Skip to main content

Advertisement

SpringerLink
Log in

Reference Values of Urinary Trans,trans-muconic Acid: Italian Multicentric Study

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

This article reports the results of a study, conducted in the framework of the scientific activities of the Italian Society for Reference Values, aimed at defining reference values of urinary trans,trans-muconic acid (t,t-MA) in the general population not occupationally exposed to benzene. t,t-MA concentrations detected in 376 subjects of the resident population in three areas of Italy, two in central (Florence and southern Tuscany) and one in northern Italy (Padua), by three laboratories, compared by repeated interlaboratory controls, showed an interval of 14.4–225.0 μg/L (5th–95th percentile) and a geometric mean of 52.5 μg/L. The concentrations measured were influenced by tobacco smoking in a statistically significant way: Geometric mean concentrations were 44.8 μg/L and 76.1 μg/Ll in nonsmokers (264 subjects) and smokers (112 subjects), respectively. In the nonsmoking population, a significant influence of gender was found when concentrations were corrected for urinary creatinine, geometric mean concentrations being 36.7 μg/g creatinine in males (128 subjects) and 44.7 μg/g creatinine in females (136 subjects). The place of residence of subjects did not seem to influence urinary excretion of the metabolite, although personal inhalation exposure to benzene over a 24-h period showed slightly higher concentrations in Padua and Florence (geometric means of 6.5 μg/m3 and 6.6 μg/m3, respectively) than in southern Tuscany (geometric mean of 3.9 μg/m3). Concentration of t,t-MA in urine samples collected at the end of personal air sampling showed little relationship to personal inhalation exposure to benzene, confirming the importance of other factors in determining excretion of t,t-MA when concentrations in personal air samples are very low.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

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 

  • Adikofer F, Scherer G, Conze C, Angerer J, Lehnert G (1990) Significance of exposure to benzene and other toxic compounds through environmental tabacco smoke. J Cancer Res Clin Oncol 116:591–598

    Article  Google Scholar 

  • Bergamaschi E, Brustolin A, De Palma G, et al. (1999) Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons. Toxicol Lett 108:241–247

    Article  CAS  Google Scholar 

  • Bini G, Di Vaio V, Liguori E, Marini E, Pagliai L (1998) Carcinogens in the urban environment of Italian cities: benzene and benzo(a)pyrenes. Med Lav 89:177–187

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Cao XL, Casey V, Seaman S, Tague B, Becalski A (2007) Determination of benzene in soft drinks and other beverages by isotope dilution headspace gas chromatography/mass spectrometry. J AOAC Int 90:479–484

    CAS  Google Scholar 

  • Carrer P, Maroni M, Alcini D, et al. (2000) Assessment through environmental and biological measurements of total daily exposure to volatile organic compounds of office workers in Milan. Indoor Air 10:258–268

    Article  CAS  Google Scholar 

  • Chan CC, Spengler JD, Ozkaynak H, Lefkopoulou M (1991) Commuter exposure to VOCs in Boston, Massachusetts. J Air Waste Manag Assoc 41:1594–1600

    CAS  Google Scholar 

  • Cocco P, Tocco MG, Ibba A, et al. (2003) Trans, trans-muconic acid excretion in relation to environmental exposure to benzene. Int Arch Occup Environ Health 76:456–460

    Article  CAS  Google Scholar 

  • Cocheo V, Sacco P, Boaretto C, et al. (2000) Urban benzene and population exposure. Nature 404:141–142

    Article  CAS  Google Scholar 

  • Crebelli R, Tomei F, Zijno A, et al. (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 

  • Ducos P, Gaudin R, Bel J, et al. (1992) Trans,trans-muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to ppm level. Int Arch Occup Environ Health 64:309–313

    Article  CAS  Google Scholar 

  • Fustinoni S, Buratti M, Campo L, et al. (2005) Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzene exposure. Chem Biol Interact 153–154:253–256

    Article  CAS  Google Scholar 

  • Gilli G, Scursatone E, Bono R (1994) Benzene, toluene and xylenes in air, geographical distribution in the Piedmont region (Italy) and personal exposure. Sci Total Environ 148:49–56

    Article  CAS  Google Scholar 

  • Gobba AM, Rovesti S, Borella P, Vivoli R, Caselgrandi E, Vivoli G (1997) Inter-individual variability of benzene metabolism to trans,trans-muconic acid and its implications in the biological monitoring of occupational exposure. Sci Total Environ 199:41–48

    Article  CAS  Google Scholar 

  • Hill RH Jr, Head SL, Baker S, et al. (1995) Pesticide residues in urine of adults living in the United States: reference range concentrations. Environ Res 71:99–108

    Article  CAS  Google Scholar 

  • Imbriani M, Fiorentino ML, Maestri L, Marsilio MG, Ghittori S (1996) Indoor pollution and biological monitoring of volatile organic compounds (VOC). G Ital Med Lav 18:151–160

    CAS  Google Scholar 

  • Johnson ES, Langard S, Lin YS (2007) A critique of benzene exposure in the general population. Sci Total Environ 374:183–198

    Article  CAS  Google Scholar 

  • Kim MY, Harrad S, Harrison RM (2001) Concentrations and sources of VOCs in urban domestic and public microenvironments. Environ Sci Technol 35:997–1004

    Article  CAS  Google Scholar 

  • Kim S, Vermeulen R, Waidyanatha S, et al. (2006) Using urinary biomarkers to elucidate dose-related patterns of human benzene metabolism. Carcinogenesis 27:772–781

    Article  CAS  Google Scholar 

  • Lagorio S, Crebelli R, Ricciarello R, et al. (1998) Methodological issues in biological monitoring of low level exposure to benzene. Occup Med 48:497–504

    Article  CAS  Google Scholar 

  • Lee BL, Ong HY, Ong YB, Ong CM (2005) A sensitive liquid chromatographic method for the spectrometric determination of urinary trans,trans-muconic acid. J Chromatogr B 818:277–283

    Article  CAS  Google Scholar 

  • Lee JW, Jo WK (2002) Actual commuter exposure to methyl-tertiary butyl ether, benzene and toluene while traveling in Korean urban areas. Sci Total Environ 291:219–228

    Article  CAS  Google Scholar 

  • Lin LC, Chiung YM, Shih JF, Shih TS, Liao PC (2006) Validation of an online-dual loop cleanup device with an electrospray ionisation tandem mass-spectrometry-based system for simultaneous quantitative analysis of urinary benzene exposure biomarkers trans, trans-muconic acid and S-phenylmercapturic acid. Anal Chim Acta 555:34–40

    Article  CAS  Google Scholar 

  • Lin LC, Shih JF, Shih TS, Li YJ, Liao PC (2004) An electrospray ionization tandem mass spectrometry based system with an online dual-loop cleanup device for simultaneous quantitation of urinary benzene exposure biomarkers trans,trans-muconic acid and S-phenylmercapturic acid. Rapid Commun Mass Spectrom 18:2743–2752

    Article  CAS  Google Scholar 

  • Manini P, Andreoli R, Mutti A (2006a) Application of liquid chromatography–mass spectrometry to biomonitoring of exposure to industrial chemicals. Toxicol Lett 162:202–210

    Article  CAS  Google Scholar 

  • Manini P, De Palma G, Andreoli R, et al. (2006b) Environmental and biological monitoring of benzene exposure in a cohort of Italian taxi drivers. Toxicol Lett 167:142–151

    Article  CAS  Google Scholar 

  • Marrubini G, Coccini T, Maestri L, Manzo L (2002) Effect of sorbic acid administration on urinary trans,trans-muconic acid excretion in rats exposed to low levels of benzene. Food Chem Toxicol 40:1799–1806

    Article  CAS  Google Scholar 

  • Marrubini G, Coccini T, Manzo L (2001) Direct analysis of urinary trans,trans-muconic acid by coupled column liquid chromatography and spectrophotometric ultraviolet detection: method applicability to human urine. J Chromatogr B Biomed Sci Appl 758:295–303

    Article  CAS  Google Scholar 

  • Melikian AA, Qu Q, Shore R, et al. (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 

  • Minoia C, Apostoli P (1999) Activity of the Italian Society of Reference Values. Int Arch Occup Environ Health 72:268–270

    Article  CAS  Google Scholar 

  • Minoia C, Apostoli P (2003) First SIVR list of reference values: definitions, methodologic criteria and analytical strategies. G Ital Med Lav Erg 25:15–21

    CAS  Google Scholar 

  • Moriguchi J, Ezaki T, Tsukahara T, et al. (2005) Decreases in urine specific gravity and urinary creatinine in elderly women. Int Arch Occup Environ Health 78:438–445

    Article  CAS  Google Scholar 

  • Nakai JS, Chu I, Li-Muller A, Aucoin R (1997) Effect of environmental conditions on the penetration of benzene through human skin. J Toxicol Environ Health 51:447–462

    Article  CAS  Google Scholar 

  • Negri S, Bono R, Maestri L, Ghittori S, Imbriani M (2005) High-pressure liquid chromatographic-mass spectrometric determination of sorbic acid in urine: verification of formation of trans,trans-muconic acid. Chem Biol Interact 153–154:243–246

    Article  CAS  Google Scholar 

  • Olmos V, Lenzken SC, Lopez CM, Villaamil EC (2006) High-performance liquid chromatography method for urinary trans,trans-muconic acid. Application to environmental exposure to benzene. J Anal Toxicol 30:258–261

    CAS  Google Scholar 

  • Ong CN (1999) Reference values and action levels of biological monitoring in occupational exposure. Toxicol Lett 108:127–135

    Article  CAS  Google Scholar 

  • Park JH, Spengler JD, Yoon DW, Dumyahn T, Lee K, Ozkaynak H (1998) Measurement of air exchange rate of stationary vehicles and estimation of in-vehicle exposure. J Exp Anal Environ Epidemiol 8:65–78

    CAS  Google Scholar 

  • Pavanello S, Simioli P, Carrieri M, Gregorio P, Clonfero E (2002) Tobacco-smoke exposure indicators and urinary mutagenicity. Mutat Res 521:1–9

    CAS  Google Scholar 

  • Pezzagno G, Maestri L, Fiorentino ML (1999) Trans,trans-muconic acid, a biological indicator to low levels of environmental benzene: some aspects of its specificity. Am J Ind Med 35:511–518

    Article  CAS  Google Scholar 

  • Qu Q, Melikian AA, Li G, et al. (2000) Validation of biomarkers in humans exposed to benzene: urine metabolites. Am J Ind Med 37:522–531

    Article  CAS  Google Scholar 

  • Qu Q, Shore R, Li G, et al. (2005) Biomarkers of benzene: urinary metabolites in relation to individual genotype and personal exposure. Chem Biol Interact 153–154:85–95

    Article  CAS  Google Scholar 

  • Renner T, Baer-Koetzle M, Scherer G (1999) Determination of sorbic acid in urine by gas-chromatography-mass spectrometry. J Chromatogr A 847:127–133

    Article  CAS  Google Scholar 

  • Rossi AM, Guarnieri C, Rovesti C, et al. (1999) Genetic polymorphisms influence variability in benzene metabolism in humans. Pharmacogenetics 9:445–451

    CAS  Google Scholar 

  • Ruppert T, Scherer G, Tricker AR, Adlkofer F (1997) Trans,trans-muconic acid as a biomarker of non-occupational environmental exposure to benzene. Int Arch Occup environ Health 69:247–251

    Article  CAS  Google Scholar 

  • Saieva C, Tumino R, Masala G, et al. (2003) Urinary 1-hydroxypyrene and t,t-muconic acid as biomarkers of exposure to environmental pollutants in two areas in Italy (EPIC-Florence and Ragusa). Tumori 89:679–686

    CAS  Google Scholar 

  • Schneider P, Lorinci G, Gebefugi L, Heinrich J, Kettrup A, Wichmann HE (1999) Vertical and horizontal variability of volatile organic compounds in homes in Eastern Germany. J Exp Anal Environ Epidemiol 9:282–292

    Article  CAS  Google Scholar 

  • Shahtaheri SJ, Ghamari F, Golbabaei F (2005) Sample preparation followed by high performance liquid chromatographic (HPLC) analysis for monitoring muconic acid as a biomarker of occupational exposure to benzene. Int J Occup Safety Ergon 11:377–388

    CAS  Google Scholar 

  • Sinclair GC, Wester RC, Maibach HI (2002) Partition coefficients for benzene in human skin. AIHA J (Fairfax, Va) 63:685–688

    Article  CAS  Google Scholar 

  • Snyder R, Hedli CC (1996) An overview of benzene metabolism. Environ Health Perspect 104(Suppl 6):1165–1171

    Article  CAS  Google Scholar 

  • Thrall KD, Gies RA, Muniz J, Woodstock AD, Higgins G (2002) Route-of-entry and brain tissue partition coefficients for common superfund contaminants. J Toxicol Environ Health A 65:2075–2086

    Article  CAS  Google Scholar 

  • Verdina A, Galati R, Falasco G, et al. (2001) Metabolic polymorphisms and urinary biomarkers in subjects with low benzene exposure. J Toxicol Environ Health 64:607–618

    Article  CAS  Google Scholar 

  • Wallace L (1996) Environmental exposure to benzene: an update. Environ Health Perspect 104(Suppl 6):1129–1136

    Article  CAS  Google Scholar 

  • Weaver VM, Buckley T, Groopman JD (2000) Lack of specificity of trans,trans-muconic acid as a benzene biomarker after ingestion of sorbic acid-preserved foods. Cancer Epidemiol Biomarker Prevent 9:749–755

    CAS  Google Scholar 

  • Wester RC, Maibach HI (2000) Benzene percutaneous absorption: dermal exposure relative to other benzene sources. Int J Occup Environ Health 6:122–126

    CAS  Google Scholar 

Download references

Acknowledgment

The article was reviewed and approved by the Directive Board of the Italian Society for Reference Values (SIVR): P. Apostoli, M. Bettinelli, C. Aprea, I. Pavan, L. Perbellini, A. Perico, M.C. Ricossa, A. Ronchi, M.L. Scapellato, and S. Spezia.

Author information

Authors and Affiliations

  1. Laboratorio di Sanità Pubblica, Azienda USL 7 di Siena, Siena, Italy

    C. Aprea, G. Sciarra, N. Bozzi & M. Pagliantini

  2. Laboratorio di Sanità Pubblica, ASF di Firenze, Firenze, Italy

    A. Perico, P. Bavazzano & A. Leandri

  3. Dipartimento di Medicina Ambientale e Sanità Pubblica, Università di Padova, Padova, Italy

    M. Carrieri, M. L. Scapellato & G. B. Bartolucci

  4. Società Italiana Valori di Riferimento, Piacenza, Italy

    M. Bettinelli

Authors
  1. C. Aprea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Sciarra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Bozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Pagliantini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Perico
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Bavazzano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Leandri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Carrieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. L. Scapellato
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Bettinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. G. B. Bartolucci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Aprea.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aprea, C., Sciarra, G., Bozzi, N. et al. Reference Values of Urinary Trans,trans-muconic Acid: Italian Multicentric Study. Arch Environ Contam Toxicol 55, 329–340 (2008). https://doi.org/10.1007/s00244-007-9119-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-007-9119-9

Keywords

Search

Navigation