Summary of the National Toxicology Program's Report of the Endocrine Disruptors Low-Dose Peer Review. (Workshop Summary)
Melnick, Ronald, Lucier, George, Wolfe, Mary, Hall, Roxanne, Stancel, George, Prins, Gail, Gallo, Michael, Reuhl, Kenneth, Ho, Shuk-Mei, Brown, Terry, Moore, John, Leakey, Julian, Haseman, Joseph, Kohn, Michael, Environmental Health Perspectives
At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when animals are evaluated, and the end points being measured following exposure to endocrine-active agents. Key words: androgen, antiandrogen, bisphenol A, developmental toxicity, endocrine disruptors, estrogen, in utero exposure, low-dose effects, multigeneration study, neonatal exposure, reproductive toxicity. Environ Health Perspect 110:427-431 (2002). [Online 12 March 2002]
At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program (NTP)/National Institute of Environmental Health Sciences (NIEHS) organized and conducted an independent and open peer review to evaluate the scientific evidence on reported low-dose effects and dose-response relationships for endocrine-disrupting chemicals in mammalian species that pertain to assessments of effects on human health. The peer review took place in Research Triangle Park, North Carolina, USA, on 10-12 October 2000.
The purpose of this meeting was to establish a sound scientific foundation upon which the U.S. EPA could determine what aspects, if any, of its standard guidelines for reproductive and developmental toxicity testing need to be modified to detect and characterize low-dose effects of endocrine disruptors. Results from this review may also influence how other national and international agencies select doses, end points, animal models, and testing regimens for reproductive and developmental toxicity studies of endocrine-active agents. In particular, the NTP is interested in evaluating the molecular and physiologic basis of dose-response relationships for reproductive toxicants. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. …