Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007)Board on Environmental Science and Toxicology
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The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new ways -- an effort requiring funding, interagency coordination, and data management strategies.
- Because of their sensitivity, toxicogenomic technologies are expected to reveal more than previously was possible about the molecules involved in development and the critical molecular level events that can be perturbed by toxicants.
- Ethical, legal, and social issues that affect the use of toxicogenomic data and the collection of data and samples needed for toxicogenomic research should be addressed.
- Fully integrating toxicogenomic technologies into predictive toxicology will require a coordinated effort approaching the scale of the Human Genome Project.
- It is unlikely that toxicogenomic signatures will be able to decipher all interactions among complex mixtures, but it should be possible to use mechanism-of-action data to design informative toxicogenomic experiments, including screening chemicals for potential points of biologic conversion (overlap) such as shared activation and detoxification pathways, enhancing identification and exploration of potential interactions, and moving beyond empirical experiments.
- The application of toxicogenomics for defining biomarkers of exposure will require consensus on what constitutes an exposure biomarker. Standardized toxicogenomic platforms that are appropriate for identifying signatures of environmental or drug exposures in target and surrogate tissues and fluids will also be required.
- There is a need to develop education and training programs relevant to toxicogenomic applications to predictive toxicology.
- Toxicogenomic approaches should be used to test the validity of methods for the ongoing challenge of estimating potential risks associated with mixtures of environmental chemicals.
- Toxicogenomic screening methods should be integrated into relevant current and future chemical regulatory and safety programs upon validation and development of adequate databases.
- Toxicogenomic studies are improving knowledge of the molecular level events that underlie toxicity and may thus advance the consideration of mechanistic information in risk assessment and decision making. Tools and approaches should continue to be developed to advance the ability of toxicogenomics to provide useful mechanistic information.
- Toxicogenomic technologies (including the analysis of gene sequences and epigenetic modifications) offer the opportunity to use genetic information in a prospective fashion to identify susceptible subpopulations and assess the distribution of differences in susceptibility in larger populations. Toxicogenomic technologies could also reduce the uncertainty surrounding assumptions used in regulatory processes to address population variability.
- Toxicogenomic technologies clearly have strong potential to affect decision making, but they are not currently ready to replace existing required testing regimes in risk assessment and regulatory toxicology. Toxicogenomic technologies are assuming an increasing role as adjuncts to and extensions of existing technologies for predictive toxicology.
- Toxicogenomic technologies offer the potential to significantly enhance confidence in animal-to-human toxicity extrapolations that constitute the foundation of risk evaluations. Using toxicogenomics to analyze species differences in toxicity will help explain the molecular basis for the differences and improve the translation of animal observations into estimates of potential human risk.
- Toxicogenomic technologies present a set of powerful tools for transforming current observation-based approaches into predictive science, thereby enhancing risk assessment and public health decision making.
- Toxicogenomic technologies provide new and potentially useful indicators for use in toxicity screening.
- Toxicogenomic technologies should be adapted and applied for the study of exposure assessment by developing signatures of exposure to individual chemicals and perhaps to chemical mixtures.
- Toxicogenomics has the potential to improve the understanding of dose response relationships, particularly at low doses.