Toluene metabolites as biological indicators of exposure
The measurement of exhaled and excreted xenobiotics and their metabolites can provide accurate, non-invasive, and time-flexible measurements of internal dose. We analyzed rates of exhaled 2H8-toluene and excreted urinary metabolites from 33 exposures of men to 50 ppm of 2H8-toluene for 2 h at rest. The total dose was distributed as follows: exhaled 2H8-toluene, 13±6.2%; 2H5-hippuric acid, 75±6.4%; 2H7-o-cresol, 0.31±0.22%; 2H7-m-cresol, 0.53±0.44%; and 2H7-p-cresol, 11±3.8%. Interindividual variability was assessed using the coefficients of variation for peak exhalation or excretion rates, and fractions of dose excreted: 2H8-toluene, c.v.=60, 47%; 2H5-hippuric acid, 29, 8.6%; 2H7-o-cresol, 80, 73%; 2H7-m-cresol, 37, 83%; and 2H7-p-cresol, 38, 34%. Excretion rates of the cresols were stable over the first 5 h post-exposure, and o-cresol was determined to be the best urinary indicator of exposure, given the lower background levels of this isomer. The hippuric acid/cresol rate ratios for the first 5 h post-exposure could be described by single exponential terms, and thus provided a means for estimating time since exposure for any finite toluene duration/exposure combination.