Bisphenol-A (BPA) For Doctors and Dentists

Bisphenol-A (BPA) For Doctors and Dentists

According to a study published in the NIH journal Environmental Health Perspectives:

"Most of the composites and sealants used in dentistry are based on bisphenol A diglycidylether methacrylate (Bis-GMA). Reports revealed that in situ polymerization is not complete and that free monomers can be detected by different analytic methods." R. Pulgar, et al. Environmental Health Perspectives v.108, n.1, Jan00 [1]

This page contains a few recent studies on Bisphenol-A (BPA). The number of studies and abstracts included here is far from being the complete body of knowledge on this subject. BPA is not the only concern with respect to the use of plastics in contact with humans and/or foods, but a good place to begin learning, because it is ubiquitous in our environment. Especially vulnerable to this, and other hormonally active agents, are the unborn; those in the womb and those of future generations.

Bisphenol A has been found to be a hormonally active agent (HAA) by E-Screen, ER Binding, Induction, and In Vivo Bioassay (Brotons et al. 1995- Krishnan et al. 1995; Sonnenschein et al. 1995; Soto et al. 1995, 1997; Sumpter and Jobling 1995; Olea et al. 1996; Nagel et al. 1998), and is listed in Hormonally Active Agents in the Environment by the National Research Council. [2]

At issue is the hormonal activity of plastics, in this case BPA, which is a known HAA. Hormones are active in our bodies in the parts-per-trillion (ppt) range. In fact, 1/10 ppt may not be a low enough detection level for researchers to test for hormonal activity. In 2000, I gave thought to organizing a study on milk in plastics jugs; HDPE or #1. At that time it was suggested to me by Dr. Arnold Schecter that parts-per-quadrillion should be considered. Dr. Schecter is a well-known authority on dioxin. His recent studies of it have taken him to Vietnam, to study the aftermath effects of the us of Agent Orange by the US military decades ago. Agent Orange got it's infamous toxicity from dioxin, a contaminant in the production process.

Dioxin is another hormonally active substance. There are 75 different forms of dioxin; 2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD, is the most toxic dioxin. There are also dioxin-like substances which can create a synergy with dioxins; 135 furans, 209 PCBs, diphenyl ethers, and naphthalenes. There is good reason to mention other HAA's because of the possible synergies formed between any number of them. It is not known which or at what levels synergies are formed; some as high or higher than 800 times the toxicity of the others individually.[3]

Please read the text I contributed to a recent medical textbook.[4] It explains the growing crisis that HAA's are creating. When you've completed that section, please continue with the other references below. I fully realize the ramifications of this news for you, as plastics play a major role in your practice. However, there are currently enough data on the hormonal activity of many chemicals to call for the use of precaution. What will the future hold in the way of professional liability? What will the future hold for the health of everyone? It is partly up to each of you to take part in redirecting the health industry towards the mission of healing and maintaining health

[5]

Notes

Pulgar, R. Determination of Bisphenol A and Related Aromatic Compounds Released from Bis-GMA-Based Composites and Sealants by High Performance Liquid Chromatography. Environmental Health Perspectives v.108, n.1, Jan00
http://www.mindfully.org/Plastic/Bisphenol-A-Aromatic-Compounds.htm
Committee on Hormonally Active Agents in the Environment, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. (2000) Hormonally Active Agents in the Environment. National Academy Press, Washington, DC.
http://books.nap.edu/books/0309064198/html/index.html
van Birgelen, APJM, KM Fase, J van der Kolk, H Poiger, A Brouwer, W Seinen and M van den Berg. 1996. Synergistic effect of 2,2',4,4',5,5'-Hexachlorobiphenyl and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin on hepatic porphyrin levels in the rat. Environmental Health Perspectives 104:550-557.
http://ehpnet1.niehs.nih.gov/docs/1996/104-5/vanbirgelenabs.html
Friedman, M., ed. Fundamentals of Naturopathic Endocrinology. Quarry Press (In Print)
http://www.mindfully.org/Pesticide/EDs-PWG-16jun01.htm
From The Hippocratic Oath: Text, Translation, and Interpretation, by Ludwig Edelstein. Baltimore: Johns Hopkins Press, 1943.
http://www.pbs.org/wgbh/nova/doctors/oath_classical.html

Further References

The Environmental Estrogen Bisphenol A Stimulates Prolactin Release in Vitro and in Vivo*
Endocrinology V.138, N.5 1780-1786 May97
http://www.mindfully.org/Pesticide/Bisphenol-A-Prolactin-Release.htm

American Dental Association Statement on Bisphenol A Leaching From Dental Sealants Estrogenic Effects of Bisphenol A Lacking in Dental Sealants
American Dental Association Statement Document 4aug98 rev.30may01
http://www.mindfully.org/Plastic/BPA-Dental-Sealants-ADA4aug98.htm

Bisphenol-A, an environmental estrogen, activates the human orphan nuclear receptor SXR/PXR-mediated transcription
European Journal of Endocrinology v.145, i.4 Oct01
http://www.mindfully.org/Plastic/BPA-Environmental-Estrogen.htm

Perinatal Exposure to Low Doses of Bisphenol A Affects Body Weight, Patterns of Estrous Cyclicity, and Plasma LH Levels
Environmental Health Perspectives v.109, n.7, Jul01
http://www.mindfully.org/Plastic/BPA-Perinatal-Exposure.htm

Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving
Endocrinology 132(6):2277-8 Jun93
http://www.mindfully.org/Plastic/BPA-Polycarbonate-Flasks.htm

Phthalates - index page on mindfully.org http://www.mindfully.org/Plastic/Phthalates.htm

Interview with Fredrick vom Saal by Frontline PBS 2jun98
http://www.mindfully.org/Pesticide/Vom-Saal-Interview-PBS2jun98.htm

Food For Thought: What's Coming Out of Baby¹s Bottle?
Janet Roloff / Science News 31jul99 v.156, n.5
http://www.mindfully.org/Pesticide/Babys-Bottle-Roloff.htm

Baby Alert: New Findings about Plastics
Consumer Reports Special Report 21apr99
http://www.mindfully.org/Plastic/Baby-Bottles-CU21apr99.htm

Final Report of the Endocrine Disruptors Low-Dose Peer Review.
National Institute of Environmental Health Sciences, NIH, National Toxicology Program 14may01
http://www.mindfully.org/Pesticide/EDs-Low-Dose-Peer14may01.htm

Survey of Bisphenols in Canned Foods Food Standards Agency UK n.13, i.01 Apr01
http://www.mindfully.org/Plastic/Bisphenols-Canned-FoodsT1.htm

Activity of Environmentally Relevant Low Doses of Endocrine Disruptors and the Bisphenol A Controversy: Initial Results Confirmed
Daniel M Sheehan, FDA 7oct00
http://www.mindfully.org/Plastic/EDs-BPA-Low-Doses.htm

Low Doses of Chemicals in Packaging May Affect Reproduction
Cat Lazaroff / ENN 15may01
http://www.mindfully.org/Plastic/Packaging-Affect-Reproduction.htm

The Estrogenic Activity of Phthalate Esters In Vitro.
Environmental Health Perspectives v.105, n.8, Aug97
http://www.mindfully.org/Plastic/Estrogenic-Phthalate-Esters.htm

Reproductive Malformation of the Male Offspring Following Maternal Exposure to Estrogenic Chemicals.
Proceedings of the Society for Experimental Biology and Medicine 224:61-68 Jun00
http://www.mindfully.org/Pesticide/Maternal-Exposure-Repro-Malform.htm

Endocrine Effects of Marine Plastics on Kelp Bass
http://www.mindfully.org/Plastic/Marine-Plastics-Kelp-Bass.htm

Activity of Environmentally Relevant Low Doses of Endocrine Disruptors and the Bisphenol A Controversy: Initial Results Confirmed.
Proceedings of the Society for Experimental Biology and Medicine 224:57-60 Jun00
http://www.mindfully.org/Pesticide/Low-Dose-EDs-BPA-Confirmed.htm

Effects of Dibutyl Phthalate as an Environmental Endocrine Disruptor on Gonadal Sex Differentiation of Genetic Males of the Frog Rana rugosa.
Environmental Health Perspectives V.108, N.12, Dec00
http://www.mindfully.org/Pesticide/Dibutyl-Phthalate-DBP-ED.htm

"Gender-bending" chemicals disrupt plants too James Randerson / New Scientist 14sep01
http://www.mindfully.org/Pesticide/EDs-Disrupt-Plants-Too.htm

Endocrine disrupters and human health Current research will establish baseline indices
Editorial / Paul T C Harrison / British Medical Journal 323:1317-1318 8dec01
http://www.mindfully.org/Pesticide/EDs-Human-Health-BMJ8dec01.htm

EPA Office of Pesticide Programs Lists of Other (Inert) Pesticide Ingredients Rev.12jun01
http://www.mindfully.org/Pesticide/EPA-Inerts-List.txt

Teratogens: Chemicals identified as having teratogenic properties
Sax's Dangerous Properties of Industrial Chemicals, 7th edition (John Wiley & Sons) as of 14nov01
http://www.mindfully.org/Pesticide/Teratogens.htm

Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999-2000: A National Reconnaissance
Environ. Sci. Technol.,36 (6),1202-1211, Mar02
http://www.mindfully.org/Water/Wastewater-Contaminants-US-StreamsMar02.htm

List of Abstracts

Disposition of Orally Administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in Pregnant Rats and the Placental Transfer to Fetuses
Environ Health Perspect 108:931-935 (2000). [Online 12 September 2000]
Osamu Takahashi and Shinshi Oishi
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Tokyo, Japan

Abstract
We studied the disposition of bisphenol A (BPA) in pregnant female F344/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36µg/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the maximum 6 hr after the administration. The maximal concentration of BPA in fetuses (9 µg/g) was also attained 20 min after the administration. BPA levels then gradually reduced in a similar manner to maternal blood. These results suggest that the absorption and distribution of BPA in maternal organs and fetuses are extremely rapid and that the placenta does not act as a barrier to BPA. Key words: bisphenol A, fetus, placenta, placental transfer. Environ Health Perspect 108:931-935 (2000). [Online 12 September 2000] http://ehpnet1.niehs.nih.gov/docs/2000/108p931-935takahashi/abstract.html

Address correspondence to O. Takahashi, Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, 24-1, Hyakunincho 3-chome, Shinjuku-ku, Tokyo 169-0073, Japan. Telephone: 81-3-3363-3231 ext. 5602. Fax: 81-3-3368-4060. E-mail: osamu@tokyo-eiken.go.jp This study was presented at the 26th annual meeting of the Japanese Society of Toxicology held 21-23 July 1999 in Sapporo, Japan. Received 29 February 2000; accepted 24 May 2000.

Perinatal Exposure to Low Doses of Bisphenol A Affects Body Weight, Patterns of Estrous Cyclicity, and Plasma LH Levels
Environmental Health Perspectives Volume 109, Number 7, July 2001
Beverly S. Rubin, Mary K. Murray, David A. Damassa, Joan C. King, and Ana M. Soto
Department of Anatomy and Cellular Biology, Tufts Medical School, Boston, Massachusetts, USA

Abstract
The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic--approximately 10,000-fold less potent than 17ß-estradiol--current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound. Key words: Bisphenol A, body weight, BPA, development, endocrine disruptors, environmental estrogens, estrous cycles, reproductive function, xenoestrogen. Environ Health Perspect 109:675-680 (2001). [Online 22 June 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p675-680rubin/abstract.html

Address correspondence to A. Soto, Department of Anatomy and Cellular Biology, Tufts Medical School, 136 Harison Avenue, Boston, MA 02111 USA. Telephone: (617) 636-6954. Fax: (617) 636-6536. E-mail: Ana.Soto@tufts.edu

We acknowledge the technical assistance of C. Lee, C. Michaelson, R. O'Donnell, P. Ronsheim, and G. Shin.

Support for these studies was provided by the Tufts Institute of the Environment and NIH-ES 08314.

Received 23 August 2000; accepted 26 January 2001.

Strain Differences in Vaginal Responses to the Xenoestrogen Bisphenol A
Environmental Health Perspectives Volume 108, Number 3, March 2000
Xinghua Long,1,2 Rosemary Steinmetz,1 Nira Ben-Jonathan,3 Andrea Caperell-Grant,1 Peter C. M. Young,1 Kenneth P. Nephew,2 and Robert M. Bigsby1

1Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indiana, USA
2Medical Sciences Program, Indiana University School of Medicine, Bloomington, Indiana, USA
3Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Abstract
Bisphenol A (BPA) is the monomer component of polycarbonate plastics and epoxy resins; human exposure derives from leachate in foodstuffs packaged in certain plastics or from epoxy-based dental appliances. BPA stimulates prolactin secretion in Fischer 344 (F344) rats but not in Sprague-Dawley (S-D) rats. The present studies were performed to determine if another classic estrogen target tissue, the rat vagina, responds to BPA in a strain-specific manner. In F344 rats BPA increased DNA synthesis in vaginal epithelium with a median effective dose (ED50) of 37.5 mg/kg body weight; DNA synthesis was not stimulated in S-D rats by any dose tested. Clearance of 3H-BPA from blood followed the same time course in both strains of rats, with a half-life of 90 min. Scatchard analysis of [3H]estradiol binding showed no strain differences in concentration or affinity of the vaginal estrogen receptor. BPA increased the level of mRNA for the immediate early gene, c-fos, with similar dose-response curves in both rat strains. Thus, F344 and S-D rats exhibit differences in sensitivity to BPA at the level of cell proliferation in the vaginal epithelium. However, metabolic clearance of BPA and the early events that lead to the proliferative response, receptor-ligand interaction and induction of immediate early genes, show no strain differences. These observations suggest that differences in intermediate effects must account for the difference in sensitivity of the proliferative response to the xenoestrogen. Furthermore, these results point to the need for caution in choosing a suitable end point and animal model when seeking to test the estrogenic effects of xenobiotics. Key words: bisphenol A, cell proliferation, c-fos, dose response, rat, vagina, xenoestrogen. Environ Health Perspect 108:243-247 (2000). [Online 9 February 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p243-247long/abstract.html

Address correspondence to R.M. Bigsby, Indiana University School of Medicine, Department of Obstetrics and Gynecology, 1001 W. Walnut Street (MF102), Indianapolis, IN 46202-5196 USA. Telephone: (317) 274-8970. Fax: (317) 278-2884. E-mail: rbigsby@iupui.edu This work was supported by the following grants: U.S. Department of Defense DAMD17-98-1-8011, NIH CA74748, NIH NS13243, and NSF IBN-9806217.

Received 4 August 1999; accepted 14 October 1999.

Uterotrophic Activity of Bisphenol A in the Immature Rat
Environmental Health Perspectives Volume 106, Number 11, November 1998
J. Ashby and H. Tinwell

Zeneca Central Toxicology Laboratory, Alderley Park, Cheshire SK10 4TJ, UK

Abstract
Bisphenol A (BPA) is active in immature AP rat uterotrophic assays when evaluated using either the oral or the subcutaneous (sc) injection routes of exposure (three daily administrations of 400-800 mg/kg BPA). Premature vaginal opening was seen for 8 of 14 animals exposed to 600 and 800 mg/kg BPA by sc injection. Vaginal opening was not produced by BPA in the gavage studies. These results are consistent with those of Dodds and Lawson [Nature 137:96 (1936)] who found that BPA induces persistent vaginal cornification in ovariectomized rats exposed to three twice-daily injections of 85 mg/kg BPA (total daily dose 170 mg/kg), but they conflict with the reported inactivity of BPA in the immature mouse uterotrophic assay. The uterotrophic activity of diethylstilbestrol in the rat is also established (0.04 mg/kg/day for three days). Key words: bisphenol A, endocrine, estrogen, uterus. Environ Health Perspect 106:719-720 (1998). [Online 14 October 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p719-720ashby/abstract.html

Address correspondence to J. Ashby, Zeneca Central Toxicology Laboratory, Alderley Park, Cheshire SK10 4TJ, UK. Received 19 March 1998; accepted 23 June 1998.

Suit accuses BPA of harming salmon Jonathan Brinckman / The Oregonian 6nov01

The Bonneville Power Administration harmed young migrating salmon this spring and summer by cranking up power production at Columbia River dams, four conservation and fishing groups claimed in a lawsuit filed Monday.

The suit is the first legal challenge to the BPA's effort to ward off financial threats and meet electricity demands earlier this year. Conservationists and tribes criticized the agency's actions, while many electricity customers praised them.

The federal salmon recovery plan normally requires the Bonneville Power Administration to send billions of gallons of water over spillways at the dams -- instead of through electricity-generating turbines -- to provide safer passage for young salmon heading for the ocean.

This year, a near-record drought reduced the amount of water available for electricity generation while skyrocketing wholesale electricity prices made it expensive for the BPA to buy power.

The agency, which markets about 45 percent of the Northwest's electricity, declared a "power emergency" and spilled only about one-fifth of the water it is usually required to spill. That increased the death rate for many of the young salmon and steelhead migrating to the ocean in the river, federal biologists said.

Fish that were carried past dams on barges or in trucks, including about 90 percent of the salmon and steelhead from Idaho, were unaffected by decreased spill because they did not remain in the river and pass through the dams.

The lawsuit alleges that the BPA violated the federal Northwest Power Planning and Conservation Act by failing to provide "equitable treatment" of salmon in its decisions on power production. Federal law requires that such lawsuits be filed in the 9th U.S. Circuit Court of Appeals in San Francisco.

"BPA's actions this summer clearly demonstrate the agency's misplaced priorities," said Glen Spain, executive director of the Pacific Coast Federation of Fishermen's Associations, one of the plaintiffs. The others are the Sierra Club, Institute for Fisheries Resources, and Idaho Rivers United.

Ed Mosey, a BPA spokesman, said the agency spilled as much water as it could without jeopardizing its ability to meet power demand. "It has always been our intent to balance fish and power. We made every effort to give as much benefit to fish as we could in one of the worst water years ever."

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