The Endocrine Society Issues Statement of Principles

A new position statement from The Endocrine Society provides a strong argument for scientists in industry, government, and academia to work together, across disciplines, to improve testing of chemicals as potential endocrine disruptors. 1 the statement focuses on the Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) to illustrate how fundamental endocrinology principles might be incorporated into more rigorous screens for endocrine activity. But according to lead author R. Thomas Zoeller, a biology professor at the University of Massachusetts, Amherst, the need for broader consideration of endocrinology extends to screening programs beyond the EDSP. The EDSP flags potential endocrine disruptors with a two-tiered system. Tier 1 assays, which were validated by the Federal Insecticide, Fungicide, and Rodenticide Act Science Advisory Panel in 2008, 2 provide information for use in identifying chemicals that could potentially interact with the endo-crine system. Tier 2 assays, which are currently undergoing validation, evaluate dose responses between those interactions and chemical exposure. The Endocrine Society statement focuses on Tier 1, which employs a variety of in vitro and in vivo assays with a long history in toxicology. Given that they mimic hormones, endocrine disruptors don't behave like other toxicants, Zoeller explains. Chemical effects generally increase with greater exposure, but hormones rarely display dose linearity. That's because if a hormone saturates its receptor, more of the same hormone will have no greater effect on response. And in some cases, high doses downregulate responses triggered by lesser exposures—in other words, different effects can appear and disappear at different doses. These " nonmonotonic " dose–response curves—commonly accepted in endocrinol-ogy—challenge a fundamental premise of toxicology: that chemical effects become more pronounced with increasing dose. The Endocrine Society's view is that exposure levels employed in the EDSP's Tier 1 assays—which start with the maximum tolerated doses identified in previous toxicology testing, then work their way down—are so high as to potentially miss low-dose, non-monotonic effects. But Lorenz Rhomberg, principal at Gradient Corporation, an environmental risk assessment firm in Cambridge, Massachusetts, counters that Tier 1 tests were designed solely to test for endocrine system interactions, so the dose doesn't matter. " Questions about dose response are dealt with in Tier 2, " he says. In response to e-mailed questions regarding the EDSP, an EPA spokesman 3 writes that the Agency's Office of Research and Development is " developing a review of the state of the science on low-dose, nonmonotonic dose–response curves …