Vinylphenylmercapturic acids in human urine as biomarkers of styrene ring oxidation

Abstract

New metabolites of styrene, three isomeric vinylphenylmercapturic acids (2-, 3-, and 4-VPMA), were recently identified by LC-ESI-MS in the urine of mice. In this study, 4-VPMA together with traces of 2- and 3-VPMA were found also in the urine of hand-lamination workers, which were exposed to styrene vapours at concentrations ranging from 23 to 244mg/m(3). Concentrations of 4-VPMA in these end-of-shift samples were 4.59±3.64ng/mL (mean±S.D.; n=10), those found next morning after the work-shift were 2.14±2.07ng/mL (mean±S.D.; n=10). Strong correlation (R=0.959) was found in the next-morning samples between concentrations of 4-VPMA and phenylglyoxylic acid, whereas correlations found between 4-VPMA and mandelic acid in both end-of-shift and next-morning samples were much weaker. The excretion of 4-VPMA accounted for only about 3.5×10(-4)% of the absorbed dose of styrene. Despite very low metabolic yield, formation of VPMAs clearly indicates occurrence and extent of styrene ring oxidation considered to be a toxicologically relevant metabolic pathway.