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EXPOSURE DOSE REPONSE MODELING FOR THE EFFECTS OF HAZARDOUS AIR POLLUTANTS ON HEALTH: TRICHLOROETHYLENE
Citation:
Bushnell, P J., W K. Boyes, M V. Evans, J E. Simmons, W M. Oshiro, K M. Crofton, AND J. H. Raymer. EXPOSURE DOSE REPONSE MODELING FOR THE EFFECTS OF HAZARDOUS AIR POLLUTANTS ON HEALTH: TRICHLOROETHYLENE. Presented at NERL/AWMA Symposium, RTP, NC, September 12-14, 2000.
Description:
Trichloroethylene (TCE) is a neurotoxic volatile organic compound (VOC) that is produced in large quantities as a degreasing agent and general solvent, and it appears on the list of 188 HAPs specified by the Clean Air Act Amendments of 1990. TCE was selected as a model VOC for developing the exposure-dose-response (EDR) approach to evaluating the neurotoxicity of VOCs. This approach seeks to link airborne exposure to internal dose via dosimetry, and to assess effects as a function of internal dose. First, the effects of a number of exposure scenarios (exposure concentrations and durations) were assessed in rats, by which it was determined that Haber's Rule (C ? t = k) did not accurately predict the effects of TCE on three neurotoxic endpoints (ototoxicity, signal detection behavior, and visual electrophysiology). Second, a physiologically-based pharmacokinetic (PBPK) model was used to estimate the concentrations of TCE in blood and brain of rats using the same exposure scenarios. These estimates accurately predicted the effects of TCE on signal detection and visual electrophysiology, and indicated that the concentration of TCE in the target tissue was the critical determinant of its effects. Finally, we observed that the efficacy of TCE on signal detection behavior decreased with repeated exposure to the compound, so characteristics of this tolerance were explored in terms of its mechanism and implications for the assessment of risk to TCE and other VOCs. (This abstract does not necessarily reflect EPA policy.)