Assessing Gestational Exposure to Di(2-Ethylhexyl) Phthalate Using Meconium

Abstract

P-132 Introduction: Phthalate diesters are multifunctional chemicals used as plasticizers, solvents or additives in a wide spectrum of commercial applications. For example, di(2-ethylhexyl) phthalate (DEHP) is a primary component in polyvinyl chloride plastics used in household products, toys, floor tiles, furniture upholstery, blood storage bags, and medical devices. DEHP and other phthalates are metabolized to their hydrolytic monoesters, which can be further metabolized to other oxidative products. Animal studies suggest that some phthalates, including DEHP, and their metabolites are reproductive and developmental toxicants. Therefore, assessing gestational exposure to phthalates is of interest. Methods: Meconium, which begins to accumulate in the human fetus at approximately week 16 of gestation and is not excreted until after delivery, could be a valid dosimeter of prenatal exposure to phthalates. To explore this hypothesis, we conducted a pilot study and measured mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic monoester of DEHP, and three DEHP oxidative metabolites, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), in human meconium samples (0.5 g). Interfering biomolecules were removed from the meconium by centrifugation followed by automated off-line solid phase extraction (SPE) of the supernatant. The phthalate metabolites in the supernatant extract were pre-concentrated by on-line SPE before separation by reversed phase high performance liquid chromatography and detection by isotope-dilution tandem mass spectrometry. Results: The four DEHP metabolites were frequently detected. MEHP was detected in all of the samples analyzed. The concentrations of DEHP oxidative metabolites varied widely; MECPP was the oxidative metabolite found at the highest concentrations. Discussion and Conclusions: Interestingly, the ratios of oxidative metabolite concentrations were quite consistent, suggesting that when MEHP is further metabolized, oxidative metabolites are formed consistently among individuals. Meconium contains enzymes capable of hydrolyzing DEHP to MEHP. Therefore, some of the MEHP present in the meconium may have resulted from the contamination of the meconium with the ubiquitous DEHP during sampling, storage or analysis. The oxidative metabolites cannot be formed by the meconium enzymes. Therefore, concentrations of the DEHP oxidative metabolites in meconium may be a more selective measure of DEHP exposure than the hydrolytic monoester metabolite MEHP. The relevance of the oxidative metabolites of DEHP as useful biomarkers for exposure to phthalates in non-conventional biological matrices will be discussed.