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

Overview

Journal Environ Health Perspect

Date 2012 Sep 27

PMID 23010619

Citations 9

Authors

Matthew Lorber

Antonia M Calafat

Affiliations

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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.

Citing Articles

Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice.

Liu S, Wang K, Svoboda L, Rygiel C, Neier K, Jones T Environ Epigenet. 2021; 7(1):dvab004.

PMID: 33986952 PMC: 8107644. DOI: 10.1093/eep/dvab004.

Short- and long-term effects of perinatal phthalate exposures on metabolic pathways in the mouse liver.

Neier K, Montrose L, Chen K, Malloy M, Jones T, Svoboda L Environ Epigenet. 2021; 6(1):dvaa017.

PMID: 33391822 PMC: 7757125. DOI: 10.1093/eep/dvaa017.

Longitudinal Metabolic Impacts of Perinatal Exposure to Phthalates and Phthalate Mixtures in Mice.

Neier K, Cheatham D, Bedrosian L, Gregg B, Song P, Dolinoy D Endocrinology. 2019; 160(7):1613-1630.

PMID: 31125050 PMC: 6589074. DOI: 10.1210/en.2019-00287.

Systematic reviews and meta-analyses of human and animal evidence of prenatal diethylhexyl phthalate exposure and changes in male anogenital distance.

Dorman D, Chiu W, Hales B, Hauser R, Johnson K, Mantus E J Toxicol Environ Health B Crit Rev. 2018; 21(4):207-226.

PMID: 30199328 PMC: 6786271. DOI: 10.1080/10937404.2018.1505354.

Perinatal exposures to phthalates and phthalate mixtures result in sex-specific effects on body weight, organ weights and intracisternal A-particle (IAP) DNA methylation in weanling mice.

Neier K, Cheatham D, Bedrosian L, Dolinoy D J Dev Orig Health Dis. 2018; 10(2):176-187.

PMID: 29991372 PMC: 6329673. DOI: 10.1017/S2040174418000430.

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