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A GLOBAL PERSPECTIVE ON ENDOCRINE DISRUPTION, WITH COMMENTS ON THE US EXPERIENCE
Citation:
Kavlock, R J. A GLOBAL PERSPECTIVE ON ENDOCRINE DISRUPTION, WITH COMMENTS ON THE US EXPERIENCE. Presented at Encocrine Disruptor Pollution in Asia and the Pacific, Tokyo, Japan, July 1, 2002.
Description:
The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. The International Programme on Chemical Safety (IPCS) of the World Health Organization has recently reviewed the current state-of-the-science on this controversial topic from a global perspective. After analysis of more than 1500 peer reviewed research papers covering the range of modes of action by which hormonal function can be altered, reports of adverse outcomes in humans and wildlife populations, and exposure sources and pathways, the IPCS noted that although the evidence that human health has been adversely affected is weak, there is sufficient evidence to conclude that adverse effects have occurred via this mechanism in some wildlife species. A unique feature of the assessment is the development of a framework for evaluating diverse data sets utilizing objective criteria to evaluate the extent to which causality between an exposure to an endocrine disrupting chemical (EDC) and a particular health outcome has been established. The framework begins with a clear statement of hypothesis regarding some health outcome (e.g., endometriosis) and some stressor (e.g., dioxins and PCBs). The available data is then evaluated along five dimensions: temporality, strength of the association, consistency of the observations, biological plausibility of the effect, and evidence for recovery following diminution of the stressor. Based on the overall strength of the evidence, an assessment is made regarding the validity of the hypothesis and, separately, the likelihood that an endocrine effect caused by the stressor was involved in the etiology. A number of examples using the framework were provided. The review concluded that studying endocrine disruption must remain a global priority and identified a number of research needs, including improved coordination and international cooperation, and monitoring and effects studies in potentially vulnerable populations. At the US Environmental Protection Agency (EPA), attention is focused on validating a battery of screening tests for the identification of chemicals with endocrine disrupting potential. The outlined screening approach includes a number of in vitro (ligand binding and transcriptional activation) and in vivo (uterotrophic, Hershberger, female pubertal development, fish reproduction and amphibian metamorphosis) assays. Collectively, the battery is intended to efficiently identify chemicals with potential to alter estrogenic, androgenic and/or thyroid hormone function and which should be put through a subsequent tier of more definitive testing. These assays are being standardized and evaluated using a core set of chemicals in multiple laboratories in order to judge their relevance, reliability and sensitivity to detecting endocrine disruption. Using a number of criteria (e.g., production volumes, environmental persistence, known health effects, and quantitative structure-activity relationships for ligand binding), the first 200 chemicals to be submitted for screening will be proposed by the EPA in December 2002. In the meantime, EPA regards endocrine disruption as a mode of action and uses this information where possible in its risk assessment and risk management decisions. One of the more contentious issues relates to shape of the dose-response curve for endocrine disruptor modes of action. Recently, EPA issued an interim policy that given the current state-of-the-science, it is premature to require testing for substances for low-dose effects within the screening program. The EPA is also beginning to develop risk management options in the event that the screening and testing programs identifies chemicals of concern. Elements of the risk management evaluation process will be discussed.