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

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In a test for DNA repair in vitro, DEA (purity, 99.3%) did not induce unscheduled DNA synthesis
in primary rat hepatocytes exposed at concentrations of up to 1000 µg/ml (Geleick, 1991a).
In an assay for micronucleus formation in mouse bone marrow, DEA (purity, 99.3%) gave
negative results for induction of micronuclei in the polychromatic erythroctes (PCE) of Tif:MAGF
mice treated once orally at doses ranging from 120 to 480 mg/kg bw (Ogorek, 1991b).
In a study of prenatal developmental toxicity, which complied with GLP and the test guidelines
of OECD and US EPA, groups of 24 mated female Tif:RAIf rats were given DEA (purity, 95.7%;
suspended in 3% corn starch) at a dose of 0, 5, 25 or 100 mg/kg bw per day by oral gavage on days
6 to 15 of gestation.
All dams survived until the end of the experiment and no treatment-related clinical observations
were made. Maternal toxicity was observed at 25 and 100 mg/kg bw per day in a dose-related
manner as evidenced by effects on body weight/weight gain and food consumption. Body weights
were significantly decreased at 100 mg/kg bw per day on days 7–20 of gestation. Body-weight gains
were significantly decreased on days 6–11 of gestation at 25 and 100 mg/kg bw per day (83% and
41% of value for controls, respectively) and on days 11–16 of gestation at 100 mg/kg bw per day
(87% of value for controls). Corrected body-weight gains were non-significantly decreased at 25 and
100 mg/kg bw per day (73% and 80% of value for controls, respectively). Food consumption was
significantly decreased on days 6–11 of gestation at 25 and 100 mg/kg bw per day (91% and 70% of
value for controls, respectively).
There were no treatment-related effects on any reproductive parameter examined, on fetal sex
ratio, mean fetal weights or the incidences of gross, visceral and skeletal malformations. At 100 mg/kg
bw per day, fetal and litter incidences of fused sternebrae 1 and 2 were significantly increased, as was
the fetal incidence of poor ossification of the proximal phalanx of posterior digit 5 (Table 15).
There was no evidence of teratogenicity.
The NOAEL for maternal toxicity was 5 mg/kg bw per day on the basis of decreased bodyweight
gain and food intake at 25 mg/kg bw per day. The NOAEL for developmental toxicity was
25 mg/kg bw per day on the basis of increased incidences of fused sternebrae and incomplete
ossification of the proximal phalanx of posterior digit 5 at 100 mg/kg bw per day (Marty, 1992b).
(ii) Deisopropyl-atrazine, DIA (G 28279)
DIA was of moderate acute oral toxicity in rats (LD 50
, 1240 mg/kg bw). In short-term studies
in rats given DIA at dietary concentrations of up to 2000 ppm, effects included reduced body-weight
gain and food consumption, extramedullary haematopoiesis in liver and spleen, and histomorphological
changes in adrenals, thyroid and pituitary. The overall NOAEL was 50 ppm, equal to
3.2 mg/kg bw per day. In a 14-week study in dogs given DIA at dietary concentrations of up to
1000 ppm, effects consisted of reduced body weight and food consumption. The NOAEL was
100 ppm, equal to 3.8 mg/kg bw per day. DIA was not genotoxic in a battery of tests including assays
for point mutation and DNA repair in vitro and testing for clastogenicity in vivo. In a study of prenatal
developmental toxicity in rats, the NOAEL for maternal toxicity was 5 mg/kg bw per day on the basis
of decreased body-weight gain and food intake at 25 mg/kg bw per day and greater. The NOAEL for
developmental toxicity was 5 mg/kg bw per day on the basis of increased incidences of fused sternebrae
at 25 mg/kg bw per day and greater. There was no evidence of teratogenicity. In a special study
on the effects of DIA on pubertal development in male rats, atrazine equimolar doses of ≥ 25 mg/kg
bw per day delayed the preputial separation, with a NOAEL of 12.5 mg/kg bw per day.
In a study of acute oral toxicity, which complied with GLP and the US EPA test guidelines, groups
of HSD:(SD) rats received DIA (purity, not reported; suspended in 2% carboxymethyl-cellulose) as a
ATRAZINE 37–138 JMPR 2007