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

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weights measured and they were subjected to external, visceral and skeletal examinations. The study
complied with GLP.
The only pre-term death was due to an intubation error in the group at the highest dose. There
were no treatment-related clinical signs in any group, but feed consumption was reduced in the group
at the highest dose from day 6 to day 15 of gestation (Table 35). This resulted in reduced bodyweight
gain from day 6 to day 10 of gestation. Thereafter, body-weight gain was comparable to the
other groups. At 160 mg/kg bw per day, there were two total litter losses and one at 60 mg/kg bw
per day but none in the other groups (Table 36). These rats had decreases in feed intake and in body
weight that were at the lower bound within their respective group and therefore contributed most to
the mean group changes. If the intrauterine deaths of the two dams at the highest dose are included,
postimplantation deaths were significantly increased to 15.6% at 160 mg/kg bw per day and this was
beyond the upper limit of the range for historical controls (11.8%; 23 control groups, 4 out of 23 with
one total loss). All postimplantation losses were described as early losses. There were no signs of
developmental toxicity.
The NOAEL for maternal and for embryo toxicity was 60 mg/kg bw per day on the basis of
body-weight gain decreases in dams and increased total litter losses at the next higher dose. The
NOAEL for developmental toxicity was 160 mg/kg bw per day, the highest dose tested (Müller,
1989b).
Table 35. Body weight, body-weight gain and feed consumption in a study of developmental
toxicity in rats given dimethomorph by gavage
Parameter
Day of
gestation
Dose (mg/kg bw per day)
0 20 60 160
Body-weight gain (g) 0–6 33.4 30.8 33.3 32.0
6–10 21.8 22.2 19.3 7.0
10–15 30.0 28.5 30.0 30.3
15–20 66.8 67.3 63.1 65.0
Body weight (g) 20 356.2 352.3 346.2 335.8**
Feed consumption (g/animal per day) 0–6 21.8 21.6 21.8 21.6
From Müller (1989b)
** p < 0.01.
6–10 23.2 23. 22.0 16.5**
10–15 26.2 25.7 25.7 21.3**
15–20 28.3 28.3 25.9 28.3
Table 36. Postimplantation losses in a study of developmental toxicity in rats given dimethomorph
by gavage
Parameter
Dose (mg/kg bw per day)
0 20 60 160
Pregnant females at terminal kill 25 20 22 22
Females with live fetuses 25 20 21 20
Females with total intrauterine deaths 0 0 1 2
% deaths in females with live fetuses 3.9 ± 6.1 6.3 ± 7.2 4.4 ± 5.9 7.2 ± 8.8
% deaths in all females 3.9 ± 6.1 6.3 ± 7.2 8.8 ± 21.2 15.6 ± 28.6
From Müller (1989b)
DIMETHOMORPH 273–315 JMPR 2007