Correspondence Volume 121 | Issue 11-12 | Nov-Dec 2013
Environ Health Perspect; DOI:10.1289/ehp.1307424R
Interpreting Bisphenol A Absorption in the Canine Oral Cavity: Gayrard et al. Respond
Véronique Gayrard, Marlène Z. Lacroix, Séverine H. Collet, Catherine Viguié, Alain Bousquet-Melou, Pierre-Louis Toutain, Nicole Picard-Hagen
INRA (Institut National de la Recherche Agronomique), UMR1331 (Unité Mixe de Recherche 1331), Toxalim (Research Center in Food Toxicology), Université de Toulouse, Toulouse, France, E-mail: email@example.com
Citation: Gayrard V, Lacroix MZ, Collet SH, Viguié C, Bousquet-Melou A, Toutain PL, Picard-Hagen N. 2013. Interpreting bisphenol A absorption in the canine oral cavity: Gayrard et al. respond [letter]. Environ Health Perspect 121:A323–A324; http://dx.doi.org/10.1289/ehp.1307424R
The authors declare they have no actual or potential competing financial interests.
Published: 27 November 2013
The comments by Teeguarden et al. offer us the opportunity to explain some possible pharmacokinetic (PK) and PK/pharmacodynamic (PK/PD) consequences of sublingual bisphenol A (BPA) absorption. Nowhere in our paper (Gayrard et al. 2013) did we report that “nanograms-per-milliliter serum concentrations of BPA resulting from sublingual absorption are plausible in humans.”
Using elementary PK computation, Teeguarden et al. concluded that peak concentrations in mixed systemic serum should be < 0.1 ng/mL even after a bolus intraveneous (iv) administration based on the 95th percentile of the aggregate daily U.S. human exposure (0.22 μg/kg body weight). Using the same scaling approach but considering a subpopulation of children 6–11 years of age with a 95th percentile of 0.481 µg/kg/day (Lakind and Naiman 2011), and taking into account our own data from dogs, the maximum initial plasma BPA concentration would be about 0.6 ng/mL. More important, what should be highlighted from our study is that, within 1 hr after administration of the low BPA dose (0.05 mg/kg), the BPA concentrations in blood collected from the jugular vein (i.e., downstream from the BPA absorption site) were higher than those measured after the corresponding iv administration (see Figure 1B of Gayrard et al. 2013). Teeguarden et al. should not be confused by the question of validity of a sampling site for making a sound pharmacokinetic computation and the biological relevance of a local concentration that is a biological fact that needs to be considered. Scaling our local jugular concentrations by human BPA exposure (0.22 μg/kg) leads to the computation of a jugular BPA concentration > 1 ng/mL. What is true for sublingual absorption and the jugular vein could be true for any sampling site located downstream of any other absorption site, such as the human cubital vein after percutaneous absorption of BPA from thermal receipt paper, leading to serum BPA concentrations > 1 ng/mL (vom Saal FS, personal communication). This means that high BPA concentrations that are neither contamination (vom Saal 2013) nor a violation of PK principles can be observed in humans.
More generally, it is our opinion that it is unwise to consider that “mixed systemic serum following sublingual exposure” and blood samples obtained “from a site reflecting systemic exposure” are the only valuable ways to describe the PK of BPA and to discuss the PK/PD relationship. The buccal absorption of BPA can be viewed as a direct infusion of BPA into the internal jugular vein (in humans) likely to lead downstream to a totally different pattern of BPA biophase exposure compared with intestinal absorption. Buccal absorption should generate a series of BPA peaks (associated with meals) and troughs (during the interdigestive period) in the blood rather than a low steady exposure following intestinal absorption. In addition, the amplitude of these intermittent jumps in BPA concentration could be higher in arterial blood that those measured peripherally. Chiou (1989) reported that after iv administration, measured peripheral venous concentrations could be initially lower or much lower than the corresponding arterial concentrations, which are the driving concentrations to consider for drug action. Chiou also showed that the shorter the terminal half-life, the greater the arteriovenous concentration difference during the distribution/redistribution phase. BPA’s half-life is short, and it makes sense to postulate that the peripheral venous blood BPA concentration measured following buccal absorption could systematically underestimate the arterial BPA concentration.
Finally, our article points to new alternative hypotheses for interpretation of the current epidemiological urinary data and also for better understanding blood BPA concentrations. First, the bioavailability of BPA is now theoretically up to 100% rather than about 1%, as expected following oral gavage. Second, given the typical feeding behavior of humans, the lack of uniformity of blood BPA concentrations after buccal absorption should not be ignored in terms of the PK/PD relationship. We are now exploring the hypothesis that sublingual absorption can lead to a possible first-pass disrupting effect on pituitary secretions.
Chiou WL. 1989. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site. Implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (part I). Clin Pharmacokinet 17:175–199.
Gayrard V, Lacroix MZ, Collet SH, Viguié C, Bousquet-Melou A, Toutain PL, et al. 2013. High bioavailability of bisphenol A from sublingual exposure. Environ Health Perspect 121:951–956; doi:10.1289/ehp.1206339.
vom Saal FS. 2013. Role of nutrition and environmental endocrine disrupting chemicals during the perinatal period on the aetiology of obesity [Abstract]. In: Proceedings of the Endocrine Society’s 95th Annual Meeting, 15–18 June 2013, San Francisco, CA. Available: https://endo.confex.com/endo/2013endo/webprogram/Paper2742.html [accessed 15 November 2013].
New Search FunctionWe're pleased to present our improved search page. Try it, and let us know what you think!
CEHN September 2014 Article of the Month“Prenatal Polybrominated Diphenyl Ether Exposures and Neurodevelopment in U.S. Children through 5 Years of Age: The HOME Study” (Environ Health Perspect; DOI:10.1289/ehp.1307562) has been selected by the Children’s Environmental Health Network (CEHN) as its September 2014 Article of the Month. These CEHN summaries discuss the potential policy implications of current children’s environmental health research.
Register Today for PPTOX IVEnvironmental Stressors in Disease and Implications for Human Health
October 26–29, 2014
Boston Marriott Long Wharf Hotel
Join the Endocrine Society for the fourth international summit of Prenatal Programming and Toxicity (PPTOX), a premiere conference series dedicated to cutting-edge discussion of environmental hazards during early life and long-term consequences.* Housing deadline: Monday, October 6
For more information, visit the Endocrine Society website.
Sign Up to Receive E-mail Alerts
Recent Advance Publications
- Asthma in Inner-City Children at 5-11 Years of Age and Prenatal Exposure to Phthalates: The Columbia Center for Children’s Environmental Health Cohort
- Comparative Assessment of the Effects of Climate Change on Heat- and Cold-Related Mortality in the United Kingdom and Australia
- Proximity to Natural Gas Wells and Reported Health Status: Results of a Household Survey in Washington County, Pennsylvania
- Green and Blue Spaces and Behavioral Development in Barcelona Schoolchildren: The BREATHE Project
- Aerial Application of Mancozeb and Urinary Ethylene Thiourea (ETU) Concentrations among Pregnant Women in Costa Rica: The Infants’ Environmental Health Study (ISA)
- Pyrethroid Pesticide Exposure and Parental Report of Learning Disability and Attention Deficit/Hyperactivity Disorder in U.S. Children: NHANES 1999–2002
- Household Cooking with Solid Fuels Contributes to Ambient PM2.5 Air Pollution and the Burden of Disease
- EHPNoonNews: Filtration system for arsenic-contaminated water http://t.co/ipwZ7jVFNr @abc7newsbayarea
- EHPNoonNews: House dust, ammunition lead to high lead levels in Inuit http://t.co/gQ4sAshGmf @nunatsiaqnews
- EHPNoonNews: Shark skin: an inspiration for hygiene? http://t.co/PvYigVMgUr @eurekalertaaas
- EHPNoonNews: Florida red tide could hit economy http://t.co/ptF2MmYmWQ @washingtonpost Related in EHP http://t.co/OF88aDTKH6
- AdvPubl: Prenatal phthalates and child asthma http://t.co/SDGhtmwyO5