Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure.

This document is a summary statement of the outcome from he meeting: “Bisphenol A: An Examination of the Relevance of cological, In vitro and Laboratory Animal Studies for Assessng Risks to Human Health” sponsored by both the NIEHS and IDCR at NIH/DHHS, as well as the US-EPA and Commonweal n the estrogenic environmental chemical bisphenol A (BPA, ,2-bis(4-hydroxyphenyl)propane; CAS# 80-05-7). The meetng was held in Chapel Hill, NC, 28–30 November 2006 due o concerns about the potential for a relationship between BPA nd negative trends in human health that have occurred in recent ecades. Examples include increases in abnormal penile/urethra evelopment in males, early sexual maturation in females, an ncrease in neurobehavioral problems such as attention deficit yperactivity disorder (ADHD) and autism, an increase in childood and adult obesity and type 2 diabetes, a regional decrease n sperm count, and an increase in hormonally mediated cancers, uch as prostate and breast cancers. Concern has been elevated y published studies reporting a relationship between treatment ith “low doses” of BPA and many of theses negative health outomes in experimental studies in laboratory animals as well as n vitro studies identifying plausible molecular mechanisms that ould mediate such effects. Importantly, much evidence suggests hat these adverse effects are occurring in animals within the ange of exposure to BPA of the typical human living in a develped country, where virtually everyone has measurable blood, issue and urine levels of BPA that exceed the levels produced y doses used in the “low dose” animal experiments. Issues relating to BPA were extensively discussed by five anels of experts prior to and during the meeting, and are sumarized in five reports included in this issue: (1) human exposure o bisphenol A (BPA) [1]; (2) in vitro molecular mechanisms of isphenol A action [2]; (3) in vivo effects of bisphenol A in aboratory animals [3]; (4) an ecological assessment of bispheol A: evidence from comparative biology [4]; (5) an evaluation

Shuk-Mei Ho | Taisen Iguchi | Laura N. Vandenberg | Patricia A Hunt | Cheryl S Watson | Ana M Soto | Carlos Sonnenschein | Jun Kanno | Michele Marcus | Louis J Guillette | John Peterson Myers | Linda S Birnbaum | Marcus Eriksen | Francesca Farabollini | Susan Jobling | Frederick S vom Saal | Benson T Akingbemi | Scott M Belcher | Angel Nadal | Laura N Vandenberg | Wade V Welshons | Jerrold J Heindel | Russ Hauser | R Thomas Zoeller | C. Richter | P. Hunt | R. Zoeller | G. Prins | L. Birnbaum | N. Olea | J. Kanno | C. Sonnenschein | A. Soto | M. Marcus | J. McLachlan | R. Keri | L. Vandenberg | D. A. Crain | L. Guillette | K. Knudsen | W. Welshons | Yelena B. Wetherill | J. P. Myers | S. Ho | R. Hauser | C. Talsness | B. Rubin | J. Heindel | B. Akingbemi | F. V. vom Saal | S. Belcher | S. Jobling | R. Newbold | T. Iguchi | C. Watson | G. LeBlanc | J. Vandenbergh | A. Nadal | M. Eriksen | John A McLachlan | Karen E Knudsen | John G Vandenbergh | Gerald A LeBlanc | D Andrew Crain | Ruth A Keri | Hans Laufer | Retha R Newbold | Nicolas Olea | Gail S Prins | Catherine A Richter | Beverly S Rubin | Chris E Talsness | Debby R Walser-Kuntz | Yelena Wetherill | H. Laufer | F. Farabollini | D. Walser-Kuntz | Taisen Iguchi | J. Mclachlan | Michele Marcus | Hans Laufer | Cheryl S. Watson | Shuk-Mei Ho | Linda S. Birnbaum | D. Crain | Scott M. Belcher | Marcus Eriksen | Francesca Farabollini | Russ Hauser | Patricia A. Hunt | John A Mclachlan | Angel Nadal | Nicolás Olea | Catherine A. Richter | Patricia A Hunt

[1]  C. Watson,et al.  Xenoestrogens at Picomolar to Nanomolar Concentrations Trigger Membrane Estrogen Receptor-α–Mediated Ca2+ Fluxes and Prolactin Release in GH3/B6 Pituitary Tumor Cells , 2005, Environmental health perspectives.

[2]  F. Olea-Serrano,et al.  Estrogenicity of resin-based composites and sealants used in dentistry. , 1996, Environmental health perspectives.

[3]  J. Vallarino,et al.  Identification of Selected Hormonally Active Agents and Animal Mammary Carcinogens in Commercial and Residential Air and Dust Samples , 2001, Journal of the Air & Waste Management Association.

[4]  E. Dodds,et al.  Synthetic Œstrogenic Agents without the Phenanthrene Nucleus , 1936, Nature.

[5]  Peter Dockery,et al.  Estrogen receptor independent rapid non-genomic effects of environmental estrogens on [Ca2+]i in human breast cancer cells , 2005, Molecular and Cellular Endocrinology.

[6]  Shuk-Mei Ho,et al.  4 Epigenetically Regulates Phosphodiesterase Type 4 Variant Increases Susceptibility to Prostate Carcinogenesis and Developmental Exposure to Estradiol and Bisphenol A , 2006 .

[7]  Paul D Jones,et al.  Removal of estrogenic activity from municipal waste landfill leachate assessed with a bioassay based on reporter gene expression. , 2003, Environmental science & technology.

[8]  P. Hunt,et al.  An evaluation of evidence for the carcinogenic activity of bisphenol A. , 2007, Reproductive toxicology.

[9]  Taisen Iguchi,et al.  An ecological assessment of bisphenol-A: evidence from comparative biology. , 2007, Reproductive toxicology.

[10]  S. Belcher,et al.  Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A. , 2005, Endocrinology.

[11]  K A Thayer,et al.  Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. , 1997, Environmental health perspectives.

[12]  Y. Kawagoshi,et al.  Estrogenic chemicals and estrogenic activity in leachate from municipal waste landfill determined by yeast two-hybrid assay. , 2003, Journal of environmental monitoring : JEM.

[13]  Frederick S vom Saal,et al.  Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. , 2006, Endocrinology.

[14]  Cheryl S Watson,et al.  In vitro molecular mechanisms of bisphenol A action. , 2007, Reproductive toxicology.

[15]  Kristina A Thayer,et al.  Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. , 2003, Environmental health perspectives.

[16]  W. Welshons,et al.  Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A. , 2006, Environmental research.

[17]  C. Moore SYNTHETIC POLYMERS IN THE MARINE ENVIRONMENT: WHAT WE KNOW, WHAT WE NEED TO KNOW, WHAT CAN BE DONE? , 2007 .

[18]  B. Soria,et al.  Low doses of the endocrine disruptor Bisphenol‐A and the native hormone 17β‐estradiol rapidly activate the transcription factor CREB , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  D. Roy,et al.  Profound effects of the weak environmental estrogen-like chemical bisphenol A on the growth of the mammary gland of Noble rats , 1997, The Journal of Steroid Biochemistry and Molecular Biology.

[20]  R. Bigsby,et al.  The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. , 1997, Endocrinology.

[21]  C. Richter,et al.  In vivo effects of bisphenol A in laboratory rodent studies. , 2007, Reproductive toxicology.

[22]  Laura N. Vandenberg,et al.  Human exposure to bisphenol A (BPA). , 2007, Reproductive toxicology.