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

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250 and 500 ppm. Body-weight gain at week 12 was decreased by 19% in males at 500 ppm and by
15% and 17% in females at 250 and 500 ppm, respectively. Food consumption was generally comparable
between all groups. There were no biologically significant effects on haematology, clinical
chemistry and urine analysis at any dose. Organ-weight changes were unremarkable and tended to be
associated with body-weight gain reductions. Macro- and micropathological examinations revealed
no treatment-related findings.
At dietary concentrations of 100 ppm or greater, the proportion of rats exhibiting normal,
4- to 5-day estrous cycles tended to be reduced, while the incidence of persistent estrus tended to
be increased, with the consequence of a reduction of the mean number of estrous cycles during
the observation period. These effects, which were more pronounced on days 70–85 than during
days 42–56, were statistically significant only at dietary concentrations of 250 ppm or greater after
70 days of treatment (Table 17). A more exact determination of effects at lower doses was precluded
by the greater variability between individual rats in data on estrous cycle in the treated groups.
There were no treatment-related effects on plasma concentrations of E2, progesterone, prolactin
and corticosterone.
The NOAEL was 100 ppm, equal to 7.6 mg/kg bw per day in females, on the basis of decreased
body-weight gain and significant effects on the estrous cycle at 250 ppm and greater (Pettersen et al.,
1991; Terranova, 1991).
In a combined short-term and long-term study of oral toxicity, which complied with GLP and
US EPA test guidelines, groups of 8–10 male and 8–10 female beagle dogs were fed diets containing
DACT (purity, 98.7%) at a concentration of 0, 5, 100 or 1500 ppm for 13 or 52 weeks. Because of
severe toxicity at the highest dose, which was evident after 6 weeks of treatment, the diet of the group
of dogs at the highest dose was chanegd to one containing DACT at 750 ppm. Females tolerated this
dose and received diet at 750 ppm until termination at 13 or 52 weeks. Since males continued to
exhibit signs of toxicity at 750 ppm, they were fed untreated diet for weeks 9–13. At 13 weeks, two
to six dogs per group were killed for interim study. Two females at the highest dose were then placed
Table 17. Data on the estrous cycle in rats given DACT in a short-term study of oral toxicity
Parameter
Dietary concentration (ppm)
0 10 100 250 500
Days 42–56
Four- to five-day cycles a 14/15 12/15 9/15 8/15 8/15
Persistent estrus a 0/15 1/15 3/15 5/15 4/15
Persistent diestrus a 2/15 2/15 3/15 4/15 1/15
Mean No. of cycles (days) 2.60 ± 0.51 2.40 ± 0.74 2.07 ± 0.88 1.87 ± 0.83 2.00 ± 1.00
Days 70–85
Four- to five-day cycles a 15/15 13/15 14/15 7/15* 6/15*
Persistent estrus a 0/15 1/15 2/15 8/15* 4/15
Persistent diestrus a 0/15 3/15 1/15 3/15 5/15
Mean No. of cycles (days) 2.80 ± 0.41 2.33 ± 0.90 2.47 ± 0.83 1.80 ± 1.01** 1.67 ± 1.11**
From Terranova (1991)
DACT, diaminochlorotriazine.
a
Total may not equal 15 since a rat might display a regular 4- to 5-day cycle followed by persistent estrus or persistent
diestrus.
* p < 0.05; ** p < 0.01.
ATRAZINE 37–138 JMPR 2007