In the News
Human Exposure to BPA From Use in Food Contact Materials Discussed at FDA Hearing
Oct 28, 2008
A Subcommittee of the Food and Drug Administration's (FDA) Science Board Advisory Committee held a public hearing on September 16, 2008 to solicit comments and expert advice in its forthcoming recommendations regarding the Agency's "Draft Assessment of Bisphenol A for use in Food Contact Applications." The draft report describes FDA's approach toward estimating the current dietary exposure to BPA and the Agency's method of establishing a no adverse effect levels (NOAELs) for adults and for infants up to one year old.
BPA is a starting reactant used to make certain plastics and epoxy resins, both of which are used in such food-contact applications as polycarbonate bottles and can coatings. In its draft report, FDA estimated that BPA exposure in infants and adults from its use in food contact materials is 2.42 µg/kg bw/day and 0.185 µg/kg bw/day, respectively. By comparison, the exposure estimate for BPA in infants in the report recently released by the National Toxicology Program (NTP) Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A is five times greater than FDA's estimate. When asked why FDA used average values of BPA in its assessment of exposure in infants and not a maximum or some other point on an intake distribution curve, Dr. Allan Bailey, a chemist with FDA responded that the Agency did not have an intake distribution for BPA in infant formula. He acknowledged that there were many other conservatisms built into the exposure estimate and it should not be considered an "upper-bound" exposure value.
An expert panel, consisting of representatives from academia, industry, and government, addressed FDA's calculation of BPA exposure in the Agency's draft assessment. Some members of the panel noted that the sample size of infant formula used to estimate exposure to infants was limited and that the samples were obtained in only one city. Other panel members suggested that high consumers of infant formula could be getting as much as twice the amount of BPA estimated by FDA. It was also pointed out that sterilization of baby bottles, which could result in release of BPA from the polycarbonate, often continues long after the two-month period FDA assumed in its assessment.
Studies Used to Determine NOAEL Questioned
Participants in the hearing also commented on FDA's no observed adverse effect level (NOAEL) for BPA of 5 mg/kg bw/day (5,000 µg/kg bw/day). FDA determined this NOAEL based on two multi-generational rodent studies. Based on FDA's exposure estimates, this NOAEL provides margins of safety (MOS) of approximately 2,000 and 27,000 for infants and adults, respectively—well above the MOS of 1,000 for a systemic toxicity endpoint, which the Agency considers a safe exposure level.
Dr. John Bucher of the National Institute of Environmental Health Science, National Institutes of Health, and a member of the team of scientists that drafted the NTP report on BPA, explained that its NOAEL of 10 µg/kg bw/day for infants in NTP's report is higher because it was based upon the totality of the publicly available data, where FDA's study focused on two studies conducted according to Agency standards and involving oral dose administration. NTP recognized that the data from some studies were more reliable than from others, and weighed the study results accordingly in its report, reported Dr. Bucher. A number of participants encouraged the Subcommittee to use NTP's higher NOAEL for infants rather than the lower NOAEL currently in FDA's draft assessment.
Dr. Frederick vom Saal, Professor at University of Missouri-Columbia, Division of Biological Sciences, commented on FDA's policy that toxicity studies need to be carried out according to Agency standards to be considered relevant. He and others suggested that Subcommittee members consider all toxicological evidence in preparing their advice to the Agency, and to invoke the precautionary principle in this case because there is so much uncertainty, especially relating to the potential long-term effects to infants exposed to BPA. The precautionary principle, which is being considered by Health Canada with regard to BPA, would call for a ban on the use of BPA in all infant products. (Click here for more discussion on this.)
When asked if it was possible to review the totality of the publicly available toxicity data for its assessment, Dr. Michelle Twaroski, a Supervisory Toxicologist with FDA, responded that a quantitative assessment was not possible because the studies are so diverse with respect to, for example, mode of administration and endpoint evaluation. She then was asked if the Agency considered establishing a benchmark dose instead of a NOAEL based on the available toxicity data. Dr. Twaroski replied that FDA would welcome such a recommendation from the Subcommittee.
The expert panel was asked if anyone was aware of a mechanism through which low doses of BPA can result in adverse health effects in humans. The consensus was that there is no clearly established pathway, and that further study is needed to link any potential mechanistic effects of BPA to adverse effects in humans at low doses.
A publication in the Journal of the American Medical Association (JAMA) that was released on-line the morning of the hearing proposed a connection between urinary levels of BPA in humans and the incidence of type 2 diabetes and heart disease. The Subcommittee asked Dr. David Melzer, an author of the JAMA paper, if there was a clear relationship between BPA intake and urine concentrations of BPA. He acknowledged that people do metabolize and excrete BPA differently, and that there was no clear relationship. The study did not find any discernible correlation between BPA urine levels and stroke or hypertension, typical indicators of heart disease.
In closing statements, the expert panel members disagreed on whether FDA's assessments and conclusions were accurate and whether the Agency should consider adopting the NOAEL from the NTP report. However, there was general agreement that more testing is required to understand the mechanism of toxicity of BPA in humans.