In a report of
a panel of experts (big
.pdf file), the National Toxicology Program of the US National Institute
of Environmental Health Sciences confirmed the existence of impacts of
endocrine-disrupting compounds at levels below those of traditional concern.
convened the panel to evaluate whether current testing procedures needed
to be altered to reflect emerging data on low-dose effects, beneath those
identified by traditional testing as thresholds for concern.
panel concluded that "that there is 'credible evidence' that some
hormone-like chemicals can affect test animals' bodily functions at very
low levels well below the "no effect" levels determined
by traditional testing."
strength of the evidence varies from compound to compound.
example, the most contentious issue is about low dose effects of bisphenol
A. The panel concluded that while several studies provide credible
evidence of low-dose effects, other studies find no low-level effect,
leaving them unable to reach a conclusion about this compound. [Additional
evidence has emerged since the panel met suggesting (1) contaminated food
supplies may have led some studies to find no impact; and (2) new
independent corroboration of bisphenol A impacts at low levels.]
panel agreed that the evidence was conclusive for a series of other estrogenic
compounds, including estradiol, diethylstilbestrol (DES), methoxychlor,
genistein and nonylphenol.
overall conclusions of the panel were (taken from the reports Executive
Summary, emphasis added):
effects, as defined for this review, were demonstrated in
laboratory animals exposed to certain endocrine active agents. The effects
are dependent on the compound studied and the endpoint measured. In
some cases where low-dose effects have been reported, the findings have
not been replicated. The toxicological significance of many of these
effects has not been determined.
shape of the dose-response curves for these effects varies with
the endpoint and dosing regimen, and may be low-dose linear, threshold-appearing,
traditional multigeneration reproduction study protocol has not revealed
major reproductive or developmental effects in laboratory animals exposed
to endocrine active agents at doses approaching their NOAELs set by
the standard testing paradigm. However, few multigenerational studies
have been conducted over expanded dose ranges, and critical endpoints
such as cancer have not been evaluated in multigenerational studies.
Panel recommended additional research to replicate previously reported
key low-dose findings, to characterize target tissue dosimetry during
critical periods of development, to identify sensitive molecular markers
that would be useful in understanding mechanistic events associated
with lowdose effects, and to determine the long-term health consequences
of low-dose effects of endocrine active agents.
findings of the Panel indicate that the current testing paradigm
used for assessments of reproductive and developmental toxicity should
be revisited to see if changes are needed regarding dose selection,
animal model selection, age when animals are evaluated, and the endpoints
being measured following exposure to endocrine active agents.