OECD/EHS, Paris, France.
NIH/NIEHS/DNTP/NICEATM, RTP, NC, USA.
Reprod Toxicol. 2018 Oct;81:259-271. doi: 10.1016/j.reprotox.2018.08.016. Epub 2018 Sep 8.
A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US EPA's chemicals screened for endocrine activity, and the library of chemicals run in US EPA 's ToxCast in vitro assays. For 134 chemicals that met pre-defined criteria, experimental results were extracted into a database used to characterize uncertainty in results and evaluate the concordance of the Hershberger assay with other in vivo rodent studies that measure androgen-responsive endpoints. Of 25 chemicals tested in >1 Hershberger study, 28% had disagreements between studies (i.e. ≥1 positive and ≥1 negative study), and of the 65 chemicals tested in Hershberger studies and other in vivo studies with androgen-responsive endpoints, 43% indicated disagreements, though in some cases these may be explained by differences in study designs or physiology of the animal model. Ultimately, 49 chemicals were identified with reproducible androgen pathway responses confirmed in ≥2 in vivo rodent studies that could be considered reference chemicals useful for validating alternative methods.
进行了系统的文献综述，以确定约 3200 种化学物质的 Hershberger 生物测定法，包括用于验证 OECD/US EPA 指导方针测定法、US EPA 筛选具有内分泌活性的化学物质以及 US EPA 在 ToxCast 体外测定法中运行的化学物质库的化学物质。对于符合预定义标准的 134 种化学物质，将实验结果提取到一个数据库中，用于描述结果的不确定性，并评估 Hershberger 测定法与其他测量雄激素反应终点的体内啮齿动物研究的一致性。在 >1 项 Hershberger 研究中测试的 25 种化学物质中，有 28%（即≥1 项阳性和≥1 项阴性研究）在研究之间存在分歧，在 Hershberger 研究和具有雄激素反应终点的其他体内研究中测试的 65 种化学物质中，有 43%（虽然在某些情况下，这些分歧可能可以通过研究设计或动物模型的生理学差异来解释。最终，确定了 49 种具有可重复的雄激素途径反应的化学物质，这些反应在≥2 项体内啮齿动物研究中得到了证实，这些化学物质可以被认为是验证替代方法的有用参考化学物质。
