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PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE.
Citation:
BOYES, W. K. PREDICTING THE RISKS OF NEUROTOXIC VOLATILE ORGANIC COMPOUNDS BASED ON TARGET TISSUE DOSE. Presented at Indian Academy of Neurosciences, Lucknow, INDIA, December 17 - 20, 2006.
Description:
Quantitative exposure-dose-response models relate the external exposure of a substance to the dose in the target tissue, and then relate the target tissue dose to production of adverse outcomes. We developed exposure-dose-response models to describe the affects of acute exposure to trichloroethylene (TCE) and other volatile organic compounds. A physiologically-based pharmacokinetic (PBPK) model predicted TCE concentrations in blood, brain and other tissues under a variety of exposure conditions. The concentration of TCE estimated in brain was used to predict changes pattern-elicited visual evoked potentials (VEP) recorded from pigmented rats. Several experiments showed that the momentary concentration of TCE in brain at the moment of assessment predicted the amount of reduction in VEP amplitude. This relationship enabled application of the model to risk assessment problems such as predicting risks across different exposure durations, or across species. In addition, we have compared effects of VOCs with those of ethanol on a tissue-dose basis in order to express VOC exposures as ethanol-equivalent doses. This allows an estimate the financial burden of impaired function caused by VOC exposures through a comparison to data available on the consequences of ethanol intoxication. Thus, exposure-dose-response models enable better use of scientific information in both risk assessment and risk management (cost/benefit) decisions.
(This abstract does not reflect the policies of the US Environmental Protection Agency.)