trans,trans-Muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level

  • P. Ducos
  • R. Gaudin
  • J. Bel
  • C. Maire
  • J. M. Francin
  • A. Robert
  • P. Wild
Original Articles


trans,trans-Muconic acid (2,4-hexadienedioic acid) (t,t-MA) is a minor benzene metabolite which can be used as a biological indicator for benzene exposure. The purpose of the study was to evaluate the limits of use of t,t-MA for detection and quantification of occupational exposures to benzene, particularly on an individual scale, phenol being used as the metabolite of reference. A simple and sensitve method previously described by the authors was carried out to analyse t,t-MA in 105 end-of-shift urinary samples from 23 workers exposed to benzene used as an extraction solvent for “concretes” recovery in the perfume industry. Good correlations were found between atmospheric benzene and both metabolites (uncorrected or corrected for creatinine) or between the metabolites themselves, with correlation coefficients from 0.81 to 0.91 (P < 0.0001). Correlation-coefficients were not improved after correction for creatinine. The overall individual benzene exposure range, median, and arithmetic mean were respectively 0.1–75, 4.5, and 9.0 ppm with corresponding t,t-MA excretion of 0.1–47.9, 5.2 and 8.9 mg/l (uncorrected) and phenol excretion of 1.4–298, 30.9, and 42.2 mg/l (uncorrected). In the control group (145 determinations for t,t-MA and 76 for phenol from 79 individuals) the range, median, and arithmetic mean were respectively < 0.04–0.66, 0.08, and 0.13 mg/l (uncorrected t,t-MA) and 1.5–42.0, 9.85 and 11.3 mg/l (uncorrected phenol). t,t-MA was far more specific than phenol and could be easily and practically used to estimate with a given probability the upper or lower corresponding benzene concentrations down to around the ppm level. Biological exposure indices for benzene exposure to 10, 5, or 1 ppm could be set at 10, 5, or 1 mg t,t-MA/l (uncorrected).

Key words

Benzene Biological monitoring trans,trans-Muconic acid Individual exposures BEIs proposals 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    AFNOR (1986) Norme française NFX43-251 Qualité de l'air. Atmosphères des lieux de travail. Détermination de la concentration des hydrocarbures aromatiques monoclycliques en phase vapeur. ParisGoogle Scholar
  2. 2.
    Bechtold WE, Lucier G, Birnbaum LS, Yin SN, Li GL, Henderson RF (1991) Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene. Am Ind Hyg Assoc J 52:473–479Google Scholar
  3. 3.
    Bowman JD, Held JL, Factor DR (1990) A field evaluation of mandelic acid in urine as a compliance monitor for styrene exposure. Appl Occup Environ Hyg 5:526–535Google Scholar
  4. 4.
    Campbell L, Marsh DM, Wilson HK (1987) Towards a biological monitoring strategy for toluene. Ann Occup Hyg 31:121–123Google Scholar
  5. 5.
    Colombi A, Buratti M, Zochetti C, Imbriani M, Ghittori S (1989) Limiti biologici di esposizione: evoluzione dei criteri interpretativi e metodologici. Med Lav 80:25–42Google Scholar
  6. 6.
    Ducos P, Gaudin R, Robert A, Francin JM, Maire C (1990) Improvement in HPLC analysis of urinary trans,trans-muconic acid, a promising substitute for phenol in the assessment of benzene exposure. Int Arch Occup Environ Health 62:529–534Google Scholar
  7. 7.
    Elia VJ, Anderson LA, MacDonald TJ, Carson A, Buncher CR, Brooks SM (1980) Determination of urinary mandelic and phenylglyoxylic acids in styrene exposed workers and a control population. Am Ind Hyg Assoc J 41:922–926Google Scholar
  8. 8.
    Engström K, Härkönen H, Pekari K, Rantanen J (1978) Evaluation of occupational styrene exposure by ambient air and urine analysis. Scand J Work Environ Health 4:121–123Google Scholar
  9. 9.
    Gad-El Karim MM, Sandagopa Ramanujam VM, Legator MS (1985) trans,trans-Muconic acid, an open chain urinary metabolite of benzene in mice. Quantification by high-pressure liquid chromatography. Xenobiotica 15:211–220Google Scholar
  10. 10.
    Heath DF (1967) Normal or log-normal: appropriate distributions. Nature 213:1159–1160Google Scholar
  11. 11.
    Hornung RW, Reed LD (1990) Estimation of average concentration in the presence of non detectable values. Appl Occup Environ Hyg 5:46–51Google Scholar
  12. 12.
    Inoue O, Seiji K, Nakatsuka H, Watanabe T, Yin S-N, Li G-L, Cai S-X, Jin C, Ikeda M (1989) Urinary t,t-muconic acid as an indicator of exposure to benzene. Br J Ind Med 46:122–127Google Scholar
  13. 13.
    Kusters E, Lauwerys R (1990) Biological monitoring of exposure to monochlorobenzene. Int Arch Occup Environ Health 62:329–331Google Scholar
  14. 14.
    Lauwerys (1983) Benzene. In: Alessio L, Berlin A, Roi R, Boni M (eds) Human biological monitoring of industrial chemical series. Commission of the European Communities. Eur 8476 ENGoogle Scholar
  15. 15.
    Liebich HM, Först C (1990) Basic profiles of organic acids in urine. J Chromatogr 525:1–14Google Scholar
  16. 16.
    Meuling WJA, Bragt PC, Braun CLJ (1990) Biological monitoring of carbon disulfide. Am J Ind Med 17:247–254Google Scholar
  17. 17.
    Miller JC, Miller JN (1988) Statistics for analytical chemistry. Ellis Horwood Limited. ChichesterGoogle Scholar
  18. 18.
    National Institute for Occupational Safety and Health (1985) Method 8305: phenol and p-cresol in urine. NIOSH Manual of analytical methods, vol 2, pp 8305-1–8305-4Google Scholar
  19. 19.
    Ong CN, Sia GL, Ong HY, Phoon WH, Tan KT (1991) Biological monitoring of occupational exposure to methyl ethyl ketone. Int Arch Occup Environ Health 63:319–324Google Scholar
  20. 20.
    Perkins JL, Cutter CN, Cleveland MS (1990) Estimating the mean, variance and confidence limits from censored (< limit of detection), lognormally distributed exposure data. Am Ind Hyg Assoc J 51:416–419Google Scholar
  21. 21.
    Westöö G (1964) On the metabolism of sorbic acid in the mouse. Acta Chem Scand 18:1373–1378Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • P. Ducos
    • 1
  • R. Gaudin
    • 1
  • J. Bel
    • 2
  • C. Maire
    • 1
  • J. M. Francin
    • 1
  • A. Robert
    • 1
  • P. Wild
    • 1
  1. 1.Institut National de Recherche et de SécuritéVandoeuvre CedexFrance
  2. 2.Association pour le Service Médical de l'AromatiqueGrasseFrance

Personalised recommendations