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

300
Clinical observations, feed consumption and body weight gain were comparable in all groups
in parents of both generations with the exception of the premating period for P, where body weight
gain was slightly decreased in the group at 1000 ppm (Table 32). Since the body-weight development
thereafter was comparable with that of the other groups and fertility was not affected, this effect was
judged not to be of toxicological relevance.
There were no treatment-related findings on mating performance, fertility and litter data in P
and F 1
. In F 1
, F 2a
and F 2b
pups at 1000 ppm, there were signs of retarded development indicated by a
decreased percentage of pups with erupted incisors when compared with the other groups (Table 34
and Figure 3). However, virtually all pups of the group at the highest dose had incisor eruption within
postnatal days 8 and 11–12, as had the pups in the other groups. No other markers for postnatal
physical development of the pups (eye opening, hair growth and pinna unfolding) were affected and
behaviour was not changed.
The NOAEL for maternal toxicity and reproductive performance was 1000 ppm, equal to
approximately 80 mg/kg bw per day, the highest dose tested. The NOAEL for pup development was
300 ppm, equal to approximately 20 mg/kg bw per day, on the basis of slight delays in incisor eruption
in pups at 1000 ppm (Osterburg, 1990).
(b)
Developmental toxicity
Rats
In a dose range-finding study, groups of eight mated female Sprague-Dawley rats received
dimethomorph (purity, 98.7%) at a dose of 0, 50, 120, or 300 mg/kg bw per day by oral gavage
suspension on days 6 to day 15 of gestation. Clinical examinations were done twice per day and
body weights were recorded regularly. On day 20, dams were terminated and the fetuses delivered
Table 33. Duration of gestation in a study of reproductive toxicity in rats fed diets containing
dimethomorph
Generation
Duration of gestation (days)
Dietary concentration (ppm)
0 100 300 1000
F 1a
22.0 ± 0.3 22.1 ± 0.3 21.9 ± 0.4 21.8 ± 0.4*
F 2a
21.9 ± 0.4 21.9 ± 0.3 22.1 ± 0.3 21.7 ± 0.5**
F 2b
21.9 ± 0.2 22.2 ± 0.5 21.9 ± 0.3 21.8 ± 0.4
From Osterburg (1990)
*Statistically different to group at 100 ppm, p < 0.05.
**Statistically different to group at 300 ppm, p < 0.05.
Table 34. Incisor eruption in a study of reproductive toxicity in rats fed diets containing
dimethomorph
Generation Group mean percentage of pups with incisor eruption on postnatal day 10
Dietary concentration (ppm)
0 100 300 1000
F 1a
82.6 ± 30.2 70.3 ± 35.9 63.7 ± 35.0 43.1 ± 37.3
F 2a
79.0 ± 24.0 68.4 ± 28.5 76.2 ± 24.8 48.0 ± 35.9
F 2b
78.8 ± 21.6 77.9 ± 27.8 71.1 ± 36.7 40.3 ± 27.0
From Osterburg (1990)
DIMETHOMORPH 273–315 JMPR 2007