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EDC testing in the future: Exploring roles of pathway-based in silico, in vitro and in vivo methods
Citation:
Ankley, G., Dan Villeneuve, AND T. Hutchinson. EDC testing in the future: Exploring roles of pathway-based in silico, in vitro and in vivo methods. Presented at SETAC Europe, Glasgow, SCOTLAND, May 12 - 16, 2013.
Impact/Purpose:
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Description:
Many thoroughly validated, robust tests with both mammalian and non-mammalian models have been developed to identify chemicals with the potential to impact endocrine pathways associated with the hypothalamic-pituitary-gonadal (HPG) and thyroidal axes. In the US, for example, the legislatively-mandated endocrine disruptor screening program (EDSP) employs 10 different Tier 1 screening assays to identify chemicals with the potential to affect endocrine function. Although highly effective in identifying endocrine-disrupting chemicals (EDCs), the full Tier 1 battery of tests is relatively resource-intensive. For example, the battery employs six different in vivo assays with rats, fish and amphibians that, in some instances, can last up to 30 days. Given current challenges relative to extensive testing, both in terms of resource availability and animal use, it is unlikely that the extant Tier 1 screening battery realistically could be used to assess the many thousands of chemicals that might be of concern relative to endocrine activity.Recent years have seen the development of many tools that, theoretically, could provide the basis for more rapid, resource-effective screening and testing of chemicals that affect specific biological pathways. These tools include short-term in vivo tests (featuring molecular and biochemical responses collected, for example, via genomic techniques), in vitro assays (also focused on molecular/biochemical responses, often in systems amenable to high through-put [HTP] testing), and computational techniques (e.g., QSAR modeling; read-across methods). There are challenges, however, relative to the implementation of these types of tools and associated endpoints in regulatory toxicology. One of the major challenges involves translation/linkage of responses at lower levels of biological organization to alterations in individuals (and, by extension, populations) that are relevant to risk assessment (e.g., decreased survival, growth, reproduction).