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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

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Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

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References

  • Adami G, Larese F, Venier M, Barbieri P, Lo Coco F, Reisenhofer E (2006) Penetration of benzene, toluene and xylenes contained in gasolines through human abdominal skin in vitro. Toxicol In Vitro 20:1321–1330

    Article  CAS  Google Scholar 

  • Agency for Toxic Substances, Disease Registry (2000) Toxicological profile for toluene. ATSDR, Atlanta

    Google Scholar 

  • Agency for Toxic Substances, Disease Registry (2007) Toxicological profile for benzene. ATSDR, Atlanta

    Google Scholar 

  • American Conference of Governmental Industrial Hygienists (2008) TLVs and BEIs for chemical substances and physical agents. ACGIH, Cincinnati

    Google Scholar 

  • Andrews LS, Lee EW, Witmer CM, Kocsis JJ, Snyder R (1977) Effects of toluene on the metabolism, disposition and hemopoietic toxicity of [3H]benzene. Biochem Pharmacol 26:293–300

    Article  CAS  Google Scholar 

  • Aprea C, Sciarra G, Bozzi N, Pagliantini M, Perico A, Bavazzano P, Leandri A, Carrieri M, Scapellato ML, Bettinelli M, Bartolucci GB (2008) Reference values of urinary trans, trans-muconic acid: Italian multicentric study. Arch Environ Contam Toxicol 55:329–340

    Article  CAS  Google Scholar 

  • Barbieri A, Violante FS, Graziosi F, Sabatini L, Mattioli S (2008) Urinary biomarkers and low-level environmental benzene concentration: assessing occupational and general exposure. Chemosphere 74:64–69

    Article  CAS  Google Scholar 

  • Benedict SR, Behre JA (1936) Some application of a new color reaction for creatinine. J Biol Chem 114:515–532

    CAS  Google Scholar 

  • Boogaard PJ, van Sittert NJ (1995) Biological monitoring of exposure to benzene: a comparison between S-phenylmercapturic acid, trans, trans-muconic acid, and phenol. Occup Environ Med 52:611–620

    Article  CAS  Google Scholar 

  • Boogaard PJ, van Sittert NJ (1996) Suitability of S-phenyl mercapturic acid and trans–trans-muconic acid as biomarkers for exposure to low concentrations of benzene. Environ Health Perspect 104(Suppl 6):1151–1157

    Article  CAS  Google Scholar 

  • Brocco D, Fratarcangeli R, Lepore L, Petricca M, Ventrone I (1997) Determination of aromatic hydrocarbons in urban air of Rome. Atmos Environ 31:557–566

    Article  CAS  Google Scholar 

  • Brugnone F, Perbellini L, Maranelli G, Romeo L, Guglielmi G, Lombardini F (1992) Reference values for blood benzene in the occupationally unexposed general population. Int Arch Occup Environ Health 64:179–184

    Article  CAS  Google 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 15:417–430

    Article  CAS  Google Scholar 

  • Buchwald H (1966) The colorimetric determination of phenol in air and urine with a stabilized diazonium salt. Ann Occup Hyg 9:7–14

    CAS  Google Scholar 

  • Carlsson A (1982) Exposure to toluene: uptake, distribution and elimination in man. Scand J Work Environ Health 8:43–55

    CAS  Google Scholar 

  • Carrieri M, Bonfiglio E, Scapellato ML, Maccà I, Tranfo G, Faranda P, Paci E, Bartolucci GB (2006) Comparison of exposure assessment methods in occupational exposure to benzene filling-station attendants. Toxicol Lett 162:146–152

    Article  CAS  Google Scholar 

  • Chidgey MA, Caldwell J (1986) Studies on benzyl acetate. I. Effect of dose size and vehicle on the plasma pharmacokinetics and metabolism of [methylene-14C]benzyl acetate in the rat. Food Chem Toxicol 24:1257–1265

    Article  CAS  Google Scholar 

  • Crebelli R, Tomei F, Zijno A, Ghittori S, Imbriani M, Gamberale D, Martini A, Carere A (2001) Exposure to benzene in urban workers: environmental and biological monitoring of traffic police in Rome. Occup Environ Med 58:165–171

    Article  CAS  Google Scholar 

  • Døssing M, Baelum J, Hansen SH, Lundqvist GR (1984) Effect of ethanol, cimetidine and propranolol on toluene metabolism in man. Int Arch Occup Environ Health 54:309–315

    Article  Google Scholar 

  • Ducos P, Berode M, Francin JM, Arnoux C, Lefèvre C (2008) Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene. Int Arch Occup Environ Health 81:273–284

    Article  CAS  Google 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):13

    Google 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 153–154:97–102

    Article  CAS  Google Scholar 

  • Fustinoni S, Buratti M, Giampiccolo R, Brambilla G, Foà V, Colombi A (2000) Comparison between blood and urinary toluene as biomarkers of exposure to toluene. Int Arch Occup Environ Health 73:389–396

    Article  CAS  Google 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 14:2237–2244

    Article  CAS  Google Scholar 

  • Fustinoni S, Mercadante R, Campo L, Scibetta L, Valla C, Consonni D, Foà V (2007) Comparison between urinary o-cresol and toluene as biomarkers of toluene exposure. J Occup Environ Hyg 4:1–9

    Article  CAS  Google Scholar 

  • Ghittori S, Fiorentino ML, Maestri L, Cordioli G, Imbriani M (1993) Urinary excretion of unmetabolized benzene as an indicator of benzene exposure. J Toxicol Environ Health 38:233–243

    Article  CAS  Google Scholar 

  • Ghittori S, Imbriani M, Maestri L, Capodaglio E, Cavalleri A (1999) Determination of S-phenylmercapturic acid in urine as an indicator of exposure to benzene. Toxicol Lett 108:329–334

    Article  CAS  Google 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 27:137–153

    CAS  Google Scholar 

  • Hellén H, Hakola H, Pirjola L, Laurila T, Pystynen KH (2006) Ambient air concentrations, source profiles, and source apportionment of 71 different C2–C10 volatile organic compounds in urban and residential areas of Finland. Environ Sci Technol 40:103–108

    Article  CAS  Google Scholar 

  • Hotz P, Carbonnelle P, Haufroid V, Tschopp A, Buchet JP, Lauwerys R (1997) Biological monitoring of vehicle mechanics and other workers exposed to low concentrations of benzene. Int Arch Occup Environ Health 70:29–40

    Article  CAS  Google Scholar 

  • Ikeda M (1999) Solvents in urine as exposure markers. Toxicol Lett 108:99–106

    Article  CAS  Google Scholar 

  • Imbriani M, Ghittori S (1997) Effects of ethanol on toluene metabolism in man. G Ital Med Lav Ergon 19:177–181

    CAS  Google 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 21:329–333

    CAS  Google Scholar 

  • Inoue O, Seiji K, Watanabe T, Kasahara M, Nakatsuka H, Yin SN, Li GL, Cai SX, Jin C, Ikeda M (1988) Mutual metabolic suppression between benzene and toluene in man. Int Arch Occup Environ Health 60:15–20

    Article  CAS  Google 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 6:190–203

    Article  CAS  Google Scholar 

  • Inoue O, Kanno E, Yusa T, Kakizaki M, Ukai H, Okamoto S, Higashikawa K, Ikeda M (2002) Urinary benzylmercapturic acid as a marker of occupational exposure to toluene. Int Arch Occup Environ Health 75:341–347

    Article  CAS  Google Scholar 

  • Inoue O, Kanno E, Kasai K, Ukai H, Okamoto S, Ikeda M (2004) Benzylmercapturic acid is superior to hippuric acid and o-cresol as a urinary marker of occupational exposure to toluene. Toxicol Lett 147:177–186

    Article  CAS  Google 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, Lyon

    Google 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, Lyon

    Google 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, Lyon

    Google 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. 77

  • 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 Dec

  • Janasik B, Jakubowski M, Jałowiecki P (2008) Excretion of unchanged volatile organic compounds (toluene, ethylbenzene, xylene and mesitylene) in urine as result of experimental human volunteer exposure. Int Arch Occup Environ Health 81:443–449

    Article  CAS  Google Scholar 

  • Kawai T, Mizunuma K, Okada Y, Horiguchi S, Ikeda M (1996) Toluene itself as the best urinary marker of toluene exposure. Int Arch Occup Environ Health 68:289–297

    Article  CAS  Google Scholar 

  • Kawai T, Ukai H, Inoue O, Maejima Y, Fukui Y, Ohashi F, Okamoto S, Takada S, Sakurai H, Ikeda M (2008) Evaluation of biomarkers of occupational exposure to toluene at low levels. Int Arch Occup Environ Health 81:253–262

    Article  CAS  Google Scholar 

  • Kim S, Vermeulen R, Waidyanatha S, Johnson BA, Lan Q, Smith MT, Zhang L, Li G, Shen M, Yin S, Rothman N, Rappaport SM (2006) Modeling human metabolism of benzene following occupational and environmental exposures. Cancer Epidemiol Biomarkers Prev 15:2246–2252

    Article  CAS  Google Scholar 

  • Koop DR, Laethem CL, Schnier GG (1989) Identification of ethanol-inducible P450 isozyme 3a (P450IIE1) as a benzene and phenol hydroxylase. Toxicol Appl Pharmacol 98:278–288

    Article  CAS  Google Scholar 

  • Laham S, Potvin M (1987) Biological conversion of benzaldehyde to benzylmercapturic acid in the Sprague–Dawley rat. Drug Chem Toxicol 10:209–225

    Article  CAS  Google Scholar 

  • Li S, Chen S, Zhu L, Chen X, Yao C, Shen X (2009) Concentrations and risk assessment of selected monoaromatic hydrocarbons in buses and bus stations of Hangzhou, China. Sci Total Environ 407:2004–2011

    Article  CAS  Google Scholar 

  • Lin DX, Friesen M, Malaveille C, Shuker DE, Bartsch H (1991) Urinary excretion of S-benzylmercapturic acid as an indicator of N-nitroso-N-methylbenzylamine exposure. Cancer Lett 57:193–198

    Article  CAS  Google Scholar 

  • Maestri L, Ghittori S, Imbriani M (1997) Determination of specific mercapturic acids as an index of exposure to environmental benzene, toluene, and styrene. Ind Health 35:489–501

    Article  CAS  Google Scholar 

  • Manini P, De Palma G, Andreoli R, Poli D, Mozzoni P, Folesani G, Mutti A, Apostoli P (2006) Environmental and biological monitoring of benzene exposure in a cohort of Italian taxi drivers. Toxicol Lett 167:142–151

    Article  CAS  Google 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 22:241–261

    CAS  Google 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 778:211–221

    Article  CAS  Google 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, Cincinnati

  • Nise G (1992) Urinary excretion of o-cresol and hippuric acid after toluene exposure in rotogravure printing. Int Arch Occup Environ Health 63:377–381

    Article  CAS  Google Scholar 

  • Nomiyama K, Nomiyama H (1974) Respiratory retention, uptake and excretion of organic solvents in man. Benzene, toluene, n-hexane, trichloroethylene, acetone, ethyl acetate and ethyl alcohol. Int Arch Arbeitsmed 32:75–83

    Article  CAS  Google Scholar 

  • Ogata M, Taguchi T (1987) Quantitation of urinary metabolites of toluene, xylene, styrene, ethylbenzene, benzene and phenol by automated high performance liquid chromatography. Int Arch Occup Environ Health 59:263–272

    Article  CAS  Google Scholar 

  • Ong CN, Kok PW, Lee BL, Shi CY, Ong HY, Chia KS, Lee CS, Luo XW (1995) Evaluation of biomarkers for occupational exposure to benzene. Occup Environ Med 52:528–533

    Article  CAS  Google Scholar 

  • Ong CN, Kok PW, Ong HY, Shi CY, Lee BL, Phoon WH, Tan KT (1996) Biomarkers of exposure to low concentrations of benzene: a field assessment. Occup Environ Med 53:328–333

    Article  CAS  Google Scholar 

  • Perbellini L, Buratti M, Fiorentino ML, Fustinoni S, Pasini F, Magnaghi S (1999) Matrix interferences in the analysis of benzene in urine. J Chromatogr B Biomed Sci Appl 724:257–264

    Article  CAS  Google Scholar 

  • Periago JF, Prado C (2005) Evolution of occupational exposure to environmental levels of aromatic hydrocarbons in service stations. Ann Occup Hyg 49:233–240

    Article  CAS  Google Scholar 

  • Pierce CH, Chen Y, Dills RL, Kalman DA, Morgan MS (2002) Toluene metabolites as biological indicators of exposure. Toxicol Lett 129:65–76

    Article  CAS  Google Scholar 

  • Qu Q, Melikian AA, Li G, Shore R, Chen L, Cohen B, Yin S, Kagan MR, Li H, Meng M, Jin X, Winnik W, Li Y, Mu R, Li K (2000) Validation of biomarkers in humans exposed to benzene: urine metabolites. Am J Ind Med 37:522–531

    Article  CAS  Google Scholar 

  • Saarinen L, Hakkola M, Kangas J (2000) Comparison of tanker drivers’ occupational exposures before and after the installation of a vapour recovery system. J Environ Monit 2:662–665

    Article  CAS  Google 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 863:115–122

    Article  CAS  Google Scholar 

  • Samoto H, Fukui Y, Ukai H, Okamoto S, Takada S, Ohashi F, Moriguchi J, Ezaki T, Ikeda M (2006) Field survey on types of organic solvents used in enterprises of various sizes. Int Arch Occup Environ Health 79:558–567

    Article  Google Scholar 

  • Sato A, Nakajima T, Fujiwara Y, Hirosawa K (1974) Pharmacokinetics of benzene and toluene. Int Arch Arbeitsmed 33:169–182

    Article  CAS  Google Scholar 

  • Saxena S, Abdel-Rahman MS (1989) Pharmacodynamics of benzyl chloride in rats. Arch Environ Contam Toxicol 18:669–677

    Article  CAS  Google Scholar 

  • Schettgen T, Musiol A, Alt A, Kraus T (2008) Fast determination of urinary S-phenylmercapturic acid (S-PMA) and S-benzylmercapturic acid (S-BMA) by column-switching liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 863:283–292

    Article  CAS  Google 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 Commission

  • Scientific Committee for Occupational Exposure Limits (2001) Recommendation from Scientific Committee on Occupational Exposure Limits for Toluene SCOEL/SUM/18H. European Commission

  • 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 334–335:177–183

    Google Scholar 

  • Smith MT, Jones RM, Smith AH (2007) Benzene exposure and risk of non-hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 16:385–391

    Article  CAS  Google Scholar 

  • Snyder R, Hedli CC (1996) An overview of benzene metabolism. Environ Health Perspect 10(supp 6):1165–1171

    Article  Google Scholar 

  • Snyder R, Witz G, Gildstein BD (1993) The toxicology of benzene. Environ Health Perspect 100:293–306

    Article  CAS  Google 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 18:78–80

    CAS  Google Scholar 

  • Takeuchi A, Kawai T, Zhang ZW, Miyama Y, Sakamoto K, Higashikawa K, Ikeda M (2002) Toluene, xylenes and xylene isomers in urine as biological indicators of low-level exposure to each solvent; a comparative study. Int Arch Occup Environ Health 75:387–393

    Article  CAS  Google Scholar 

  • Ukai H, Kawai T, Inoue O, Maejima Y, Fukui Y, Ohashi F, Okamoto S, Takada S, Sakurai H, Ikeda M (2007) Comparative evaluation of biomarkers of occupational exposure to toluene. Int Arch Occup Environ Health 81:81–93

    Article  CAS  Google Scholar 

  • Van Doorn R, Leijdekkers CM, Bos RP, Brouns RM, Henderson PT (1981) Alcohol and sulphate intermediates in the metabolism of toluene and xylenes to mercapturic acids. J Appl Toxicol 1:236–242

    Article  Google Scholar 

  • Van Vleet TR, Bombick DW, Coulombe RA Jr (2001) Inhibition of human cytochrome P450 2E1 by nicotine, cotinine, and aqueous cigarette tar extract in vitro. Toxicol Sci 64:185–191

    Article  Google Scholar 

  • Waidyanatha S, Rothman N, Fustinoni S, Smith MT, Hayes RB, Bechtold W, Dosemeci M, Guilan L, Yin S, Rappaport SM (2001) Urinary benzene as a biomarker of exposure among occupationally exposed and unexposed subjects. Carcinogenesis 22:279–286

    Article  CAS  Google Scholar 

  • World Health Organization (1993) Environmental health criteria 155. Benzene. WHO, Geneva

    Google Scholar 

  • World Health Organization (2000) Air quality guidelines for Europe, 2nd edn. Toluene. WHO, Regional Office for Europe, Copenhagen

    Google Scholar 

  • Yasugi T, Endo G, Monna T, Odachi T, Yamaoka K, Kawai T, Horiguchi S, Ikeda M (1998) Types of organic solvents used in workplaces and work environment conditions with special references to reproducibility of work environment classification. Ind Health 36:223–233

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Research conducted with Grant COFIN-PRIN 2004 MUR no. 2004062283 from Ministry of University and Research, Italy.

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Lovreglio, P., Barbieri, A., Carrieri, M. et al. 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. Int Arch Occup Environ Health 83, 341–356 (2010). https://doi.org/10.1007/s00420-009-0469-7

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