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

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Table 6. Selected findings from a study in rats fed diets containing atrazine for 104 weeks
Finding
Dietary concentration (ppm)
0 70 400
Unscheduled deaths, weeks 1–55 (No. of rats) 0 0 5
Unscheduled deaths, weeks 1–104 (No. of rats) 5 6 8
Palpable mammary masses, a weeks 1–54 (No. of rats) 6 3 14
Palpable mammary masses, a weeks 55–104 (No. of rats) 10 13 8
Fluid-filled uterus, weeks 1–54 (No. of rats/No. examined histopathologically) 4/40 10/40 14/40
Fluid-filled uterus, weeks 1–104 (No. of rats/No. examined histopathologically) 5/70 15/70 15/70
Mammary galactocoele, weeks 1–54 (No. of rats/No. examined
histopathologically)
Mammary galactocoele, weeks 1–104 (No. of rats/No. examined
histopathologically)
Mammary fibroadenoma, weeks 1–54 (No. of rats/No. examined
histopathologically)
6/39 9/38 20/41
29/69 30/67 41/69
1/39 0/38 4/41
Mammary carcinoma, weeks 1–54 (No. of rats/No. examined histopathologically) 0/39 1/38 6/41
Mammary fibroadenoma, weeks 1–104 (No. of animals) 8/69 12/67 13/69
Mammary carcinoma, weeks 1–104 (No. of rats/No. examined histopathologically) 9/69 4/67 11/69
Pituitary adenoma, weeks 1–54 (No. of rats/No. examined histopathologically) 2/39 2/40 8/43
Pituitary adenoma, weeks 1–104 (No. of rats/No. examined histopathologically) 22/68 16/69 20/69
From Thakur (1991a)
a
Histologically confirmed as tumours.
The NOAEL was 70 ppm, equivalent to 3.5 mg/kg bw per day, on the basis of increased mortality,
decreased body-weight gain and an earlier onset of mammary and pituitary tumours at 400 ppm
(Thakur, 1991a).
From the rats in the supplementary study of carcinogenicity described above (Thakur, 1991a),
data on estrous cycles, vaginal cytology and selected serum hormone levels were also collected from
rats killed at 1, 3, 9, 12, 15, 18 and 24 months. Results were evaluated as a function of treatment and
as a function of treatment over time.
Normal age-related changes noted in rats in the control group included an increase in the number
of days when high density cornified cells were evident in vaginal smears during 12 months, with a
decrease in this index between 12 and 18 months. Beginning at approximately age 1 year, episodes of
persistent vaginal estrus occurred, resulting in an increase in percentage of total days in estrus at the
expense of days in diestrus. Serum estradiol (E2) concentrations increased between 1 and 9 months
of the study, followed by decreased levels between months 9 and 18.
Atrazine-treated rats had a dose-related increase in percentage days in estrus at each interval
between 9 and 18 months. Compared with rats in the control group, the cornified cell index in treated
rats showed a similar increase to that in controls until 12 months, but a slower decline between 12 and
18 months. Episodes of persistent vaginal estrus were observed earlier in treated groups. Although
serum concentrations of E2 increased in the control group and in the groups treated with atrazine,
the magnitude of the increase was greater than that in the control group between 1 and 9 months in
the group at 400 ppm. Overall, treatment with atrazine accelerated the development of typical agerelated
changes in female Sprague-Dawley rats. As a result, rats treated with atrazine were exposed
to persistent endogenous estrogens for longer periods of time (Eldridge et al., 1993a).
ATRAZINE 37–138 JMPR 2007