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

61
Table 9. Selected findings of a study of carcinogenicity in rats fed diets containing atrazine
Finding
Dietary concentration (ppm)
0 25 50 70 400
Intact females
Body weight (g), week 52 412 428 414 419 390*
Survival, week 104 26/60 19/60 17/59 19/60 13*/60
No. of rats with palpable masses 29/80 34/80 43/80 39/80 46/80
Palpable masses; week of first observation 29 28 38 32 14
Mammary tumours, weeks 1–53:
Fibroadenomas 0/22 2/22 2/23 2/23 1/25
Carcinomas 2/22 2/22 0/23 2/23 6/25
Total No. with mammary neoplasia 2/22 3/22 2/23 4/23 6/25
Mammary tumours, weeks 1–104:
Fibroadenomas 16/80
(20%)
25/80
(31%)
33/78**
(42%)
Adenomas 0/80 0/80 1/78
(1.3%)
Carcinomas 12/80
(15%)
Adenomas/carcinomas 12/80
(15%)
Total No. with mammary neoplasia 24/80
(30%)
Ovariectomized females
18/80
(23%)
18/80
(23%)
34/80
(43%)
20/78
(26%)
21/78*
(27%)
44/78**
(56%)
29/80*
(36%)
25/80*
(31%)
0/80 0/80
14/80
(18%)
14/80
(18%)
38/80*
(48%)
27/80**
(34%)
27/80**
(34%)
43/80**
(54%)
Body weight (g), week 52 523 528 524 526 479*
Survival, week 104 44/60 42/60 46/59 45/60 44/60
No. of rats with palpable masses 3/80 2/80 2/80 2/80 6/80
Palpable masses; week of first observation 35 87 75 91 56
Total No. with mammary neoplasia 0/64 0/66 0/70 0/71 0/72
From Morseth (1996d, 1998)
* p < 0.05; ** p < 0.01.
Data for historical controls from 14 studies: adenomas, 1.3% (0–5.6%); carcinomas, 21.5% (6.0–32.8%); fibroadenomas,
47.8% (35.3–65.0%).
The NOAEL for mammary carcinogenicity was 25 ppm, equal to 1.5 mg/kg bw per day, on
the basis of a statistically significant increase in mammary neoplasia in intact female rats at 50 ppm,
equal to 3.1 mg/kg bw per day, and greater compared with the concurrent control group. The carcinogenic
effect of atrazine was abolished in ovariectomized rats (Morseth, 1996d, 1998).
In a study of carcinogenicity reported in a published paper, groups of 53–56 male and 50–55
female Fischer 344 rats received diets containing atrazine (purity, 98.9%) for the lifespan of most of
the rats (126 weeks in males, 123 weeks in females). Dietary concentrations of 500 and 1000 ppm
were used at commencement and were reduced to 350 and 750 ppm after 8 weeks because of excessive
retardation in body-weight gain. Histological examination was conducted on a full spectrum of
tissues, except that in decedents, results were only considered if a satisfactory evaluation was possible.
There was no clinical pathology, diet analysis or evidence of GLP quality-assurance auditing, and the
level of detail presented in the paper would be inadequate, in isolation, for regulatory submission.
ATRAZINE 37–138 JMPR 2007