Project Summary (1995-2000)

The objective of this project is to investigate the effects of occupational and environmental exposure to volatile organic solvents. Volatile organic solvents are among the most common toxic substances found at Superfund or hazardous waste sites. Exposures to these chemicals can occur both by evaporation from the site as well as contamination of drinking water. The relationships among human exposures, time-varying levels of toxicants or metabolites in body tissues/fluids, and short/long term biological responses are greatly influenced by factors that are specific to the person exposed or even to the actual exposure event. This project utilizes tools developed in earlier phases of research (controlled exposures to stable isotope-labeled/unlabeled compounds, and physiologically based models) to achieve its goals. To date, differences in breathing rate, age, gender, body weight, adiposity, and rate of metabolism have all been found to affect the amount of solvents in the body. The physiologic factors affecting the toxicokinetics of toluene, styrene, and the xylenes are being characterized. The ability of the stable isotope probes and model framework to account for toxicological variability observed in different subjects is also being tested. The probe/model framework is now being applied to characterize uncontrolled exposures, such that background, environmental, and occupational levels of solvents are now being predicted from measured levels in breath, blood, and urine.