Concentration-time relationships for the effects of inhaled trichloroethylene on signal detection behavior in rats

The risk from inhaled volatile organic compounds (VOCs) is presently assessed on the basis of lifetime exposure to average concentrations of the vapor. This strategy yields rational predictions of risk if the product of concentration (C) and the duration of exposure (t) yields constant effects on health (Haber's Rule). The validity of this assumption was evaluated by assessing the acute behavioral effects of inhaled trichloroethylene (TCE) vapor at various values of C and t. Adult male Long-Evans rats (n = 11) were trained to perform a signal detection task in which a press on one lever produced food on trials containing a signal (a brief, unpredictable light flash); a press on a second lever produced food on trials lacking a signal. Response time (RT) and indices of sensitivity (SI) and bias (RI) derived from the theory of signal detection were calculated at three times during repeated daily 60-min tests conducted in air containing 0, 400, 800, 1200, 1600, 2000, or 2400 ppm TCE. Behavior remained stable during tests in air. In TCE, SI declined and RT increased as functions of both C and t. RI was not affected by TCE. Effects on SI and RT were not predictable from the C x t product: both endpoints were more affected by C than by t. To quantify the change in the effect of TCE across exposure times, concentration-effect relationships for inhaled TCE on SI and RT were modeled with cubic polynomial functions at each of the three exposure durations. Concentrations of inhaled TCE associated with preselected changes in SI and RT were then estimated for each animal from these functions. Criterion concentrations, SI0.1 and RT100, were defined as the concentration of TCE associated with a 0.1-unit decrease in SI or a 100-msec increase in RT, respectively. Both SI0. 1 and RT100 increased as exposure duration decreased, but did so more slowly than would be predicted by Haber's Rule. This pattern indicates that application of Haber's Rule overestimates the concentration of inhaled TCE associated with changes in signal detection and thus underestimates the risk of behavior change from short-term exposures to TCE. On the other hand, the fact that SI0.1 and RT100 did increase with shorter exposure times indicates that the converse assumption, that the toxicity of inhaled TCE is independent of the duration of exposure, yields an overly conservative estimate of risk.