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

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(iii) Diaminochlorotriazine, DACT (G 28273)
DACT was of low acute oral toxicity in rats (LD 50
, 2310 to 5460 mg/kg bw). In a short-term
study in rats given DACT at dietary concentrations of up to 500 ppm, effects included reduced bodyweight
gain and food consumption and an increased number of females with shortened or prolonged
estrous cycles and with persistent estrus or diestrus. The NOAEL was 10 ppm, equal to 0.7 mg/kg bw
per day. In a 13/52-week study in dogs given DACT at dietary concentrations of up to 750–1500 ppm,
effects included clinical signs and mortality, cardiac damage and failure, liver toxicity and decreased
erythrocyte parameters. The NOAEL was 100 ppm, equal to 3.5 mg/kg bw per day. DACT was not
genotoxic in a battery of tests, including in-vitro assays for point mutation and DNA repair and
tests for clastogenicity in vivo. In a study of prenatal developmental toxicity in rats, the NOAEL for
maternal toxicity was 2.5 mg/kg bw per day on the basis of decreased body-weight gain at 25 mg/
kg bw per day and greater. 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. There was no evidence of teratogenicity. In special studies
on the effects of DACT on pubertal development in male and female rats, atrazine equimolar doses
of ≥ 12.5 or ≥ 50 mg/kg bw per day delayed preputial separation or vaginal opening, respectively,
with NOAELs of 6.25 or 25 mg/kg bw per day, respectively.
In a study of acute oral toxicity, which complied with GLP and the US EPA test guidelines,
Blu:(SD) rats received DACT (purity, not reported; 16.65% w/v suspension in corn oil) as a single
dose at 2463, 3547 or 4256 mg/kg bw by gavage. The group at the lowest dose contained five females
and the group at the highest dose contained five males; 10 male and 10 females were used in the
group at the intermediate dose. The rats were observed for clinical signs and mortality for 14 days.
The oral LD 50
s for males, females and both sexes combined were 3690, 2360 and 2310 mg/kg bw,
respectively (Mehta, 1980a).
In a study of acute oral toxicity, which complied with GLP and the US EPA test guidelines,
Blu:(SD) rats received DACT (purity, not reported; 33.3% w/v suspension in corn oil) as a single
dose at 2491, 3547, 5050, or 7189 mg/kg bw by gavage. The group at the lowest dose contained five
males, and five males and five females were used in all other groups. The rats were observed for clinical
signs and mortality for 14 days. The oral LD 50
s for males, females and both sexes combined LD 50
were 11 300, 5230 and 5460 mg/kg bw, respectively (Mehta, 1980b).
In a study of acute oral toxicity, which complied with GLP and the US EPA test guidelines,
HSD:(SD) rats received DACT (purity, not reported; 40% w/v suspension in deionized water) as a
single dose at 4000, 5050, or 5500 mg/kg bw. The groups at the lowest dose and the highest dose
contained five females, and the group at the intermediate dose contained five males and five females.
The rats were observed for clinical signs and mortality for 14 days. The LD 50
was > 5050 mg/kg bw
for males and > 5500 mg/kg bw for females (Kuhn, 1991b).
In a short-term study of oral toxicity , which complied with GLP and the test guidelines of
OECD and US EPA, groups of 15 male and 15 female Crl:CD(SD)BR rats were fed diets containing
DACT (purity, 98.2%) at a concentration of 0, 10, 100, 250 or 500ppm, equal to 0, 0.7, 6.7, 16.7
and 34.1 mg/kg bw per day in males and 0, 0.7, 7.6, 19.7 and 40.2 mg/kg bw per day in females, for
90 days. In addition to the standard examinations, the estrous cycles and hormone concentrations of
female rats were evaluated.
No mortalities or treatment-related clinical symptoms were observed during the study. There
was a statistically significant decrease in body-weight gain in males at 500 ppm and in females at
ATRAZINE 37–138 JMPR 2007