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 a ssessed on the basis of Lifetime exposure to average concentrations of the vapor. This strategy yields rational predictions of risk if the p roduct of concentration (C) and the duration of exposure (t) yields co nstant effects on health (Haber's Rule). The validity of this assumpti on 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 t ask in which a press on one lever produced food on trials containing a signal (a brief, unpredictable light flash); a press on a second leve r produced food on trials lacking a signal. Response time (RT) and ind ices of sensitivity (SI) and bias (RI) derived from the theory of sign al detection were calculated at three times during repeated daily 60-m in tests conducted in air containing 0, 400, 800, 1200, 1600, 2000, or 2400 ppm TCE. Behavior remained stable during tests in air. In TCE, S I declined and RT increased as functions of both C and t. RI was not a ffected by TCE. Effects on SI and RT mere not predictable from the C x t product: both endpoints were more affected by C than by t. To quant ify the change in the effect of TCE across exposure times, concentrati on-effect relationships for inhaled TCE on SI and RT were modeled with cubic polynomial functions at each of the three exposure durations. C oncentrations of inhaled TCE associated with preselected changes in SI and RT were then estimated for each animal from these functions. Crit erion concentrations, SI0.1 and RT(100), were defined as the concentra tion of TCE associated with a 0.1-unit decrease in SI or a 100-msec in crease in RT, respectively. Both SI0.1 and RT(100) increased as exposu re duration decreased, but did so more slowly than would be predicted by Haber's Rule. This pattern indicates that application of Haber's Ru le overestimates the concentration of inhaled TCE associated with chan ges in signal detection and thus underestimates the risk of behavior c hange from short-term exposures to TCE. On the other hand, the fact th at SI0.1 and RT(100) did increase with shorter exposure times indicate s that the converse assumption, that the toxicity of inhaled TCE is in dependent of the duration of exposure, yields an overly conservative e stimate of risk. (C) 1997 Society of Toxicology.