Limited Validity of o-Cresol and Benzylmercapturic Acid in Urine as Biomarkers of Occupational Exposure to Toluene at Low Levels

Abstract

This study was initiated to evaluate o-cresol and benzylmercapturic acid in urine in comparison with other biomarkers, as tools to estimate the intensity of occupational exposure to toluene at low levels. In total, 108 solvent exposed workers (engaged in tape production) and 17 non-exposed controls (all men) participated in the study. The surveys were conducted in the second half of working weeks. Diffusive sampling was conducted to measure 8-h time-weighted average intensity of occupational exposure to toluene. Blood and urine samples were collected at the end of a working shift. Blood samples were subjected to analysis for toluene (Tol-B), and urine samples were analyzed for benzyl alcohol (BeOH-U), benzylmercapturic acid (BMA-U), ocresol (o-CR-U), hippuric acid (HA-U) and toluene (Tol-U) by the methods previously described. The toluene concentrations in workplaces were low in general, with a geometric mean (GM) and the maximum concentration of 1.9 ppm and 8.8 ppm, respectively. The statistical analyses of the six biomarkers for correlation with air-borne toluene showed that both Tol-B and Tol-U gave a high correlation coefficient of 0.58 to 0.61 (p<0.01), whereas the coefficients for BeOH-U and BMA-U together with HA-U were all low (up to 0.22, depending on the correction for urine density) and statistically insignificant (p>0.10) in most cases. o-CR-U had an intermediary coefficient of 0.20 (p<0.05). Comparison with previous publications disclosed that BeOH-U, BMA-U and HA-U correlate with toluene in air when the exposure is intense (e.g., 50 ppm or above), but no longer proportional to air-borne toluene when the exposure is low, e.g., 2 ppm. Such appeared to be also the case for o-CR-U. In over-all evaluation, the validity of o-CR-U in monitoring occupational exposure to toluene at low levels (e.g., 2 ppm) appear to be limited, and BMA-U is not an appropriate biomarker. BeOH-U and HA-U are also inappropriate for this purpose. Only Tol-B and Tol-U may be employed to estimate toluene exposure at low levels.

Impact of coexposure on toluene biomarkers in rats

“…Indeed, results obtained in rats with HA, oCre and Tol-B can be transposed to humans rather directly because the percentage of these biomarkers excreted in urine or dissolved in blood respect to the inhaled dose are comparable (ATSDR, 2000;Cosnier et al, 2013;ECB, 2003). It is however noted that MAs formation is ten to hundred times greater in rats than in humans (Angerer et al, 1998;Cosnier et al, 2013;Ikeda et al, 2008;Inoue et al, 2004Inoue et al, , 2008. From an analytical point of view, this species difference would not be a problem because rather simple analytical methods are now available to measure low levels of these MAs (Cosnier et al, 2012).…”

Biomarkers of toluene exposure in rats: mercapturic acids versus traditional indicators (urinary hippuric acid ando-cresol and blood toluene)

“…In contrast, oCre appears to perform better than HA at lower TOL concentrations (below 50 ppm) (Truchon et al, 1999). However, due to background levels, oCre cannot be used as an indicator of very low concentrations, close to 2 ppm (Inoue et al, 2008).…”

“…Correction for creatinine is controversial since it does not always improve the correlation between the external doses and urinary exposure marker levels (Inoue et al, 2008, Kawai et al, 2010.…”

Diazepam influences urinary bioindicator of occupational toluene exposure

“…Indeed, TOL metabolism is similar in humans and rats. Although a significant amount of o-C might be present in urine of non-exposed subjects, it is not usable when they exposure level is below 2 ppm TOL (Cosnier et al, 2013;Inoue et al, 2008).…”