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The results of standardized 8 h lasting exposures of n = 18 volunteers to ethylbenzene (EthBz) at levels of 25 and 100% of the maximum allowable concentrations at the workplace (MAK) value of 100 ppm as well as the results of field studies are considered to evaluate a biological tolerance (BAT) value for EthBz. On the basis of the relationship between the external and internal exposure a BAT value of 1.5 mg/l has been set for the EthBz concentration in blood as the most sensitive and specific parameter of exposure to this aromatic hydrocarbon. The interpretation of EthBz blood values has to take into account the short half-life of t1/2 = 0.5 +/- 0.08 h in the first hour after the end of exposure in which this aromatic hydrocarbon is eliminated from the blood. The additional determination of the EthBz metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA), respectively, excreted in post shift urine as well as in urine samples at the beginning of the next shift shows good correlations with the external exposure. The biological half-life of MA was calculated to t1/2 = 5.3 +/- 1.1 h. Because the time of sampling can vary the relationship between the levels of MA to PGA the total concentration of the excreted metabolites depends less on this influence and is therefore better suited for monitoring exposed persons. On the basis of the standardized experiments a BAT value has been proposed of 2 g MA plus PGA corrected per gram creatinine. Both BAT values are adjusted to data which result from earlier standardized exposures during 30 min to EthBz under physical activity of 50 watt on a bicycle ergometer.

The objective of the present study was to compare the influence of various binary mixtures containing ethylbenzene (EBZ), toluene (TOL) or xylene (XYL) administered by inhalation, with the influence exerted by a ternary mixture, on the kinetics of these solvents in blood. Groups of four rats were exposed for 4 h to TOL, XYL and EBZ, singly or in combination. The concentration of TOL, XYL and EBZ in blood was measured at various times (5, 30, 60, 90 and 120 min) following the end of exposure and the areas under the blood concentration curves (AUC) were calculated. Results showed that exposures to binary and ternary mixtures resulted in significantly higher (P < 0.05) blood concentrations of unchanged solvents as a result of metabolic interaction between these solvents. When the comparison was based on individual solvents, there was no difference between effect exerted by the ternary mixture and the binary mixtures, except for one. However, a comparison based on the total concentration of unchanged solvents disclosed that exposure to the ternary mixture resulted in greater interactive effects (3.17-fold increase) than exposures to binary mixtures (1.97-fold increase), whereas four out of six binary mixtures produced higher total levels of unchanged solvents in blood compared to the ternary mixture. This study shows that the greater risk of toxicity often thought to be associated with exposures to complex mixtures should not only be related to the magnitude of interactive effects among components (i.e., degree of mutual metabolic interaction) resulting from combined exposures, but also should take into account, as is universally recognized, the internal total dose of toxic chemicals in target organs/tissues.