INTERINDIVIDUAL VARIABILITY OF BENZENE METABOLISM TO TRANS,TRANS-MUCONIC ACID AND ITS IMPLICATIONS IN THE BIOLOGICAL MONITORING OF OCCUPATIONAL EXPOSURE

Unmodified benzene (UBz) and trans,trans-muconic acid (t,t-MA) were me asured in urine samples collected at the end of the first half-shift i n 80 bus drivers from a large city in Northern Italy. Mean UBz was 115 5 ng/l (S.D. = 494), range 85-1980 ng/l; these values roughly correspo nd to 10-1000 mu g/m(3) of benzene in air. Mean t,t-MA was 297 mu g/g creatinine; the range was large (20-1295 mu g/g creatinine), and the d istribution of values was bimodal. At further analysis of t,t-MA data, two subgroups of 59 and 18 subjects were identified (3 outliers were excluded): mean values of the index were 108 (S.D. = 65) and 916 (S.D. = 264) mu g/g creatinine respectively and the values within each subg roup were normally distributed. The mean ratio between t,t-MA and UBz in the subgroups were 0.15 and 0.85, respectively; the difference was significant. The first subgroup was defined as 'poor t,t-MA metabolize rs', the other as 'efficient t,t-MA metabolizers'. No inter-subgroup d ifferences were observed regarding the main characteristics (age, diet ary and smoking habits, etc.). As the parent compound of t,t-MA, trans ,trans-muconaldehyde is myelotoxic, and its production has been implic ated in benzene-induced leukemia. 'efficient' t,t-MA metabolizers may be at higher risk of developing benzene toxicity. If confirmed in furt her studies, the inter-individual Variability rate of metabolizing ben zene to t,t-MA may introduce some limitations in the application of th is metabolite as an exposure index of low benzene exposure. Neverthele ss, the t,t-MA/UBz ratio may be an important index of susceptibility t o benzene toxicity. (C) 1997 Elsevier Science B.V.