Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, China; Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China.
Toxicology. 2018 Feb 15;395:23-33. doi: 10.1016/j.tox.2018.01.002. Epub 2018 Jan 8.
Phthalate diesters, including di-(2-ethylhexyl) phthalate (DEHP) and diethyl phthalate (DEP), are chemicals to which humans are ubiquitously exposed. Humans are exposed simultaneously to multiple environmental chemicals, including DEHP and DEP. There is little information available about how each chemical may interact to each other if they were exposed at same time. The present study investigated effects of the combinational exposure of rats to DEP and DEHP on fetal Leydig cell development. The results showed that the gestational (GD12-20) exposure of DEP + DEHP resulted in synergistic and/or dose-additive effects on the development of fetal Leydig cell. The lowest observed adverse-effect levels (LOAEL) for fetal Leydig cell (aggregation and cell size), and StAR expressions were of 10 mg/kg and, lower than when these chemicals were exposed alone. Also, mathematical modeling the response curves supports the dose-addition model over integrated-addition model. Overall, these data demonstrate that individual phthalate with a similar mechanism of action can elicit cumulative, dose additive, and sometimes synergistic, effects on the development of male reproductive system when administered as a mixture.
邻苯二甲酸酯二酯，包括邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二乙酯（DEP），是人类普遍接触的化学物质。人类同时接触多种环境化学物质，包括 DEHP 和 DEP。关于如果同时暴露于这些化学物质，它们之间如何相互作用的信息很少。本研究调查了大鼠同时暴露于 DEP 和 DEHP 对胎儿睾丸间质细胞发育的影响。结果表明，妊娠（GD12-20）暴露于 DEP+DEHP 对胎儿睾丸间质细胞的发育具有协同作用和/或剂量相加作用。胎儿睾丸间质细胞（聚集和细胞大小）和 StAR 表达的最低观察到的不良效应水平（LOAEL）为 10mg/kg，低于单独暴露于这些化学物质时的水平。此外，对响应曲线进行数学建模支持剂量相加模型而不是综合相加模型。总的来说，这些数据表明，当作为混合物给予时，具有相似作用机制的个体邻苯二甲酸酯对男性生殖系统的发育具有累积、剂量相加和有时协同的作用。
