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

Abstract

1. Toluene (TOL) is a neurotoxic, ototoxic and reprotoxic solvent which is metabolized via the glutathione pathway, producing benzylmercapturic, o-, m- and p-toluylmercapturic acids (MAs). These metabolites could be useful as biomarkers of TOL exposure. 2. The aims of this study were (1) to provide data on MAs excretion in rat urine following TOL exposure by inhalation, (2) to compare them to data from traditional TOL biomarkers, i.e. TOL in blood (Tol-B), and urinary hippuric acid (HA) and o-cresol (oCre) and (3) to establish a relationship between these different indicators and the airborne TOL concentration (Tol-A). 3. Sprague-Dawley rats were exposed to a range of TOL concentrations. Blood and urine were collected and analyzed to determine biomarker levels. 4. Levels of the four MAs correlate strongly with Tol-A (comparable to the correlation with Tol-B). 5. MAs are thus clearly superior to oCre and HA as potential markers of exposure to TOL.

Impact of coexposure on toluene biomarkers in rats

“…The first groups of rats were exposed to TOL at 2, 5, 20, 50, 200 and 500 ppm, which correspond to 0.1, 1 and 10 times the American and French 8-hour OELs: 20 and 50 ppm (until July 2012), respectively. The results from these groups were partially reported in a previous study (Cosnier et al, 2013).…”

“…c Data already published in Cosnier et al (2013). DOI: 10.3109/00498254.2013.830204 with coexposure, (3) the differences between the slopes of regression lines (mixtures versus TOL alone) (D slope ), (4) the difference between the values obtained for Tol-A ¼ 50 ppm, with or without coexposure (D concentration ) and (5) the day effect (not detailed in this article).…”

“…The different urinary metabolites: HA, oCre, oTMA, mTMA, pTMA and BMA were measured, as previously detailed in (Cosnier et al, 2012(Cosnier et al, , 2013. For these assays, LODs in urine (in mmol/L) were 22.3 for HA, 0.3 for oCre, 0.01 for oTMA and mTMA, and 0.02 for pTMA and BMA.…”

“…Blood collection had to be performed and completed on one rat before taking out another animal from the chamber. The procedure for this was detailed in Cosnier et al (2013). Briefly, blood was collected from the tails of rats anaesthetized with isoflurane; sampling was completed within 5 min.…”

“…In rats exposed to TOL vapours (between 2 and 500 ppm), the four MAs were compared to Tol-B, HA and oCre. We demonstrated that the concentrations of the four MAs correlate as well as Tol-B with Tol-A, and that MAs are clearly more suitable than oCre and HA as excreted TOL biomarkers (Cosnier et al, 2013).…”