Bisphenol A levels in blood depend on age and exposure

Mielke, Hans; Gundert‐Remy, Ursula

doi:10.1016/j.toxlet.2009.06.861

“…C'est ainsi que pour la DJA, la clairance que nous avons estimée (24.74mL/kg/min) permet de prédire une concentration plasmatique de 1,4 ng/mL et en prenant en compte une biodisponibilité par voie orale de 5%, les concentrations plasmatiques ne devraient pas dépasser 70 pg/mL. Cette estimation est similaire à celle obtenue par Mielke et Gundert-Remy qui ont prédit des concentrations plasmatiques de BPA à l'équi-libre chez l'homme de l'ordre de 2,6 pg/mL mais pour une dose ingérée de 1µg/kg/j (Mielke & Gundert-Remy, 2009). Ces valeurs ne sont pas cohérentes avec celles rapportées dans les études d'épidémio-surveillance qui font état de concentrations plasmatiques qui peuvent atteindre de 2 à 4 ng/mL.…”

Section: Discussionunclassified

Disposition du bisphénol A chez le cheval : établissement d’une relation allométrique chez les mammifères

Chevallereau¹

2014

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Pharmacokinetic of bisphenol a in horse : etablishment of an allometric relation for mammals. This thesis aimed at describing the BPA pharmacokinetic parameters in the horse, in order to complement the allometric approach of its clearance previously established from the data obtained to five mammals species and, thus, to predict its clearance in man. The average clearance of the BPA in horse was estimated at 6,1L/min. This value enabled us to estimate the BPA clearance in man by interpolation of the allometric relation which binds the BPA clearance to the physical weight of species, to 1,7L/min for a 70kg man, that is 24,74mL/(kg. min). This pharmacokinetic data is significant to interpret the results of biosurveillance studies and to predict the levels of human internal exposure at the BPA within the context of risks related to man exposure at this xenœstrogene.

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“…The difference in the children/adult ratio between the two studies (about 3 in Mielke and Gundert-Remy (2009) and in the range 2-11 in Edginton and Ritter (2009), depending on different ages) may be explained with both the pattern of exposure and the consideration of sulfation in BPA metabolism. The simulation by Mielke and Gundert-Remy suggests that the well-expressed sulfation activity in the newborn can counteract at least partly the lower glucuronidation activity in neonates, as already highlighted in the EFSA opinion of 2008.…”

Section: Human Physiologically Based Pharmacokinetic (Pbpk) Modellingmentioning

confidence: 94%

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

Flavourings¹

2010

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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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“…This pattern is the one which has been used in human PBPK models to account for possible limited UGT activity for BPA conjugation during early life (Edginton and Ritter, 2009;Mielke and Gundert-Remy, 2009). Notably, most information on UGT ontogeny refers to the liver, which is usually endowed with the highest glucuronidation activity.…”

Section: The Enzymes Involved In Bpa Biotransformationmentioning

confidence: 99%

“…In two recent studies (Edginton and Ritter, 2009;Mielke and Gundert-Remy, 2009), physiologically based pharmacokinetic (PBPK) modelling was applied to estimate levels of BPA in the blood in young children. Both studies used a similar approach, assessing the age dependence of the toxicokinetics of BPA and its glucuronidated metabolite, by using a human based model.…”

Section: Human Physiologically Based Pharmacokinetic (Pbpk) Modellingmentioning

confidence: 99%

Untitled

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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Bisphenol A levels in blood depend on age and exposure

Cited by 125 publications

References 63 publications

Disposition du bisphénol A chez le cheval : établissement d’une relation allométrique chez les mammifères

Disposition du bisphénol A chez le cheval : établissement d’une relation allométrique chez les mammifères

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

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