Placental transport and in vitro effects of Bisphenol A

Mørck, Thit Juul; Sorda, Giuseppina; Bechi, Nicoletta; Rasmussen, Brian Schou; Nielsen, Jesper Bo; Ietta, Francesca; Rytting, Erik; Mathiesen, Line; Paulesu, Luana; Knudsen, Lisbeth E.

doi:10.1016/j.reprotox.2010.02.007

Cited by 176 publications

(114 citation statements)

References 51 publications

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“…Each set of cells grown on the Transwell inserts had similar TEER values. Acceptable TEER values for BeWo cell monolayers have been reported previously for the b30 clone [27,28]. These ranges of TEER values are the same which resulted in strong comparisons of transplacental permeability measured by both BeWo cell transport studies and ex vivo placental perfusions [15,29].…”

Section: Cell Culturesupporting

confidence: 66%

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

et al. 2015

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Background: Fetal arrhythmias can lead to fetal congestive heart failure and hydrops fetalis. Digoxin (the first-line treatment) has low transplacental permeability and high risk of maternal side effects. Biodegradable digoxin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles may increase digoxin transport across BeWo b30 cell monolayers (an in vitro model of trophoblast in human placenta) by reducing the drug's interaction with P-gp. Results/methodology: The nanoparticles showed high encapsulation efficiency and sustained release over 48 h. Transport studies revealed significantly increased permeability across BeWo cell layers of digoxin-loaded nanoparticles when compared with free digoxin. P-gp inhibition also increased the permeability of digoxin, but not digoxin-loaded nanoparticles. Conclusion: This represents a novel treatment strategy for fetal cardiovascular disease which may improve maternal and fetal outcomes.

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Section: Cell Culturesupporting

confidence: 66%

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

et al. 2015

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“…Exposure of pregnant women is of particular concern because of the potential health impact on the vulnerable foetus, in which exposure may inflict lifelong adverse health effects. Some of these chemicals have been shown to cross the placenta, enter the foetus and recycle via amniotic fluid (Bradman et al 2003, Mose et al 2007, Morck et al 2010. Thus, a number of chemicals measured in maternal urine, serum and breast milk have also been found in amniotic fluid, cord blood and meconium (Ikezuki et al 2002, Main et al 2006, Barr et al 2007, Jensen et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Current exposure of 200 pregnant Danish women to phthalates, parabens and phenols

Renzy-Martin

Frederiksen

Christensen³

et al. 2014

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Many phthalates, parabens and phenols are suspected to have endocrine-disrupting properties in humans. They are found in consumer products, including food wrapping, cosmetics and building materials. The foetus is particularly vulnerable and exposure to these chemicals therefore is of concern for pregnant women. We investigated current exposure to several commonly used phthalates, parabens and phenols in healthy, pregnant Danish women. A total of 200 spot urine samples were collected between 8 and 30 weeks of gestation and analysed for metabolites of ten phenols, seven parabens and 16 phthalate by liquid chromatography-tandem mass spectrometry representing 26 non-persistent compounds. The majority of analytes were present in the urine sample collected from most women who participated. Thus, in 174 of the 200 women, metabolites of more than 13 (O50%) of 26 compounds were detected simultaneously. The number of compounds detected per woman (either as the parent compound or its metabolite(s)) ranged from 7 to 21 with a median of 16. The majority of compounds correlated positively with each other within and between chemical groups, suggesting combined exposure sources. Estimated daily intakes (DIs) of phthalates and bisphenol A (BPA) were below their individual tolerable DI (TDI) and with hazard quotients below 1. In conclusion, we found detectable levels of phthalate metabolites, parabens and phenols in almost all pregnant women, suggesting combined multiple exposures. Although the estimated DI of phthalates and BPA for an individual was below TDI, our results still raise concern, as current toxicological risk assessments in humans do not take into account simultaneous exposure. The true cumulative risk for the foetus may therefore be underestimated.

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“…Data on percutaneous absorption with human in vitro reconstituted skin, were obtained with an extremely high dose of BPA (17.5 mM corresponding to 3.99 g/L, inconsistent with BPA solubility) over a 48 h period (Mørck et al, 2010). However, the exaggerated BPA application used does not allow any conclusion to be drawn from this study.…”

Section: Bpa Repeated Exposurementioning

confidence: 88%

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2010

EFSA Journal

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Bisphenol A (BPA) is used in the manufacture of plastics, to produce reusable drinking bottles, infant feeding bottles and other food storage containers. EFSA was asked to evaluate a dietary developmental neurotoxicity study in rats (Stump, 2009) and recent scientific literature (2007)(2008)(2009)(2010) in terms of relevance for the risk assessment of BPA. The impact of these studies on the current Tolerable Daily Intake (TDI) of 0.05 mg BPA/kg body weight (b.w.)/day as set by EFSA in 2006 was assessed. Advice on the Danish risk assessment underlying the Danish ban of BPA in food contact materials for infants aged 0-3 years is included. Overall, based on this comprehensive evaluation of recent toxicity data, the Panel on food contact materials, enzymes, flavourings and processing aids (CEF) concluded that no new study could be identified, which would call for a revision of the current TDI. This TDI is based on the No-Observed-Adverse-Effect-Level (NOAEL) of 5 mg/kg b.w./day from a multi-generation reproductive toxicity study in rats, and the application of an uncertainty factor of 100. This factor is regarded as conservative based on all information on BPA toxicokinetics. The Panel noted that some studies conducted on developing animals have suggested other BPA-related effects of possible toxicological relevance, in particular biochemical changes in brain, immune-modulatory effects and enhanced susceptibility to breast tumours. These studies had several shortcomings. At present the relevance of these findings for human health cannot be assessed. Should any new relevant data become available in the future, the Panel will reconsider this opinion. A minority opinion is expressed by a Panel member and presented in an Annex to this opinion. © European Food Safety Authority, 2010 KEY WORDSBisphenol A, BPA, CAS No. 00080-05-7, developmental toxicity, neurobehaviour, low dose effects. In order to provide a global view on the risk assessment of Bisphenol A, the CEF Panel decided to address the three mandates as given above in a single opinion and postponed the adoption of this comprehensive document to 23 rd September 2010.The three different questions raised by the Commission are dealt with in three different parts (PARTS I to III) of the opinion. PART IV presents an overview of the conclusions from PARTS I to III, together with an overall conclusion. PART IThe GLP compliant study by Stump (2009) was performed according to OECD guideline 426 to address any uncertainty regarding potential neurodevelopmental effects of BPA. BPA was administered daily in the diet at concentrations of 0, 0.15, 1.5, 75, 750, and 2250 mg/kg feed to female Sprague-Dawley rats from gestational day (GD) 0 to postnatal day (PND) 21. The relative estimated intakes (in mg/kg b.w./day) were 0, 0.01, 0.12, 5.85, 56.4 and 164 during gestation and 0, 0.03, 0.25, 13.1, 129 and 410 during lactation. The CEF Panel considers this treatment schedule as relevant to human exposure in utero and via either breastfeeding or infant bottle feeding (in this...

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Placental transport and in vitro effects of Bisphenol A

Cited by 176 publications

References 51 publications

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

Transport of digoxin-loaded Polymeric Nanoparticles Across BeWo cells, an In Vitro Model of Human Placental Trophoblast

Current exposure of 200 pregnant Danish women to phthalates, parabens and phenols

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