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

55
Table 5. Incidence of mammary tumours in female rats at terminal kill
Mammary tumours
Dietary concentration (ppm)
0 10 70 500 1000
12- & 13-month kill, including early decedents
No. of animals examined 22 5 1 5 25
Adenocarcinoma 0 1 1 0 8 (32%)
All mammary tumours 0 1 1 1 9 (36%)
Terminal kill (including deaths occuring between 12 and 24 months)
No. of animals examined 66 64 68 65 64
Adenocarcinoma 15 (23%) 15 (23%) 26* (38%) 27* (42%) 35** (55%)
Carcinosarcoma 0 0 0 0 2 (3.1%)
Fibroadenoma 29 (44%) 29 (45%) 35 (51%) 38 (58%) 42** (66%)
Adenoma 1 (1.5%) 0 1 (1.5%) 1 (1.5%) 2 (3.1%)
Malignant + benign tumours 35 (53%) 39 (63%) 47 (69%) 47* (72%) 56** (89%)
All rats combined (original report)
No. of animals examined 88 69 69 70 89
Benign tumours 29 (33%) 29 (42%) 36 (52%) 39 (56%) 46** (52%)
Malignant tumours 15 (17%) 16 (23%) 27* (39%) 27** (39%) 45** (51%)
Malignant + benign tumours 35 (40%) 40 (58%) 48 (70%) 48** (69%) 65** (73%)
All rats combined (peer review) a
No. of animals examined 88 69 69 70 89
Benign tumours 31 (35%) 35 (51%) 38 (55%) 62 (89%) 58 (65%)
Malignant tumours 15 (17%) 16 (23%) 32 (46%) 35 (50%) 56 (63%)
From Mayhew (1986)
* p < 0.05; ** p < 0.01.
a
No statistical analysis reported.
The NOAEL was 70 ppm, equal to 2.6 mg/kg bw per day, in males, on the basis of decreased
body-weight gain at 500 ppm and greater, and 10 ppm, equal to 0.5 mg/kg bw per day, in females, on
the basis of an increased incidence of mammary tumours in females at doses of 70 ppm and greater
(Mayhew, 1986).
In a long-term study of toxicity conducted in compliance with GLP and EPA guidelines, groups
of 50 male and 50 female Sprague-Dawley rats were fed diets containing atrazine (purity, 97.6%) at
a concentration of 0, 10, 50 and 500 ppm, equal to 0, 0.5, 2.3, and 23.6 mg/kg bw per day in males
and 0.7, 3.5 and 37.6 mg/kg bw per day in females, for 52 weeks (males) or 104 weeks (females)
commencing in utero. The rats were male and female offspring culled from the F1 a
generation of a
previously conducted two-generation study of reproductive toxicity. Of the 50 males and 50 females
per group, 10 males and 10 females were killed after 8 weeks and a further 10 females at 35 weeks.
Of the remaining 30 females in the group at the highest dose, 10 were placed on withdrawal after
65 weeks, and 10 females in the control group were placed on diet containing atrazine at the highest
dose, 500 ppm. Dietary exposure was verified by regular analysis of diets. Examinations conducted
included ophthalmoscopy, blood and urine analyses, and estrous smears. Sections of pituitary
were stained immunochemically for prolactin, follicle-stimulating hormone (FSH) and luteinizing
hormone (LH).
ATRAZINE 37–138 JMPR 2007