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

293
0–9%, mean, 3.5%; only one out of 12 control groups with an incidence of equal or higher incidence
than 6%, control groups were from studies performed in 1997–2002). Although the historical control
groups were not contemporary, no altered time trend in the background incidence of mammary
adenocarcinomas between 1993 and 2003 was evident. In males at the highest dose, the incidence
of lung adenoma was higher than in controls but lower than in the group receiving the next lower
dose and, also considering the lack of any other histological changes in the lungs, a relationship with
treatment is questionable.
The NOAEL was 100 mg/kg bw per day on the basis of reduced body-weight gain in males
and increased incidence of mammary adenocarcinomas in females at 1000 mg/kg bw per day
(Smith, 1991).
Rats
In a 24-month study of toxicity, groups of 20 male and 20 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, 9.4, 36.3, 99.9 mg/kg bw per day in males and 0, 11.9, 57.7, 157.2 mg/kg bw in females).
The rats were daily observed for mortalities, clinical signs and palpable masses; body weights, feed
and water consumption were recorded weekly and ophthalmoscopy was performed pre-trial and at
weeks 51 and 102. Data on haematology, clinical chemistry, and urine analysis were collected from
Table 23. Body-weight development in mice fed diets containing dimethomorph
Dietary concentration (ppm) Body weight (g) Body-weight gain Terminal body weight
Week 0 Week 17 Week 52 Week 104 (g) % of control % of control
Males
0 30.7 38.8 43.8 43.0 12.3 — —
10 30.6 37.3* 41.4* 43.4 12.8 104 101
100 30.4 37.7 42.4 42.0 11.6 94 98
1000 30.1 36.7** 40.5** 40.3* 10.2 83 94
Females
0 23.2 30.9 34.9 38.8 15.6 — —
10 23.7 31.9 36.0 38.1 14.4 92 98
100 23.3 31.4 34.7 37.3 14.0 89 96
1000 24.2 31.7 34.6 36.4 12.2 78 94
From Smith (1991)
* p < 0.05; **p < 0.01.
Table 24. Gross pathology, non-neoplastic and neoplastic histological changes in mice fed diets
containing dimethomorph
Gross histopathological change
Dose (mg/kg bw per day)
Males (n = 50) Females (n = 50)
0 10 100 1000 0 10 100 1000
Spleen, enlarged 4 4 5 7 14 12 14 20
Lung, adenomas 13 14 23 17 9 5 12 5
Mammary, adenocarcinoma — — — — 1 0 1 3
From Smith (1991)
DIMETHOMORPH 273–315 JMPR 2007