Perioperative Exposure to Suspect Neurotoxicants From Medical Devices in Newborns With Congenital Heart Defects

Gaynor, J. William; Ittenbach, Richard F.; Calafat, Antònia M.; Burnham, Nancy; Bradman, Asa; Bellinger, David C.; Henretig, Frederick M.; Wehrung, Erin E.; Ward, J. Laurenson; Russell, William; Spray, Thomas L.

doi:10.1016/j.athoracsur.2018.06.035

Cited by 32 publications

(30 citation statements)

References 32 publications

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“…However, a recent study carried out specifically in newborns in cardiac surgery showed that extracoporeal circulation medical devices remain highly exposed to DEHP. Indeed, Gaynor et al (2019) [41] demonstrated that the level of 5-OH-MEHP passes from 0.01 µg/mL to 0.229 µg/mL after cardiopulmonary bypass. Our study showed that MEHP had partial agonist effects in the T-screen bioassay, suggesting an action on TRs at concentrations of 10 µg/mL to 20 µg/mL.…”

Section: In Vitro Data Versus Biomonitoring Valuesmentioning

confidence: 99%

Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies

et al. 2021

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Plasticizers added to polyvinylchloride (PVC) used in medical devices can be released into patients’ biological fluids. Di-(2-ethylhexyl)phthalate (DEHP), a well-known reprotoxic and endocrine disruptor, must be replaced by alternative compounds. Di-(2-ethylhexyl) terephthalate (DEHT) is an interesting candidate due to its lower migration from PVC and its lack of reprotoxicity. However, there is still a lack of data to support the safety of its human metabolites with regard to their hormonal properties in the thyroid system. The effects of DEHT metabolites on thyroid/hormone receptors (TRs) were compared in vitro and in silico to those of DEHP. The oxidized metabolites of DEHT had no effect on T3 receptors whereas 5-hydroxy-mono-(ethylhexyl)phthalate (5-OH-MEHP) appeared to be primarily an agonist for TRs above 0.2 µg/mL with a synergistic effect on T3. Monoesters (MEHP and mono-(2-ethylhexyl)terephthalate, MEHT) were also active on T3 receptors. In vitro, MEHP was a partial agonist between 10 and 20 µg/mL. MEHT was an antagonist at non-cytotoxic concentrations (2–5 µg/mL) in a concentration-dependent manner. The results obtained with docking were consistent with those of the T-screen and provide additional information on the preferential affinity of monoesters and 5-OH-MEHP for TRs. This study highlights a lack of interactions between oxidized metabolites and TRs, confirming the interest of DEHT.

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Section: In Vitro Data Versus Biomonitoring Valuesmentioning

confidence: 99%

Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies

et al. 2021

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“…While environmental exposure to BPA is continuous at a relatively low dose (Koch & Calafat, 2009; Vandenberg et al, 2007, 2010)—clinical (Calafat et al, 2009; Duty et al, 2013; Gaynor et al, 2018) and occupational (C. J. Hines et al, 2018; Ribeiro, Ladeira, & Viegas, 2017) environments can result in higher BPA exposures (Table 1) (Calafat et al, 2009; Duty et al, 2013; Gaynor et al, 2018; Huygh et al, 2015). BPA has been detected in 60% of neonatal intensive care unit (ICU) supplies, and experimental studies have identified estrogenic activity in >25% of extracts from these items (Iribarne‐Durán et al, 2019).…”

Section: Bisphenol‐amentioning

confidence: 99%

“…In the final product, DEHP can contribute up to 40% of the finished weight of plastic medical products (e.g., intravenous fluid bags, blood storage bags), and up to 80% of the weight of flexible medical tubing (Halden, 2010; Jaeger & Rubin, 1973, 2010; Plonait, Nau, Maier, Wittfoht, & Obladen, 1993). Since phthalates are not covalently bound to PVC, these chemical additives are known to leach or migrate into surrounding solutions, including blood (Table 2) (Barry et al, 1989; D'Alessandro et al, 2019; Demirel et al, 2016; Gaynor et al, 2018; Green et al, 2005; Kaestner et al, 2020; Karle et al, 1997; Mallow & Fox, 2014; Münch et al, 2020; Peck et al, 1979; Rael et al, 2009; Sjöberg, Bondesson, Sedin, & Gustafsson, 1985; Sjoberg et al, 1985; Stroustrup et al, 2018; Su et al, 2012; Takatori et al, 2008; van der Meer et al, 2014). Moreover, DEHP leaching is exacerbated under conditions of prolonged use, mechanical stress, higher temperature and/or in the presence of lipid‐containing fluids.…”

Section: Di‐2‐ethylhexyl Phthalatementioning

confidence: 99%

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes

Ramadan

Cooper

Posnack

2020

Birth Defects Research

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Phthalates and bisphenols are high production volume chemicals that are used in the manufacturing of consumer and medical products. Given the ubiquity of bisphenol and phthalate chemicals in the environment, biomonitoring studies routinely detect these chemicals in 75-90% of the general population. Accumulating evidence suggests that such chemical exposures may influence human health outcomes, including cardiovascular health. These associations are particularly worrisome for sensitive populations, including fetal, infant and pediatric groups-with underdeveloped metabolic capabilities and developing organ systems. In the presented article, we aimed to review the literature on environmental and clinical exposures to bisphenols and phthalates, highlight experimental work that suggests that these chemicals may exert a negative influence on cardiovascular health, and emphasize areas of concern that relate to vulnerable pediatric groups. Gaps in our current knowledge are also discussed, so that future endeavors may resolve the relationship between chemical exposures and the impact on pediatric cardiovascular physiology.

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“…Phthalate exposures increase after neonatal cardiac surgical treatment, 37 and gestational exposures in the general population have been associated with neurodevelopmental outcomes in children. [38][39][40][41][42]…”

Section: Limitationsmentioning

confidence: 99%

Association of Neurodevelopmental Outcomes With Environmental Exposure to Cyclohexanone During Neonatal Congenital Cardiac Operations

et al. 2020

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IMPORTANCE Cyclohexanone is an industrial solvent used as a coupling agent in medical plastics. Perioperative exposure to cyclohexanone could play a role in lower scores on measures of neurodevelopmental outcomes after neonatal cardiac operations. OBJECTIVE To examine the presence and association of serum cyclohexanone level with neonatal cardiac operations and neurodevelopmental outcomes. DESIGN, SETTING, AND PARTICIPANTS This ad hoc secondary analysis used data from the Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass randomized clinical trial.

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Perioperative Exposure to Suspect Neurotoxicants From Medical Devices in Newborns With Congenital Heart Defects

Cited by 32 publications

References 32 publications

Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies

Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes

Association of Neurodevelopmental Outcomes With Environmental Exposure to Cyclohexanone During Neonatal Congenital Cardiac Operations

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