Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. II. 1,1,1-Trichloroethane and trichloroethylene.

The purpose of the present study was to investigate the influence of different exposure scenarios on the elimination of trichloroethylene (TRI) and 1,1,1-trichloroethane (1,1,1-TRI) in alveolar air and other biological fluids in human volunteers. In addition, it was sought to establish an interactive process between experimental data gathering and simulation modeling in an attempt to predict the influence of the different scenarios of exposure to TRI and 1,1,1-TRI on their respective biological monitoring indices and thus to establish the flexibility and validity of simulation models. Two adult male and two adult female Caucasian volunteers were exposed by inhalation, in a dynamic controlled exposure chamber, to various concentrations of TRI (12.5-25 ppm) or 1,1,1-TRI (87.5-175 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period; this proportionality was still observable in 1,1,1-TRI expired air samples 16 h after the end of the third exposure day. In the case of urinary excretion of TCE and TCA, the proportionality between excretion and exposure concentration was not as good. It was once again observed that the slow excretion of both metabolites leads to progressive cumulation and that their urinary determination is subject to considerable interindividual variations. After adjustment (lowering) of the exposure concentration to account for a prolongation of the duration of exposure (from 8 to 12 h) it was observed that the concentrations of TRI or 1,1,1-TRI towards the end of both exposure periods are more a reflection of the actual exposure concentration than of the exposure duration. Despite important interindividual variations, these adjusted and nonadjusted exposures led to almost identical average total urinary excretion over 24 h) of TCE and TCA after exposure to 1,1,1-TRI, as was also the case for TCE but not for TCA after exposure to TRI. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar air concentrations for both solvents. After exposure to peak concentrations there was a lag period before alveolar air concentrations returned to prepeak levels. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of TRI were increased by 50% while those of 1,1,1-TRI increased by only 12%. After optimization of the physiologically based toxicokinetic model parameters with experimental data collected during the first exposure scenario, results pertaining to the three other scenarios were adequately simulated by the optimized models. Overall, the results of the present study suggest that alveolar air solvent concentration is a reliable index of exposure to both TRI and 1,1,1-TRI under various experimental exposure scenarios. These results also suggest that urinary excretion of TCE and TCA must be interpreted with caution when assessing exposure to either solvents. For exposure situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.