Dose Reconstruction of Di(2-ethylhexyl) Phthalate Using a Simple Pharmacokinetic Model

Matthew Lorber¹ and Antonia M. Calafat²

¹Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA; ²National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

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.

Key words: DEHP, dose reconstruction, pharmacokinetic model, phthalate exposure. 

Environ Health Perspect 120:1705–1710 (2012). http://dx.doi.org/10.1289/ehp.1205182 [Online 24 September 2012]

Address correspondence to M. Lorber, 1200 Pennsylvania Ave. NW, Washington, DC, 20460 USA. Telephone: (703) 347-8535. Fax: (703) 347-8692. E-mail: lorber.matthew@epa.gov

Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205182).

We thank M. Silva, E. Samandar, and J. Preau [Centers for Disease Control and Prevention (CDC)] for their assistance in measuring the urinary concentrations of DEHP metabolites, and A. Sjödin for designing the original study to assess the variability of urinary concentrations of polycylic aromatic hydrocarbon metabolites and for providing the samples that we used for the present analysis. We also thank P. Lioy (Environmental and Occupational Health Sciences Institute, Robert Wood Johnson Medical School and Rutgers University) for constructive discussions during manuscript development.

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.

Received 7 March 2012; Accepted 24 September 2012; Online 24 September 2012.