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INTERNAL DOSE AND RESPONSE IN REAL-TIME.
Citation:
BOYES, W. K. INTERNAL DOSE AND RESPONSE IN REAL-TIME. Presented at 2006 Toxicology and Risk Assessment Conference, Cincinnati, OH, April 24 - 27, 2006.
Description:
Abstract: Rapid temporal fluctuations in exposure may occur in a number of situations such as accidents or other unexpected acute releases of airborne substances. Often risk assessments overlook temporal exposure patterns under simplifying assumptions such as the use of time-weighted averages (TWA) or cumulative exposures to assess risks. These simplifying assumptions may be appropriate in some situations, but not in others, depending on the nature of the compound and its toxic mode of action. We have developed and applied an exposure-dose-response model to study the neurotoxic effects caused in Long-Evans rats by acute exposure to trichloroethylene (TCE) vapors. The exposure-dose-response model includes a physiologically-based pharmacokinetic (PBPK) component that predicts momentary changes in the concentration of TCE in brain during and after acute exposure. The momentary brain concentration is then compared to the amplitude of a pattern-elicited visual evoked potential VEP) recorded from electrodes over visual cortex. Each VEP waveform takes about 1 minute to record, and VEPs can be obtained repeatedly from rats during TCE exposure sessions. This enables assessment of the relationship between momentary brain concentration and neurophysiological function during and after exposure. The data suggest that the brain concentration of TCE at the moment of assessment is sufficient to describe changes in VEP amplitude, whereas cumulative exposure, area under the curve, or TWA was not. Momentary brain concentration may be an appropriate ¿dose metric¿ for use in assessing the risks of neurological impairment caused by acute exposure to TCE or other volatile organic compounds that cause similar acute neurological effects.
This abstract does not reflect EPA policy.