Taxvig C, Vinggaard A M, Hass U, Axelstad M, Metzdorff S, Nellemann C
Department of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Søborg, Denmark.
Int J Androl. 2008 Apr;31(2):170-7. doi: 10.1111/j.1365-2605.2007.00838.x. Epub 2007 Dec 6.
The endocrine-disrupting potential of four commonly used azole fungicides, propiconazole, tebuconazole, epoxiconazole and ketoconazole, were tested in two short-term in vivo studies. Initially, the antiandrogenic effects of propiconazole and tebuconazole (50, 100 and 150 mg/kg body weight/day each) were examined in the Hershberger assay. In the second study, pregnant Wistar rats were dosed with propiconazole, tebuconazole, epoxiconazole or ketoconazole (50 mg/kg/day each) from gestational day (GD) 7 to GD 21. Caesarian sections were performed on dams at GD 21. Tebuconazole and propiconazole demonstrated no antiandrogenic effects at doses between 50 and 150 mg/kg body weight/day in the Hershberger assay. In the in utero exposure toxicity study, ketoconazole, a pharmaceutical to treat human fungal infections, decreased anogenital distance and reduced testicular testosterone levels, demonstrating a demasculinizing effect on male fetuses. Tebuconazole, epoxiconazole and ketoconazole induced a high-frequency of post-implantation loss, and both ketoconazole and epoxiconazole caused a marked increase in late and very late resorptions. Overall the results show that many of the commonly used azole fungicides act as endocrine disruptors in vivo, although the profile of action in vivo varies. As ketoconazole is known to implicate numerous endocrine-disrupting effects in humans, the concern for the effects of the other tested azole fungicides in humans is growing.
在两项短期体内研究中测试了四种常用唑类杀菌剂（丙环唑、戊唑醇、环氧唑和酮康唑）的内分泌干扰潜力。最初，在赫什伯格试验中检测了丙环唑和戊唑醇（各50、100和150毫克/千克体重/天）的抗雄激素作用。在第二项研究中，从妊娠第7天至第21天，给怀孕的Wistar大鼠分别灌胃丙环唑、戊唑醇、环氧唑或酮康唑（各50毫克/千克/天）。在妊娠第21天对母鼠进行剖腹产。在赫什伯格试验中，戊唑醇和丙环唑在50至150毫克/千克体重/天的剂量下未表现出抗雄激素作用。在子宫内暴露毒性研究中，用于治疗人类真菌感染的药物酮康唑缩短了肛门与生殖器之间的距离，并降低了睾丸睾酮水平，表明对雄性胎儿有去雄化作用。戊唑醇、环氧唑和酮康唑导致着床后丢失的频率很高，酮康唑和环氧唑均导致晚期和极晚期吸收显著增加。总体而言，结果表明，许多常用的唑类杀菌剂在体内可作为内分泌干扰物，尽管其体内作用模式各不相同。由于已知酮康唑在人类中会引发多种内分泌干扰作用，人们对其他受试唑类杀菌剂对人类的影响越来越担忧。
