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THE EFFECTS OF ATRAZINE ON FEMALE WISTAR RATS: AN EVALUATION OF THE PROTOCOL FOR ASSESSING PUBERTAL DEVELOPMENT AND THYROID FUNCTION
Citation:
Laws, S C., J M. Ferrell, T E. Stoker, J E. Schmid, AND R L. Cooper. THE EFFECTS OF ATRAZINE ON FEMALE WISTAR RATS: AN EVALUATION OF THE PROTOCOL FOR ASSESSING PUBERTAL DEVELOPMENT AND THYROID FUNCTION. TOXICOLOGICAL SCIENCES 58(2):366-376, (2000).
Description:
Female rats were dosed by oral gavage from postnatal day (PND) 22 through PND 41 with 0, 12.5, 25, 50, 100 or 200 mg ATR /kg. Half of the females in each treatment group were killed on PND 41 and organ weights (e.g., liver, kidney, adrenal, ovary, uterus and pituitary) and serum were collected. Estrous cyclicity was monitored in the remaining females until PND 149. Vaginal opening was significantly delayed 2.3, 3.9 or greater than 7.1 days as compared to the control by 50, 100 and 200 mg/kg, respectively. Vaginal opening did not occur in 18 of 31 females in the highest atrazine dose group by the end of the dosing period, but once treatment was terminated vaginal opening occurred in these females within 3 - 4 days. Body weight on the last day of dosing (PND 41) and the total body weight gain from PND 22 - 41 were reduced in the ATR 200 group by 11.2% and 16%, respectively, but were unaltered in the 50 and 100 mg/kg groups. Adrenal, kidney, pituitary, ovary and uterine weights were significantly reduced in the ATR 200 group. Using an ANCOVA the adjusted means for the liver reflected a significant increase in liver weight relative to necropsy body weight in the ATR 50, 100 and 200 groups, as well as, a reduction in kidney weight at 100 and 200 mg/kg. Serum T3, T4 and TSH were unaltered by atrazine treatment and were consistent with no morphological changes observed in the thyroid following histological examinations. To examine the influence of reduced body weight on pubertal development, a group of pair-fed females was included whose daily food intake was dependent upon the amount consumed by their respective mate in the ATR 200 group. Although body weight was reduced to the same extent as the ATR 200 females, vaginal opening in the pair-fed group was not significantly delayed as compared to the controls. Of those females that continued on study after the treatment period, irregular estrous cycles were observed in the pair-fed, ATR 50 and ATR 100 groups between vaginal opening and PND 41. Once treatment was discontinued, vaginal opening occurred in all females in the ATR 200 group. Estrous cyclicity in these females also remained irregular through the first 15-days following vaginal opening. Irregular cycles occurring in the atrazine and the pair-fed groups were due to an increase in the number of days of diestrus. By the end of the second 15-day interval (PND 57-71) and during the remaining observation periods, no difference in estrous cyclicity was observed in any ATR treatment group.
These data demonstrate that atrazine can delay the onset of puberty in the female Wistar rat. The LOAEL was 50 mg/kg with a NOAEL of 25 mg/kg. Reduced food consumption and body weight did not account for the delay in vaginal opening and irregular estrous cycles because (1) delayed vaginal opening was not observed in the pair-fed females, and (2) irregular estrous cycles were observed in the 50 and 100 mg/kg atrazine groups where no reduction in body weight occurred. While this study was not intended to identify a specific mechanism of action, these data support an effect of atrazine on the central nervous system and hormonal control of gonadal function during pubertal development.