Relevance of Phenotypic Variation in Risk Assessment: The Scientific Viewpoint
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Everyone knows that people vary widely in their responses to local environmental changes such as heat or cold, pollen, rotation, or high altitudes. We know a great deal about such responses; how they depend on an individual’s previous exposures, lifestyle and age, for example. A much more difficult problem, because of the absence of good, human data, is the evaluation of dose-response curves for exposures to radiations or environmental chemicals. If we had such data, it would be possible to estimate risk from exposure; unfortunately, almost all the human data that exist are not the result of chronic exposures, but come from acute, high doses. Likewise, animal data almost always represent effects at high doses. Thus the problem is how to extrapolate from high doses to low doses. One can either do the extrapolation arbitrarily or take some scientific approach to the problem. One such approach is to understand the mechanisms at the molecular level responsible for the observed effects and then to use this understanding to construct theories permitting the extrapolation from high to low doses. Therefore, what we need are good biological theories. However, superimposed on such theories must be an analysis of the variability in the responses of the human population. These variabilities can be thought of as subsets within rather broad categories, as indicated in Table 1.
KeywordsSkin Cancer Ataxia Telangiectasia Xeroderma Pigmentosum Ataxia Telangiectasia Pyrimidine Dimer
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