Stoker Tammy E, Guidici D L, Laws S C, Cooper R L
Gamete and Early Embryo Biology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Toxicol Sci. 2002 Jun;67(2):198-206. doi: 10.1093/toxsci/67.2.198.
Recently we reported that atrazine (ATR), a chlorotriazine herbicide, alters the onset of puberty in male Wistar rats. In this study, we examined the same reproductive parameters in the developing male rat following a similar exposure to the primary, chlorinated metabolites of atrazine. Intact male Wistar rats were gavaged from postnatal day (PND) 23 through PND 53 and several reproductive endpoints were examined. The doses selected were the molar equivalents to atrazine in our previous work. Deethylatrazine (DEA), deisopropyl-atrazine (DIA), and diaminochlorotriazine (DACT) were administered by gavage at doses equivalent to the atrazine equimolar doses (AED) of 6.25, 12.5, 25, 50, 100, or 200 mg/kg. Preputial separation (PPS) was significantly delayed by DEA at 25, 100, and 200 AED, by DIA at 25, 100, and 200 AED, and by DACT at 12.5 through 200 AED. When the males were killed on PND 53, DEA (100 and 200 AED), DIA (50 through 200 AED), and DACT (200 AED) treatments caused a significant reduction in ventral prostate weight, while only the highest doses of DIA and DEA resulted in a significant decrease in lateral prostate weight. Seminal vesicle weight was reduced by DEA (25, 100, and 200 AED), DIA (100 and 200 AED), and 100 and 200 AED of DACT. Epididymal weights were reduced in the DEA (200 AED), DIA (200 AED), and DACT (100 and 200 AED) treatment groups. Serum testosterone was reduced only in the males receiving the 2 highest doses of DIA. Serum estrone was increased in the 2 highest doses of the DACT group, while serum estradiol was not different in any group. No differences were observed in any of the thyroid measures. In summary, the metabolites of ATR delay puberty in a manner similar to that observed in the previous study testing atrazine. These data also suggest that the 3 chlorinated metabolites are similar to ATR, by affecting the CNS control of the pituitary/gonadal axis and subsequent development of the reproductive tract.
最近我们报道了一种氯代三嗪除草剂阿特拉津（ATR）会改变雄性Wistar大鼠青春期的起始时间。在本研究中，我们在发育中的雄性大鼠中检测了在类似暴露于阿特拉津的主要氯化代谢产物后的相同生殖参数。完整的雄性Wistar大鼠从出生后第23天（PND）至第53天经口灌胃给药，并检测了多个生殖终点指标。所选剂量为我们之前研究中阿特拉津的摩尔当量。脱乙基阿特拉津（DEA）、脱异丙基阿特拉津（DIA）和二氨基氯三嗪（DACT）通过灌胃给予，剂量相当于阿特拉津等摩尔剂量（AED）的6.25、12.5、25、50、100或200mg/kg。DEA在25、100和200 AED时显著延迟包皮分离（PPS），DIA在25、100和200 AED时显著延迟，DACT在12.5至2op AED时显著延迟。当雄性大鼠在PND 53处死时，DEA（l00和200 AED）、DIA（50至200 AED）和DACT（200 AED）处理导致腹侧前列腺重量显著降低，而只有最高剂量的DIA和DEA导致侧叶前列腺重量显著下降。精囊重量在DEA（25、100和200 AED）、DIA（100和200 AED）以及DACT的100和Z0op AED时降低。附睾重量在DEA（200 AED）、DIA（200 AED）和DACT（100和200 AED）处理组中降低。仅接受最高剂量DIA的雄性大鼠血清睾酮降低。DACT组最高的两个剂量组血清雌酮升高，而任何组的血清雌二醇均无差异。在任何甲状腺指标中均未观察到差异。总之，ATR的代谢产物以类似于先前测试阿特拉津的研究中观察到的方式延迟青春期。这些数据还表明，这三种氯化代谢产物与ATR相似，通过影响垂体/性腺轴的中枢神经系统控制以及随后生殖道的发育。
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