A Practical Approach, Second Edition=Ronald D. Ho.pdf

DEVELOPMENTAL AND REPRODUCTIVE TOXICITY RISK ASSESSMENT 867database for existing chemicals will be very useful for screening purposes. For example, the databasecould be queried about a chemical with DNA microarray data but other missing information (e.g.,unknown MOA). While this technology generates a lot of detailed information on gene expression,it is critical to establish the links between the microarray expression profile and the adverse effectsof a given chemical before this technique can be used routinely in risk assessment. EPA’s SciencePolicy Council Interim Policy on Genomics 168 states that the incorporation of genomics data intorisk assessment will be on a case-by-case basis.Toxicogenomic data will become increasingly available. Thus, it will be important to establishwhether observed gene expression changes are required for the adverse effects, are part of acompensatory mechanism, or are related to effects seen only at high doses. In the future, data onproteomics and metabonomics may ultimately be found more useful than gene microarray data.High-throughput techniques for these assays are becoming available, but there will continue to beissues with analysis and interpretation of the data for some time to come, as there have been withgenomics. A more detailed coverage of gene expression profiling can be found in Chapter 15.E. Implications of Benefits Analysis for Risk AssessmentBenefits analysis (assessing the benefits of reducing potential health effects) is an area that iscurrently being explored. This approach typically has been used for cancer, where a linear lowdoseresponse relationship is assumed and modeling of data can be used to estimate risks at lowlevels. Estimating the benefit of reducing exposure is relatively straightforward in this case. Benefitsanalysis for other types of health effects for which a nonlinear low dose response relationship isassumed also requires the development of quantitative estimates of risk at low levels. 169–175 However,an approach for low dose quantitative risk estimation has not been adopted, so the total benefit ofreducing exposures cannot be determined and is likely underestimated. Because the draft Guidelinesfor Carcinogen Risk Assessment 16 introduced the possibility of a nonlinear dose response relationshipfor some types of cancers (e.g., thyroid tumors resulting from long-term stimulation of thethyroid), efforts are underway to develop dose response models for extrapolating nonlinear doseresponse relationships to low levels of environmental exposure. This is an area that holds a gooddeal of promise for moving forward with dose response modeling of all types of health effects andmore accurate assessment of the financial impact of health effects on society.REFERENCES1. National Research Council, Risk Assessment in the Federal Government: Managing the Process,Committee on the Institutional Means for the Assessment of Risks to Public Health, Commission onLife Sciences, National Research Council, National Academy Press, Washington, D.C., 1983, p. 17.2. Kimmel, C.A. and Kimmel, G.L., Principles of developmental toxicity risk assessment, in Handbookof Developmental Toxicology, Hood, R.D., Ed., CRC Press, Boca Raton, 1996, p. 667.3. US Environmental Protection Agency, Guidelines for developmental toxicity risk assessment, Fed.Reg., 56, 63798, December 5, 1991.4. US Environmental Protection Agency, Guidelines for reproductive toxicity risk assessment, Fed. Reg.,61, 56274, October 31, 1996.5. U.S. Environmental Protection Agency, Guidelines for neurotoxicity risk assessment, Fed. Reg., 63,26926, May 14, 1998.6. Palmer, A.K., Regulatory requirements for reproductive toxicology: theory and practice, in DevelopmentalToxicology, Kimmel, C.A. and Buelke-Sam, J., Eds., Raven Press, New York, 1981, p. 259.7. U.S. Environmental Protection Agency, Guidelines for the health assessment of suspect developmentaltoxicants, Fed. Reg., 51, 34028, 1986.8. National Research Council, Pesticides in the Diets of Infants and Children, Committee on Pesticidesin the Diets of Infants and Children, National Research Council, 408, p. 1993.© 2006 by Taylor & Francis Group, LLC