both sexes, swollen hind limbs, pancreas masses and dilated blood vessels,
in females also ovary cysts (Table 28). Non-neoplastic histological findings in the liver at 750 and
2000 ppm were found in females and in males at 2000 ppm and arteritis was found in the pancreas for
males and females at 2000 ppm (Table 29). In males, increased incidences of tumours in the adrenal
medulla and the testes were found. The interstitial testes tumours coincided with increased interstitial
Table 28. Gross pathology in rats fed diets containing dimethomorph for 24 months
Gross pathology
Dietary concentration (ppm)
Males (n = 50) Females (n = 50)
0 200 750 2000 0 200 750 2000
Adrenals, enlarged 1 2 5 5 0 0 0 0
Lymph node, cysts 2 4 4 9 0 0 2 0
Hind feet, hindlimbs, swollen 11 16 12 20 5 4 6 19
Pancreas, masses 1 3 1 5 0 2 1 8
Blood vessel, dilated 1 0 4 13 0 1 1 4
Ovary, cysts — — — — 8 2 9 15
From Everett (1991)
Table 29. Non-neoplastic and neoplastic histological changes in rats fed diets containing
dimethomorph for 24 months
Histological change
Dietary concentration (ppm)
Males (n = 50) Females (n = 50)
0 200 750 2000 0 200 750 2000
Liver, ground-glass foci 17 18 21 27 12 9 16 18
Liver, periacinar hepatocyte pigmentation 0 0 0 0 1 0 4 26
Liver, periacinar hypertrophy 0 0 0 0 0 0 1 15
Lymph node, mesenteric, reactive hyperplasia 0 0 0 3 0 0 0 1
Pancreas, arteritis 3 2 0 24 0 3 2 6
Testes, interstitial cell hyperplasia 6 6 10 10 — — — —
Testes, interstitial adenoma 5 7 8 10 — — — —
Adrenals, benign medulla tumours 4 5 4 8 2 3 1 2
From Everett (1991)
DIMETHOMORPH 273–315 JMPR 2007