title: Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms.
abstract: Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices. Gas station attendants, urban policemen, bus drivers, and two groups of controls were studied (415 subjects). Median benzene exposure was 61, 22, 21, 9 and 6 microg/m(3), respectively, with higher levels in workers than in controls. U-benzene, but not t,t-MA and S-phenylmercapturic acid, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to 8-fold higher in smokers compared with nonsmokers. Significant correlations of the biomarkers with each other and with urinary cotinine were found. A possible influence of genetic polymorphism of CYP2E1 (RsaI and/or DraI) on t,t-MA and U-benzene in subjects with a variant allele was found. Multiple linear regression analysis correlated the urinary markers with exposure, smoking status, and CYP2E1 (RsaI; R(2) up to 0.55 for U-benzene). In conclusion, in the range of investigated benzene levels (<478 micro/m(3) or <0.15 ppm), smoking may be regarded as the major source of benzene intake; among the study indices, U-benzene is the marker of choice for biomonitoring low-level occupational and environmental benzene exposure.
authors.affiliation: Department of Occupational and Environmental Health, University of Milan, Italy. silvia.fustinoni@unimi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.forename: Laura
authors.initials: L
authors.lastname: Campo
authors.forename: Marina
authors.initials: M
authors.lastname: Buratti
authors.forename: Antonio
authors.initials: A
authors.lastname: Colombi
authors.forename: Angela C
authors.initials: AC
authors.lastname: Pesatori
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonzini
authors.forename: Pier A
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Vito
authors.initials: V
authors.lastname: Foà
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Levy
authors.forename: Mauro
authors.initials: M
authors.lastname: Pala
authors.forename: Federico
authors.initials: F
authors.lastname: Valerio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fontana
authors.forename: Arianna
authors.initials: A
authors.lastname: Desideri
authors.forename: Domenico F
authors.initials: DF
authors.lastname: Merlo
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D001554:Benzene / Q000032:analysis* / Q000378:metabolism; D002273:Carcinogens / Q000032:analysis* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012907:Smoking / Q000009:adverse effects; D013011:Sorbic Acid / Q000031:analogs & derivatives / Q000032:analysis; D014186:Transportation
chemical_list: D002273:Carcinogens; C005939:muconic acid; C053003:S-phenyl-N-acetylcysteine; D001554:Benzene; D000111:Acetylcysteine; D013011:Sorbic Acid