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SPECIFYING PHYSIOLOGICAL PARAMETERS FOR THE KINETICS OF INHALED TOLUENE IN RATS PERFORMING THE VISUAL SIGNAL DETECTION TASK (SDT).
Citation:
Oshiro, W M., T E. Samsam, Q T. Krantz, J. P. Nolan, W P. Watkinson, AND P J. Bushnell. SPECIFYING PHYSIOLOGICAL PARAMETERS FOR THE KINETICS OF INHALED TOLUENE IN RATS PERFORMING THE VISUAL SIGNAL DETECTION TASK (SDT). Presented at Behavioral Toxicology Society, RTP, NC, 4/20-22/2002.
Description:
A physiologically-based pharmacokinetic (PBPK) model is being developed to estimate the dosimetry of toluene in rats inhaling the VOC under various experimental conditions. The effects of physical activity are currently being estimated utilizing a three-step process. First, we determined the heart rate and body temperature of rats at rest and while performing a signal-detection task (SDT) at 4, 7, 10 and 13 trials per minute (tpm). This generated a function relating telemetered heart rate to trial rate. Second, we trained other rats to perform a simple and rapidly-acquired lever-pressing task (LPT) and collected heart rates in these animals at rest and at the same trial rates used above. Both groups of rats were exposed to toluene (SDT at 0, 1200, 1600, 2000 and 2400 ppm; LPT at 0 and 2000 ppm). Third (in progress), we will expose rats to toluene while they perform the LPT and collect tissues to determine the effect of activity level on the kinetics of toluene. The telemetered heart rate will be converted to an estimate of cardiac output and ventilation rate, and these parameters of the PBPK model will be set for each activity level used during toluene exposure. We expect that adjusting the cardiac output and ventilation rate parameters of the PBPK model according to increments in heart rate will yield more accurate predictions of blood and brain toluene concentrations for each trial rate. If so, tissue concentrations of toluene can be better predicted in rats performing the SDT. This will tell us the target-organ dosimetry associated with decrements in signal detection behavior in rats. A comparison of the sensitivity of rats to toluene with that of humans performing the same task, in terms of inhaled concentration and time, blood concentration (measured in both species), and target-organ dose (measured in rats and estimated in humans) will then be possible. This abstract does not necessarily reflect EPA policy. Mention of trade names or commercial products does not constitute endorsement or recommendation of use.