Summit Toxicology, LLP, Falls Church, Virginia 22044, USA.
J Expo Sci Environ Epidemiol. 2011 Nov-Dec;21(6):615-24. doi: 10.1038/jes.2011.28. Epub 2011 Aug 17.
Exposure assessment analyses conducted in Europe have concluded that the primary pathway of exposure to di(2-ethylhexyl) phthalate (DEHP) is through the diet. The purpose of this study is to evaluate whether urinary DEHP metabolite data from the 2007-2008 National Health and Nutritional Examination Survey (NHANES) demonstrate relationships with reported food-fasting time consistent with diet as the predominant exposure pathway. Previous controlled-dosing data demonstrate that DEHP metabolite concentrations in urine first rise and then decline over time, with first-order elimination becoming evident at about 6 h post exposure. Regression of the concentrations of four key DEHP metabolites vs reported fasting times between 6 and 18 h in adults resulted in apparent population-based urinary elimination half-lives, consistent with those previously determined in a controlled-dosing experiment, supporting the importance of the dietary pathway for DEHP. For fasting times less than about 6 h, sampling session (morning, afternoon, or evening) affected the measured metabolite concentrations. Evening samples showed the highest metabolite concentrations, supporting a hypothesis of recent daily dietary exposures from multiple meals, whereas morning and afternoon samples for fasting times less than 6 h were similar and somewhat lower than evening samples, consistent with less-substantial early day dietary exposure. Variations in children's bodyweight-normalized creatinine excretion and food intake rates contribute to a strong inverse relationship between urinary DEHP metabolite concentrations and age under age 18. Finally, a previously published pharmacokinetic model for DEHP demonstrates that time since previous urinary void, a parameter not measured in NHANES, is predicted to result in non-random effects on measured urinary concentrations.
欧洲进行的暴露评估分析得出结论，二-(2-乙基己基)邻苯二甲酸酯（DEHP）的主要暴露途径是通过饮食。本研究旨在评估 2007-2008 年全国健康和营养检查调查（NHANES）中的尿液 DEHP 代谢物数据是否与报告的食物禁食时间相关，这些数据是否与饮食作为主要暴露途径一致。先前的对照剂量研究表明，尿液中 DEHP 代谢物的浓度会随着时间的推移先上升后下降，在接触后约 6 小时即可明显看出一级消除。对成年人在 6 至 18 小时之间报告的禁食时间与四种关键 DEHP 代谢物浓度进行回归分析，得到了基于人群的尿液消除半衰期，与对照剂量实验中确定的半衰期一致，这支持了饮食途径对 DEHP 的重要性。对于禁食时间小于约 6 小时的情况，采样时间（上午、下午或晚上）会影响测量的代谢物浓度。晚上的样本显示出最高的代谢物浓度，支持了最近来自多顿饭的每日饮食暴露的假设，而禁食时间小于 6 小时的上午和下午样本与晚上样本相似，略低于晚上样本，这与早期饮食暴露量较少一致。儿童体重标准化肌酐排泄率和食物摄入量率的变化导致尿液 DEHP 代谢物浓度与 18 岁以下年龄呈强烈负相关。最后，先前发表的 DEHP 药代动力学模型表明，上次排尿后的时间（NHANES 未测量的参数）预计会对测量的尿液浓度产生非随机影响。
