Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
Environ Health Perspect. 2012 Dec;120(12):1705-10. doi: 10.1289/ehp.1205182. Epub 2012 Sep 24.
Di(2-ethylhexyl) phthalate (DEHP), used primarily as a plasticizer for polyvinyl chloride, is found in a variety of products. Previous studies have quantified human exposure by back calculating intakes based on DEHP metabolite concentrations in urine and by determining concentrations of DEHP in exposure media (e.g., air, food, dust).
To better understand the timing and extent of DEHP exposure, we used a simple pharmacokinetic model to "reconstruct" the DEHP dose responsible for the presence of DEHP metabolites in urine.
We analyzed urine samples from eight adults for four DEHP metabolites [mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-carboxypentyl) phthalate]. Participants provided full volumes of all voids over 1 week and recorded the time of each void and information on diet, driving, and outdoor activities. Using a model previously calibrated on a single person self-dosed with DEHP in conjunction with the eight participants' data, we used a simple trial-and-error method to determine times and doses of DEHP that resulted in a best fit of predicted and observed urinary concentrations of the metabolites.
The average daily mean and median reconstructed DEHP doses were 10.9 and 5.0 µg/kg-day, respectively. The highest single modeled dose of 60 µg/kg occurred when one study participant reported consuming coffee and a bagel with egg and sausage that was purchased at a gas station. About two-thirds of all modeled intake events occurred near the time of reported food or beverage consumption. Twenty percent of the modeled DEHP exposure occurred between 2200 hours and 0500 hours.
Dose reconstruction using pharmacokinetic models-in conjunction with biomonitoring data, diary information, and other related data-can provide a powerful means to define timing, magnitude, and possible sources of exposure to a given contaminant.
邻苯二甲酸二（2-乙基己基）酯（DEHP）主要用作聚氯乙烯的增塑剂，存在于多种产品中。先前的研究通过根据尿液中 DEHP 代谢物浓度反推摄入量以及确定暴露介质（如空气、食物、灰尘）中的 DEHP 浓度来量化人体接触量。
为了更好地了解 DEHP 暴露的时间和程度，我们使用简单的药代动力学模型“重建”导致尿液中存在 DEHP 代谢物的 DEHP 剂量。
我们分析了 8 名成年人的尿液样本中的四种 DEHP 代谢物[邻苯二甲酸单（2-乙基己基）酯、邻苯二甲酸单（2-乙基-5-羟基己基）酯、邻苯二甲酸单（2-乙基-5-氧代己基）酯和邻苯二甲酸单（2-乙基-5-羧基戊基）酯]。参与者提供了一周内所有尿液的全部量，并记录了每次排尿的时间以及饮食、驾驶和户外活动的信息。我们使用之前在一个人身上自我服用 DEHP 时校准的模型，并结合八名参与者的数据，使用简单的试错法确定导致预测和观察到代谢物尿液浓度最佳拟合的时间和 DEHP 剂量。
平均每日平均和中位数重建的 DEHP 剂量分别为 10.9 和 5.0 µg/kg-day。当一名研究参与者报告食用在加油站购买的含有鸡蛋和香肠的咖啡和百吉饼时，最高的单次模型剂量为 60 µg/kg。大约三分之二的所有模型摄入事件发生在报告的食物或饮料消费附近。20%的模型 DEHP 暴露发生在 2200 时至 0500 时之间。
使用药代动力学模型（结合生物监测数据、日记信息和其他相关数据）进行剂量重建，可以为定义暴露于特定污染物的时间、程度和可能来源提供有力手段。
