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Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management.

ABSTRACT: Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates' exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers' exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used for care management, and (2) by measuring the patients' urinary levels of each plasticizers' metabolites. 104 neonates were enrolled. They were exposed to di-isononylphthalate (DINP), especially via transfusion and infusion MD, and to DEHP via ECMO (Extra Corporeal Membrane Oxygenation) and respiratory assistance MD. Mean exposure doses exceeded the derived no-effect level of DINP and DEHP by a 10-fold and a 1000-fold factor. No PVC MD were plasticized with di-isononylcyclohexane-1,2-dicarboxylate (DINCH). High urinary concentrations of DEHP metabolites were directly correlated with DEHP exposure through ECMO MD. Urinary concentrations of DINP metabolites in transfused patients were also high. DINCH metabolites were found in urine, suggesting another route of exposure. Neonates in NICU are considerably exposed to plasticizers, with magnitudes varying with the type of MD used. The high exposure to DEHP and DINP leads to a risk of their metabolites' toxicity.

SUBMITTER: Bernard L

PROVIDER: S-EPMC8073472 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management.

Bernard Lise L Bouattour Yassine Y Masse Morgane M Boeuf Benoît B Decaudin Bertrand B Genay Stéphanie S Lambert Céline C Moreau Emmanuel E Pereira Bruno B Pinguet Jérémy J Richard Damien D Sautou Valérie V For The Armed Study Group

Metabolites 20210419 4

Care management of newborns in the neonatal intensive care unit (NICU) requires numerous PVC (PolyVinyl Chloride) medical devices (MD) containing plasticizers that can migrate and contaminate the patient. We measured the magnitude of neonates' exposure to plasticizers (di-ethylhexylphthalate (DEHP) and alternatives) in relation to urinary concentrations of their metabolites. Plasticizers' exposure was evaluated (1) by calculating the amounts of plasticizers prone to be released from each MD used ...[more]

PMID: 33921860

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Project description:BackgroundMedical devices (MDs) in polyvinyl chloride (PVC) are not a well-known source of exposure to plasticizers, in particular during pregnancy. Because of its toxicity, the di-(2-ethylhexyl) phthalate (DEHP) has been replaced by other plasticizers such as di (isononyl)-cyclohexane-1,2-dicarboxilic acid (DINCH), tri-octyltrimellitate (TOTM) and di-(isononyl) phthalate (DiNP). Our study aimed to quantify the plasticizers (DEHP and alternative plasticizers) contained in PVC medical devices used for hospitalised pregnant women and to describe which these MDs had been used (type, number, duration of exposure).MethodsThe plasticizers contained in the MDs used for daily care in the Obstetrics Department of a French University Hospital were extracted from PVC (after contact with a chloroform solution), identified and quantified by gas-chromatography-mass-spectrometry analysis. A total of 168 pregnant women hospitalised in the Obstetrics Department with at least one catheter were included in the observational study. The median number of MDs containing plasticizers used and the daily duration of exposure to the MDs were compared in three groups of pregnant women: "Pathology group" (women hospitalised for an obstetric disorder who did not give birth during this hospitalisation; n = 52), "Pathology and delivery group" (hospitalised for an obstetric disorder and who gave birth during this stay; n = 23) and "Delivery group" (admitted for planned or spontaneous delivery without obstetric disorder; n = 93).ResultsDiNP, TOTM and DINCH were the predominant plasticizers contained in the MDs at an amount of 29 to 36 g per 100 g of PVC. Women in the "Pathology group" (preterm labour or other pathology) were exposed to a median number of two MDs containing TOTM and one MD containing DiNP, fewer than those in the "Pathology and delivery group" (p < 0.05). Women in the "Pathology group" had a median exposure of 3.4 h/day to MDs containing DiNP and 8.2 h/day to MDs containing TOTM, longer than those in the "Delivery group" (p < 0.01).ConclusionsOur study shows that the medical management of pregnant women in a hospital setting entails exposure to MDs containing alternative plasticizers (DiNP, TOTM and DINCH).

Project description:BackgroundChildren who have been critically ill face long-term developmental impairments. Iatrogenic exposure to di(2-ethylhexyl)phthalate (DEHP), a plasticizer leaching from plastic indwelling medical devices used in the pediatric intensive care unit (PICU), has been associated with the pronounced attention deficit observed in children 4 years after critical illness. As concerns about DEHP toxicity increased, governmental authorities urged the phase out of DEHP in indwelling medical devices and replacement with alternative plasticizers. We hypothesized that exposure to DEHP decreased over the years, attenuating the pronounced long-term attention deficit of these vulnerable children.MethodsWe compared plasma concentrations of 3 oxidative DEHP metabolites (5cx-MEPP, 5OH-MEHP, 5oxo-MEHP) on the last PICU day in 216 patients who participated in the Tight Glucose Control study (2004-2007) and 334 patients who participated in the PEPaNIC study (2012-2015) and survived PICU stay. Corresponding minimal exposures to these metabolites (plasma concentration multiplied with number of days in PICU) were also evaluated. In patients with 4-year follow-up data, we compared measures of attention (standardized reaction times and consistency). Comparisons were performed with univariable analyses and multivariable linear regression analyses adjusted for baseline risk factors.ResultsIn the PEPaNIC patients, last PICU day plasma concentrations of 5cx-MEPP, 5OH-MEHP, 5oxo-MEHP and their sum, and corresponding minimal exposures, were reduced to 17-69% of those in the Tight Glucose Control study (p < 0.0001). Differences remained significant after multivariable adjustment (p ≤ 0.001). PEPaNIC patients did not show better attention than patients in the Tight Glucose Control study, also not after multivariable adjustment for risk factors.ConclusionExposure of critically ill children to DEHP in the PICU decreased over the years, but the lower exposure did not translate into improved attention 4 years later. Whether the residual exposure may still be toxic or whether the plasticizers replacing DEHP may not be safe for neurodevelopment needs further investigation.

Project description:Chlorinated alkyl and non-chlorinated aryl organophosphate flame retardants (OPFRs) and some brominated flame retardants (FR) were introduced as replacements for polybrominated diphenyl ethers (PBDEs) after PBDEs phase-out in 2004 and 2013. Organophosphorous (OP) insecticides are mainly used in agricultural settings since the Food Quality Protection Act of 1996 phased-out most residential uses of OP insecticides in the United States. Urinary metabolites of FRs and OPs are known exposure biomarkers to FRs and OP insecticides, respectively. For large population-based studies, concurrent quantification of these metabolites using a small urine volume is desirable, but until now was not possible. We developed an analytical approach to quantify in 0.2 mL urine 10 FRs and six OP insecticide metabolites: diphenyl phosphate, bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, bis(2-chloroethyl) phosphate, dicresyl phosphates, dibutyl phosphate, dibenzyl phosphate, 2,3,4,5-tetrabromobenzoic acid, 2-((isopropyl)phenyl)phenyl phosphate, 4-((tert-butyl)phenyl)phenyl phosphate, dimethyl phosphate, diethyl phosphate, dimethyl thiophosphate, dimethyl dithiophosphate, diethyl thiophosphate, and diethyl dithiophosphate. The method relies on enzymatic deconjugation, automated off-line solid phase extraction, high-performance liquid chromatography, and isotope dilution tandem mass spectrometry. Detection limits ranged from 0.05 to 0.5 ng mL-1, accuracy from 89 to 118%, and imprecision was <10%. . This method is the first to quantify simultaneously trace levels of 16 biomarkers of FRs and OP insecticides in only four drops of urine. We confirmed the method suitability for use in large epidemiological studies to assess background and occupational exposures to these classes of environmental pollutants by analyzing 303 samples collected from the general population and a group of firefighters. FR metabolite and DAPs concentrations in the general population group were lower than in the firefighters group, and within the ranges reported in the U.S. general population and other non-occupationally exposed populations.

Dataset Information

Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management.

Publications

Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management.

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