EFFECT OF VARIOUS EXPOSURE SCENARIOS ON THE BIOLOGICAL MONITORING OF ORGANIC-SOLVENTS IN ALVEOLAR AIR .2. 1,1,1-TRICHLOROETHANE AND TRICHLOROETHYLENE

The purpose of the present study was to investigate the influence of d ifferent exposure scenarios on the elimination of trichloroethylene (T RI) and 1,1,1-trichloroethane (1,1,1-TRI) in alveolar air and other bi ological fluids in human volunteers. In addition, it was sought to est ablish an interactive process between experimental data gathering and simulation modeling in an attempt to predict the influence of the diff erent scenarios of exposure to TRI and 1,1,1-TRI on their respective b iological monitoring indices and thus to establish the flexibility and validity of simulation models. Two adult male and two adult female Ca ucasian volunteers were exposed by inhalation, in a dynamic controlled exposure chamber, to various concentrations of TRI (12.5-25 ppm) or ( 87.5-175 ppm) in order to establish the influence of exposure concentr ation, duration of exposure, variation of concentration within day, an d work load on biolo,oical exposure indices. The concentrations of unc hanged solvents in end-exhaled air and in blood as well as the urinary excretion of trichloroethanol (TCE) and trichloroacetic acid (TCA) we re determined. The results show that doubling the exposure concentrati on for both solvents led to a proportional increase in the concentrati ons 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 b etween excretion and exposure concentration was not as good. It was on ce again observed that the slow excretion of both metabolites leads to progressive cumulation and that their urinary determination is subjec t to considerable interindividual variations. After adjustment (loweri ng) of the exposure concentration to account for a prolongation of the duration of exposure (from 8 to 12 h) it was observed that the concen trations 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, thes e adjusted and nonadjusted exposures led to almost identical average t otal 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 t o TRI. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar air concent rations for both solvents. After exposure to peak concentrations there was a lag period before alveolar air concentrations returned to prepe ak levels. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of TRI were increased by 50% whil e 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 optimiz ed models. Overall, the results of the present study suggest that alve olar air solvent concentration is a reliable index of exposure to both TRI and 1,1,1-TRI under various experimental exposure scenarios. Thes e results also suggest that urinary excretion of TCE and TCA must be i nterpreted with caution when assessing exposure to either solvents. Fo r exposure situations likely to be encountered in the workplace, physi ologically based toxicokinetic modeling appears to be a useful tool bo th for developing strategies of biological monitoring of exposure to v olatile organic solvents and for predicting alveolar air concentration s under a given set of exposure conditions.