Benigni Romualdo, Battistelli Chiara Laura, Bossa Cecilia, Giuliani Alessandro, Tcheremenskaia Olga
Environment and Health Department, Istituto Superiore di Sanita', Viale Regina Elena 299, 00161, Rome, Italy.
Environment and Health Department, Istituto Superiore di Sanita', Viale Regina Elena 299, 00161, Rome, Italy.
Regul Toxicol Pharmacol. 2017 Jun;86:18-24. doi: 10.1016/j.yrtph.2017.02.013. Epub 2017 Feb 20.
The protection from endocrine disruptors is a high regulatory priority. Key issues are the characterization of in vivo assays, and the identification of reference chemicals to validate alternative methods. In this exploration, publicly available databases for in vivo assays for endocrine disruption were collected and compared: Rodent Uterotrophic, Rodent Repeated Dose 28-day Oral Toxicity, 21-Day Fish, and Daphnia magna reproduction assays. Only the Uterotrophic and 21-Day Fish assays results correlated with each other. The in vivo assays data were viewed in relation to the Adverse Outcome Pathway, using as a probe 18 ToxCast in vitro assays for the ER pathway. These are the same data at the basis of the EPA agonist ToxERscore model, whose good predictivity was confirmed. The multivariate comparison of the in vitro/in vivo assays suggests that the interaction with receptors is a major determinant of in vivo results, and is the critical basis for building predictive computational models. In agreement with the above, this work also shows that it is possible to build predictive models for the Uterotrophic and 21-Day Fish assays using a limited selection of Toxcast assays.
防范内分泌干扰物是一项高度优先的监管任务。关键问题在于体内试验的特性描述，以及用于验证替代方法的参考化学品的识别。在本次探索中，收集并比较了公开可用的内分泌干扰体内试验数据库：啮齿动物子宫增重试验、啮齿动物28天重复剂量经口毒性试验、21天鱼类试验和大型溞繁殖试验。只有子宫增重试验和21天鱼类试验的结果相互关联。利用18种针对雌激素受体（ER）途径的体外ToxCast试验作为探针，结合不良结局途径来查看体内试验数据。这些数据是美国环境保护局（EPA）激动剂ToxERscore模型的基础数据，该模型良好的预测能力得到了证实。体外/体内试验的多变量比较表明，与受体的相互作用是体内试验结果的主要决定因素，也是构建预测性计算模型的关键基础。与此相符的是，这项工作还表明，使用有限数量的ToxCast试验就有可能为子宫增重试验和21天鱼类试验构建预测模型。
