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S-Phenylmercapturic acid (PMA), a urinary metabolite which derives from the conjugation of benzene epoxide with glutathione, has been recently included in the list of the biological markers of benzene exposure. We have evaluated the urinary PMA levels in 145 workers exposed to benzene and in 87 subjects not occupationally exposed to the solvent (45 smokers and 42 non-smokers). In non-exposed persons, the background PMA excretion was nearly constant during one day (urine samples were collected in the morning, afternoon, and evening) and in smokers the mean PMA levels were higher than in non-smokers (9.6 vs 1.3 micrograms/g creatinine). This difference was presumably due to the extra-exposure to benzene (from cigarette smoke) in smokers compared with non-smokers, in fact a close relationship was found between PMA excretion and urinary benzene concentration (r = 0.86). Urine samples from workers exposed to benzene (airborne mean concentration = 0.52 ppm) showed higher mean levels of PMA (37.6 micrograms/g creatinine) than samples taken from not occupationally exposed subjects, both smokers and non-smokers. The mean biotransformation rate of benzene to PMA was 0.073%, with a large inter-individual variability (range = 0.002-0.21%). Also, statistical analysis of data revealed a clear bimodal distribution pattern of the conversion rate frequencies in the population examined: this is consistent with the hypothesis of the presence of "slow" and "fast" converters, due to the polymorphism of glutathione-S-transferase isozymes.

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., Discussion: 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.

Benzene is a widely diffuse solvent (atmosphere, cigarette smoke, some foods); in the industrial environment benzene is currently present at concentrations of ppm. A valid method of biological monitoring that is easy to perform is needed for assessing occupational and non-occupational exposures. A new method has been developed to evaluate low concentrations of benzene in urine samples by means of a "dynamic" headspace (50 ml of urine in a 120 ml vial). The urine is saturated with anhydrous Na2SO4 in order to support the entrance of benzene in the air over the urine. The solvent is stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap 100 tube) by means of a suction pump (150 ml/min). A simultaneous intake of filtered air through a charcoal tube allows wash-up of the headspace. Benzene is thermically desorbed and injected in a column (Thermal tube desorber-Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1 60 m length, 0.75 mm I.D., 1 micron film thickness; G.C. Dani 8580-FID). The detection limit of the method is about 50 ng/l and the variation coefficient is 4.7%. The method was checked on urine samples of 5 non-smokers and 5 smokers: mean values of 135 and 944 ng/l respectively were obtained. A further analysis on urine samples of 60 smokers revealed a significant relationship (p less than 0.001) between urinary benzene concentrations and C0 alveolar concentrations (r = 0.626). A close relationship between benzene exposure levels and urinary concentrations was found in a group of workers exposed to low environmental benzene concentrations (mean value 1200 micrograms/m3) (r = 0.763).