Estimation of Background Exposure to Toluene Using a Physiologically‐Based Kinetic Model

Abstract

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 'H8-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 1H 8-toluene exposure was 47 ± 44 ppb (mean ± 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 'He toluene background exposures exist. (J Occup Health 1997; 39: 130-137)

Biological monitoring of controlled toluene exposure

“…This observation was con®rmed by comparison of measured blood levels ( Fig. 3) with average background concentrations of 3±16 nmol/l [6,11,12,22,25,59,71]. In contrast, background levels of hippuric acid and p-cresol were prominent throughout the pre-and postexposure periods (Figs.…”

“…An alveolar breath concentration of 10 lmol/m 3 is 13±71 times higher than the levels of 0.14±0.76 lmol/m 3 measured in nonoccupationally exposed groups [11,59]. Although breath samples are more bulky to transport than urine or blood samples and may incur fears of alcohol measurement, they can be taken even in a contaminated environment and can be corrected for dierent breathing styles using CO 2 adjustment.…”

“…3). Breath levels from the controlled exposure did not reach measured background levels of 138±764 nmol/m 3 [11,59] until ³40 h postexposure (Fig. 3).…”

“…The model was also used to estimate background levels of environmental exposure to [ 1 H 8 ]-toluene [59] and to compare the toxicokinetics of [ 1 H 8 ]-and [ 2 H 8 ]-toluene using blood and breath concentrations [60]. In the present study the PBK model was used to simulate a 40-h work week to determine optimal times for sampling of toluene breath levels as indicators of exposure.…”

“…The ideal indicator would accurately reect the target-tissue concentration ± the brain and reproductive tissues for toluene ± of the toxicologically active species (parent or metabolite) in a time frame related to the onset of the eect (acute, subchronic, or chronic). As exposure standards are lowered, nonoccupational contributions to potential biological indicators will be more likely to obscure work-related dosimetry [59]. Biological levels of a parent toxicant generally more closely re¯ect the absorbed dose than do the levels of primary or secondary metabolites, given potentially complex metabolite kinetics [62].…”