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af lead toxicity. . Case report. J of occupational ipational Health chewing plastic 25. F . American Journal of Industrial Medicine 25:297-300 (1994) i COMMENTARY Muconic Acid in Urine: A Reliable Indicator of Occupational Exposure to Benzene Robert R. Lauwerys, MD, PhD, Jean-Pierre Buchet, PhD, and Fabian Andrien, MSC In male subjects not occupationally exposed to benzene, the concentration of muconic acid (MA) in urine is usually below 0.5 mg/g creatinine. At ambient levels of benzene exposure (below 0.01 pprn), the mean M A level was greater in 21 smokers than in 14 nonsmokers. In 38 male subjects employed in garages and coke ovens, a statistically significant correlation was found between the airborne concentration of benzene measured with passive monitors and M A in postshift urine. The mean postshift M A concentrations correspondingto a benzene 8-hour time-weighted average exposure (TWA) of 0.5 and 1 pprn were 0.8 and 1.4mg/g creatinine, respectively. 0 1994Wiley-Liss, h. Key words: benzene exposure, biological monitoring, smoking exposures, biological markers INTRODUCTION Johnson and Lucier [I9921 have recently drawn the attention to the interest of urinary muconic acid (MA) as a biomarker of exposure to benzene. Our own data, briefly summarized below, support this conclusion but suggest that the background level of MA in not occupationally exposed male subjects and the relation between the airborne concentration of benzene at workplaces and MA (end of shift) permit the detection of occupational exposure as low as 0.5 ppm (8 hour TWA). MUCONIC ACID CONCENTRATION IN ADULT MALE SUBJECTS NOT OCCUPATIONALLY EXPOSED TO BENZENE We have measured MA in morning and afternoon urine samples collected from adult male subjects (21 nonsmokers and 14 smokers). We used the method described by Ducos et al. [1990]. Ambient exposure to benzene during the day of urine collection was below 0.01 ppm. For both groups combined, the 95 percentile value of MA (afternoon sample) amoanted to 0.41 mg/g creatinine. This result is in agreement with that reported by Bechtold et al. [1991]. However, the geometric mean value of Industrial Toxicology and Occupational Medicine Unit, Faculty of Medicine, Catholic University of Louvain, Brussels, Belgium. Address reprint requests to Dr.Robert R. Lauwerys, Industrial Toxicology and Occupational Medicine Unit, Faculty of Medicine, Catholic University of Louvain, 30.54.Clos Chapelle-aux-Champs, 1200 Brussels, Belgium. Accepted for publication February 7, 1993. 0 1994 Wiley-Liss, Inc. 298 Lauwerys et al. 001 a025 01 025 06 001 OMS 01 025 06 Muconic acid in urine (mgig creat.) Fig. 1. Cumulative frequency distributions of M A in male nonsmokers and smokers not occupationally exposed to benzene. M A is twice as high in smokers (0.130m u g creatinine) as in nonsmokers (0.06).The impact of cigarette consumption on M A is clearly illustrated in Figure 1. In nonsmokers, the morning and afternoon M A are not significantly different; in smokers, the cumulative frequency distribution of M A is shifted to significantly higher values in the afternoon, apparently reflecting exposure to benzene present in tobacco smoke (paired t test p < 0.05). The highest individual values, however, were found in nonsmokers, an observation possibly due to small numbers or high environmental exposure of some nonsmokers to benzene. Johnson and Lucier [I9921 state that the only significant source of M A formation in the body is through the metabolism of benzene, suggesting that even the background M A level found in nonsmokers results from environmental exposure to benzene. However, it has been demonstrated by Ducos et al. [1990] that sorbitol, which is present in certain foods, may also be biotransformed to MA. Therefore, the different background levels of M A reported in nonsmokers not occupationally exposed to benzene may also partly reflect differences in dietary habits. Whatever the main factors responsible for the background level of M A , our preliminary data suggest that in Belgium the average M A level in not occupationally exposed subjects (smokers and nonsmokers combined) is usually below 0.5 mg/g creatinine. RELATION BETWEEN MUCONIC ACID CONCENTRATION IN POSTSHIFT URINE AND OCCUPATIONAL EXPOSURE TO BENZENE We have also assessed whether in workers moderately exposed to benzene (up to 2 ppm) in garages and coke ovens there was a relationship between benzene in air Biological Monitoring of Exposure to Benzene 299 EW .- L E 0 n=38 r=O81,pc00001 u c log y = 0.15 + 0 86 log I " 001 01 1 Benzene in (ur Ippm) 10 Fig. 2. Relation between benzene in air and MA in postshift urine. (measured with 3 M 3500 organic vapor monitor) and MA in postshift urine. As illustrated in Figure 2, a statistically significant relation was found. No difference between smokers and nonsmokers could be ascertained. This suggests that either the impact of occupational exposure to benzene on MA has masked the influence of smoking habits or the amount of benzene collected on passive samplers reflects both the amount present in cigarette smoke and that contaminating the work environment. Another possibility is that the number of observations was too limited to detect an additive effect of smokmg and occupational exposure to benzene. Our results (Fig. 2) indicate that the mean postshift MA levels in subjects exposed to 0.5 or 1 ppm benzene (8 hour TWA) ranged from 0.8 or 1.4 mg/g creatinine, respectively; these values are significantly higher than the background MA level found in subjects not occupationally exposed. It should be noted that in the two groups reported here, benzene in air was monitored with passive personal samplers. It would be useful to assess whether the same relationship holds when benzene in air is collected with a dynamic (pump) personal sampling system to clarify the possibility of underestimated exposures. Such a study has recently been reported by Ducos et al. [1992], but it involved workers from 3 perfume-producing factories whose average exposure to benzene (9 ppm) was higher than in our study. Nevertheless, their estimate of the mean MA (1.17 mg/l) corresponding to a benzene TWA of 1 ppm is in rather good agreement with our results. In conclusion, our preliminary findings suggest that MA is a reliable indicator of exposure to benzene, even at a TWA level as low as 0.5 ppm. ACKNOWLEDGMENTS This study was funded by the European Community of Coal and Steel. I 300 Lauweryset al. REFERENCES Bechtold WE, Lucier G, Birnbaum LS, Yin SN, Li GL, Henderson RF (1991): Muconic acid determi- nations in urine as a biological exposure index for workers occupationally exposed to benzene. Am Ind Hyg A s s J 52~473-478. Ducos P, Gaudin R, Robert A, Francin JM, Maire C (1990): Improvement in HPLC analysis of urinary trans, trans-muconic acid, a promising substitute for phenol in the assessment of benzene exposure. Int Arch Occup Environ Health 62529-534. Ducos P, Gaudin R, Bel J, Maire C, Francin JM, Wild P (1992):Trans, trans-muconic acid, a reliable biological indicator for the detection of individual benzene exposure down to the ppm level. int Arch Occup Environ Health 64309-313. Johnson ES, Lucier G (1992): Perspectives on risk assessment impact of recent reports on benzene. Am J Ind Med 21:749-757.