Endocrine disruption occurring at doses lower than those predicted by classical chemical toxicity evaluations: The case of bisphenol A

The meaning of the term "low dose" is discussed in relation to endocrine toxicity data for chemicals. Consideration is also given to experimental conditions likely to impinge on the interpretation and extrapolation of such low-dose effects, and the importance of gathering appropriate control data is emphasized. In the specific case of bisphenol A (BPA), it is concluded that despite the extensive endocrine disruptor (ED) database available for this chemical, it is still not possible to locate a single study that passes the most rudimentary scientific requirements-that the observations are capable of independent confirmation. Two possible explanations for this are considered. First, that BPA possesses subtle low-dose ED toxicities that only become evident under certain undefined experimental conditions. Until these conditions are defined and understood, it will be a matter of chance what individual investigators observe experimentally for BPA or any other chemical. Second, that the general failure of investigators to define and understand natural variability among control parameters monitored in ED studies allows artefactual positive results to be encountered for chemicals, especially in limited and nonreproduced studies. Whichever of these conclusions is correct, the positive low-dose data currently available for BPA cannot be extrapolated to humans with any confidence.