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

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Litter parameters, including litter size, sex ratio, and postnatal survival indices, of the F 1
and
F 2
generations were not affected by treatment with atrazine at any dose. There were no clinical symptoms,
necropsy findings or malformations that were considered to be related to treatment. Slightly
lower body weights (8–10%) were noted in both generations of male pups at 500 ppm on postnatal
day 21.
No treatment-related pathological or micropathological findings were noted in any of the reproductive
organs of F 0
or F 1
generations. Relative testes weights were increased in F 1
and F 2
males at
500 ppm as a result of decreased terminal body weights.
The NOAEL for parental toxicity was 50 ppm, equal to 3.6 and 4.0 mg/kg bw per day in males
and females, respectively, on the basis of decreased body-weight gains and food consumption at
500 ppm. The NOAEL for reproductive toxicity was 50 ppm on the basis of decreased body weights
of male pups at 500 ppm on postnatal day 21 (Mainiero et al., 1987).
(b)
Studies of developmental toxicity
Rats
In a study of prenatal developmental toxicity, which complied with GLP and US EPA test
guidelines, groups of 27 pregnant female Crl:COBS CD(SD)BR rats were given atrazine (purity,
96.7%; suspended in 3% corn starch with 0.5% Tween 80) at a dose of 0, 10, 70 and 700 mg/kg bw
per day by oral gavage on days 6 to 15 of gestation.
A total of 21 dams treated at 700 mg/kg bw per day died between days 13 and 20. All other
dams survived the study. Treatment-related clinical signs were confined to the group at 700 mg/kg bw
per day and included salivation, oral/nasal discharge, ptosis, swollen abdomen and blood on the vulva.
Necropsy findings included enlargement of the stomach. A marked reduction in food intake was
recorded for the group at 700 mg/kg bw per day and was associated with a marked loss of maternal
body weight. In the group at 70 mg/kg bw per day, significant reductions of food consumption and
body-weight gain were reported at days 6–7 or 6–10 of gestation, respectively.
Fetal toxicity, attributed to maternal toxicity, was observed in the groups at 70 and 700 mg/kg
bw per day and manifested as a marked reduction of fetal weight at 700 mg/kg bw per day (no skeletal
examination was performed in this group). A marginal increase in numbers of runted pups at all doses
was within the range of data for historical controls. Skeletal variations in the group at 70 mg/kg bw
per day included incomplete ossification of skull, teeth, metacarpals and hindpaw distal phalanges,
and bipartite metacarpals. These findings can be considered to be developmental delays attributable
to maternal toxicity, although it should be noted that maternal toxicity at 70 mg/kg bw per day was
minimal and fetal weights were not different to those of the controls (Table 12).
There was no evidence of teratogenicity.
The NOAEL for maternal toxicity was 10 mg/kg bw per day on the basis of decreased bodyweight
gain and food intake at 70 mg/kg bw per day and greater. The NOAEL for developmental
toxicity was 10 mg/kg bw per day on the basis of incomplete ossification at several sites at 70 mg/kg
bw per day and greater (Infurna, 1984).
In a study of prenatal developmental toxicity, which complied with GLP and US EPA test
guidelines, groups of 26 pregnant female Crl:COBS CD(SD)BR rats were given atrazine (purity,
97.6%; suspended in 3% corn starch with 0.5% Tween 80) at a dose of 0, 5, 25 and 100 mg/kg bw per
day by oral gavage on days 6 to 15 of gestation.
One female at the highest dose died without obvious cause on day 20 of gestation. At the highest
dose, an increased incidence of salivation was seen. Also at the highest dose, food consumption
ATRAZINE 37–138 JMPR 2007