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

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Abstract
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).