A DOSIMETRIC ANALYSIS OF BEHAVIORAL-EFFECTS OF ACUTE TOLUENE EXPOSUREIN RATS AND HUMANS

The literature on behavioral effects of exposure to toluene is difficu lt to assess due, in part, to a wide variety of exposure conditions em ployed and outcomes measured. This study investigated whether previous experiments would be more consistent with each other if toluene expos ure parameters were expressed not as concentration and duration, but a s estimated amount of toluene in tissues. A physiologically based phar macokinetic (PBPK) model was used to estimate concentration of toluene in arterial blood ((C) over tilde a(TOL)) from published studies in r ats and humans exposed acutely to toluene vapor. Data for rats were se lected from studies of avoidance behavior using both rate of respondin g and measures of successful responding. Data for humans were from stu dies of choice reaction time (CRT). Behavioral measures were converted to proportion of baseline to place them on a common scale across expe riments. A meta-analysis was done to fit dose-effect curves using (C) over tilde a(TOL) and the rescaled effects. Results demonstrated that effects were an orderly function of (C) over tilde a(TOL) and were not influenced by concentration or duration of exposure, except as exposu re influenced (C) over tilde a(TOL). In rats, response rates first inc reased, reached a peak, and then declined as (C) over tilde a(TOL) inc reased. Successful avoidance in rats and CRT in humans always declined as (C) over tilde a(TOL) increased. In rats, response rates were incr eased by 10% at (C) over tilde a(TOL) approximate to 13 ml/L. In human s, reaction times increased by 10% at (C) over tilde a(TOL) approximat e to 3 ml/L. Cross-species comparisons were made with the following ca veats: PBPK uncertainties, few human data, and poor task comparability .