Environmental News Science panel confirms low-dose estrogenic effects
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ow-dose effects in animals have been clearly demonstrated for the endocrinedisrupting chemical estradiol and some estrogenic compounds, according to the preliminary conclusions of a panel of 36 scientists meeting under the rubric of the National Toxicology Program (NTP). The analysis occurred after the U.S. EPA asked NTP, an arm of the National Institute of Environmental Health Sciences, whether EPA's current testing protocol for reproductive and developmental toxicity testing of endocrine-active chemicals is missing effects that occur down at the lower reaches of dose, says Gary Timm, senior scientist in EPA's
cal structure from nonylphenol and the phytoestrogen genistein. But for other compounds, both the presence and absence of low-dose effects were seen. As such, the panel concluded that study design differences, including choice of animal species and endpoint evaluated, lead to discrepancies. It recommended that study design and the biological and environmental factors (such as lighting and noise) that might affect experimental outcomes be considered more carefully. For example, the panel advocated the use of species and strains that are highly responsive to endocrine-active compounds. Paul Foster, a panel member and Chemical Industry Institute of Toxicology (CUT) program director for endoLow-dose effects confirmed crine reproduction and deThe panel found there are low-dose effects velopmental toxicology, associated with nonylphenol, genistein, and thinks the preliminary conother estrogenic compounds. clusion about estradiol and some estrogenic compounds is unfounded. CIIT's two-year, low-dose testing program for endocrine-active chemicals ended without finding any evidence of an effect on animals, he says. The panel's preliminary word "was a surprising conclusion, in my view," he says.
Office of Prevention, Pesticides, and Toxic Substances (OPPTS). The group's findings, discussed during a two-day October meeting, came as a surprise to some, and many expect them to have far-reaching implications. But the group's analysis has again raised discussion over how to test for low-dose effects and how to define them. The scientists also concluded that there are low-dose effects on the immune system and neurologi-
Foster also notes that although a number of scientists were critical of EPA's definition of "low-dose effects", the panel did not reach a consensus definition. For this meeting, "low-dose effects" referred to biological changes that either occur in the range of human exposures or at doses that are lower than those typically used in EPA's testing regime. Lynn Goldman, currently professor at the Johns Hopkins University School of Public Health and former chief of EPA's OPPTS, said she believes that the final
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report is bound to be considered carefully by the broader scientific community. Scientists are eager to discover what the panel concludes on endocrine disrupters for cases in which the data are more definitive, as with estradiol. But more significantly, as in the case of bisphenol A, the group found a conflict in the data in the literature but no "fatal flaws" in the studies, Goldman adds. Instead, the panel listed "many, many potential reasons why the laboratories couldn't replicate the findings of one study showing a low-dose effect," she says, including a difference in the level of soy included in the animals' diet. "This should prompt the broader scientific community to search for scientific differences in the studies, rather than to simply look for mistakes in the study and reject the work," Goldman says. Essentially, EPA officials are interested in knowing whether the current literature shows effects at low doses even though EPA's testing protocols are designed for high-dose testing. "It doesn't look as if there is a clear enough understanding [of the science] to warrant a change in the agency's current testing strategy," Timm notes. EPA reserves final judgement until the report is released next spring, Timm cautions. Once final, the panel's report will assist EPA with the many protocols under development that guide commercial reproductive and developmental toxicity testing of endocrine-active chemicals in certain products, says Timm. The final report also will be considered for the in vivo mammalian components of EPA's Endocrine Disrupter and Screening Program. For a summary of the NTP's preliminary findings, go to: http://ntp-server.niehs.nih. gov. —CATHERINE M. COONEY © 2000 American Chemical Society
