Measurement of the urinary benzene metabolite trans,trans-muconic acid from benzene exposure in humans.

The concentration of the urinary benzene metabolite trans, trans-muconic acid was measured after exposure to benzene contained in environmental tobacco smoke (ETS). Volunteers were exposed to environmental tobacco smoke at different exposure levels and for different exposure durations. Urine samples were collected preexposure and postexposure for 24 h on exposure days. To determine background levels, urine samples were also collected on three individual days when no exposure to ETS occurred. Urinary muconic acid was elevated following benzene exposure in ETS compared to an individual's background level and can be a useful biomarker in control, characterized studies of sub-parts-per-million (sub-ppm) benzene exposures. However, the use of muconic acid as a bio-marker of benzene exposure at sub-ppm levels in the general population is problematic because of variability in the time between exposure and excretion and in an individual's background excretion rate. Urinary muconic acid associated with benzene in ETS exposure was excreted within 12 h of the exposure. A higher proportion of the benzene dose following environmental exposure in the sub-ppm range was excreted as urinary muconic acid (mean of 25%, range 7.2-58%) than found in either animal or occupational studies at higher benzene doses. The higher proportion of benzene excretion as urinary muconic acid at low benzene exposure indicates that the relationship between exposure and metabolism by the ring opening pathway is nonlinear in humans, and extrapolation from high doses to environmental benzene exposure potentially underestimates health risks mediated by the ring opening metabolic pathway that produces muconic acid, as has been suggested by previous animal data.