Breckenridge Charles B, Sawhney Coder Pragati, Tisdel Merrill O, Simpkins James W, Yi Kun Don, Foradori Chad D, Handa Robert J
Department of Toxicology and Health Sciences, Syngenta Crop Protection, LLC, Greensboro, North Carolina.
WIL Research, Ashland, Ohio.
Birth Defects Res B Dev Reprod Toxicol. 2015 Oct;104(5):204-17. doi: 10.1002/bdrb.21154. Epub 2015 Oct 6.
Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post-weaning (G/L/PW cohort) to F1 generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen-primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F1 females received the vehicle or ATZ from PND 21-133 or from PND 120-133. Slight reductions in fertility and the percentage of F1 generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F1 generation offspring. The onset of puberty was delayed in of the F1 generation G/L/PW females at doses of 25 and 50 mg/kg/day. F1 generation females in the PW high-dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F1 generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F1 generation females exposed from gestation through to PND 133 or only for two weeks from PND 120-133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults.
通过灌胃法每日给怀孕的雌性斯普拉格-道利大鼠施用莠去津(ATZ),剂量分别为0、6.25、25或50毫克/千克/天,给药时间为妊娠、哺乳期和断奶后(G/L/PW组),直至F1代雌性后代;或者仅从出生后第21天(PND 21)开始,直至性成熟(阴道开口)后五天,此时评估雌激素预处理后的促黄体生成素(LH)激增情况(PW组)。F1雌性的其他亚组从PND 21至133天或从PND 120至133天接受赋形剂或ATZ。在妊娠期间暴露于50毫克/千克剂量组中,生育力略有下降,F1代幼崽存活至PND 21的百分比降低,同时母鼠和F1代后代的食物摄入量和体重也有所下降。在25和50毫克/千克/天的剂量下,F1代G/L/PW雌性的青春期开始延迟。PW高剂量ATZ组中的F1代雌性青春期开始也出现延迟。无论F1代雌性是从妊娠开始治疗还是仅在青春期前后治疗,ATZ对性成熟5天后去卵巢大鼠的LH峰值或LH曲线下面积均无影响。ATZ处理对从妊娠至PND 133暴露或仅从PND 120至133暴露两周的F1代雌性的发情周期、LH峰值或LH曲线下面积均无影响。这些结果表明,与成年后暴露于ATZ的动物相比,发育中的雌性暴露于ATZ时并不更敏感。