The missed electric moment
The FDA hearing on BPA on 16 September produced a prodigious amount of reporting, with stories from around the world. But the most electric moment of the hearing wasn't mentioned by anyone.
During his morning presentation, Dr. Fred vom Saal presented a critique of the paper that the FDA has called its gold standard for determining the safety of bisphenol A. This is research led by Dr. Rochelle Tyl of RTI, published this spring in the peer-reviewed journal Toxicological Sciences. It reports that low doses of BPA did not increase the prostate size of mice exposed in the womb. The Tyl et al. finding is a key piece of evidence for the FDA in reaching its conclusion that work by vom Saal reported in the 1990s-- the findings that opened the whole 'low-dose' issue in the first place-- isn't reliable.
Here is the reference: Tyl RW, Myers C, Marr M, Sloan CS, Castillo N, Veselica MM, et al. 2008a. Two-Generation Reproductive Toxicity Study of Dietary Bisphenol A (BPA) in CD-1® (Swiss) Mice. Toxicological Sciences 104(2), 362–384.
vom Saal's critique of the Tyl paper included several points but the most important was quite simple. Tyl et al. reported that the average weight of the prostate in control animals was approximately 70 milligrams. vom Saal pointed out that this average was almost 75% bigger than the weights of control animals reported by three separate and independent labs for animals of the same age. He proposed there were only two explanations. Either the dissection was performed inaccurately or the animals had diseased prostates. Either of these interpretations would render the results invalid and not useful for the FDA in its effort to assess BPA safety.
Fortunately, Tyl was in the audience and though not scheduled to speak, requested permission from the Chair to address vom Saal's criticisms. She then reported to the panel, in front of a large audience including many reporters, that vom Saal was misrepresenting her results. She said that vom Saal was comparing apples and oranges: His data and that from those other labs were about animals that are 3 months old while hers were from animals that were 6 months old.
This is a crucial observation. In mice (and men) the prostate grows into young adulthood and then stops growing until it becomes diseased during old age. The prostate of a 6 month-old mouse can be expected to be significantly larger than that of a 3 month-old mouse.
vom Saal, however, had Tyl's published paper on his computer. He reported to the panel that in her paper, in at least two places, Tyl describes the mice as being just over 3 months old. He asked the panel: Are there two misprints in the paper? Is Tyl misremembering her own data. Or is she misrepresenting her studies?
Here is a screenshot from Tyl et al.
This does not bode well for the continued use of the Tyl paper as the 'gold standard' for FDA evaluations of the safety of bisphenol A.