The low down on low-dose endocrine disruptors.

most complex environmental health threats known today. By mimicking natural hormones such as estrogen and testosterone, these chemicals can interact with the body's endocrine system and exert toxic effects that may lead to reproductive and developmental abnormalities or cancer. In October 2000, the National Toxicology Program (NTP) and the NIEHS convened an independent panel of experts from academia, government, and industry to evaluate the evidence for low-dose effects and dose–response relationships for endocrine dis-ruptors. " This was a highly experienced panel, " says NIEHS toxicologist Ron Melnick, chair of the panel organizing committee. " Members had broad experience in areas including molecular biology, reproductive and developmental toxicology, and statistical and mathematical modeling. Many of them were professors and department chairs from some of the leading biomedical research institutes in the country. " The panel's conclusions were released 14 May 2001 in the National Toxicology Program's Report of the Endocrine Disruptors Low-Dose Peer Review. The peer review panel was assembled at the request of the U.S. Environmental Protection Agency (EPA), which is now validating test methods to screen 87,000 chemicals for hormonal effects [see EHP 107:A458–A460 (1999)]. In assessing public health risks from endocrine disruptors, the EPA faces some difficult challenges. Unlike traditional toxicology, in which the dose always starts out from zero, exposure to endocrine disruptors adds incre-mentally to what's already present in the body as naturally occurring hormone. In some instances, the natural hormone is associated with a certain degree of risk. Estrogen, for example, is known to cause breast cancer in humans. " The question is, what happens to the risk when exposure to endocrine disruptors drives hormone levels higher than what they normally would be? " explains George Lucier, chair of the peer review panel. For this specific review, the EPA's main concern was to resolve questions concerning the effects of low-dose exposures. Humans are usually exposed to these chemicals at extremely low levels. Yet the standard tests used by the EPA to evaluate reproductive and developmental toxicity (contained in the agency's August 1998 document Health Effects Test Guidelines OPPTS 870.3800: Reproduction and Fertility Effects) often fail to consider the impact of doses lower than those producing no evidence of overt adverse effects, described as the no-observed-effect level, or NOEL. For this review, the panel evaluated evidence of biologic changes due to exposure to endocrine disrup-tors at doses below the NOEL. Melnick says biologic changes were emphasized …