Skip to main content
SpringerLink
Log in

Metabolites of the PAH diol epoxide pathway and other urinary biomarkers of phenanthrene and pyrene in workers with and without exposure to bitumen fumes

  • Original Article
  • Published:
International Archives of Occupational and Environmental Health Aims and scope Submit manuscript

Abstract

Purpose

This study investigates the diol epoxide pathway of phenanthrene (PHE) together with phenolic metabolites of PHE and pyrene (PYR) in workers with and without exposure to bitumen fumes.

Methods

The metabolite concentrations were determined in urine samples collected from 91 mastic asphalt workers and 42 construction workers as reference group before and after shift. During shift, vapours and aerosols of bitumen were measured according to a German protocol in the workers’ breathing zone.

Results

The median concentration of vapours and aerosols of bitumen in mastic asphalt workers was 6.3 mg/m3. Metabolite concentrations were highest in post-shift urines of smokers with bitumen exposure and showed an increase during shift. The Spearman correlations between the creatinine-adjusted concentrations of metabolites and vapours and aerosols of bitumen in non-smokers were weak (e.g. sum of Di-OH-PYR: 0.28) or negligible (e.g. 1,2-PHE-diol: 0.08; PHE-tetrol: 0.12). Metabolites from the diol epoxide pathway of PHE were excreted in higher concentrations than phenolic metabolites (post-shift, non-smoking asphalt workers: 1,2-PHE-diol 2.59 µg/g crea vs. sum of all OH-PHE 1.87 µg/g crea). 1,2-PHE-diol was weakly correlated with PHE-tetrol (Spearman coefficient 0.30), an endpoint of the diol epoxide pathway. By contrast, we found a close correlation between the sum of 1,6-DiOH-PYR and 1,8-DiOH-PYR with 1-OH-PYR (Spearman coefficient 0.76).

Conclusions

Most urinary PAH metabolites were higher after shift in bitumen-exposed workers, although the association with bitumen was weak or negligible likely due to the small PAH content. The additional metabolites of PHE and PYR complete the picture of the complex metabolic pathways. Nevertheless, none of the PAH metabolites can be considered to be a specific biomarker for bitumen exposure.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Agostini M, Fransman W, de Vocht F, Wendel Van, de Joode Berna, Kromhout H (2011) Assessment of dermal exposure to bitumen condensate among road paving and mastic crews with an observational method. Ann Occup Hyg 55(6):578–590. doi:10.1093/annhyg/mer026

    Article  CAS  Google Scholar 

  • Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL (2005) Urinary creatinine concentrations in the US population: implications for urinary biologic monitoring measurements. Environ Health Persp 113(2):192–200

    Article  CAS  Google Scholar 

  • Becker K, Schulz C, Kaus S, Seiwert M, Seifert B (2003) German Environmental Survey 1998 (GerES III): environmental pollutants in the urine of the German population. Int J Hyg Environ Health 206(1):15–24. doi:10.1078/1438-4639-00188

    Article  CAS  Google Scholar 

  • Bernigau W (2004) PAK-Metabolite im Urin der Bevölkerung in Deutschland - Belastungsquellen und -pfade; Forschungsbericht 201 62 214/12. Umweltforschungsplan des Bundesministeriums für Umwelt, Naturschutz und Reaktorsicherheit, vol 2004,4. Umweltbundesamt, Berlin

  • Boeniger MF, Lowry LK, Rosenberg J (1993) Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am Ind Hyg Assoc J 54(10):615–627. doi:10.1080/15298669391355134

    Article  CAS  Google Scholar 

  • Breuer D (2008) Bitumen (Dämpfe und Aerosole, Bitumenkondensat-Standard) Method 6305-2. In: Measurement of hazardous substances—BGIA Arbeitsmappe (BGIA Folder), determination of exposure to chemical and biological agents. Erich Schmidt Verlag, Bielefeld, Germany

  • Breuer D, Hahn JU, Höber D, Emmel C, Musanke U, Rühl R, Spickenheuer A, Raulf-Heimsoth M, Bramer R, Seidel A, Schilling B, Heinze E, Kendzia B, Marczynski B, Welge P, Angerer J, Brüning T, Pesch B (2011) Air sampling and determination of vapours and aerosols of bitumen and polycyclic aromatic hydrocarbons in the Human Bitumen Study. Arch Toxicol 85(Suppl 1):S11–S20. doi:10.1007/s00204-011-0678-1

    Article  Google Scholar 

  • Campo L, Buratti M, Fustinoni S, Cirla PE, Martinotti I, Longhi O, Cavallo D, Foà V (2006) Evaluation of exposure to PAHs in asphalt workers by environmental and biological monitoring. Ann NY Acad Sci 1076(1):405–420. doi:10.1196/annals.1371.013

    Article  CAS  Google Scholar 

  • Cavallari JM, Osborn LV, Snawder JE, Kriech AJ, Olsen LD, Herrick RF, McClean MD (2012) Predictors of dermal exposures to polycyclic aromatic compounds among hot-mix asphalt paving workers. Ann Occup Hyg 56(2):125–137. doi:10.1093/annhyg/mer108

    Article  CAS  Google Scholar 

  • Cavallo D, Ursini CL, Bavazzano P, Cassinelli C, Frattini A, Perniconi B, Di Francesco A, Ciervo A, Rondinone B, Iavicoli S (2006) Sister chromatid exchange and oxidative DNA damage in paving workers exposed to PAHs. Ann Occup Hyg 50(3):211–218. doi:10.1093/annhyg/mei072

    Article  CAS  Google Scholar 

  • Cirla PE, Martinotti I, Buratti M, Fustinoni S, Campo L, Zito E, Prandi E, Longhi O, Cavallo D, Foà V (2007) Assessment of exposure to polycyclic aromatic hydrocarbons (PAH) in Italian asphalt workers. J Occup Environ Hyg 4(sup1):87–99. doi:10.1080/15459620701354325

    Article  CAS  Google Scholar 

  • Ekström LG, Kriech AJ, Bowen C, Johnson S, Breuer D (2001) International studies to compare methods for personal sampling of bitumen fumes. J Environ Monit 3(5):439–445

    Article  Google Scholar 

  • Elkins HB, Pagnotto LD, Smith HL (1974) Concentration adjustments in urinalysis. Am Ind Hyg Assoc J 35(9):559–565. doi:10.1080/0002889748507072

    Article  CAS  Google Scholar 

  • Fustinoni S, Campo L, Cirla PE, Martinotti I, Buratti M, Longhi O, Foà V, Bertazzi P (2010) Dermal exposure to polycyclic aromatic hydrocarbons in asphalt workers. Occup Environ Med 67(7):456–463. doi:10.1136/oem.2009.050344

    Article  CAS  Google Scholar 

  • Gasthauer E, Maze M, Marchand JP, Amouroux J (2008) Characterization of asphalt fume composition by GC/MS and effect of temperature. Fuel 87(7):1428–1434

    Article  CAS  Google Scholar 

  • Glatt H, Wameling C, Elsberg S, Thomas H, Marquardt H, Hewer A, Phillips DH, Oesch F, Seidel A (1993) Genotoxicity characteristics of reverse diol-epoxides of chrysene. Carcinogenesis 14(1):11–19. doi:10.1093/carcin/14.1.11

    Article  CAS  Google Scholar 

  • Hansen ÅM, Mathiesen L, Pedersen M, Knudsen LE (2008) Urinary 1-hydroxypyrene (1-HP) in environmental and occupational studies—a review. Int J Hyg Environ Health 211(5–6):471–503. doi:10.1016/j.ijheh.2007.09.012

    Article  CAS  Google Scholar 

  • Haufroid V, Lison D (1998) Urinary cotinine as a tobacco-smoke exposure index: a minireview. Int Arch Occup Environ Health 71(3):162–168

    Article  CAS  Google Scholar 

  • Hecht SS, Hochalter JB (2014) Quantitation of enantiomers of r-7, t-8,9, c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene in human urine: evidence supporting metabolic activation of benzo[a]pyrene via the bay region diol epoxide. Mutagenesis 29(5):351–356. doi:10.1093/mutage/geu024

    Article  CAS  Google Scholar 

  • Hecht SS, Chen M, Yagi H, Jerina DM, Carmella SG (2003) r-1, t-2,3, c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene in human urine: a potential biomarker for assessing polycyclic aromatic hydrocarbon metabolic activation. Cancer Epidemiol Biomarkers Prev 12(12):1501–1508

    CAS  Google Scholar 

  • Hecht SS, Chen M, Yoder A, Jensen J, Hatsukami D, Le C, Carmella SG (2005) Longitudinal study of urinary phenanthrene metabolite ratios: effect of smoking on the diol epoxide pathway. Cancer Epidemiol Biomarkers Prev 14(12):2969–2974. doi:10.1158/1055-9965.EPI-05-0396

    Article  CAS  Google Scholar 

  • Hecht SS, Berg JZ, Hochalter JB (2009) Preferential glutathione conjugation of a reverse diol epoxide compared to a bay region diol epoxide of phenanthrene in human hepatocytes: relevance to molecular epidemiology studies of glutathione-s-transferase polymorphisms and cancer. Chem Res Toxicol 22(3):426–432. doi:10.1021/tx800315m

    Article  CAS  Google Scholar 

  • Hecht SS, Carmella SG, Villalta PW, Hochalter JB (2010) Analysis of phenanthrene and benzo[a]pyrene tetraol enantiomers in human urine: relevance to the bay region diol epoxide hypothesis of benzo[a]pyrene carcinogenesis and to biomarker studies. Chem Res Toxicol 23(5):900–908. doi:10.1021/tx9004538

    Article  CAS  Google Scholar 

  • Hecht SS, Hochalter JB, Carmella SG, Zhang Y, Rauch DM, Fujioka N, Jensen J, Hatsukami DK (2013) Longitudinal study of [D10]phenanthrene metabolism by the diol epoxide pathway in smokers. Biomarkers 18(2):144–150. doi:10.3109/1354750X.2012.753553

    Article  CAS  Google Scholar 

  • Heikkilä P, Riala R, Hämeilä M, Nykyri E, Pfäffli P (2002) Occupational exposure to bitumen during road paving. AIHA J (Fairfax, Va) 63(2):156–165

    Article  Google Scholar 

  • Hochalter JB, Zhong Y, Han S, Carmella SG, Hecht SS (2011) Quantitation of a minor enantiomer of phenanthrene tetraol in human urine: correlations with levels of overall phenanthrene tetraol, benzo[a]pyrene tetraol, and 1-hydroxypyrene. Chem Res Toxicol 24(2):262–268. doi:10.1021/tx100391z

    Article  CAS  Google Scholar 

  • IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2013) Bitumens and bitumen emissions, and some N- and S-heterocyclic aromatic hydrocarbons. IARC monographs on the evaluation of carcinogenic risks to humans, vol. 103. IARC Press, Lyon

  • Jacob J, Seidel A (2002) Biomonitoring of polycyclic aromatic hydrocarbons in human urine. J Chromatogr B 778(1–2):31–47

    Article  CAS  Google Scholar 

  • Jacob J, Raab G, Soballa V, Schmalix WA, Grimmer G, Greim H, Doehmer J, Seidel A (1996) Cytochrome P450-mediated activation of phenanthrene in genetically engineered V79 Chinese hamster cells. Environ Toxicol Phar 1(1):1–11. doi:10.1016/1382-6689(95)00003-8

    Article  CAS  Google Scholar 

  • Jacob J, Grimmer G, Dettbarn G (1999) Profile of urinary phenanthrene metabolites in smokers and non-smokers. Biomarkers 4(5):319–327

    Article  CAS  Google Scholar 

  • Järvholm B, Nordström G, Högstedt B, Levin JO, Wahlström J, Ostman C, Bergendahl C (1999) Exposure to polycyclic aromatic hydrocarbons and genotoxic effects on nonsmoking Swedish road pavement workers. Scand J Work Environ Health 25(2):131–136

    Article  Google Scholar 

  • Kriech AJ, Emmel C, Osborn LV, Breuer D, Redman AP, Hoeber D, Bochmann F, Ruehl R (2010) Side-by-side comparison of field monitoring methods for hot bitumen emission exposures: the German BGIA method 6305, the U.S. NIOSH method 5042, and the total organic matter method. J Occup Environ Hyg 7(12):712–725. doi:10.1080/15459624.2010.529792

    Article  CAS  Google Scholar 

  • Li Z, Sandau CD, Romanoff LC, Caudill SP, Sjodin A, Needham LL, Jr Patterson, Donald G (2008) Concentration and profile of 22 urinary polycyclic aromatic hydrocarbon metabolites in the US population. Environ Res 107(3):320–331. doi:10.1016/j.envres.2008.01.013

    Article  CAS  Google Scholar 

  • McClean MD, Rinehart RD, Ngo L, Eisen EA, Kelsey KT, Herrick RF (2004) Inhalation and dermal exposure among asphalt paving workers. Ann Occup Hyg 48(8):663–671. doi:10.1093/annhyg/meh062

    Article  CAS  Google Scholar 

  • NIOSH (2000) Health effects of occupational exposure to asphalt. U.S. Department of Health and Human Services, Cincinnati

    Google Scholar 

  • Pesch B, Kappler M, Straif K, Marczynski B, Preuss R, Rossbach B, Rihs HP, Weiss T, Rabstein S, Pierl C, Scherenberg M, Adams A, Käfferlein HU, Angerer J, Wilhelm M, Seidel A, Brüning T (2007) Dose-response modeling of occupational exposure to polycyclic aromatic hydrocarbons with biomarkers of exposure and effect. Cancer Epidemiol Biomarkers Prev 16(9):1863–1873. doi:10.1158/1055-9965.EPI-07-0033

    Article  CAS  Google Scholar 

  • Pesch B, Spickenheuer A, Kendzia B, Schindler BK, Welge P, Marczynski B, Rihs HP, Raulf-Heimsoth M, Angerer J, Brüning T (2011) Urinary metabolites of polycyclic aromatic hydrocarbons in workers exposed to vapours and aerosols of bitumen. Arch Toxicol 85(Suppl 1):S29–S39. doi:10.1007/s00204-011-0680-7

    Article  Google Scholar 

  • Polanska K, Dettbarn G, Jurewicz J, Sobala W, Magnus P, Seidel A, Hanke W (2014a) Effect of prenatal polycyclic aromatic hydrocarbons exposure on birth outcomes: the Polish mother and child cohort study. BioMed Res Int 2014:408939. doi:10.1155/2014/408939

    Article  Google Scholar 

  • Polanska K, Hanke W, Dettbarn G, Sobala W, Gromadzinska J, Magnus P, Seidel A (2014b) The determination of polycyclic aromatic hydrocarbons in the urine of non-smoking Polish pregnant women. Sci Total Environ 487:102–109. doi:10.1016/j.scitotenv.2014.04.006

    Article  CAS  Google Scholar 

  • Raulf-Heimsoth M, Angerer J, Pesch B, Marczynski B, Hahn JU, Spickenheuer A, Preuss R, Rühl R, Rode P, Brüning T (2008) Biological monitoring as a useful tool for the detection of a coal-tar contamination in bitumen-exposed workers. J Toxicol Env Health A 71(11–12):746–750. doi:10.1080/15287390801985315

    Article  CAS  Google Scholar 

  • Raulf-Heimsoth M, Pesch B, Rühl R, Brüning T (2011) The Human Bitumen Study: executive summary. Arch Toxicol 85(Suppl 1):S3–S9. doi:10.1007/s00204-011-0679-0

    Article  Google Scholar 

  • Rihs HP, Pesch B, Kappler M, Rabstein S, Rossbach B, Angerer J, Scherenberg M, Adams A, Wilhelm M, Seidel A, Brüning T (2005) Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms. Toxicol Lett 157(3):241–255. doi:10.1016/j.toxlet.2005.02.012

    Article  CAS  Google Scholar 

  • Seidel A, Dahmann D, Krekeler H, Jacob J (2002) Biomonitoring of polycyclic aromatic compounds in the urine of mining workers occupationally exposed to diesel exhaust. Int J Hyg Environ Health 204(5–6):333–338. doi:10.1078/1438-4639-00116

    Article  CAS  Google Scholar 

  • Seidel A, Spickenheuer A, Straif K, Rihs H, Marczynski B, Scherenberg M, Dettbarn G, Angerer J, Wilhelm M, Brüning T, Jacob J, Pesch B (2008) New biomarkers of occupational exposure to polycyclic aromatic hydrocarbons. J Toxicol Env Health A 71(11–12):734–745. doi:10.1080/15287390801985265

    Article  CAS  Google Scholar 

  • Shimada T, Takenaka S, Murayama N, Kramlinger VM, Kim J-H, Kim D, Liu J, Foroozesh MK, Yamazaki H, Guengerich FP, Komori M (2016) Oxidation of pyrene, 1-hydroxypyrene, 1-nitro-pyrene and 1-acetylpyrene by human cytochrome P450 2A13. Xenobiotica 46:211–224. doi:10.3109/00498254.2015.1069419

    Article  CAS  Google Scholar 

  • Spickenheuer A, Rühl R, Höber D, Raulf-Heimsoth M, Marczynski B, Welge P, Breuer D, Gabriel S, Musanke U, Rode P, Heinze E, Kendzia B, Bramer R, Knecht U, Hahn JU, Brüning T, Pesch B (2011) Levels and determinants of exposure to vapours and aerosols of bitumen. Arch Toxicol 85(Suppl 1):S21–S28. doi:10.1007/s00204-011-0677-2

    Article  Google Scholar 

  • Taussky HH (1954) A microcolorimetric determination of creatine in urine by the Jaffe reaction. J Biol Chem 208(2):853–862

    CAS  Google Scholar 

  • Väänänen V, Hämeilä M, Kontsas H, Peltonen K, Heikkilä P (2003) Air concentrations and urinary metabolites of polycyclic aromatic hydrocarbons among paving and remixing workers. J Environ Monit 5(5):739–746

    Article  Google Scholar 

  • Väänänen V, Hämeilä M, Kalliokoski P, Nykyri E, Heikkilä P (2005) Dermal exposure to polycyclic aromatic hydrocarbons among road pavers. Ann Occup Hyg 49(2):167–178. doi:10.1093/annhyg/meh094

    Article  Google Scholar 

  • Vollmann H, Becker H, Corell M, Streeck H (1937) Beiträge zur Kenntnis des Pyrens und seiner Derivate. Liebigs Ann Chem 531(1):1–159. doi:10.1002/jlac.19375310102

    Article  CAS  Google Scholar 

  • Voncken P, Schepers G, Schäfer KH (1989) Capillary gas chromatographic determination of trans-3′-hydroxycotinine simultaneously with nicotine and cotinine in urine and blood samples. J Chromatogr 479(2):410–418

    Article  CAS  Google Scholar 

  • Weaver VM, Kotchmar DJ, Fadrowski JJ, Silbergeld EK (2016) Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment? J Expo Sci Env Epid 26(1):1–8. doi:10.1038/jes.2015.8

    Article  CAS  Google Scholar 

  • Weiss T, Koch HM, Wiethege T, Brüning T (2012) Passivrauch. In: Triebig G, Drexler H, Letzel S, Nowak D (eds) Biomonitoring in Arbeitsmedizin und Umweltmedizin. Orientierungshilfe für Betrieb, Praxis und Klinik: Schwerpunktthema Jahrestagung DGAUM 2011. Ecomed Medizin, Heidelberg, pp 279–298

  • Zhong Y, Carmella SG, Upadhyaya P, Hochalter JB, Rauch D, Oliver A, Jensen J, Hatsukami D, Wang J, Zimmerman C, Hecht SS (2011) Immediate consequences of cigarette smoking: rapid formation of polycyclic aromatic hydrocarbon diol epoxides. Chem Res Toxicol 24(2):246–252. doi:10.1021/tx100345x

    Article  CAS  Google Scholar 

  • Zielińska-Danch W, Wardas W, Sobczak A, Szołtysek-Bołdys I (2007) Estimation of urinary cotinine cut-off points distinguishing non-smokers, passive and active smokers. Biomarkers 12(5):484–496. doi:10.1080/13547500701421341

    Article  Google Scholar 

Download references

Acknowledgments

The Human Bitumen study was assigned by the German Committee for Hazardous Substances (AGS) and the German Bitumen Forum and financially supported by: German Social Accident Insurance (DGUV), Eurobitume, Deutscher Asphaltverband e.V., Concawe, Zentralverband des Deutschen Dachdeckerhandwerks, Industrieverband Bitumen-, Dach- und Dichtungsbahnen e.V., Berufsgenossenschaft Rohstoffe und Chemische Industrie (BG RCI), Aksys GmbH, Beratungsstelle Gussasphaltanwendungen (bga), Berufsgenossenschaft der Bauwirtschaft (BG BAU), and Arbeitsgemeinschaft der Bitumenindustrie (Arbit). We thank all workers having participated in the Human Bitumen Study. We gratefully acknowledge the support of the field team, especially Anne Flagge, Anja Molkenthin, Bianca Wachter, Dieter Höber, Gerd Zoubek, and in parts of the study Klaus Schott (†) and Hans-Jürgen Schicke, and we thank Evelyn Heinze for her support in data management.

Author information

Authors and Affiliations

  1. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Anne Lotz, Beate Pesch, Monika Raulf, Peter Welge, Hans-Peter Rihs & Thomas Brüning

  2. Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer-Foundation, Lurup 4, 22927, Grosshansdorf, Germany

    Gerhard Dettbarn & Albrecht Seidel

  3. Institute for Occupational Safety of the German Social Accident Insurance (IFA), Alte Heerstraße 111, 53757, Sankt Augustin, Germany

    Dietmar Breuer, Stefan Gabriel & Jens-Uwe Hahn

Authors
  1. Anne Lotz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beate Pesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gerhard Dettbarn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Monika Raulf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter Welge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hans-Peter Rihs
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dietmar Breuer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stefan Gabriel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jens-Uwe Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Thomas Brüning
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Albrecht Seidel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Albrecht Seidel.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 676 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lotz, A., Pesch, B., Dettbarn, G. et al. Metabolites of the PAH diol epoxide pathway and other urinary biomarkers of phenanthrene and pyrene in workers with and without exposure to bitumen fumes. Int Arch Occup Environ Health 89, 1251–1267 (2016). https://doi.org/10.1007/s00420-016-1160-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00420-016-1160-4

Keywords

Search

Navigation