An integrated approach to biomonitoring exposure to styrene and styrene-(7,8)-oxide using a repeated measurements sampling design

Abstract

The aim of this work was to investigate urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers. We obtained three or four air and urine samples from each exposed worker (eight reinforced plastics workers and 13 varnish workers), one air and urine samples from 22 control workers (automobile mechanics) and one blood sample from all subjects. Median levels of exposure to Sty and StyOX, respectively, were 18.2 mg m(-3) and 133 microg m(-3) for reinforced plastics workers, 3.4 mg m(-3) and 12 microg m(-3) for varnish workers, and <0.3 mg m(-3) and <5 microg m(-3) for controls. Urinary levels of styrene, mandelic acid, phenylglyoxylic acid, phenylglycine (PHG), 4-vinylphenol (VP) and mercapturic acids (M1+M2), as well as cysteinyl adducts of serum albumin (but not those of haemoglobin) were significantly associated with exposure status (controls<exposed workers). Also, levels of VP and M1+M2 were significantly affected by smoking, and levels of M1+M2 were significantly affected by GSTM1 polymorphisms. Multiple linear regression analyses of the subject-specific (logged) metabolite levels across exposed workers showed that Sty was a significant predictor for all urinary analytes while StyOX was a significant predictor of PHG only. Interestingly, the log scale regression coefficients for Sty in these models were significantly less than one for all metabolites except M1+M2. This suggests that the natural scale relationships between levels of all Sty metabolites, except M1+M2, displayed downward concavity with increasing Sty exposure, suggestive of saturable metabolism. Levels of the protein adducts were not associated with exposure to either Sty or StyOX among exposed subjects.

Mercapturic acids: recent advances in their determination by liquid chromatography/mass spectrometry and their use in toxicant metabolism studies and in occupational and environmental exposure studies

“…The most abundant stereoisomers R,R-MA1 and S,R-MA2 are derived from the less genotoxic (S)7,8-SO. This result suggests stereoselective conjugation of (S)7,8-SO at a less sterically hindered C8 over a more hindered C7 (Fustinoni et al, 2008). Formation of these mercapturates is a minor detoxification route, representing about 1% of inhaled styrene (Manini et al, 2003), but tandem HPLC/MS-MS analysis of these mercapturates offers a sensitive and specific tool for styrene biotransformation studies (Manini et al, 2000).…”

“…GSH conjugation of both S- and R- enantiomers yields four possible isomeric PHEMAs, the structures of which are shown in Figure 6 (Linhart et al, 1998). The relative proportions of the stereoisomers MA1 and MA2 was used to investigate the stereoselectivity of GSTM1 conjugation of 7,8-SO (Linhart et al, 1998, DePalma et al, 2001, Fustinoni et al, 2008). The most abundant stereoisomers R,R-MA1 and S,R-MA2 are derived from the less genotoxic (S)7,8-SO.…”

Report: 20 Suspected Carcinogens Need More Research to Fill Knowledge Gaps

“…In addition to characterizing exposures, biomonitoring studies continue to evaluate possible markers of styrene exposure. For example, Fustinoni et al (2008) investigated "urinary analytes and haemoglobin and albumin adducts as biomarkers of exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) and to evaluate the influence of smoking habit and genetic polymorphism of metabolic enzymes GSTM1 and GSTT1 on these biomarkers." While protein adducts were not associated with styrene or styrene oxide exposures urinary metabolites were.…”