Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007) / Chapter Skim
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12 Conclusions and Recommendations
12 Conclusions and Recommendations
Pages 201-212
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From page 201... ...
Toxicogenomics can provide molecular level information and tests that add to the "weight of the evidence" for or against the safety of specific environmental toxicants and drugs. Ultimately, toxicogenomic technologies are envisioned to be more sensitive and more informative than existing technologies and may supplant some approaches currently in use, or at least be a component of batteries that will replace certain tests.
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From page 202... ...
Substantially enhance agency capability to integrate toxicogenomic approaches into risk assessment practice, focusing on exposure assessment, hazard screening, identification and understanding of variation in human susceptibility, mechanistic insight, assessment of dose-response relationships, cross-species extrapolation, and assessment of mixtures.
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From page 203... ...
data resource could provide context to toxicogenomic data generated by drug and chemical manufacturers. Regulatory agencies could use the data resource in risk assessment to inform exposure limits, and the data could improve understanding of the effects of a broad range of exposures ranging from pollution to natural disasters to terrorist attacks.
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From page 204... ...
EXPOSURE ASSESSMENT The application of toxicogenomics to define biomarkers of exposure requires consensus on what constitutes an exposure biomarker and standardization of toxicogenomic platforms that are appropriate for identifying signatures of environmental or drug exposures in target and surrogate tissues and fluids. Additional challenges include the individual variation in response to an environmental exposure and the persistence of a toxicogenomic signature after exposure.
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From page 205... ...
The process of deriving useful toxicogenomic signatures for screening would be accelerated if these data were publicly available. Recommendation 5: Upon validation and development of adequate databases, integrate toxicogenomic screening methods into relevant current and future chemical regulatory and safety programs.
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From page 206... ...
Toxicogenomic technologies could reduce the uncertainty about assumptions used in regulatory processes to address population variability. Recommendation 6: Use toxicogenomic information to prospectively identify, understand the mechanisms of, and characterize the extent of genetic and epigenetic influences on variations in human susceptibility to the toxic effects of chemicals, with the goal of improving the certainty about assumptions used in the regulatory processes to address population variability.
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From page 207... ...
MECHANISTIC INFORMATION Toxicogenomic studies are improving our knowledge of the underlying biology and the regulatory networks that integrate the signaling cascades involved in toxicity and thus may advance the introduction of mechanistic insight into risk assessment and fulfill the promise of more accurate and expedited elucidation of class-related biologic effects. An immediate need in the field of toxicogenomics is for more accurate identification of orthologous genes or proteins across species.
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From page 208... ...
To effectively address questions about risks associated with human exposures to environmental chemicals, which may be much lower than doses currently used in toxicology studies, attention must focus on characterizing toxicogenomic responses at low doses. Such efforts will be more valuable when toxicogenomic studies are tied to conventional toxicity responses, such as incorporating toxicogenomics into traditional toxicity-testing programs.
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From page 209... ...
Using toxicogenomics to analyze species differences in toxicity will help explain the molecular basis for the differences, improving the translation of animal observations into credible estimates of potential human risk. In addition, by providing comparisons between humans and other species at the molecular level, toxicogenomics may assist in identifying those animal species and strains that are most relevant for specific assays.
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From page 210... ...
such as shared activation and detoxification pathways, enhancing identification and exploration of potential interactions, and moving beyond empirical experiments. Recommendation 11: Use toxicogenomic approaches to test the validity of methods for estimating potential risks associated with mixtures of environmental chemicals.
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From page 211... ...
To minimize the risk of adverse impacts on socially vulnerable populations from toxicogenomic research and implementation, access to adequate health care for diagnostic and treatment purposes will be critical and should be a priority for funding agencies and legislators.
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From page 212... ...
f. Appropriate federal agencies should develop "points to consider" that identify and discuss ethical, legal, and social issues relevant to individual researchers, institutional review boards, research institutes, companies, and funding agencies participating in toxicogenomic research and applications.
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