Link to detailed summary of a discovery that links bisphenol A to the mechanism that causes birth defects and spontaneous miscarriage in people, plus press coverage

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bisphenol A

Some wildly popular water bottles are made of polycarbonate

Another compound first synthesized during that era, diethylstilbestrol, turned out to be more powerful as an estrogen, so bisphenol A was shelved... until polymer chemists discovered that it could be polymerized to form polycarbonate plastic. Unfortunately, the ester bond that links BPA monomers to one another to form a polymer is not stable and hence the polymer decays with time, releasing BPA into materials with which it comes into contact, for example food or water.

Bisphenol A is now deeply imbedded in the products of modern consumer society, not just as the building block for polycarbonate plastic (from which it then leaches as the plastic ages) but also in the manufacture of epoxy resins and other plastics, including polysulfone, alkylphenolic, polyalylate, polyester-styrene, and certain polyester resins.

Its uses don't end with the making of plastic. Bisphenol A has been used as an inert ingredient in pesticides (although in the US this has apparently been halted), as a fungicide, antioxidant, flame retardant, rubber chemical, and polyvinyl chloride stabilizer.

These uses create a myriad of exposures for people. Bisphenol A-based polycarbonate is used as a plastic coating for children's teeth to prevent cavities, as a coating in metal cans to prevent the metal from contact with food contents, as the plastic in food containers, refrigerator shelving, baby bottles, water bottles, returnable containers for juice, milk and water, micro-wave ovenware and eating utensils.

Other exposures result from BPA's use in "films, sheets, and laminations; reinforced pipes; floorings; watermain filters; enamels and vanishes; adhesives; artificial teeth; nail polish; compact discs; electric insulators; and as parts of automobiles, certain machines, tools, electrical appliances, and office automation instruments" (Takahashi and Oishi 2000).

BPA contamination is also widespread in the environment. For example, BPA can be measured in rivers and estuaries at concentrations that range from under 5 to over 1900 nanograms/liter. Sediment loading can also be significant, with levels ranging from under 5 to over 100 µg/kg (ppb) BPA is quite persistent as under normal conditions in the environment it does not readily degrade (Rippen 1999).

What this all means is that most of your life you are within arm's length or closer to bisphenol A. No wonder the debate over its toxicity is so intense.

Some important recent studies of bisphenol A:

In a small prospective study, researchers in Japan report that bisphenol A levels are higher in women with a history of repeated spontaneous miscarriages. This research was based on proof that BPA causes meiotic aneuploidy in mice. Meiotic aneuploidy is the commonest cause of miscarriage in people. The researchers also followed the pregnancies of the women to completion, and found evidence of aneuploidy in several of the miscarried fetuses. More...

Bisphenol A and the birth control pharmaceutical ethinylestradiol cause adverse effects in prostate development in mice at levels to which millions of Americans are exposed each year. The results implicate these compounds in human prostate diseases, including prostate cancer. The research also shows the futility of predicting the developmental consequences of low-dose exposures based on high-dose experiments. More...

A flood of new information about bisphenol A revealing both widespread human exposure and effects at extremely low doses sparks a call for a new risk assessment of the ubiquitous compound. Bisphenol A, the basic building block of polycarbonate plastic, alters development of the reproductive tract, the immune system, increases prostate tumor proliferation, changes brain chemistry and structure and affects an array of behaviors, including hyperactivity. Of 11 studies of the compound's effects at low doses, none funded by industry reported impacts. In contrast, 94 out of 104 government-funded studies found effects. This summary includes audio files of an international teleconference about bisphenol A. More...

Several 'weakly' estrogenic compounds including bisphenol A and endosulfan are as powerful as estrogen at increasing calcium influx into cells and stimulating prolactin secretion. The effects are mediated by a cell membrane surface receptor instead of nuclear hormone receptors, the focus of most studies to date. Changes in calcium and prolactin occur at extremely low doses, well within the range of human exposures. Wozniak, AL, NN Bulayeva and CS Watson. 2005. Xenoestrogens at Picomolar to Nanomolar Concentrations Trigger Membrane Estrogen Receptor-alpha-Mediated Ca++ Fluxes and Prolactin Release in GH3/B6 Pituitary Tumor Cells. Environmental Health Perspectives, in press.

Bisphenol A at extremely low levels causes changes in brain structure and behavior in rats. The locus coeruleus is believed to be a key brain center for anxiety and fear. Normally this is larger in females than in males. Rats exposed to BPA at levels beneath the current 'safe' exposure level established by the US EPA show a reversal in sex dimorphism, with males' LC larger than females.' . Kubo, K, O Arai, M Omura, R Wantanabe, R Ogata, and S Aou. 2003. Low dose effects of bisphenol A on sexua| differentiation of the brain and behavior in rats. Neuroscience Research 45: 345-356.

Exposures to 1/5th the level considered safe are sufficient to alter maternal behavior in mice, including reductions in time spent nursing, increases in time resting away from offspring, and increases in time spent out of the nest. Palanza, P, KL Howdeshell, S Parmigiani and FS vom Saal. 2002. Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice. Environmental Health Perspectives 110 (suppl 3): 415-422.

An accident in the lab, followed by careful analysis and a series of experiments, reveals that bisphenol A causes aneuploidy in mice at low levels of exposure. Because aneuploidy in humans causes spontaneous miscarriages and some 10-20% of all birth defects, including Down Syndrome, this implicates bisphenol A in a broad range of human developmental errors. Hunt, PA, KE Koehler, M Susiarjo, CA Hodges, A Ilagan, RC Voigt, S Thomas, BF Thomas and TJ Hassold. 2003. Bisphenol A exposure causes meiotic aneuploidy in the female mouse. Current Biology 13: 546-553.

Experiments by researchers at the University of Missouri raise the possibility of widespread contamination of laboratory experiments by bisphenol A. Their results demonstrate that at room temperature significant amounts of this estrogenic substance leach into water from old polycarbonate animal cages. This inadvertent contamination could interfere with experiments designed to test the safety of estrogenic chemicals, and lead to false negatives and conflicting results. Howdeshell, KA, PH Peterman, BM Judy, JA Taylor, CE Orazio, RL Ruhlen, FS vom Saal, and WV Welshons 2003. Bisphenol A is released from used polycarbonate animal cages into water at room temperature. Environmental Health Perspectives doi:10.1289/ehp.5993.

An analysis of the biochemical mechanisms of endocrine disruption suggests why industry has been unable to replicate crucial low-dose impacts of bisphenol A on prostate development. Welshons, WV, KA Thayer, BM Judy, JA Taylor, EM Curran and FS vom Saal. 2003. Large effects from small exposures. I. Mechanisms for endocrine disrupting chemicals with estrogenic activity. Environmental Health Perspectives doi:10.1289/ehp.5494

Using new analytical methods, a team of German scientists measured bisphenol A in the blood of pregnant women, in umbilical blood at birth and in placental tissue. All samples examined contained BPA, at levels within the range shown to alter development. Thus widespread exposure to BPA at levels of concern is no longer a hypothetical issue. It is occurring. Schönfelder, G, W Wittfoht, H Hopp, CE Talsness, M Paul and I Chahoud. 2002. Parent Bisphenol A Accumulation in the Human Maternal-Fetal-Placental Unit. Environmental Health Perspectives 110:A703-A707.

At extremely low levels, BPA promotes fat cell (adipocyte) differentiation and accumulation of lipids in a cell culture line used as a model for adipocyte formation. These two steps, differentiation and accumulation, are crucial in the development of human obesity. Hence this result opens up a whole new chapter in efforts to understand the origins of the world-wide obesity epidemic. Masuno, H, T Kidani, K Sekiya, K Sakayama, T Shiosaka, H Yamamoto and K Honda. 2002. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. Journal of Lipid Research 3:676-684.

In cell culture experiments, BPA at very low (nanomolar levels) stimulates androgen-independent proliferation of prostate cancer cells. This finding is especially important because when prostate tumors become androgen-independent they no longer respond to one of the key therapies for prostate cancer. Wetherill, YB, CE Petre, KR Monk, A Puga, and KE Knudsen. 2002. The Xenoestrogen Bisphenol A Induces Inappropriate Androgen Receptor Activation and Mitogenesis in Prostatic Adenocarcinoma Cells. Molecular Cancer Therapeutics 1: 515–524.

BPA causes changes in rat ventral prostate cells that appear similar to events that make nascent prostate tumors in humans more potent: Ramos, JG, J Varayoud, C Sonnenschein, AM Soto, M Muñoz de Toro and EH Luque. 2001. Prenatal Exposure to Low Doses of Bisphenol A Alters the Periductal Stroma and Glandular Cell Function in the Rat Ventral Prostate. Biology of Reproduction 65: 1271–1277.

BPA induces changes in mouse mammary tissue that resemble early stages mouse and human of breast cancer: Markey, CM, EH Luque, M Muñoz de Toro, C Sonnenschein and AM Soto. 2001. In Utero Exposure to Bisphenol A Alters the Development and Tissue Organization of the Mouse Mammary Gland. Biology of Reproduction 65: 1215–1223.

BPA lowers sperm count in adult rats even at extremely low levels: Sakaue, M, S Ohsako, R Ishimura, S Kurosawa, M Kurohmaru, Y Hayashi, Y Aoki, J Yonemoto and C Tohyama. 2001. Bisphenol-A Affects Spermatogenesis in the Adult Rat Even at a Low Dose. Journal of Occupational Health 43:185 -190.

BPA at extremely low levels creates superfemale snails. Oehlmann, J, U Schulte-Oehlmann, M Tillmann and B Markert. 2000. Effects of endocrine disruptors on Prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part I: Bisphenol A and Octylphenol as xenoestrogens. Ecotoxicology 9:383-397.

BPA is rapidly transfered to the fetus after maternal uptake: Takahashi, O and S Oishi. 2000. Disposition of Orally Administered 2,2-Bis(4-hydroxyphenyl) propane (Bisphenol A) in Pregnant Rats and the Placental Transfer to Fetuses. Environmental Health Perspectives 108:931-935.

An independently funded, academic laboratory can verify controversial BPA results, even though industry can't: Gupta, Chhanda. 2000. Reproductive malformation of the male offspring following maternal exposure to estrogenic chemicals. Proceedings of the Society for Experimental Biology and Medicine 224:61-68.

Metabolic differences between rats and humans probably mean that humans are more sensitive to BPA than are rats: Elsby, R, JL Maggs, J Ashby and BK Park. 2001. Comparison of the modulatory effects of human and rat liver microsomal metabolism on the estrogenicity of bisphenol A: implications for extrapolation to humans. Journal of Pharmacology and Experimental Therapeutics 297-103-113.

A confirmation of BPA low dose effects, and demonstration that the effects include impacts on estrous cyclicity and plasma LH levels: Rubin, BS, MK Murray, DA Damassa, JC King and AM Soto. 2001. Perinatal Exposure to Low Doses of Bisphenol A Affects Body Weight, Patterns of Estrous Cyclicity, and Plasma LH Levels. Environmental Health Perspectives 109: 675-680.

BPA speeds the pace of sexua| development in mice, and causes mice to be obese: Howdeshell, K, AK Hotchkiss, KA Thayer, JG Vandenbergh and FS vom Saal. 1999. Plastic bisphenol A speeds growth and puberty. Nature 401: 762-764.

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