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. 2012 Dec;120(12):1705-10.
doi: 10.1289/ehp.1205182. Epub 2012 Sep 24.

Dose reconstruction of di(2-ethylhexyl) phthalate using a simple pharmacokinetic model

Matthew Lorber  1 , Antonia M Calafat
Affiliations

Dose reconstruction of di(2-ethylhexyl) phthalate using a simple pharmacokinetic model

Matthew Lorber et al. Environ Health Perspect. 2012 Dec.

Abstract

Background: 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).

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Conflict of interest statement

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the U.S. Environmental Protection Agency or the CDC.

The authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Observed and predicted urinary concentrations of the four DEHP metabolites for subject 1 throughout the study period. (A) MEHP. (B) MEHHP. (C) MECPP. (D) MEOHP. Corresponding figures for subjects 2–8 are available in Supplemental Material, Figures S1–S7 (http://dx.doi.org/10.1289/ehp.1205182).
Figure 2
Figure 2
Correlations between observed and predicted urinary concentrations of the four DEHP metabolites for all 427 urination events for the eight study participants. (A) MEHP. (B) MEHHP. (C) MECPP. (D) MEOHP.
Figure 3
Figure 3
Average hourly model-based DEHP intakes for the eight study participants. Dotted lines highlight intakes that occurred between 0800 and 1700 hours (6.7 µg/kg‑day of the 10.9‑µg/kg‑day total).
Figure 4
Figure 4
Observed (Obs) and predicted (Pred) urinary concentrations of MEHHP for the individual with highest nighttime DEHP intake (subject 3). Boxes indicate time of day, volume of urine, and MEHHP urinary concentrations (µg/L). Circles show time of day and magnitude of the calibrated exposure events.
See this image and copyright information in PMC

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