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Predicting the acute behavioral effects in rats inhaling toluene (or up to 24 hrs: Inhaled vs. internal dose metrics.
Citation:
OSHIRO, W. M., Q. T. KRANTZ, C. J. Gordon, E. M. KENYON, AND P. J. BUSHNELL. Predicting the acute behavioral effects in rats inhaling toluene (or up to 24 hrs: Inhaled vs. internal dose metrics. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
These results confirm the importance of internal dose as the appropriate metric for the acute behavioral effects of toluene and support the use of kinetic models to predict acute effects of longer exposures to VOCs. (This abstract does not necessarily reflect EPA policy.)
Description:
The acute toxicity oftoluene, a model volatile organic compound (VOC), depends on the concentration (C) and duration (t) ofexposure, and guidelines for acute exposures have traditionally used ext relationships to extrapolate protective and/or effective concentrations across durations ofexposure. Recent research suggests an alternative approach for duration adjustment, which uses PBPK model-derived estimates of internal dose as the basis for duration extrapolation. For example, acute behavioral effects observed in rats performing a visual signal detection task (SDT) while being exposed to common VOCs (including toluene) for up to 1 hour arebetterpredictedbythemomentaryconcentration oftheVOC inthebrainatthetime ofthe observed effect than by the ext product. The current study was designed to compare the ability ofthe two approaches to predict acute effects incurred during exposures to toluene lasting up to 24 h. Thus, 16 male, Long-Evans rats were trained to perform the SDT, and then were exposed to toluene at concentrations of0, 1125 and 1450 ppm for 24 h and to 1660 ppm for 21 h. During each exposure the animals were tested at times predetermined to yield comparable ext products (2900, 8700, 27,000 and 34,800 ppm-h) but differing estimates ofbrain toluene concentrations (estimated by a PBPK model to range from 80 to 140 mg/L). Results showed that toluene reduced accuracy and increased response time, and these affects were better predicted by the brain toluene concentration than by the C x t product ofexposure. These results confirm the importance of internal dose as the appropriate metric for the acute behavioral effects oftoluene and support the use ofkinetic models to predict acute effects oflonger exposures to VOCs. (This abstract does not necessarily reflect EPA policy.)