June 4, 2010
Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Room 1061
Rockville, MD 20852
Comments of the Patient, Consumer, and Public Health Coalition
“Food Additives; Bisphenol A”
[Docket No. FDA-2010-N-0100]
The Patient, Consumer, and Public Health Coalition-which includes nonprofit organizations that represent patients, consumers, scientists, and researchers-is commenting on documents prepared by the FDA’s Center for Food Safety and Applied Nutrition (CFSAN) regarding the safety assessment of Bisphenol A (BPA).
In January 2010, the FDA announced that its National Center for Toxicological Research, in cooperation with the National Toxicology Program, is “carrying out in-depth studies to answer key questions and clarify uncertainties about the risks of BPA.” The FDA said that it “shares the perspective of the National Toxicology Program that recent studies provide reason for some concern about the potential effects of BPA on the brain, behavior, and prostate gland of fetuses, infants and children.” The FDA also “recognizes substantial uncertainties” with the interpretation of BPA studies and how BPA may affect human health. Despite those uncertainties, the FDA is supporting “a more robust regulatory framework for oversight of BPA to be able to respond quickly, if necessary, to protect the public.”
Document 1 – BPA in low doses
Document 1 reviews animal studies individually, evaluating each study against specific criteria that it has set forth. It concludes that most studies are not adequate to establish risks of BPA and that based on the research to date the NOAEL (no observed adverse effect level) of 5 mg/kg/day “is the most appropriate for use in the risk assessment.”
Document 2 reviewers from National Institute of Environmental Health Sciences (NIEHS) disagree with the FDA analysis and conclusions, and we found their criticisms to be scientifically solid and compelling. For example, Dr. John Bucher pointed out that “our standard in in vivo rodent safety assessment test protocols are not designed to detect subtle behavioral changes” and that “endocrine active chemicals may show unexpected dose response relationships…and differential effects …during critical periods of development.” Kristina Thayer, Ph.D from NIEHS made a similar observation, noting that based on more recent research “there appears to be more support for biologically meaningful effects at low doses, especially in the realm of effects on brain and behavior.” These are key issues for BPA research. The FDA assumption of BPA safety is based in part on a lack of a dose-response relationship. If estrogenic chemicals don’t show a typical dose-response relationship, and if exposures at different developmental phases differ significantly, then the FDA conclusions will be erroneous. We agree with Dr. Bucher’s conclusion that “The FDA should acknowledge that this uncertainty exists, and conclude that current NOAEL cannot be assumed to assure safety for humans.” And, we agree with Dr. Thayer’s conclusion that although the “adversity of the reported low dose effects has not been fully demonstrated…the converse is also true: the existing literature does not support an assurance of safety of BPA at doses below 5mg/kg/day.”
Jerrold Heindel, Ph.D., also from NIEHS, made important criticisms of the FDA’s reliance on Good Laboratory Practices (GLP) guidelines that are consistent with the criticisms noted above. Dr. Heindel notes that “If the animal model is not appropriate, or the dose selection wrong or the endpoints not sensitive or specific then the results are not valid, GLP not withstanding.” Dr. Heindel further states, “The guideline studies that found no effect of BPA…are flawed and should not be accepted. Perhaps it is not the hundreds of positive publications that are wrong but the GLP guideline studies.4”
Perhaps most important, Dr. Heindel appropriately questions the FDA’s study-by-study approach to the research literature, saying that “looking at each manuscript individually to determine how close it comes to the guideline studies has its limitations and should not have been given so much weight. There is a body of literature and it should be looked at together” rather than “in a vacuum.” He added “Studies need to be assessed for their scientific relevance and not how they fit guideline studies.”….”Why not look at all low dose studies, for example, and see what they are telling us, what endpoints at what doses and in what species….Together they might provide a weight of evidence that is not evident when studies are studied by species. Why not start by making a chart or timelines of dose and effects to see how all the data comes together and what it as a composite is telling us about the toxicity of BPA.” He also concludes that “the NOAEL has not been determined.”
Document 4 – BPA used in packaging for infant formula
The highest estimated daily intakes of BPA occur in infants and children. Until recently, many plastic baby bottles contained BPA, and BPA is more likely to leach out of plastic when its temperature is increased, as when one warms a baby bottle or warms up food in the microwave.4 In March 2009, the six major manufacturers of baby bottles in the United States announced that they would no longer sell baby bottles made with BPA in the U.S. A few days later, SUNOCO, a BPA manufacturer, announced that it would require customers to confirm that no BPA would be used in food or water containers for children under 3 years of age.
Document 4 focuses on BPA used in packaging for infant formula, nursing bottles, and toddler and adult canned foods. Based on new analyses conducted by the FDA of canned food sold in the East Coast and West Coast, it notes that BPA is in liquid infant formula, many toddler foods, and adult canned foods.
Document 5 pointed out that in studies of humans, those that had fasted before being evaluated for BPA levels in humans were expected to have lower levels of BPA, but the results did not support that assumption. They concluded “this suggests substantial non-food exposure” to BPA, “such as water and dust that have been implicated in previous studies.” The authors point out that this conclusion is opposite of the frequent statement in the research literature that food is the major source of BPA exposure. They also point out that while scientists have stated that BPA is quickly excreted through urine, “frequent exposures could result in accumulation if BPA distributes to tissues that release BPA slowly.”
There are many unanswered questions about the risks of BPA on human health, especially prenatal exposures, infants, and children. Exposure from food must be considered in the context of potential exposure from non-food sources and cumulative exposures to BPA and to other estrogenic chemicals. Given the body of literature indicating health risks, and the numerous unanswered questions, we strongly urge FDA to abandon its NOAEL of 5 mg/kg/day dose of BPA, which cannot assure safety for humans. In addition, we urge the FDA to reconsider its approach to the research literature, which is out of step with scientific analyses and data from independent researchers across the country, as well as experts at NIEHS.
Breast Cancer Action
Breast Cancer Fund
Community Access National Network (CANN)
Consumer Federation of America (CFA)
Government Accountability Project (GAP)
National Consumers League
National Research Center for Women & Families/Cancer Prevention and Treatment Fund
U.S. Public Interest Research Group (U.S. PIRG)
For additional information, contact Paul Brown, Government Relations Manager for the National Research Center for Women & Families/Cancer Prevention and Treatment Fund at 202-223-4000 or firstname.lastname@example.org
 U.S. Food and Drug Administration (January 2010). Update on Bisphenol A for Use in Food Contract Applications. Retrieved May 4, 2010 from http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm197739.htm
 Bucher J. (2009, October 19). Comments regarding BPA to Jesse L. Goodman, MD, MPH, Chief Scientist and Deputy Commissioner for Science and Public Health, Food and Drug Administration.
 Thayer K. (2009, October 21). Comments regarding BPA to Jesse L. Goodman, MD, MPH, Chief Scientist and Deputy Commissioner for Science and Public Health, Food and Drug Administration.
 Heindel J. (2009, October 14). Comments regarding BPA to Jesse L. Goodman, MD, MPH, Chief Scientist and Deputy Commissioner for Science and Public Health, Food and Drug Administration.
 National Toxicology Program. U.S. Department of Health and Human Services (HHS). (2008, September). NTP-CEHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A. Retrieved April 3, 2009 from http://cerhr.niehs.nih.gov/chemicals/bisphenol/bisphenol.pdf
 Layton, L. (2009, March 6). No BPA for Baby Bottles in U.S. The Washington Post. Retrieved on April 3, 2009 from http://www.washingtonpost.com/wp-dyn/content/article/2009/03/05/AR2009030503285.html
 Rust, S. and Kissinger, M. (2009, March 12). Maker acknowledges BPA worries. JSOnline. Milwaukee Wisconsin Journal Sentinel. Retrieved on April 3, 2009 from http://www.jsonline.com/watchdog/watchdogreports/41186522.html