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Use of Toxicogenomics Data in Risk Assessment: Case Study for a Chemical in the Androgen-Mediated Male Reproductive Development Toxicity Pathway
Impact/Purpose:
To address the question of whether TG data can improve health risk assessments, a case study will be performed in which TG data for one chemical will be incorporated qualitatively within the hazard characterization step of a recent or ongoing EPA chemical health or risk assessment. Integrating TG data into an assessment case study will identify areas that may be impacted by TG data and contribute to the development of criteria and approaches for incorporating TG data in assessments. The chemical for the case study will be selected from among those that affect the androgen-mediated male reproductive development toxicity pathway.
This pathway was selected because it is well-characterized, there are published TG studies, and a number of genes in the pathway have been identified. Criteria for chemical election for the case study will include: 1) a relative abundance of available TG data; 2) a recent or ongoing EPA assessment; and 3) an interest by EPA Program and/or Regional Offices. Using the most recent or ongoing (depending on the selected chemical) EPA assessment as a starting point, the team members will conduct an evaluation of the data presented in the assessment, focusing on the hazard characterization and dose response sections.
The following questions will be considered: Is the mode of action fully understood for all of the endpoints of concern? Could gene expression information aid in a further understanding of the MOA? Does the TG data provide insights into other aspects of the assessment (e.g., dose-response)? The TG data analysis will then be integrated into the assessment. A report of the case study will be developed and conclusions will be drawn about whether the TG data strengthened or corroborated the risk assessment, qualitatively, and the utility of the approach for incorporating TG data for future risk or health assessments.
Description:
The goal of this project is to address the question, “Can existing toxicogenomics (TG) data improve Environmental Protection Agency (EPA) chemical health or risk assessments?” Although genomics data promises to impact multiple areas of science, medicine, law, and policy, there are only a few areas where genomics data currently has application (e.g., biomarkers of disease). As the technology continues to advance, EPA will need to prepare for genomics data availability and submission by: 1) identifying areas of risk assessment where such data may be particularly useful; 2) developing acceptance criteria for inclusion of toxicogenomics data in risk assessment; and 3) developing approaches for the use of toxicogenomics in risk assessment. These needs will likely require an iterative and collaborative research process between risk assessors and scientists (inside and outside the Agency). At the NCEA sponsored Genomics and Risk Assessment Colloquium in 2003, one of the recommendations was to conduct case studies that could provide a practical attempt to incorporate currently available toxicogenomics data that would illuminate issues and the methods development. This project is responds to this recommendation.