title: Trans,trans-muconic acid, a biological indicator to low levels of environmental benzene: some aspects of its specificity.
abstract: BACKGROUND
  The specificity of trans,trans-muconic acid (MA) as a biomarker of exposure to low benzene levels and the role of sorbic acid (SA) as a confounding factor were evaluated. MA, a urinary ring-opened metabolite of benzene, has been recently proposed for the biological monitoring of populations exposed to low levels of this chemical. The usual presence of MA in urine of non-occupationally exposed people is generally attributed to benzene world-wide contamination (mainly by smoking habits, urban pollution, and maybe by food contamination). However, the scientific literature reveals that the common food preservative and fungistatic agent SA is converted into MA though in trace amounts.
  
  
  METHODS
  Urinary benzene and MA before and after administration of SA were measured in smokers and non-smokers. Benzene dissolved in urine was analyzed injecting a headspace sample in a gas-chromatografic system. Urinary MA was measured by means of a HPLC apparatus.
  
  
  RESULTS
  The mean background values of MA were about 60 mg/L (or 50 mg/g creat.); after experimental administration of SA (447 mg), the mean urinary MA concentration became more than 20 times higher. The biotransformation rates of SA into MA after ingestion of 447 mg of SA ranged from 0.05 to 0.51%. The ratio between unmetabolized benzene in the two groups of smokers and non-smokers was significantly different from the ratio between MA in the same two groups.
  
  
  CONCLUSIONS
  Other sources of MA excretion, different from benzene, influence the urinary concentration of the metabolite: only 25% of MA background values can be attributed to benzene. The urinary MA induced by 100 mg of ingested MA is 77% of that expected after an 8-hour benzene exposure to 0.5 ppm (current threshold limit value according to ACGIH). In conclusion, MA is not a sufficiently specific biomarker of low benzene exposure; a significant effect of SA ingestion is predictable.
authors.affiliation: Department of Preventive, Occupational and Community Medicine, University of Pavia, Italy. fpr.pavia@fsm.it
authors.forename: G
authors.initials: G
authors.lastname: Pezzagno
authors.forename: L
authors.initials: L
authors.lastname: Maestri
authors.forename: M L
authors.initials: ML
authors.lastname: Fiorentino
mesh_terms: D000328:Adult; D001554:Benzene / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis* / Q000652:urine; D001711:Biotransformation; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000032:analysis*; D005260:Female; D005506:Food Contamination; D005520:Food Preservatives / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D012907:Smoking / Q000378:metabolism / Q000652:urine; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D005520:Food Preservatives; C005939:muconic acid; D001554:Benzene; D013011:Sorbic Acid