Timeline: BPA from Invention to Phase-Out

By Jane Houlihan, April 2008

Bisphenol A (BPA) is a plastics chemical invented nearly 120 years ago and currently used in enormous amounts to manufacture hard plastic water bottles and to make epoxy linings of metal food cans, like those for canned infant formula. Although its long-time use in consumer products has come with assurances of its safety from industry, studies conducted over the past 20 years now show it to be not only a ubiquitous pollutant in the human body - it contaminates nearly 93% of the population - but also a potent developmental toxin at very low doses.

In April 2008 the National Toxicology Program of NIH determined that BPA may pose risks to human development, raising concerns for early puberty, prostate effects, breast cancer, and behavioral impacts from early-life exposures. Pregnant women, infants and young children are most vulnerable to the harmful effects of BPA. Although FDA has yet to act to tighten safety standards, two Congressional investigations have been launched to shed light on industry influence of government science evaluations, and Wal-Mart and other retailers are pulling BPA-containing products off of store shelves. The major events that have transformed our understanding of this chemical, shown its potential role in human health problems, and revealed industry's inside fight to keep it on the market despite the health risks are described below.

The first 100 years - widespread exposures, unknown risks

1891: BPA is invented. Chemists synthesize the chemical bisphenol A (BPA) in the laboratory.

1930’s: First evidence of BPA toxicity. Scientists discover that BPA is an artificial estrogen (Dodds 1938). Its use as a pharmaceutical hormone is precluded by the invention of another synthetic chemical, DES, with even more potent estrogenic properties. (DES was later taken off the market when it was linked to reproductive cancers in girls born to mothers taking DES during pregnancy, in retrospect an early warning signal for the similar toxic properties confirmed for BPA many years later).

1940’s and 1950's: New use of BPA in plastic. The chemical industry begins to use BPA to manufacture a hard plastic called polycarbonate, and to make epoxy resins used as linings for metal food cans and a variety of other products. Although BPA leaches out of plastic long after its manufacture, the material is used in consumer products with no requirement that companies prove it is safe. The 70 years that follow BPA's introduction in these industries see the explosion of BPA-based plastics to encompass products as wide-ranging as bicycle helmets, water coolers, and baby bottles.

1976: First law to regulate industrial chemicals, fails to establish safety of BPA. Congress passes the Toxic Substances Control Act, the first law in the U.S. to regulate industrial chemicals. BPA is one of 62,000 chemicals "grandfathered" in, presumed safe by the Environmental Protection Agency with no evaluation of the evidence.

1982: Government assessment of BPA toxicity holds no regulatory weight. The National Toxicology Program determines that the lowest adverse effect level (LOAEL) for BPA in laboratory animals is 1,000 parts per million (ppm), equivalent to 50 milligrams of BPA per kilogram of body weight per day (50 mg/kg/d) (NTP 1982). This study becomes the basis for EPA's 1988 safety standard which would remain in place for 20 years and counting, sorely out of step with scores of low-dose BPA toxicity studies published in the interim. [1982 NTP study of BPA toxicity (pdf)].

Late 1980s through 1990's - First BPA safety standard at odds with first low-dose BPA studies

1988: EPA's safety standard for BPA is up to 25 times higher than harmful levels. US EPA sets a safety standard (reference dose) for BPA, based on crude, high-dose BPA studies showing reduced body weight of exposed animals, establishing the standard in 1988 and reaffirming it in 1993. The "safe" exposure level established by EPA, at 50 micrograms of BPA per kilogram of body weight per day (50 ug/kg/d), is 1,000 times lower than amounts found to affect the growth of animals in high-dose industry studies. But when a series of studies over the next 20 years show BPA to be toxic at doses far below EPA's safety standard (as low as 2 ug/kd/d), the Agency fails to update the standard to reflect the new information. [EPA's summary of their 1993 (current) BPA safety standard]

March 13, 1996: First FDA assessment of Americans' exposures to BPA. A memorandum from FDA technical staff estimate that through contaminated canned food, adults are exposed to 11 micrograms of BPA daily, while infants are exposed to 7 micrograms per day. This assessment will stand as FDA's official position for many years even as the science on BPA toxicity expands exponentially, demonstrating risks at levels deemed safe in this FDA assessment.

March 1997: Studies show BPA to be toxic at levels that are in people. Just four years after EPA establishes its BPA safety standard, Fred vom Saal at the University of Missouri-Columbia finds that low level exposure to bisphenol A harms the prostate. This is the first of many studies from academic labs that will find harmful effects of BPA at levels of exposure far below the government's BPA safety standards, in the range of what is found in people. Over the next 11 years the body of literature on low-dose BPA toxicity will grow to include more than 100 publications linking BPA to breast and prostate damage, early puberty, behavioral problems, and other effects at levels up to 25 times lower than EPA's "safe" dose. [vom Saal's landmark 1997 prostate study]

November 1997: Government tests reveal BPA contamination in infant formula. FDA finds BPA contamination in 12 of 14 samples of canned infant formula, from BPA leaching out of the metal can linings (Biles 1997). At the levels found, between 1 and 13 parts per billion (ppb), many formula-fed infants will be exposed to BPA in excess of amounts found to harm development (prostate, breast, early puberty, behavior), but FDA fails to do an assessment of the risks.

May 1999: BPA found to leach from baby bottles. Consumer Reports finds BPA leaching from baby bottles when heated, prompting renewed debate over the safety of babies' exposures (Consumers Union 1999).

May 1999: FDA publicly asserts the safety of BPA for bottle-fed infants, ignoring emerging evidence of low-dose BPA toxicity. FDA Product Policy Director George Pauli states, “Our conclusion is we should go with the track record. We have evaluated in a thorough manner, and concluded its use is safe. We haven’t seen anything that would persuade us to change that” (FDA 1999). FDA releases no information on any additional analyses they may have conducted besides the assessments of infant exposures based on 14 tests of infant formula.

October 1999: Scientist from the University of Missouri report in the Journal Nature that exposure to BPA hastens puberty in female mice. The authors conclude that exposing female mouse fetuses to endocrine disruptors that are "within the range typical of the environmental exposure of humans alters the postnatal growth rate and brings on early puberty in these mice" (Howdeshell 1999). The study raises significant concerns about the possible links between early puberty and BPA exposures in girls. [study abstract]

2002: Study finds brain and behavioral effects from BPA exposure. Italian scientists expose mice to BPA during pregnancy and lactation. The offspring, once adults, exhibit fewer maternal behaviors. The authors attribute brain and behavioral changes to BPA exposure (Palanza 2002). The harmful dose, at 200 ug/kg/d, is 40 times lower than the study EPA used to set its 1993 safety standard. [study - BPA harms brain and behavior]

2003-2006: First serious government evaluation of BPA low-dose toxicity, led by industry consultant

2003: BPA to be evaluated for risks to people. The National Institute of Health (NIH) nominates BPA for evaluation by the Center for the Evaluation of Risk to Human Reproduction (CERHR) at the National Toxicology Program (NTP) as a reproductive and developmental toxin. NIH hires an industry contractor to lead the assessment, Sciences International (SI).

2003-2006: Industry consultant conducts initial BPA assessment, hand picks gov't advisory panel. Sciences International performs the literature review for BPA toxicity, choosing and summarizing studies and providing an assessment of each study's relevance. SI and CERHR staff hand pick 15 scientists to serve on the expert government advisory panel charged with reviewing SI's assessments and making recommendations on BPA toxicity, but they deliberately exclude from the panel all scientists who have significant expertise in BPA, because of concerns that expertise may inject bias into the evaluation process.

December 2006: Report by industry consultant and advisory panel tows industry line - "BPA is safe." CERHR publishes their advisory panel report on BPA, largely written by Sciences International. NRDC and Dr. vom Saal submit public comments outlining errors in interpretation of studies and also list studies that show low dose toxicity of BPA which were excluded by Sciences International from the draft. [Dec 2006 Advisory panel report] [Dr. VomSaal's critique] [NRDC's critique] [All public comments]

First half of 2007: Industry influence on BPA science is revealed, Agency fires contractor

February 28, 2007: EWG discovers that the government's BPA consultant works for BPA manufacturers. EWG learns that Sciences International, the firm reviewing BPA toxicity for the government, has corporate clients like Dow Chemical and BASF that are major manufacturers of BPA. [SI ties to BPA industry]

February 28, 2007: Congress launches investigation of gov't conflict of interest policies on BPA. The powerful House Oversight and Government Reform Committee launches and investigation of conflict of interest policies of NIEHS, the NIH agency responsible for hiring the industry contractor SI to conduct the BPA review. Congressman Waxman and Senator Boxer request that the Director of NIEHS, Dr. David Schwartz, provide information on potential conflicts of interest involving Sciences International. [Congressional committee request for information on BPA assessment]

March 4, 2007: LA Times reports on conflicts of interest in government's choice of BPA contractors. LA Times' Marla Cone reports that Sciences International’s clients include chemical companies that manufacture BPA, noting concerns that these ties may compromise their ability to conduct an unbiased assessment of BPA toxicity for the government. [LA Times story on SI's conflicts]

March 5-7, 2007: Government suspends contract of industry consultant, but fails to throw out its work. At the first public meeting of the CERHR advisory panel, CERHR announces that they have suspended Sciences International because of concerns over their potential conflicts of interest. CERHR fails to throw out SI's work; instead, the advisory panel edits the BPA assessment originally prepared by SI.

March 5, 2007: First broad study of canned food shows widespread BPA contamination. An EWG study of 97 canned foods demonstrates widespread, high exposures to BPA when the chemical leaches from metal food can linings. EWG's study presents data showing the highest concentrations in canned soup, pastas, and infant formula, with information on potential health risks for vulnerable populations. Results show that many Americans are exposed to BPA above levels shown to be harmful in laboratory studies. [EWG canned food investigation]

April 13, 2007: Government fires industry contractor. NIEHS fires their industry contractor, Sciences International, due to concerns over conflicts of interest. However, the BPA advisory panel continues building upon draft expert panel report that was prepared by SI, despite concerns raised by advocates and independent scientists that the document is deeply biased and inaccurate. [Government news release on contractor firing]

April 20 - June 20, 2007: Government assessment contains nearly 300 errors. CERHR publishes another draft of their advisory panel's BPA assessment and requests public comments. EWG finds in the report many examples of arbitrary and inconsistent application of scientific criteria to BPA studies in the report. In comments, EWG notes that the expert panel found 70% of industry-funded and only 30% of non-industry funded studies to be adequate for purposes of assessing BPA toxicity; the panel rejects independent studies at 3 times the rate of industry funded studies. NRDC and 6 other independent scientists also submit to CERHR to correct the interpretation of their studies by the panel. In particular, Dr. Ana Soto’s lab at Tufts University submits a comprehensive report outlining errors in the draft, page by page. Altogether, BPA experts find 297 errors of fact and interpretation in the government's draft BPA assessment, according to an EWG analysis of the comments. [June 2007 advisory (expert) panel report on BPA] [EWG comments on BPA assessment draft (pdf)] [all public comments] [EWG assessment of 297 errors in the document]

Second half of 2007: Government panel ignores low-dose BPA toxicity in favor of industry studies, BPA experts warn of health risks

July 24, 2007: NTP exonerates the work of their contractor, but fails to analyze the bias and adequacy of the contractor's work. NIEHS-NTP release findings of their self-audit regarding potential conflict of interest involving the contractor they hired, Sciences International; they conclude that there was no impropriety in SI's work on BPA. The audit does not include an evaluation of the verity and completeness of the analysis of BPA literature that was provided by Sciences International. Many BPA experts have maintained that the audit should have evaluated whether Sciences International injected bias into their analysis of BPA studies from the peer-reviewed literature; experts' analyses of SI's work suggests that it did. [results of NTP's self-audit (pdf)]

August 2, 2007: Independent BPA experts complete an assessment raising concerns of BPA risks for people. An NIH-funded panel of 38 independent scientists who conduct BPA research conclude a comprehensive review of current knowledge of BPA health risks and human exposures. This group of scientists, known as the Chapel Hill panel, conclude that BPA exposure at current levels presents a clear risk to human health. They publish a consensus statement on BPA risk to human health and reproduction and five articles outlining their findings in the peer-reviewed journal Reproductive Toxicology. [summary of Chapel Hill panel findings]

August 6-8, 2007: 2nd advisory panel meeting focuses on errors in their assessment. EWG releases an analysis of critiques of the advisory panel assessment of BPA from independent scientists that were submitted to CERHR in June of 2006, and presents findings showing that the interim draft expert panel report contains hundreds of potential errors and inconsistencies. [EWG assessment of 297 errors in the document]

August 8, 2007: EWG study shows many infants exposed to BPA contaminated in infant formula. EWG publishes analyses of BPA tests in infant formula, showing that showing that one of every 16 formula-fed babies are exposed to levels of BPA that have been shown to be toxic in animal studies. EWG's study shows that FDA's 1997 assessment (Biles 1997) significantly underestimated infant exposures to BPA. [infant exposures to BPA in contaminated formula]

November 26, 2007: BPA advisory panel issues its final report, minimizing BPA risks, ignoring many risks of concern to Chapel Hill panel. In their final report, the advisory panel expresses “some concern” about the neural and behavioral impacts of fetal exposure to low doses of BPA, but rejects the independent studies linking BPA exposure to breast and prostate cancer, obesity, and reproductive problems. Their findings are out of step with conclusions of the Chapel Hill panel of BPA experts. Their report does not correct many of the 297 errors of fact and interpretation reported by BPA experts earlier in the year. [November 2007 advisory (expert) panel report on BPA]

Late 2007, Early 2008 - FDA and infant formula manufacturers' positions on safety of BPA for babies come under fire, Congress investigates

December 5, 2007: BPA used by every infant formula manufacturer. EWG reports that every major U.S. infant formula maker uses BPA to line the metal portions of their formula cans. In light of multiple studies now showing that infants are exposed to BPA at levels of concern, EWG conducts a survey of formula makers' use of BPA, and releases a guide to infant formula, providing information for parents on how to minimize BPA exposure from canned infant formula. EWG's survey of manufacturers reveals that every major formula maker uses a BPA-based can lining that can leach BPA into the formula. [EWG's infant formula guide for parents]

January 17 - February 5, 2008: Major Congressional investigation of FDA, infant formula manufacturers, and industry consultants. In light of growing concerns over children's exposures to BPA, the US House of Representatives Committee on Energy and Commerce launches an investigation into the use of BPA in the lining of metal cans that contain infant formula. Representatives John D. Dingell and Bart Stupak request that infant formulas provide information on their use of BPA in their products and whether they conduct BPA testing on their formula. They also demand that FDA clarify its position on the safety of BPA and provide evidence to support their assertion that there is “no safety concern at the current exposure level." Lastly, the committee asks a private consulting firm, the Weinbert Group, to document their work for BPA manufacturers, asking them to clarify “whether science is for sale." [Congressional inquiries to formula manufacturers] [Congress demands FDA provide rationale for BPA safety assertions] [Congress action regarding the Weinberg Group] [all records of Congressional BPA inquiry]

January 29 to February 8, 2008: Infant formula companies reveal that they do not know how much BPA is in their formula. Infant formula manufacturers respond to the request for information from Congress. Most reveal that they have not tested their products for BPA. Two, Hain-Celestial and Abbott, have tested but used assays with limits of detection that were so high that they would not detect levels of BPA that studies show may be toxic and that were found by both EWG and FDA tests. [formula makers' responses to Congress].

February 7, 2008: BPA leaches from baby bottles. A coalition of environmental and public health groups in the U.S. and Canada release a study showing that BPA leaches out of baby bottles into heated liquids, raising renewed concerns about the safety of plastic bottles. [BPA in baby bottles].

February 25, 2008: FDA responds to Congressional investigation, reveals that two industry studies are the basis of its safety evaluation. FDA's response to a congressional inquiry on their BPA evaluations reveals that the agency’s assertion that current levels of BPA exposure do not pose a health concern are based on two studies that were sponsored by the American Plastics Council. Of note, one of these studies was widely criticized by BPA experts for its fatal design flaws. The other study has not been made available to the public and has not been published in a peer-reviewed journal to date. Dozens of studies published in the peer reviewed literature link BPA exposure at extremely low levels to a number of adverse health effects, including breast and prostate cancer, early puberty, infertility, obesity, and behavioral problems. FDA has used none of these studies in its evaluations of BPA safety. [FDA’s response]

April 4, 2008: Congress again demands that FDA reveal the basis of its assertions that BPA is safe. Following FDA revealing that their BPA safety assessment is based on 2 industry studies, one of them unpublished, The Committee on Energy and Commerce demands that FDA provide previously requested details about their safety assessment for infant formula or face a Congressional subpeona. [Congress requests data on infant exposures from FDA (pdf)] [Complete record of Congressional BPA inquiry]

Spring 2008 - Government finds BPA poses risks to humans, Wal-Mart and other retailers pull BPA products from shelves

April 16, 2008: NTP releases its own determination of BPA toxicity, for the first time raising substantial concerns about BPA risk to human development. NTP releases their own evaluation of BPA's risks to human reproduction and development, based on their review of the advisory panel report, the Chapel Hill panel findings, and other recent scientific publications. The draft is a dramatic departure from the advisory panel's findings, raising concerns for BPA's links to early puberty, breast cancer, prostate effects, and behavioral problems. NTP highlights that pregnancy and early life are especially sensitive periods given higher exposure and limited ability to metabolize the chemical. [NTP draft assessment of BPA]

April 16, 2008: Congress calls on FDA to reassess its safety standards for BPA based on new concerns over health risks. Following NTP's dramatic findings on BPA concerns, Representative John Dingell, Chairman of the Committee on Energy and Commerce, calls on FDA to promptly reconsider the safety of BPA in products for infants and children. [Congress calls on FDA to reassess BPA risks]

April 18, 2008: Health Canada announces that BPA will be deemed a "dangerous substance." Canada becomes the first country to complete a comprehensive human exposures assessment for BPA and take actions to reduce exposures nationally. Based on the findings of their assessment, they announce that "to be prudent, the Government of Canada is proposing to reduce bisphenol A exposure in infants and newborns by proposing a number of actions: to ban polycarbonate baby bottles; to develop stringent migration targets for bisphenol A in infant formula cans; to work with industry to develop alternative food packaging and develop a code of practice; and to list bisphenol A under Schedule 1 of the Canadian Environmental Protection Act." [Canadian actions to reduce BPA exposures]

April 18-21, 2008: Major manufacturers and retailers abandon BPA in plastics. Within days of the NTP and Canadian judgements major BPA manufacturers including Playtex (which makes bottles and cups) and Nalgene announce a shift to BPA-free products. Major retailers including Wal-Mart and Toys R Us announce they will quickly phase-out BPA-containing baby bottles. [Wal-Mart to phase out BPA] [Toys-R-Us - BPA phase-out] [Nalgene goes BPA free]

References

Biles JE, McNeal T.P., Begley T.H. 1997. FDA. Determination of bisphenol A migrating from epoxy can coatings to infant formula liquid concentrates. . J Agric Food Chem 45: 4697-700.

Consumers Union. 1999. "Baby Alert: New findings about plastics" Consumer Reports 64(May):28.

Dodds, EC and W Lawson 1938. Molecular structure in relation to oestrogenic activity. Compounds without a phenanthrene nucleus. Proceedings of the Royal Society. London B. 125:222-232.

FDA. 1996. Cumulative Exposure Estimated for Bisphenol A (BPA), Individually for Adults and Infants from Its Use in Epoxy-Based Can Coatings and Polycarbonate (PC) Articles, verbal request of 10-23-95, memorandum to G. Diachenki, Ph.D, Division of Product Manufacture and Use, HGS-245, from Allan B. Bailey, Ph.D., Chemistry Review Branch, HFS-245. Department of Health and Human Services, Food and Drug Administration.

FDA. 1999. Statement by George Pauli, referenced in "FDA Unimpressed By Low Dose Claims" Endocrine/Estrogen Letter. 5(10):106

Howdeshell KL, Hotchkiss, A.K., Thayer, K.A., Vandenbergh, J.G., vom Saal, F.S. 1999. Exposure to bisphenol A advances puberty. Nature 401(6755): 763-4.

NTP (National Toxicology Program). 1982. NTP Technical Report on the carcinogenesis bioassay of bisphenol A (CAS No. 80-05-7) in F344 rats and B6C3F1 mice (feed study). NTP-80-35. NIH Publ. No. 82-1771.

Palanza PL, Howdeshell KL, Parmigiani S, vom Saal FS. 2002. Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice. Environ Health Perspect 110 Suppl 3: 415-22.