Dose-Response Relationships time after exposure

The accumulation of human data on a wider scale, and in quantitative form, has enabled radiation epidemiology to advance from an essentially descriptive stage to an analytic one in which numerical, dose-spedfic, risk estimates have begun to be treated statistically in order to identify determinants of risk. As presently conceived, these determinants include characteristics of the radiation exposure, underlying dose-response relationships, host factors, other environmental factors, differential tissue sensitivity, time after exposure, and natural levels of incidence. 

Pharmacokinetic information that relates blood concentration to toxic response is critical in defining such dose-response relationships, but information on peak blood concentrations or blood concentrations over time (area under the curve (AUC)) is seldom available. One agent for which such information has been published is 2-methoxyacetic acid (2-MAA), the active metabolite of 2-methoxyethanol. Terry et al. (1994) showed that peak concentration was related to neural tube defects observed after exposure in mice on gestation day 8, whereas area under the curve was shown to be related to limb defects after exposure to 2-MAA on gestation day 11 (Clarke et al. 1992), suggesting that the time of exposure and pattern of development of the susceptible organ... 

While biomarkers can be used for inter- and intraindividual comparisons and for studies of time-trends and the effects of personal protection equipment, biomarkers are at present not suited for assessment of outcome, in terms of health effects, due to lack of knowledge. If peak exposures are significant for the outcome of exposure to isocyanates, biomarkers may also have a poor relationship to outcome. Nevertheless, biomarkers are determined in samples taken after exposure, which makes it possible to analyze samples taken by the initiative of the individual worker, physician, or industrial hygienist. In addition, biomonitoring is an asset in the establishment of human dose-response models, and further research in this field is likely to progress in the future. 

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