title: Assessment of biotransformation of the arene moiety of styrene in volunteers and occupationally exposed workers.
abstract: Styrene is a chemical widely used in the plastic industry. The main pathway of styrene metabolism in humans occurs via the oxidation to styrene-7,8-oxide (7,8-SO). The aim of this study was the investigation of a minor metabolic route, involving the oxidation of the arene moiety of styrene, by means of the characterization of the conjugated urinary metabolites of 4-vinylphenol (4-VP). 4-vinylphenol-glucuronide (4-VP-G) and -sulfate (4-VP-S), were measured by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) from 174 workers belonging to three cohorts recruited in European countries and from 26 volunteers exposed to 50 mg/m(3) (11.8 ppm) of styrene for 8 h. The 4-VP conjugates represented about 0.5-1% of the total excretion of styrene metabolites. Both 4-VP-G and 4-VP-S are eliminated with a monophasic kinetic, the glucuronide being excreted faster (half-time, 2.2 +/- 0.2 h) than the sulfate (half-time 9.7 +/- 1.7 h). The urinary 4-VP was found to be significantly correlated both with airborne styrene (r = 0.607, p < 0.001) and the sum of MA and PGA (r = 0.903, p < 0.001 in "end-of-shift" samples). Apart from 7,8-SO, 4-VP is the only styrene metabolite not shared with ethylbenzene and therefore thought to be a highly specific marker of styrene exposure. However, a measurable background excretion of 4-VP was also found in all urine samples from controls not occupationally exposed to styrene. This background appears to be highly correlated to smoking (p < 0.001) and possibly also to the dietary intake of styrene or 4-VP. Consequently, the use of 4-VP as a biomarker of styrene exposure is recommended for exposures exceeding 1 ppm.
authors.affiliation: ISPESL Research Center at the University of Parma, Italy. paola.manini@unipr.it
authors.forename: Paola
authors.initials: P
authors.lastname: Manini
authors.forename: Luca
authors.initials: L
authors.lastname: Buzio
authors.forename: Roberta
authors.initials: R
authors.lastname: Andreoli
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Enrico
authors.initials: E
authors.lastname: Bergamaschi
authors.forename: Marek
authors.initials: M
authors.lastname: Jakubowski
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
mesh_terms: D000328:Adult; D001711:Biotransformation; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000706:statistics & numerical data; D010084:Oxidation-Reduction; D010636:Phenols / Q000378:metabolism / Q000652:urine; D010969:Plastics / Q000032:analysis / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D018709:Statistics, Nonparametric; D020058:Styrene / Q000737:chemistry* / Q000378:metabolism* / Q000652:urine
chemical_list: D010636:Phenols; D010969:Plastics; D020058:Styrene; C030626:4-vinylphenol