Exposure to Di-(2-Ethylhexyl) Phthalate Among Premature Neonates in a Neonatal Intensive Care Unit

Abstract

ABSTRACT. Objective. Premature neonates who spend time in a neonatal intensive care unit may be at increased risk of adverse health effects from exposure to di-(2-ethylhexyl) phthalate (DEHP) because of their increased risk of high exposure, their small body size, and their physical condition. DEHP, a reproductive toxicant in animals, is a major component in polyvinyl chloride (PVC) plastics, which are frequently used in medical tubing and blood storage bags. DEHP is not covalently bound to PVC, and it may be easily released from the PVC medical devices. The objective of this study was to determine whether premature infants who undergo medical procedures, such as blood transfusions, intravenous therapy, enteral and parenteral nutrition support, and dialysis, are at increased risk of exposure to DEHP than the general population. Because of their smaller size, children and especially premature and small infants may receive a larger dose of DEHP on a milligram per kilogram basis than adults when the same-size medical device is used for all ages.Methods. Premature neonates who seemed to have the potential to be on intravenous infusion for >2 weeks and were expected to survive were eligible for enrollment in the study. We assessed exposure to DEHP in 6 premature newborns by measuring in 41 urine samples the levels of 3 DEHP metabolites: mono-(2-ethylhexyl) phthalate (mEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP).Results. mEHHP and mEOHP were detected in all 41 urine samples, and mEHP was detected in 33. Because only 33 of the samples had detectable amounts for all 3 metabolites, statistical analyses were limited to those 33. The levels of all 3 DEHP metabolites varied widely, and the urinary mean and median concentrations of mEOHP and mEHHP were 1 order of magnitude higher than those for mEHP. Furthermore, the geometric mean urinary concentrations of mEOHP (1617 ng/mL), mEHHP (2003 ng/mL), and mEHP (100 ng/mL) in these 6 premature infants who underwent intensive therapeutic interventions were found to be severalfold higher than in the US general population (for mEHP, geometric mean in those 6 years and older was 3.43 ng/mL).Conclusions. This study provides the first quantitative evidence confirming that newborns who undergo intensive therapeutic medical interventions are exposed to higher concentrations of DEHP than the general population. Although the overall benefits of medical procedures using PVC devices outweigh the risks associated with exposure to DEHP, more research is needed to determine whether infants and children who undergo intensive therapeutic interventions using DEHP-containing devices are at higher risk for altered health outcomes than infants and children who undergo similar treatments but are not potentially exposed to DEHP. Pediatrics 2004;113:e429 -e434. URL: http://www.pediatrics.org/ cgi/content/full/113/5/e429; DEHP, phthalate, plasticizer, urine, biomarker.ABBREVIATIONS. PVC, polyvinyl chloride; DEHP, di-(2-ethylhexyl) phthalate; mEHP,...

Concentrations of Bisphenol A and Seven Other Phenols in Pooled Sera from 3–11 Year Old Children: 2001–2002 National Health and Nutrition Examination Survey

“…Because conjugation (i.e., Phase II biotransformation) is considered to be a detoxification process (47,48), the presence of the unconjugated (i.e., free) species in circulation can be taken to reflect exposure to the biologically active form of the compounds (35, 49-51). Of note, even young children soon after birth appear to have some capacity to metabolize nonpersistent compounds to their corresponding conjugates, as suggested from studies on exposure to BPA, triclosan, benzophenone-3, methyl-and propyl-parabens and phthalates in premature infants (39,52). Therefore, we also measured the free serum concentrations of BPA and the other phenols in these pooled serum samples ( Table 2).…”

Response to ‘Dr Raymond David, BASF Corporation’

“…The maximum estimated daily DEHP intake was 2300 µg/kg bw/d, which is separated from the NOAEL (4.8 mg/kg bw/d) for testicular and developmental toxicity in rats only by a factor of two (Wolfe and Layton 2003). Based on the data of Calafat et al (2004a) even higher maximal DEHP exposures up to 6000 µg/kg bw/d have been estimated well above the NOAEL observed in the rat study (CERHR 2005).…”

“…The urinary concentrations of DEHP metabolites in neonates undergoing intensive medical interventions have been found to vary widely and reach levels that are much higher than those found in the general population (Table 9). Compared to adults the ratios among the metabolites are shifted in favour of the oxidative metabolites with 5cx-MEPP being the main metabolite (Calafat et al 2004a, Koch et al 2006). percentile indicate a great variability in DEHP exposure for newborns in intensive care, which may reflect the variety and intensity of the medical procedures performed.…”

Urine-sampling methods for environmental chemicals in infants and young children

“…The cotton insert may be frozen and shipped to the laboratory, where it is centrifuged to extract urine, although the volume recovered is often small (Calafat et al, 2004). Urine may also be extracted from the cotton pad through use of a disposable syringe on-site (Hu et al, 2000;Shalat et al, 2003;Zohouri et al, 2006) by placing the gauze into an empty syringe, replacing the plunger and squeezing urine into vials (Weuve et al, 2006).…”