Abstract
Acute exposure to chemical agents can occur as a result of industrial or transportation accidents, fires, natural disasters, or terrorist acts, and may affect both occupational and residential populations. Exposure time and dose are both critical determinants of health risk in such situations. Yet the effects of differing exposure duration along with differing concentration are seldom systematically examined in standard acute toxicology studies. A key consideration for assessing acute exposure risks is how toxicological modes of action (MOA) differ between the acute and chronic exposure situation. Many MOA of concern for chronic exposure will not be relevant for the acute exposure situation. It is also important to understand acute dosimetry and the conditions under which algebraic approaches such as Haber's rule (concentration × time = constant) will serve as an appropriate tool for dose extrapolation. Our analysis shows that Haber's rule is only relevant in the initial stages of exposure, where the relationship between internal dose and time is linear. At later stages of exposure when the internal dose approaches steady state conditions, Haber's rule will be an inappropriate basis for dose-extrapolation. This may be a particular problem for chemicals which approach steady state conditions soon after the start of exposure. One alternative for conducting acute exposure extrapolations is physiologically-based toxicokinetic modeling. As illustrated with an example involving acute exposure to fire retardants, this type of modeling has the potential to generate biologically-informed extrapolations of target organ doses for various exposure points.
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Lewandowski, T.A., Rhomberg, L. (2009). Dose Response Extrapolation for Acute Effects of Toxic Agents and its Relevance to Predict Health Risk Related to Disaster and Terrorism Associated Events. In: Simeonov, L.I., Hassanien, M.A. (eds) Exposure and Risk Assessment of Chemical Pollution — Contemporary Methodology. NATO Science for Peace and Security Series C: Environmental Security. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2335-3_2
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DOI: https://doi.org/10.1007/978-90-481-2335-3_2
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