Laws S C, Ferrell J M, Stoker T E, Schmid J, Cooper R L
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Toxicol Sci. 2000 Dec;58(2):366-76. doi: 10.1093/toxsci/58.2.366.
The effects of atrazine (ATR), a chlorotriazine herbicide, on the onset of puberty were evaluated in Wistar rats. Female rats were dosed by oral gavage from postnatal day(s) (PND) 22 through PND 41 with 0, 12.5, 25, 50, 100, or 200 mg ATR/kg. Vaginal opening (VO) was significantly delayed 3.4, 4.5, or greater than 6.8 days by 50, 100, and 200 mg/kg, respectively. VO had not occurred in 4 of 15 females in the 200 mg/kg group by the time of necropsies (PND 41). Body weight (bw) at necropsy was reduced in the 200 mg/kg group by 11.6%, but was not different from the control (0) in the 50 and 100 mg/kg groups. To examine the influence of reduced bw on pubertal development, a group of pair-fed controls was included whose daily food intake was dependent upon the amount consumed by their counterpart in the 200 mg/kg group. Although necropsy bw was reduced to the same extent as the ATR females, VO in the pair-fed controls was not significantly delayed. Adrenal, kidney, pituitary, ovary, and uterine weights were reduced by 200 mg/kg ATR. Serum T(3), T(4), and TSH were unaltered by ATR, which was consistent with no histopathologic/morphologic changes in the thyroid. Estrous cyclicity was monitored in a second group of females from VO to PND 149. The number of females displaying regular 4- or 5-day estrous cycles during the first 15-day interval after VO was lower in the 100 and 200 mg/kg ATR and pair-fed controls. Irregular cycles were characterized by extended periods of diestrus. By the end of the second 15-day interval (PND 57-71), no effects on estrous cyclicity were observed. These data show that ATR can delay the onset of puberty and alter estrous cyclicity in the female Wistar rat ( NOAEL of 25 mg/kg). Reduced food consumption and bw did not account for the delay in VO, because this effect was not observed in the pair-fed controls. In addition, the effect on estrous cyclicity was observed in the 100 mg/kg ATR group where no significant reduction in bw was observed.
评估了氯三嗪除草剂阿特拉津（ATR）对Wistar大鼠青春期启动的影响。从出生后第22天（PND）至第41天，对雌性大鼠进行灌胃给药，剂量分别为0、12.5、25、50、100或200毫克ATR/千克。50、100和200毫克/千克的剂量分别使阴道开口（VO）显著延迟3.4、4.5或超过6.8天。在尸检时（PND 41），200毫克/千克组的15只雌性中有4只未出现阴道开口。200毫克/千克组尸检时的体重（bw）降低了11.6%，但50和100毫克/千克组与对照组（0）无差异。为了研究体重减轻对青春期发育的影响，纳入了一组配对喂养的对照组，其每日食物摄入量取决于200毫克/千克组对应大鼠的摄入量。尽管尸检时体重减轻程度与ATR处理的雌性大鼠相同，但配对喂养对照组的阴道开口并未显著延迟。200毫克/千克ATR使肾上腺、肾脏、垂体、卵巢和子宫重量减轻。ATR未改变血清T(3)、T(4)和促甲状腺激素（TSH）水平，这与甲状腺无组织病理学/形态学变化一致。在第二组雌性大鼠中，从阴道开口至PND 149监测发情周期。在阴道开口后的第一个15天间隔内，100和200毫克/千克ATR组以及配对喂养对照组中表现出规律的4天或5天发情周期的雌性数量较少。不规律周期的特征是动情间期延长。在第二个15天间隔结束时（PND 57 - 71），未观察到对发情周期的影响。这些数据表明，ATR可延迟雌性Wistar大鼠青春期的启动并改变发情周期（无观察到有害作用水平为25毫克/千克）。食物消耗和体重减轻并不能解释阴道开口延迟的现象，因为在配对喂养对照组中未观察到这种影响。此外，在100毫克/千克ATR组中观察到对发情周期的影响，而该组体重无显著降低。
