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SAFE FOOD
Description:
NHEERL research is providing the scientific basis for policy decisions regarding the need for an additional safety factor for children, the need to assess cumulative exposures, and the best way to deal with risk management issues related to common mode of action. Research can be broadly divided into methods development work, which includes not only new and modified approaches to the identification and evaluation of hazard, but also application of existing test methods in innovative ways, and model development, which includes both PBPK and BBDR-based models. The models are designed to predict the effects of exposure to pesticides and other toxic chemical in sensitive subpopulations. This is accomplished primarily through the modification of existing models initially developed to model effects in healthy adult organisms. The question of whether current regulatory practices are protective of susceptible subpopulations is approached by evaluating the sufficiency of an uncertainty factor to account for intraspecies variation. The FQPA mandates application of an additional 10-fold uncertainty factor to allow for the increased susceptibility of children to pesticide exposure. NHEERL is conducting laboratory studies to determine whether age-based differences in sensitivity can be demonstrated, as well as the range in magnitude of any such differences. Model development is focusing on the fetal compartment and potential differences in PK dynamics associated with post-natal development. Subpopulations other than children are also considered within this research area, including those based on genetic factors and health status, to include pre-existing disease. The question of how to best measure or predict the effects of cumulative exposure is addressed by NHEERL though modification of existing testing and evaluation approaches, primarily those currently employed by OPPTS to gather data from pesticide manufacturers. Modifications are based on parameters such as age of test subjects, duration of exposure, and pattern of exposure. The modified protocols are applied in long-term laboratory studies with prototype pesticides with the goal of providing a method suitable for test guideline application. We are addressing the question posed by the need to combine the risk from exposure to two or more chemical with the same mechanism through studies that combine biochemical and behavioral endpoints. Mechanism of action must be determined for both the primary and additional potentially relevant actions. A major research issue in this area centers on the similarities and differences in the biochemical mechanism of action and reversal of activity between organophosphate and carbamate compounds.