title: Influence of genetic polymorphisms of styrene-metabolizing enzymes on the levels of urinary biomarkers of styrene exposure.
abstract: Styrene exposure is still present in different occupational settings including manufacture of synthetic rubber, resins, polyesters and plastic. The aim of this work was to investigate the effects of polymorphic genes CYP2E1, EPHX1, GSTT1, and GSTM1 on the urinary concentrations of the styrene metabolites mandelic acid (MA), phenylglyoxylic acid (PGA) and on the concentration ratios between (MA+PGA) and urinary styrene (U-Sty) and airborne styrene (A-Sty), in 30 workers from two fiberglass-reinforced plastic manufacturing plants and 26 unexposed controls. Personal air sampling and biological monitoring results revealed that sometimes exposure levels exceeded both the threshold limit value (TLV) and the biological exposure index (BEI) suggested by the American Conference of Governmental Industrial Hygienists. A significantly reduced excretion of styrene metabolites (MA+PGA) in individuals carrying the CYP2E1*5B and CYP2E1*6 heterozygote alleles, with respect to the homozygote wild type, was observed only in the exposed group. A reduction was also detected, in the same group, in subjects carrying the slow allele EPHX1 (codon 113), through the lowering of (MA+PGA)/urinary styrene concentration ratio. In addition, the ratio between MA+PGA and the personal airborne styrene concentration appeared to be modulated by the predicted mEH activity, in the exposed group, as evidenced by univariate linear regression analysis. Our results confirm some previous hypotheses about the role of the polymorphism of genes coding for enzymes involved in the styrene detoxification pathway: this may significantly reduce the levels of excreted metabolites and therefore it must be taken into account in the interpretation of the biological monitoring results for occupational exposure.
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: d.carbonari@inail.it.
authors.forename: Damiano
authors.initials: D
authors.lastname: Carbonari
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: a.mansi@inail.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mansi
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: a.proietto@inail.it.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Proietto
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: e.paci@inail.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Paci
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: r.bonanni@inail.it.
authors.forename: Rossana Claudia
authors.initials: RC
authors.lastname: Bonanni
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: m.gherardi@inail.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Gherardi
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: mp.gatto@inail.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Gatto
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: r.sisto@inail.it.
authors.forename: Renata
authors.initials: R
authors.lastname: Sisto
authors.affiliation: INAIL Research, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene Via di Fontana Candida 1, 00040 Monte Porzio Catone, Rome, Italy. Electronic address: g.tranfo@inail.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tranfo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004784:Environmental Monitoring; D004798:Enzymes / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020058:Styrene / Q000378:metabolism* / Q000652:urine
chemical_list: D015415:Biomarkers; D004798:Enzymes; D020058:Styrene; D019392:Cytochrome P-450 CYP2E1; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human
keywords: Biological monitoring; CYP2E1; EPHX1; MA+PGA; Styrene occupational exposure; Urinary styrene