Effect of sorbic acid administration on urinary trans,trans-muconic acid excretion in rats exposed to low levels of benzene

Food Chem Toxicol. 2002 Dec;40(12):1799-806. doi: 10.1016/s0278-6915(02)00185-0.


Trans,trans-muconic acid (t,t-MA) is a biomarker of benzene exposure reflecting metabolic activation to trans,trans-muconaldehyde. t,t-MA background urinary levels are highly variable, thus limiting its use to exposure monitoring of levels over 1 ppm of benzene. Actually, sorbic acid (SA) is known to influence background excretion of t,t-MA in man, but only a few examples suggest that SA ingestion can enhance t,t-MA levels occurring together with benzene exposure. In this study, the effect of SA was investigated in benzene-exposed male Sprague-Dawley rats exposed to 1 ppm benzene for 6 h. Exposed animals had a 24-h urinary t,t-MA excretion higher than that observed in non-exposed animals (87+/-13 microg/kg vs 19+/-3 microg/kg body weight). The oral dose of 8 mg/kg body weight SA had no effect on urinary t,t-MA both in control and in benzene-exposed rats. Increases of t,t-MA levels in urine occurred at SA doses of 50-200 mg/kg body weight, and co-exposure to benzene and SA (50 and 100 mg/kg body weight) produced additive enhancement of t,t-MA excretion. These data demonstrate the dose-response relationship between SA administration and t,t-MA excretion. Our study showed that SA ingestion at doses equal to or greater than 50 mg/kg body weight significantly affects the t,t-MA urinary levels in rats exposed to 1 ppm of benzene for 6 h. These data support the conclusion that in man t,t-MA is not suitable for biomonitoring of low levels of benzene exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzene / toxicity*
  • Biomarkers / urine
  • Dose-Response Relationship, Drug
  • Environmental Exposure
  • Environmental Monitoring / methods
  • Food Preservatives / administration & dosage*
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sorbic Acid / administration & dosage*
  • Sorbic Acid / analogs & derivatives*
  • Sorbic Acid / metabolism*
  • Sorbic Acid / pharmacokinetics*


  • Biomarkers
  • Food Preservatives
  • muconic acid
  • Benzene
  • Sorbic Acid