Validity of new biomarkers of internal dose for use in the biological monitoring of occupational and environmental exposure to low concentrations of benzene and toluene
- 722 Downloads
This study analyzes the validity of new, more sensitive and specific urinary biomarkers of internal dose, namely, urinary benzene for benzene and urinary toluene and S-benzylmercapturic acid (SBMA) for toluene, to assess their efficacy when compared to traditional biomarkers for biological monitoring of occupational exposure to low concentrations of these two toxic substances.
Assessment was made of 41 workers occupationally exposed to benzene and toluene, 18 fuel tanker drivers and 23 filling-station attendants, as well as 31 subjects with no occupational exposure to these toxic substances (controls). Exposure to airborne benzene and toluene was measured using passive Radiello® personal samplers worn throughout the work shift. In urine samples collected from all subjects at the end of the workday, both the traditional and the new internal dose biomarkers of benzene and toluene were assessed, as well as creatinine so as to apply suitable adjustments.
Occupational exposure to benzene and toluene resulted significantly higher in the fuel tanker drivers than the filling-station attendants, and higher in the latter than in controls. Significantly higher concentrations of t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), urinary benzene, SBMA and urinary toluene were found in the drivers than the filling-station attendants or the controls. Instead, urinary phenol and hippuric acid were not different in the three groups. In the entire sample, airborne benzene and toluene values were significantly correlated, as were the respective urinary biomarkers, showing coefficients ranging from 0.36 to 0.98. Subdividing the subjects by smoking habit, higher coefficients were evident in non-smokers than in smokers; at multiple regression analysis t,t-MA, SPMA and urinary benzene and toluene were dependent on the number of cigarettes smoked daily and on airborne benzene and toluene, respectively. Instead, SBMA was dependent only on airborne toluene.
Our research confirmed the validity of t,t-MA and SPMA for use in the biological monitoring of exposure to low concentrations of benzene. Urinary benzene showed comparable validity to SPMA; both parameters are affected by smoking cigarettes in the hours before urine collection, so it is best to ask subjects to refrain from smoking for 2 h before urine collection. Urinary toluene was found to be a more specific biomarker than SBMA.
KeywordsBiological monitoring Urinary benzene Urinary toluene S-Phenylmercapturic acid (SPMA) S-Benzylmercapturic acid (SBMA)
Research conducted with Grant COFIN-PRIN 2004 MUR no. 2004062283 from Ministry of University and Research, Italy.
Conflict of interest statement
The authors declare that they have no conflict of interest.
- Agency for Toxic Substances, Disease Registry (2000) Toxicological profile for toluene. ATSDR, AtlantaGoogle Scholar
- Agency for Toxic Substances, Disease Registry (2007) Toxicological profile for benzene. ATSDR, AtlantaGoogle Scholar
- American Conference of Governmental Industrial Hygienists (2008) TLVs and BEIs for chemical substances and physical agents. ACGIH, CincinnatiGoogle Scholar
- Benedict SR, Behre JA (1936) Some application of a new color reaction for creatinine. J Biol Chem 114:515–532Google Scholar
- Bruinen de Bruin Y, Koistinen K, Kephalopoulos S, Geiss O, Tirendi S, Kotzias D (2008) Characterization of urban inhalation exposures to benzene, formaldehyde and acetaldehyde in the European Union: comparison of measured and modelled exposure data. Environ Sci Pollut Res Int 15:417–430CrossRefGoogle Scholar
- Buchwald H (1966) The colorimetric determination of phenol in air and urine with a stabilized diazonium salt. Ann Occup Hyg 9:7–14Google Scholar
- Carlsson A (1982) Exposure to toluene: uptake, distribution and elimination in man. Scand J Work Environ Health 8:43–55Google Scholar
- European Parliament (2000) Directive 2000/69/CE of the European Parliament and of the Council of the 16 November 2000 concerning the limit values for benzene and carbon monoxide in environmental air. Off J European Union L313(12–21):13Google Scholar
- Farmer PB, Kaur B, Roach J, Levy L, Consonni D, Bertazzi PA, Pesatori A, Fustinoni S, Buratti M, Bonzini M, Colombi A, Popov T, Cavallo D, Desideri A, Valerio F, Pala M, Bolognesi C, Merlo F (2005) The use of S-phenylmercapturic acid as a biomarker in molecular epidemiology studies of benzene. Chem Biol Interact 153–154:97–102CrossRefGoogle Scholar
- Fustinoni S, Consonni D, Campo L, Buratti M, Colombi A, Pesatori AC, Bonzini M, Bertazzi PA, Foà V, Garte S, Farmer PB, Levy LS, Pala M, Valerio F, Fontana V, Desideri A, Merlo DF (2005) Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms. Cancer Epidemiol Biomarkers Prev 14:2237–2244CrossRefGoogle Scholar
- Ghittori S, Ferrari M, Maestri L, Negri S, Zadra P, Gremita P, Imbriani M (2005) Il significato del monitoraggio ambientale e biologico nei lavoratori addetti alle stazioni di servizio dopo la eliminazione del piombo tetraetile dalle benzine. G Ital Med Lav Erg 27:137–153Google Scholar
- Imbriani M, Ghittori S (1997) Effects of ethanol on toluene metabolism in man. G Ital Med Lav Ergon 19:177–181Google Scholar
- Imbriani M, Ghittori S, Cavalleri A (1999) Significance of urinary concentrations of S-benzyl-N-acetylcysteine (S-BMA) in subjects exposed to toluene. G Ital Med Lav Ergon 21:329–333Google Scholar
- Inoue O, Kanno E, Yusa T, Kakizaki M, Watanabe T, Higashikawa K, Ikeda M (2001) A simple HPLC method to determine urinary phenylmercapturic acid and its application to gasoline station attendants to biomonitor occupational exposure to benzene at less than 1 ppm. Biomarkers 6:190–203CrossRefGoogle Scholar
- International Agency for Research on Cancer (1982) Some industrial chemicals and dyestuffs. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans 29. IARC, LyonGoogle Scholar
- International Agency for Research on Cancer (1987) Overall evaluation of carcinogenicity: an update of IARC monographs, vol 1–42. IARC monographs on the evaluation of carcinogenic risks to humans, Suppl 7. IARC, LyonGoogle Scholar
- International Agency for Research on Cancer (2004) Tobacco smoke and involuntary smoking. IARC monographs on the evaluation of carcinogenic risks to humans 83. IARC, LyonGoogle Scholar
- Italian Government (2005) Legislative Decree of 21 March 2005, no. 66. Adozione della direttiva 2003/17/CE relativa alla qualità della benzina e del combustibile diesel. Off J Ital Repub No. 96, 27 Apr, Ordinary Supplement No. 77Google Scholar
- Italian Parliament (1997) Law 4 November 1997, No. 413. Misure urgenti per la prevenzione dell’inquinamento atmosferico da benzene. Off J Ital Repub No. 282, 3 DecGoogle Scholar
- Maranelli G, Romeo L, Apostoli P, Perbellini L, Betta A, Marchiori L, Vega V, Brugnone F (2000) Linee guida per la valutazione e la gestione dei rischi da benzene per la salute dei lavoratori addetti alle stazioni di servizio carburanti. G Ital Med Lav Erg 22:241–261Google Scholar
- Melikian AA, Qu Q, Shore R, Li G, Li H, Jin X, Cohen B, Chen L, Li Y, Yin S, Mu R, Zhang X, Wang Y (2002) Personal exposure to different levels of benzene and its relationships to the urinary metabolites S-phenylmercapturic acid and trans, trans-muconic acid. J Chromatogr B Analyt Technol Biomed Life Sci 778:211–221CrossRefGoogle Scholar
- National Institute of Occupational Safety and Health (2003) Hydrocarbons, aromatic: method 1501. In: Schlecht PC, O’Connor PF (eds) NIOSH manual of analytical methods, 4th edn. NIOSH, CincinnatiGoogle Scholar
- Sabatini L, Barbieri A, Indiveri P, Mattioli S, Violante FS (2008) Validation of an HPLC–MS/MS method for the simultaneous determination of phenylmercapturic acid, benzylmercapturic acid and o-methylbenzylmercapturic acid in urine as biomarkers of exposure to benzene, toluene and xylenes. J Chrom B 863:115–122CrossRefGoogle Scholar
- Scientific Committee for Occupational Exposure Limits (1998) Recommendations of the Scientific Committee for Occupational Exposure Limits to Chemical Agents 1994–97. Directorate General for Employment, Industrial Relations and Social Affairs Unit V/F.5. 3. European CommissionGoogle Scholar
- Scientific Committee for Occupational Exposure Limits (2001) Recommendation from Scientific Committee on Occupational Exposure Limits for Toluene SCOEL/SUM/18H. European CommissionGoogle Scholar
- Simon V, Baer M, Torres L, Olivier S, Meybeck M, Della Massa JP (2004) The impact of reduction in the benzene limit value in gasoline on airborne benzene, toluene and xylenes levels. Sci Total Environ 334–335:177–183Google Scholar
- Takahashi S, Kagawa M, Shiwaku K, Matsubara K (1994) Determination of S-benzyl-N-acetyl-l-cysteine by gas chromatography/mass spectrometry as a new marker of toluene exposure. J Anal Toxicol 18:78–80Google Scholar
- World Health Organization (1993) Environmental health criteria 155. Benzene. WHO, GenevaGoogle Scholar
- World Health Organization (2000) Air quality guidelines for Europe, 2nd edn. Toluene. WHO, Regional Office for Europe, CopenhagenGoogle Scholar