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Bisphenol A
[some recent important studies of bisphenol A]
"...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..." Scientific studies have also indicated that it causes or may be linked to...proliferation of prostate cancer & other prostate problems...human obesity epidemic...breast cancer...speeds the pace of sexual development. "Bisphenol A is one of the most commonly used plastic materials in food containers, in beverage containers. This is a ubiquitous chemical ... at least in the developed world. It is one of the top 50 chemicals in production."
Bisphenol A was invented in the 1930's during the search for synthetic estrogens. The first evidence of its estrogenicity came from experiments in the 1930's feeding BPA to ovariectomised rats (Dodds and Lawson 1936, 1938).
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.
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, 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; water main filters; enamels and varnishes; 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 g/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 very important recent scientific studies of Bisphenol A:
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. Howdeshell, KA, PH Peterman, BM Judy, JA Taylor, CE Orazio, RL Ruhlen, FS vom Saal, and WV Welshons 2003. 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 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 sexual 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.
Study Links Common Plastic to Birth Defects
WASHINGTON (Reuters) - A common ingredient used to make plastics such as baby bottles causes birth defects in mice -- defects that could also occur in people, U.S. researchers said on Monday.
They urged more research into the potential effects of bisphenol A, a chemical long criticized by environmentalists as being a hormone disruptor that could cause defects in embryos.
The defects they found, when they occur in humans, can cause miscarriages or mental retardation such as Down Syndrome -- and they seem to be caused at what were considered to be low levels of exposure, the researchers report in the journal Current Biology.
The discovery came by accident, Patricia Hunt and colleagues at Case Western Reserve University in Ohio report.
Her team first noted a higher than normal increase in abnormalities in developing egg cells in female mice.
"We were looking at the processes as cells start to undergo division," Hunt, a geneticist, said in a telephone interview.
"The chromosomes are supposed to line up in an orderly fashion so they can divide in an orderly fashion. What we saw was a tremendous increase in the number of cells in which the alignment of chromosomes in the cells were not orderly at all -- they were very disorderly."
In the mice they were studying this only usually happens 2 percent of the time, but Hunt's team said 40 percent of the eggs were developing these problems.
They spent weeks looking for the cause.
"Nothing turned up. But ... I noticed that the plastic cages looked kind of the worst for wear," Hunt said.
It turned out that a harsh detergent used to clean the cages had broken down the plastic, releasing bisphenol A. Do any of you wash your plastic cups, plates, dishes et cetera? If you do, then you are getting plenty of bisphenol A in your diet.
Hunt's team deliberately exposed mice to small amounts of bisphenol A for short periods of time and found the abnormalities increased again.
CHEMICALS THAT DISRUPT HORMONES
Many labs are studying the effects of bisphenol A and other chemicals that act as endocrine disruptors -- affecting the actions of hormones in the body. Some scientists fear that developing fetuses and young children are especially vulnerable to these effects.
"Pat Hunt hasn't shown damage in fetuses yet, but it has to be a subject of concern," said Fred vom Saal, an expert on the effects of toxins on reproduction at the University of Missouri.
"Bisphenol A is one of the most commonly used plastic materials in food containers, in beverage containers. This is a ubiquitous chemical ... at least in the developed world. It is one of the top 50 chemicals in production."
Hunt, who studies the effects of aging on egg cells and fertility, said she was not even looking for chemical influences. "That's one of the things I think makes our study unusual," she said.
While the study says nothing about the effects of bisphenol A in humans, Hunt said there is reason to believe they would be similar. The changes in the mice cause aneuploidy -- a misalignment of the chromosomes that is seen in human birth defects and miscarriages.
"You don't wait to prove that it does that in people before you take some regulatory action," Vom Saal said, adding that he hopes Congress may now agree to fund more studies on the effects of bisphenol A.
"We are talking about these mice essentially drinking out of old baby bottles," Vom Saal said -- noting that hard plastic containers like bottles start leaching bisphenol A when they begin to look cracked or etched. He urged the chemical industry to make more plastic products that do not contain bisphenol A.
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