Comparison of the influence of binary mixtures versus a ternary mixture of inhaled aromatic hydrocarbons on their blood kinetics in the rat.

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.