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

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In an assay for reverse mutation in bacteria, DACT (purity, 97%) did not induce gene mutations
at the histidine locus of S. typhimurium when tested at concentrations of up to 5000 µg/plate
(Deparade, 1987).
In two tests for DNA repair in vitro, DACT (purity, 97%) did not induce unscheduled DNA
synthesis in primary rat hepatocytes exposed at concentrations of up to 400 µg/ml (Hertner, 1988b)
and in human fibroblasts exposed at concentrations of up to 600 µg/ml (Meyer, 1987).
In an assay for micronucleus formation in mouse bone marrow , DACT (purity, 97%) gave
negative results for micronucleus formation in the PCE of Tif:MAGF mice treated once orally at
doses ranging from 1250 to 5000 mg/kg bw (Strasser, 1988).
In a study of prenatal developmental toxicity, which complied with GLP and the US EPA test
guidelines, groups of 26 mated female Crl:COBS CD(SD)BR rats were given DACT (purity, 98.7%;
suspended in 3% corn starch) at a dose of 0, 2.5, 25, 75 or 150 mg/kg bw per day by oral gavage on
days 6 to 15 of gestation.
No mortalities or treatment-related clinical observations were noted. Food consumption was
significantly decreased throughout the treatment period at 150 mg/kg bw per day and during days
6–8 of gestation at 75 mg/kg bw per day, while a non-significant decrease was noted at 25 mg/kg bw
per day during the first 3 days of treatment. Body-weight loss was observed during the first 3 days
of treatment (days 6–8 of gestation) in females at 75 and 150 mg/kg bw per day, and body weight
was significantly decreased in the dams at the highest dose during the rest of the treatment period.
Total (−33%) and corrected (−43%) body-weight gain (days 0–20 of gestation) was also significantly
decreased at the same dose. A tendency towards a reduced body-weight gain was observed
at 75 mg/kg bw per day for days 6–16 of gestation (−28%) and for days 6–8 of gestation (−32%)
at 25 mg/kg bw per day. These decreases were of transient nature; total and corrected body-weight
gains in the group at 25 mg/kg bw per day were comparable to those of rats in the control group.
The number of corpora lutea and implantation sites was comparable between all groups. The
number of resorptions was significantly increased in the group at the highest dose. Fetal body weights
were significantly decreased in the groups at 75 and 150 mg/kg bw per day.
No treatment-related malformations were observed, although incidental malformations included
an umbilical hernia observed in one fetus at the lowest dose and one fetus at the highest dose; one
fetus at the lowest dose had a protruding tongue, one fetus at 75 mg/kg bw per day had a filamentous
tail, and one fetus at the highest dose was acaudate. Visceral malformations were restricted to
a single fetus at 25 mg/kg bw per day. A significantly increased incidence of visceral variations was
observed in fetuses at the highest dose (pitted kidneys and absent renal papillae). No skeletal malformations
were observed at any dose. There was a dose-related increase of incomplete ossification of
several bones at 75 and 150 mg/kg bw per day and in three skull bones (interparietal, parietals; hyoid
[unossified]) at 25 mg/kg bw per day and greater (Table 18).
There was no evidence of teratogenicity.
The NOAEL for maternal toxicity was 2.5 mg/kg bw per day on the basis of decreased bodyweight
gain during the initial 3 days of treatment at 25 mg/kg bw per day. The NOAEL for developmental
toxicity was 2.5 mg/kg bw per day on the basis of increased incidences of incompletely
ossified interparietals or parietals and unossified hyoids at 25 mg/kg bw per day and greater (Hummel
et al., 1989).
(iv) Hydroxyatrazine (G 34048)
Hydroxyatrazine was of low acute oral toxicity in rats (LD 50
, > 5050 mg/kg bw). In short-term
studies in rats given hydroxyatrazine at dietary concentrations of up to 750 ppm, effects included
ATRAZINE 37–138 JMPR 2007