Reproductive Toxicology Branch, TAD, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Reprod Toxicol. 2010 Sep;30(2):261-70. doi: 10.1016/j.reprotox.2010.06.001. Epub 2010 Jun 15.
Risk assessments are typically conducted on a chemical-by-chemical basis; however, many regulatory bodies are developing frameworks for assessing the cumulative risk of chemical mixtures of chemicals. The current investigation examined how chemicals that disrupt rat sex differentiation via two diverse mechanisms disrupt F1 male rat reproductive development, when administered together orally on days 14-18 of gestation. Experiment 1 used a mixture of 50 mg/kg-d procymidone and 500 mg/kg-d dibutyl phthalate (DBP), whereas experiment 2 used 150 mg/kg-d procymidone and 1125 mg/kg-d DBP (top dose), or 0, 4.17, 8.33, 16.7, 33.3, 50, 66.7, and 83.3% of the top dose. When we compared the dose and response addition predictions to the observed effects we found that dose addition models were more accurate than response addition models, indicating that compounds that act by different mechanisms of toxicity produce cumulative dose-additive effects.
风险评估通常是针对单个化学物质进行的；然而，许多监管机构正在制定评估化学混合物累积风险的框架。本研究考察了通过两种不同机制干扰大鼠性别分化的化学物质在妊娠第 14-18 天经口同时给药时，如何干扰 F1 雄性大鼠的生殖发育。实验 1 使用了 50mg/kg-d 菌核净和 500mg/kg-d 邻苯二甲酸二丁酯（DBP）的混合物，而实验 2 使用了 150mg/kg-d 菌核净和 1125mg/kg-d DBP（最高剂量），或 0、4.17、8.33、16.7、33.3、50、66.7 和 83.3%的最高剂量。当我们将剂量-反应加和预测与观察到的效应进行比较时，我们发现剂量-反应加和模型比反应加和模型更准确，这表明作用机制不同的化合物产生累积的剂量加和效应。
