A reanalysis of the evidence for increased efficiency in benzene metabolism at airborne exposure levels below 3 p.p.m.

An analysis of monitoring data on workers in Tianjin, China, reported a 9-fold increase in the production of benzene metabolites per unit exposure as air concentrations declined from 88.9 to 0.03 p.p.m. The increase is attributed to an enhanced efficiency of benzene metabolism at lower air concentrations. This finding, however, is not consistent with other studies demonstrating that adsorbed benzene is almost completely metabolized at airborne levels ranging from <1 to 70 p.p.m. In this article (i) the modeling performed in Kim et al. is repeated and the model predictions are reproduced; (ii) the impacts of technical issues in the corrections for background levels of metabolites, accounting for biases in the regression modeling, and the uncertainties introduced by the use of a calibration model to estimate benzene air levels for certain workers are evaluated and (iii) alternative methods of correcting for background levels of metabolites are examined. The new analysis indicates that findings of increased production are probably smaller and are highly uncertain, 4.8 fold [0.1-18] (mean and [95% confidence limits]). Defining background levels as either the levels in all workers with no occupational exposures or in workers with predicted air levels of <0.03 p.p.m. results in estimates of 2.4 fold [<0.1-15] and 3.3 fold [<0.1-19] increases, respectively. Based on this reanalysis, the Tianjin data appear to be too uncertain to support any conclusions of a change in the efficiency of benzene metabolism with variations in exposure.