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

59
was decreased when compared with the control group, although no statistically significant increase
in mammary tumours was observed at the end of the study. The incidences of pituitary tumours did
not indicate any larger numbers or earlier onset in the treated groups compared with the controls
(Table 7).
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 tumours at 400 ppm (Thakur,
1992a).
In a supplementary long-term study of toxicity conducted to determine the effects of atrazine
on the mammary and pituitary glands, the estrous cycle, and plasma levels of E2, LH, progesterone
and prolactin, groups of 55 female CD (Sprague-Dawley derived) rats were fed diets containing atrazine
(purity, 97.1%) at a concentration of 0, 15, 30, 50, 70 and 400 ppm, equal to 0, 0.8, 1.7, 2.8, 4.1
and 23.9 mg/kg bw per day, for up to 12 months. The study was conducted in compliance with GLP
and EPA guidelines. For estrous cycle determinations and plasma hormone concentration analysis,
interim kills of 10 rats per group were conducted after 3, 6 and 9 months of treatment. Fifteen rats per
group were sampled continuously throughout the study, i.e. at 3, 6, 9 and 12 months and subsequently
killed for pathology evaluation at 12 months. Survivors of the remaining 10 females per group were
killed after 12 months, following estrous cycle determinations and blood sample collection.
Table 7. Summary of selected findings of a study of carcinogenicity in rats fed diets containing
atrazine for 104 weeks
Finding
Dietary concentration (ppm)
0 70 400
Mortality (No. of rats) 29 35 38*
Palpable mammary masses, a weeks 1–52 (No. of rats) 2 3 9*
Palpable mammary masses, a weeks 53–104 (No. of rats) 44 31 40
Mammary tumours (No. of rats/No. examined histopathologically) 46/60 34/59 49/60
Pituitary tumours (No. of rats/No. examined histopathologically) 44/58 46/58 47/60
Pituitary and mammary tumours (No. of animals) 34 26 39
From Thakur (1992a)
a
Histologically confirmed as tumours.
* p < 0.05.
Table 8. Incidence of mammary gland tumours in groups of 55 rats fed diets containing atrazine
for 12 months
Mammary gland tumour
Dietary concentration (ppm)
0 15 30 50 70 400
Adenocarcinoma 1 2 0 1 1 6
Adenoma 0 0 1 0 1 1
Fibroadenoma 2 2 2 1 4 4
Mammary tumours, combined 3 4 3 2 6 10*
From Pettersen & Turnier (1995)
* p < 0.05.
ATRAZINE 37–138 JMPR 2007