Use of Di(2-Ethylhexyl) Phthalate-Containing Medical Products and Urinary Levels of Mono(2-Ethylhexyl) Phthalate in Neonatal Intensive Care Unit Infants
Green, Ronald, Hauser, Russ, Calafat, Antonia M., Weuve, Jennifer, Schettler, Ted, Ringer, Steven, Huttner, Kenneth, Hu, Howard, Environmental Health Perspectives
OBJECTIVE: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in medical products made with polyvinyl chloride (PVC) plastic and may be toxic to humans. DEHP is lipophilic and binds noncovalently to PVC, allowing it to leach from these products. Medical devices containing DEHP are used extensively in neonatal intensive care units (NICUs). Among neonates in NICUs, we studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP.
DESIGN: We used a cross-sectional design for this study.
PARTICIPANTS: We studied 54 neonates admitted to either of two level III hospital NICUs for at least 3 days between 1 March and 30 April 2003.
MEASUREMENTS: A priori, we classified the infants' exposures to DEHP based on medical products used: The low-DEHP exposure group included infants receiving primarily bottle and/or gavage feedings; the medium exposure group included infants receiving enteral feedings, intravenous hyperalimentation, and/or nasal continuous positive airway pressure; and the high exposure group included infants receiving umbilical vessel catheterization, endotracheal intubation, intravenous hyperalimentation, and indwelling gavage tube. We measured MEHP in the infants' urine using automated solid-phase extraction/isotope dilution/high-performance liquid chromatography/ tandem mass spectrometry.
RESULTS: Urinary MEHP levels increased monotonically with DEHP exposure. For the low-, medium-, and high-DEHP exposure groups, median (interquartile range) MEHP levels were 4 (18), 28 (58), and 86 ng/mL (150), respectively (p = 0.004). After adjustment for institution and sex, urinary MEHP levels among infants in the high exposure group were 5.1 times those among infants in the low exposure group (p = 0.03).
CONCLUSION: Intensive use of DEHP-containing medical devices in NICU infants results in higher exposure to DEHP as reflected by elevated urinary levels of MEHP.
KEY WORDS: di(2-ethylhexyl) phthalate, hospital equipment and supplies, mono(2-ethylhexyl) phthalate, neonatal intensive care units, newborn infants.
doi:10.1289/ehp.7932 available via http://dx.doi.org/[Online 8 June 2005]
Di(2-ethylhexyl) phthalate (DEHP) is an aromatic diester used primarily to soften and plasticize the rigid polymer polyvinyl chloride (PVC); DEHP may represent between 20 and 40% of the finished weight of the plastic (Jaeger and Rubin 1973). Among other properties, DEHP imparts to PVC flexibility, strength, optical clarity, and resistance to broad-range temperature variations (Shea 2003). In its pure form, DEHP is a clear, oily liquid, which is highly lipophilic (fat soluble) and poorly soluble in water. In PVC plastic, DEHP resides in the PVC matrix as a semisolid and readily migrates out of the plastic into blood or other lipid-containing solutions in contact with the plastic, a phenomenon observed with blood stored in PVC bags (Peck and Albro 1982; Rock et al. 1984). Because of its versatile properties, DEHP is also found in many commercial and household products such as vinyl floor and wall coverings, furniture, raincoats, and shower curtains, as well as cosmetics, personal care products, and food packaging [Agency for Toxic Substances and Disease Registry (ATSDR) 2002].
DEHP has been used as a plasticizer in a variety of medical products, such as bags containing blood, plasma, intravenous fluids, and total parenteral nutrition, tubing associated with their administration, nasogastric tubes, enteral feeding tubes, umbilical catheters, extracorporeal membrane oxygenation (ECMO) circuit tubing, hemodialysis tubing, respiratory masks, endotracheal tubes, and examination gloves. The rate of DEHP leaching varies not only with the type of solution in contact with the plastic material but also with storage and temperatures at the time of use, storage time, and percent DEHP in the plastic product (Marcel 1973). …