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 var ious binary mixtures containing ethylbenzene (EBZ), toluene (TOL) or x ylene (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 4h to TOL, XYL and EBZ, singly or in com bination. 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 expo sure and the areas under the blood concentration curves (AUG) were cal culated. Results showed that exposures to binary and ternary mixtures resulted in significantly higher (P < 0.05) blood concentrations of un changed solvents as a result of metabolic interaction between these so lvents. When the comparison was based on individual solvents, there wa s no difference between effect exerted by the ternary mixture and the binary mixtures, except for one. However, a comparison based on the to tal concentration of unchanged solvents disclosed that exposure to the ternary mixture resulted in greater interactive effects (3.17-fold in crease) than exposures to binary mixtures (1.97-fold increase), wherea s four out of six binary mixtures produced higher total levels of unch anged solvents in blood compared to the ternary mixture. This study sh ows that the greater risk of toxicity often thought to be associated w ith exposures to complex mixtures should not only be related to the ma gnitude of interactive effects among components (i.e., degree of mutua l metabolic interaction) resulting from combined exposures, but also s hould take into account, as is universally recognized, the internal to tal dose of toxic chemicals in target organs/tissues.