Endocrine disruption occurring at doses lower than those predicted
by classical chemical toxicity evaluations: The case bisphenol A
J. Ashby
Syngenta Central Toxicology Laboratory, Alderley Park,
Cheshire, UK
Abstract: 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.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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