The Tangled Story of Bisphenol-a – The NTP’s Expert Report is Out

The Center for Evaluation of Risks to Human Reproduction (CERHR) has finalized its Expert Panel report assessing the reproductive and developmental toxicity of bisphenol-a (BPA). CERHR will be accepting public comments on the report through the end of January 2008. Once comments have been received, the NTP will prepare a NTP-CERHR Monograph for BPA. The Monograph contains the NTP Brief, the Expert Panel Report and the public comments on the Expert Panel Report. The NTP Brief is a summary for decision makers and presumably will represent a milestone in determining what steps are needed (if any) to reduce exposures to BPA.

What will happen after that is anyone’s guess. The NTP does not regulate chemicals – the EPA and FDA do that. It can be anticipated that the NTP’s report will churn slowly through the processes those agencies have for assessing health risks from chemicals; if the weight of evidence persuades regulators that BPA poses a significant human health risk, there will be rulemaking and negotiation with manufacturers. If you’re expecting regulations to be enacted banning BPA, be prepared to wait several years for them. Under that scenario, you can also anticipate manufacturers being given a few years after that to get BPA out of the production stream. Then, there will still be tens of millions of sports bottles and sippy cups in use for years to come after that.

Hopefully, there isn’t anything terribly bad associated with BPA exposure, because we’re all exposed to low levels of it, and probably will be for the better part of a generation.

The first draft of the Expert Panel report was prepared by an NTP contractor, Sciences International (SI). In March 2007, the Environmental Working Group reported that SI had working relationships with companies manufacturing chemicals being assessed by CERHR. CERHR apparently required contractors to make conflict of interest disclosures but didn't place any further restrictions on them. Officials at the National Toxicology Program terminated SI's contract with CERHR on April 13, 2007, but stood by the quality of the previous assessments conducted by the contractor. Representative Henry Waxman's Governmental Oversight Committee has looked further into the conflict of interest matter, but does not appear to have started an investigation as yet.

In March 2007, the National Institutes of Environmental Health Sciences (NIEHS) conducted an audit of two key activities carried out by SI as part of the bisphenol-a (BPA) review: (1) selection of literature relevant for review by the expert panel on bisphenol A (BPA) and (2) incorporation of input from expert panel members into draft reports. The NIEHS audit concluded that the draft BPA expert panel reports "include consideration of all relevant references and reliably include changes requested by the expert panel members. NTP concludes that the draft expert panel reports are useful for the CERHR evaluation of BPA". (Note: the expert panel members are selected by a CERHR Core Committee consisting of scientists in government service.) What this appears to mean that NIEHS was satisfied that the comments from the CERHR's expert panel, which issues the authoritative decision-makers' summary on a chemical, were incorporated into the report. Some of the public comments on the BPA report, for example from Fredrick Vom Saal, give a different perspective about how well the available scientific literature has been incorporated into the BPA review (particularly how his papers were incorporated into the review). The Pump Handle provides a summary by NRDC of the overall criticisms related to the BPA review process.

The NTP also convened a working group of the Board of Scientific Counselers to assess its contracts for conflicts of interest (COI). The methods and results as described in their report were described as follows:

In conducting their review, the WG analyzed each NTP contract and Statement of Work (SOW) as well as the extent of government oversight to determine the degree of risk for potential conflicts and/or impaired objectivity. Questions were sent to a crosssection of NTP contractors in an effort to assess the compliance of their COI policies with law and regulation, and to determine the existence of any COI. The WG relied on the contractor’s self-certifications regarding conflicts with current clients as the HHS Office of the General Counsel (OGC) has indicated that this is normal, reasonable business practice in the absence of specific factual allegations of impropriety. To gain a better understanding of the contracts and how they operate and interrelate, the WG also held discussions with NTP project officers responsible for various contracts including the NTP contract for pathology support. Based on the data provided, the WG did not find any evidence of actual or apparent COI in any of the cross-section of contracts reviewed.

The WG identified a number of best practices and specific areas where improvements could be made by NTP/NIEHS, as well as by the entire NIH, that could result in identifying COI as early in the acquisition process as possible in order to avoid, neutralize or mitigate those COI.

Representative Waxman's committee criticized those methods, stating that the contractors's processes for identifying and disclosing COIs were not adequate.

The working group's reliance on contractor reports is a questionable way to assess conflicts of interest. Most of the contractors do not appear to have adequate systems for tracking such conflicts. According to the report, although "most" of the ten contractors that completed questionnaires had a designated official to solicit and review financial dislosure statements from their investigators, "[f]ewer" contractors collected disclosure statements listing significant financial interests from their investigators. "Even fewer" contractors updated these disclosure statements during the life of their NTP contracts. And "very few" conractors kept the disclosure statements for the mandatory three-year period following the completion of their NTP contracts. In other words, many of the contractors that provided self-certifications to the working group did not collect or retain the information necessary to determine whether individual conflicts of interest existed under their NTP contracts.

I'm immune to the censorious tone of the NRDC and Representative Waxman ("I'm shocked, shocked to find that gambling is going on in here!"). It's hard to find a party, institution or organization that is free of conflict of interest (didja hear that, Congress?). For myself, there seem to be sufficient checks and balances with the BSC review alerting us that the BPA assessment might contain uncertainties that understate the developmental toxicity risk, the public comments from academic scientists which critically review the CERHR's scientific report, and supplemental reviews such as the Chapel Hill Consensus. Perhaps out of this event will come better contracting procedures and business practices for disclosing and managing conflicts of interest. In the long run, consulting firms who wish to keep their client lists confidential might have to forgo the pleasures of performing work for government agencies. In the meantime, there are enough points of view available that the BPA story needs to be brought up to date. For the moment, what's been done is to point out that some care may need to be taken in using the information developed from the government's review process.

And, if you're not willing to wait for a definitive, authoritative statement about BPA risks to emerge (not like that's going to happen anyway), you can start doing the precautionary thing now.