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CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS
Citation:
BIRNBAUM, L. S. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS. Presented at Impact of Endocrine Distuptors (Weybridge +10) Workshop, Helsinki, FINLAND, November 07 - 10, 2006.
Description:
For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. Much of the focus has been on the estrogens and androgens, with growing interest in thyroid hormones. Of course, there is also growing recognition of multiple other endocrine systems which can be perturbed as well as the extensive cross talk that occurs not only between endocrine systems, but between the immune and nervous systems as well. The relatively simplistic notion that only by identifying compounds which could act as agonists or antagonists to specific receptors would be protective of all hormonal perturbation has evolved into a greater understanding of the complexity of hormone actions and interactions. The importance of cross-talk and context is being considered. Also, the multiple sites in which endocrine action can be altered - from hormone synthesis, breakdown, and transport, roles of co-regulators and co-repressors, as well as multiple receptor isoforms, has led to increased understanding. While isolated in vitro constructs have their role, the use of more complex biological models is key. The use of "omics" approaches offers great potential to cluster responses and develop predictive power based on early biomarkers of response. The issue of cumulative risk is paramount given that real world exposures are to complex mixtures. We need to improve our ability to predict the effects of such complex mixtures, especially when multiple modes of action are present. Increasing attention is being paid to low-dose effects, the possibility of non-monotonic dose/response curves, and the issues of additivity to endogenous hormonal background. An overarching challenge is the latent effects of early life stage exposure to endocrine disruptors. Such exposures not only can lead to detectable adverse impacts at the time, but can lead to altered susceptibility and sensitivity as life progresses, resulting in such chronic diseases as obesity, diabetes, heart problems, and cancer. We also need to focus on the issue of population risk, as well as individual risk - subclinical effects in an individual may have major population impacts. (This abstract does not reflect Agency policy.)