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J Occup Health year 1997 volume 39 number 2 page 130 - 137
Classification Original
Title Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model
Author Crispin H. Pierce1, Russell L. Dills1, Thomas A. Lewandowski1, Michael S. Morgan1, Mike A. Wessels1, Danny D. Shen2 and David A. Kalman1
Organization 1Department of Environmental Health and 2Department of Pharmaceutics, University of Washington
Keywords Toluene, Toxicokinetics, PBPK, Model, Isotope
Abstract Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model: Crispin H. Pierce, et al. Department of Environmental Health, University of Washington-Estimation of environmental exposure to toxicants has generally been limited to concentration measurements in air, water, and foods. Measurement of background levels of toxicants in biological tissues for this purpose has been limited by analytical detection. After developing a sensitive headspace GC-MS method, we conducted 33 controlled human exposures of 50 ppm 1H8-toluene and 50 ppm 2H8-toluene for 2 h, and measured concentrations in blood and breath for 100 h post-exposure. Blood and breath samples from a separate cohort of 9 men exposed to 2H8-toluene only were also measured for background 1H8-toluene levels. A physiologically-based kinetic (PBK) model, previously constructed and validated in an analysis of the 2H8-toluene data, was used to predict the level of ambient 1H8-toluene exposure that produced the observed breath levels. The model-derived estimate of mean background 1H8-toluene exposure was 47 plusmn 44 ppb (mean plusmn s.d.), which is consistent with indoor air measurements from this and previous studies of 3-27 ppb and outdoor measurements of 2-43 ppb. According to the PBK model, background exposure was expected to produce an average blood concentration of 5.9 nmol/l, which was within a measured range of 3-16 nmol/l, and a corresponding alveolar air concentration of 310 nmol/m3, within a range of 138-764 nmol/m3. This work extends the use of physiologic modeling to back-predict environmental dose, and found that significant differences in inter-individual 1H8-toluene background exposures exist.