Comments to the Science Board of the Food and Drug Administration
Jane Houlihan, MSCE, Senior Vice President for Research Sonya Lunder, MPH, Senior Analyst
Summary
Nine months ago this Science Board issued strong recommendations that should have convinced the federal Food and Drug Administration to act swiftly and decisively to protect the public from the artificial hormone and common food contaminant bisphenol A (BPA).
Your clear and carefully considered advice should cause FDA to overhaul its BPA safety assessment, based on a concerted and honest reckoning of what the latest science tells us about the dangers to human health of this potent endocrine-disrupting chemical.
Two months after you issued this recommendation, Assistant Commissioner Dr. Josh Sharfstein committed to “tak[ing] a fresh look at this important issue from a scientific and policy position, incorporating emerging science and appropriate input from both inside and outside the agency.”
At this Science Board’s August 17th meeting, FDA’s new leadership will provide its first public update on its new review of BPA.
Your call for a dramatic reversal would undo past FDA decisions that, by EWG’s lights, are endangering the futures of millions of Americans.
The stakes could not be higher, and the evidence could not be more compelling. Most of the estimated 3 million babies born since you issued your recommendations face daily exposures to BPA from baby bottles, infant formula, and food. During those same 9 months, scientists have published many new studies further solidifying the evidence of BPA’s low-dose toxicity:
- BPA wreaks havoc on brain function in monkeys, disabling their capacity for thought (Leranth 2008) and feminizing the behavior of male monkeys (Nakagami 2009).
- BPA spurs early puberty, premature menopause (Adewale 2009) and permanent menstrual periods in animals (Fernandez 2009).
- Premature infants fighting for their lives are being bombarded with BPA via plastic IVs and other medical devices used by hospitals. As well, they may be receiving large doses, for their weights, in formula (Calafat 2009). We do not know the eventual toll on these unfortunate children, but it cannot be good.
Many experts agree that BPA may endanger human health. Health Canada prohibits the sale of polycarbonate baby bottles and is taking action to reduce BPA levels in formula, due to concerns about the chemical’s effect on infant brain development (Canada 2008). The Endocrine Society called for regulation to reduce people’s exposures to hormone disruptors—particularly BPA (D'Antuono 2001). In the face of FDA inaction, more than 20 U.S. states and municipalities are considering steps to limit BPA exposure for pregnant women and young children (NCEL 2009).
Consumers have spoken as well. Major manufacturers and retailers including Playtex, Nalgene, Wal-Mart and Toys “R” Us are replacing BPA-based polycarbonate bottles with other materials. Infant formula makers have told Congress that they are investigating alternatives to BPA-based metal can liners. The formula manufacturer PBM has acknowledged the urgency of using safer materials, announcing that "the possibility that Bisphenol A may pose adverse health risks to the infants and children who are fed our formula was more than sufficient for us to begin the process of eliminating Bisphenol A from our infant formula packaging" (PBM 2008).
More than 92% of the population is exposed to BPA (Calafat 2008). FDA has found that the fetus, infants and children face the greatest risks from BPA exposure.
FDA could fall into the common trap of authorizing interminable studies of BPA. This would be the wrong choice. Many hundreds of studies demonstrate the dangers of BPA exposures. Research will always spawn more questions to be answered in subsequent work. For BPA, we know enough to take action now.
We await FDA’s final assessment of BPA to learn whether the agency has embraced the Science Board’s recommendations, and, ultimately, the Administration’s commitment to bring real change to Washington.
Science Panel recommends overhaul of BPA assessment. In October 2008, this Science Panel deemed FDA’s risk assessment for BPA in food to be flawed. Two faults you revealed lie at the heart of FDA’s current failings in assessing the safety of BPA:
- You found that FDA’s assumed “safe” level (5 milligrams of BPA per kilogram of body weight per day, or 5 mg/kg/d) is “substantially” higher than it should be, based on available science.
- You also found the current margin of safety to be “inadequate,” an indication that people are exposed to BPA in concentrations approaching the dose that could be harmful.
FDA must correct these and the other problems noted below if its “fresh look” at BPA is to protect the public from this potent endocrine-disrupting chemical.
BPA widely pollutes the population and widely contaminates food. The Centers for Disease Control and Prevention has detected BPA in more than 92% of individuals tested (Calafat 2008). In its draft assessment FDA has correctly identified the developing fetus, infants and children as the populations at greatest risk.
A recent Harvard University study found an average of 69% more BPA in the urine of adults when they drink from BPA-based (polycarbonate) bottles compared to other kinds of containers (Carwile 2009). Infants fed from polycarbonate baby bottles would consume even greater amounts of BPA, for their body weights, because their diets consist solely of liquid formula, commonly warmed in the bottles.
Product-testing by Environmental Working Group, Health Canada and FDA confirms that BPA leaches into liquid infant formula from epoxy can linings (Cao 2008; EWG 2007; FDA 2009). BPA is also found in jarred baby food and canned foods commonly fed to infants and children (Cao 2009; EWG 2007).
Experts deem BPA a public health concern, policymakers take action. In June, the Endocrine Society issued a statement calling for “regulation seeking to decrease human exposure to the many endocrine-disrupting agents” and specifically cited BPA as one of the chemicals of concern (Diamanti-Kandarakis 2009). The Endocrine Society noted that “even infinitesimally low levels of exposure – indeed, any level of exposure at all – may cause endocrine or reproductive abnormalities…particularly if exposure occurs during a critical developmental window. Surprisingly, low doses may even exert more potent effects than higher doses.”
A group of 38 hormone disruption experts convened by NIEHS reviewed the evidence of BPA’s low dose toxicity and concluded that “much evidence suggests that these adverse effects are occurring in animals within the range of exposure to BPA of the typical human living in a developed country” (Vom Saal 2007).
Minnesota and Connecticut have restricted BPA in baby bottles, sippy cups and other food containers for children. The National Caucus of Environmental Legislators (NCEL) reports that more than 20 state legislatures are considering similar legislation (NCEL 2009).
New studies underscore low dose toxicity. Since FDA published its draft assessment (FDA 2008), a series of new studies have confirmed the established risks of low-dose exposures to BPA. These studies show that BPA impairs normal development of the neurological system (Kiguchi 2008; Monje 2009; Nakagami 2009; Tanida 2009), damages the reproductive system (Adewale 2009; Fernandez 2009; Muhlhauser 2009; Newbold 2009; Salian 2009; Vandenberg 2008), and harms normal cell functions (Ben-Jonathan 2009; Huang 2009; Ricupito 2009).
One of the more striking studies, conducted by researchers at Yale, found that adult African green monkeys exposed to BPA suffered dramatic losses of estrogen-cued synapse development in regions of the brain that involve cognition and mood (Leranth, Hajszan 2008). In some cases synapse formation was reduced by more than 50%. These results confirmed earlier studies that reported inhibition of synaptic formation in rodents with early life exposure to BPA (Leranth, Szigeti-Buck 2008; MacLusky 2005).
A second study by scientists at Japan Women's University found that male cynomolgus monkeys exposed to BPA in utero were feminized, demonstrating reduced maternal clinging and social exploration exhibited by unexposed female monkeys (Nakagami 2009). These basic behavioral changes indicate brain alterations. The researchers noted that the monkeys’ bloodstreams contained BPA at a level found in some human mothers at the time of delivery (12 ng/mL in plasma) (Padmanabhan 2008). Six other studies that the National Toxicology Program found to be of “high quality” (NTP 2008) have also noted loss of typical behavioral differences between males and females (“sexually dimorphic behavior”) in rodents after exposure to BPA, (Della Seta 2006; Gioiosa 2007; Laviola 2005; Negishi 2004; Palanza 2002; Ryan 2006).
FDA’s reassessment- changes needed. The Food Safety and Enhancement Act of 2009 requires FDA to finalize its safety assessment for BPA by the end of this year. FDA scientists have a lot to do if they plan to address the deficiencies the Science Board pinpointed. We have several concerns with FDA’s progress to date, based on FDA staff presentations to the Board at its February meeting.
First, FDA’s Dr. Mitchell Cheeseman discussed modeling methods that suggested that the agency would consider basing a “safe” BPA dose for people on the dose that harms 10% of animals tested, implying that such a level is similar to a dose causing “No Effect” (FDA 2009). Adopting this approach for BPA would be disastrous for public health, and is contrary to recent recommendations by the National Research Council (NRC 2009).
Of equal concern is the fact that FDA selected studies for use in setting BPA health standards (Tyl 2002; Tyl 2008) that have been criticized for fundamental design flaws (Myers 2009). Absent from the FDA’s February update was any discussion of how the agency plans to address the Science Board’s disagreement with the exclusion of “the large number of non-GLP studies” and suggestion that FDA include all recent publications in its review.
Also, a recent CDC study reported high BPA levels in premature infants, 11 times higher than in the general population. The study also suggests that BPA may be leaching out of medical devices made with the plasticizer bis-2-ethylhexyl phthalate (DEHP) (Calafat 2009). Although an advance copy of this study was available to FDA last February, the agency did not identify patients with exposure to DEHP-containing medical devices as a high-risk group for further study. We hope that the FDA will rectify this serious oversight.
FDA’s February presentation suggested that the agency’s improved exposure modeling showed that compared to previous FDA estimates, “average babies” are exposed to 40% more BPA, and babies at the 90th percentile of exposure are exposed to 3 times more BPA. But FDA must also consider the safety of the 1 in 10 infants exposed to even more BPA than these amounts.
The Science Board must hold the FDA to the highest standard of excellence. The law is clear. The FDA’s mission is to ensure that the nation’s food supply is pure. Scientific research has provided ample evidence to support the conclusion that BPA, even in very low does, is dangerous to human health. It is past time for FDA to recognize that fact and to take action to end rampant BPA contamination of food, especially infant formula and other foods consumed by pregnant women and young children.
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