Tarui Hirokazu, Tomigahara Yoshitaka, Nagahori Hirohisa, Sugimoto Kenji, Mogi Masayuki, Kawamura Satoshi, Isobe Naohiko, Kaneko Hideo
Environmental Health Science Laboratory, Sumitomo Chemical, Co., Ltd.
LSI Medience Corporation.
J Pestic Sci. 2018 May 20;43(2):79-87. doi: 10.1584/jpestics.D17-079.
To clarify species differences in the developmental toxicity of procymidone (Sumilex®, a fungicide for agricultural use), placental transfer studies were conducted using C-labeled procymidone in pregnant rats, rabbits, and monkeys. These studies demonstrated that maternal-to-fetal transfer of the parent compound and its hydroxylated metabolite, which are both weak anti-androgenic agents, occurred more easily than that of other metabolites, with much higher absolute concentrations achieved in the fetal circulation of rats than of rabbits or monkeys. Notably, in rats, the fetal plasma concentration of the hydroxylated metabolite was higher than that of procymidone, especially after repeated oral administration of procymidone. These results suggest that the hydroxylated metabolite is the most relevant metabolite involved in teratogenic activity in rats.
为阐明腐霉利（Sumilex®，一种农用杀菌剂）发育毒性的物种差异，在怀孕大鼠、兔子和猴子中使用碳标记的腐霉利进行了胎盘转运研究。这些研究表明，母体化合物及其羟基化代谢物（二者均为弱抗雄激素剂）从母体向胎儿的转运比其他代谢物更容易，大鼠胎儿循环中的绝对浓度比兔子或猴子高得多。值得注意的是，在大鼠中，羟基化代谢物的胎儿血浆浓度高于腐霉利，尤其是在反复口服腐霉利后。这些结果表明，羟基化代谢物是参与大鼠致畸活性的最相关代谢物。
