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

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mice (evaluated as roughly equivalent numbers in each group) received treatment with 1% rotenone
for a mite infestation. During the early months of the study, diets were mixed sufficiently infrequently
that substantial degradation of atrazine (20–30%) may have occurred before feeding. In some tissues,
substantial numbers of samples were lost to autolysis. There were other practices that did not meet
modern guideline requirements. Histopathology was performed by an independent laboratory. Treatment
with atrazine caused a significant reduction in the body weights of mice at 1000 ppm. Survival
among males was not affected by treatment although survival was significantly lower in females at
1000 ppm. The cause of death of these female decedents does not appear to have been documented.
However, eventual survival and duration of this study was adequate for the evaluation of carcinogenicity.
Histopathology revealed no evidence of a treatment-related change in inflammatory, degenerative,
proliferative or neoplastic lesions in treated mice. Atrazine was not carcinogenic in mice, in this
study suitable to be used as supportive data.
The NOAEL was 300 ppm, equivalent to approximately 30 mg/kg bw per day, on the basis of
reduced survival and reduced body weight at 1000 ppm (Sumner, 1981).
In a study of carcinogenicity performed according to US EPA guidelines and in compliance
with GLP, groups of 60 male and 60 female CD1 mice were given diets containing atrazine technical
(purity, 97.6%) at a concentration of 0, 10, 300, 1500, or 3000 ppm for 91 weeks. Mean daily intakes
were equal to 0, 1.2, 38.4, 194.0 and 385.7 mg/kg bw per day in males and 0, 1.6, 47.9, 246.9 and
482.7 mg/kg bw per day in females. Blood samples for haematology were collected from all animals
at necropsy, and blood smears prepared from all survivors at weeks 52 and 78. Survival was not
affected by treatment in males (59%, 55%, 60%, 65% and 60% at 0, 10, 300, 1500 and 3000 ppm)
while decreased survival was reported for the females at 3000 ppm (43%, 39%, 43%, 45% and 25%
at 0, 10, 300, 1500 and 3000 ppm). No treatment-related clinical signs occurred during the study.
Lower mean body weights and body-weight gains were recorded for males and females at 300, 1500
and 3000 ppm, which correlated with lower food consumption at 1500 and 3000 ppm. Haematology
investigations revealed a slight reduction in mean haemoglobin concentration, erythrocyte volume
fraction and in erythrocyte count in males at 1500 and in males and females at 3000 ppm. Analysis
of organ weight data did not reveal variations with toxicological significance. A lower brain weight in
males and females at 3000 ppm was not accompanied by any histopathological correlates. Histopathology
revealed an increased incidence of cardiac thrombi primarily in the atria of decedents in males
at 3000 ppm and in females at 1500 and 3000 ppm. No cardiac changes were apparent to account for
this change. No evidence of compound-related neoplastic lesions was found in this study.
The NOAEL was 10 ppm, equal to 1.2 and 1.6 mg/kg bw per day in males and females, respectively,
on the basis of lower body weight/body-weight gain at 300 ppm and greater (Hazelette &
Green, 1987).
Rats
In a study of carcinogenicity conducted before GLP, groups of 60 male and 60 female Sprague-
Dawley rats were fed diets containing atrazine technical (purity, 98.0%) at a concentration of 0, 10,
100 or 1000 ppm, equal to 0, 0.35, 4 and 40 mg/kg bw per day in males and 0, 0.45, 5.5 and 60 mg/
kg bw per day in females, for up to 2 years. Accuracy of diet preparation was confirmed by analysis
on only three occasions during the study. Clinical pathology was not investigated in rats receiving the
intermediate or lowest dose.
Body-weight gain was reduced significantly at 1000 ppm throughout the study reaching 22%
and 27% lower than that of the controls for males and females, respectively. Weight gain for the
rats at 100 ppm was reduced to a lesser extent (about 10% lower than that of controls). A decrease
in erythroid parameters was reported at the highest dose, and no measurements were performed at
the lower doses. Clinical chemistry data showed slight variations in the serum transaminases and
ATRAZINE 37–138 JMPR 2007