Concentration--Duration Relationships for Acute Trichloroethylene on Rat Nervous System Function. W. K. Boyes, P. Bushnell, K. Crofton, M. V. Evans, and J. E. Simmons, USEPA, Research Triangle Park, NC 27711
In assessing the risks of short term exposures to volatile organic compounds, it is often necessary to extrapolate critical outcome measures across exposure concentrations (C) or durations (t). Models based on external measures of exposure, such as Haber’s rule (C x t = k) have been used often, but may not accurately predict risk. This research project examined adult Long-Evans rats exposed by inhalation to trichloroethylene (TCE) over varying values of C and t. Three different outcome measures indicative of neurological function were used: visual function, signal detection behavior, and hearing loss. Measures of internal tissue dose were derived from a physiologically-based pharmacokinetic (PBPK) model, developed to predict blood and brain levels of TCE under the experimental conditions used. The results of all three functional measures indicated that Haber’s rule under-predicted risk when extrapolating from longer to shorter duration exposures, and over-predicted risk in when extrapolating from shorter to longer duration exposures. In contrast, peak arterial blood TCE concentration, as estimated from the PBPK model, was a good predictor of outcomes across exposure scenarios. The results indicate that use of internal measures of dose, such as those derived from a PBPK model, better predict risks across C and t than do models based on external exposure such as Haber’s rule.