Biomonitoring exposure to styrene and styrene-(7,8)-oxide by repeated measurements

Aims: To investigat the use of urinary analytes and protein adducts as biomarkers of occupational exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) adopting a repeated measurements sampling design. Methods: Using this protocol (1 to 4 samplings), we sampled reinforced plastics workers (n=8), varnish workers (n=13), and control workers (n=22). Results: Median levels of personal exposure in these groups were 18.2, 3.4 and <0.3 mg/m3 for Sty and 133, 12 and <5 µg/m3 for StyOX. Among the exposed workers, levels of Sty and StyOX were positively correlated (Pearson r=0.794). Levels of urinary styrene (StyU), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), 4-vinylphenol (VP), and mercapturic acids (M1+M2), were significantly higher in exposed than in controls, and were positively correlated with both Sty and StyOX (r up to 0.974), and with each other. Although cysteinyl albumin and hemoglobin adducts of styrene-(7,8)-oxide adduct levels were consistently greater in exposed than in controls, the differences were not statistically significant. Levels of 2PE-albumin were negatively correlated with levels of M1+M2; suggesting a competition of glutathione and cysteinyl residues of albumin toward StyOX. A screening of effects on biomarker levels of job, smoking, and GST genotype showed that job was the major determinant, although GSTM1 polymorphism and cigarette smoking significantly influenced M1+M2 and VP, respectively. Multiple linear regression of the logged levels of urinary biomarkers vs. Sty and StyU (R2 up to 0.944) showed that values of βSty were close to one for StyU, M1+M2, and MA, and significantly less than one for VP, indicating that the natural scale relationships would be concave downwards with increasing Sty; such behavior would suggest saturable metabolism of the pathways leading to VP. Conclusion: The repeated measurements sampling design strengths the relationship between biomarkers and exposure and together with the use of several biomarkers greatly improve our capability to investigate metabolism of Sty and StyOx in humans.