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

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Figure 3. Cumulative percentage of F 1a
, F 2a
, F 2b
pups with erupted incisors at postnatal days in a
study of reproductive toxicity in rats fed dimethomorph
100
90
80
70
% of pups
60
50
40
30
20
10
0 ppm F1a
0 ppm F2a
0 ppm F2b
1000 ppm F1a
1000 ppm F2a
1000 ppm F2b
0
7 8 9 10 11 12 13 14
postnatal day
From Osterburg (1990)
by caesarian section. The numbers of corpora lutea, implantation sites, viable fetuses and resorptions
were recorded. Fetuses were sexed, body weights measured and they were subjected to external
examinations. The study complied with GLP.
At 300 mg/kg bw per day, one rats showed bloody urine for 2 days and another died from an
emphysema in the lung; relationship to treatment is questionable. No treatment-related body-weight
changes in dams were seen. Additionally, pregnancy and fetal parameters in the treated groups were
not different from those of the control group.
The NOAEL was 300 mg/kg bw per day, the highest dose tested. No effect on dams and the
investigated reproductive parameters was seen (Osterburg, 1986).
In a second, very poorly reported dose-range finding study, a group of four mated female
Sprague-Dawley rats received dimethomorph (purity not stated) at a dose of 150 mg/kg bw per day
by oral gavage as a suspension and another group of three females received dimethomorph at a dose
of 300 mg/kg bw per day on day 6 until day 15 of gestation. In the group at 150 mg/kg bw per day,
one female had a total litter loss and the other three had each one to three postimplantation losses. In
the group at 300 mg/kg bw per day, two females had a total litter loss and the third had one postimplantation
loss. Mean pup weight at 300 mg/kg bw per day was reduced (Müller, 1987b).
In the definitive study of developmental toxicity in rats, groups of 30 mated female Sprague-
Dawley rats received dimethomorph (purity, 96.6%) at a dose of 0, 20, 60, or 160 mg/kg bw per day
as a suspension at 10 ml/kg bw by oral gavage on day 6 until day 15 of gestation. Clinical examinations
were done twice per day and feed consumption and body weights were recorded regularly. On
day 20, dams were terminated and the fetuses delivered by caesarian section. The numbers of corpora
lutea, implantation sites, viable fetuses and resorptions were recorded. Fetuses were sexed, body
DIMETHOMORPH 273–315 JMPR 2007