Exposure to Phthalates in Neonatal Intensive Care Unit Infants: Urinary Concentrations of Monoesters and Oxidative Metabolites
Weuve, Jennifer, Sanchez, Brisa N., Calafat, Antonia M., Schettler, Ted, Green, Ronald A., Hu, Howard, Hauser, Russ, Environmental Health Perspectives
OBJECTIVE: We previously demonstrated that among 54 infants in neonatal intensive care units, exposure to polyvinyl chloride plastic medical devices containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) is associated with urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), a DEHP metabolite. In this follow-up report, we studied the neonates' exposure to DEHP-containing devices in relation to urinary concentrations of two other DEHP metabolites, and to urinary concentrations of metabolites of dibutyl phthalate (DBP) and benzylbutyl phthalate (BzBP), phthalates found in construction materials and personal care products.
MEASUREMENTS: A priori, we classified the intensiveness of these 54 infants' exposure to DEHP-containing medical products. We measured three metabolites of DEHP in infants' urine: MEHP and two of its oxidative metabolites, mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured monobutyl phthalate (MBP), a metabolite of DBP, and monobenzyl phthalate (MBzP), a metabolite of BzBP.
RESULTS: Intensiveness of DEHP-containing product use was monotonically associated with all three DEHP metabolites. Urinary concentrations of MEHHP and MEOHP among infants in the high-DEHP-intensiveness group were 13-14 times the concentrations among infants in the low-intensiveness group (p [less than or equal to] 0.007). Concentrations of MBP were somewhat higher in the medium-and high-DEHP-intensiveness group; MBzP did not vary by product use group. Incorporating all phthalate data into a structural equation model confirmed the specific monotonic association between intensiveness of product use and biologic measures of DEHP.
CONCLUSION: Inclusion of the oxidative metabolites MEHHP and MEOHP strengthened the association between intensiveness of product use and biologic indices of DEHP exposure over that observed with MEHP alone.
KEY WORDS: di(2-ethylhexyl) phthalate (DEHP), infants, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), monobenzyl phthalate (MBzP), monobutyl phthalate (MBP), neonatal intensive care unit (NICU), phthalate, structural equation model. Environ Health Perspect 114:1424-1431 (2006). doi:10.1289/ehp.9169 available via http://dx.doi.org/ [Online 8 June 2006]
Phthalates are industrial chemical additives used primarily to soften and confer flexibility to plastics. In their pure form, phthalates are clear, oily liquids that are highly lipophilic and poorly soluble in water. They are a key component in a wide range of products, including but not limited to flexible polyvinyl chloride (PVC) plastics, vinyl tile, food packaging, insecticides, pharmaceuticals, and personal care products [Agency for Toxic Substances and Disease Registry (ATSDR) 2001, 2002; National Toxicology Program Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) 2003; Schettler 2006]. Because they are not chemically bound to the plastics, phthalates can be released as the products are used and discarded. The Centers for Disease Control and Prevention (CDC) measured urinary concentrations of phthalate metabolites in representative samples of the noninstitutionalized U.S. population, and for several phthalates, detectable levels of their metabolites were present in more than three-quarters of the participants (CDC 2005). These data confirm that the general population in the United States is exposed to phthalates.
Some animal studies suggest that at least some phthalates are developmental and reproductive toxicants (ATSDR 2001, 2002; NTPCERHR 2000a, 2000b, 2003, 2005), although the effects on human health have not been extensively described, and the effective toxic doses of phthalates in these animal studies are many times higher than typical human exposures. Unusually high levels of exposure may occur, however, among infants admitted to neonatal intensive care units (NICUs), because of their small body mass and the use of phthalate-containing medical devices in their care (Calafat et al. …