Abstract:
Equilibrium phase distribution coefficients are used to describe the degree of transfer from inhaled air to blood, or from blood to exhaled air in models of solvent pharmacokinetics such as are used for toxicological assessment pruposes. A review of the literature shows examples of interexperimental blood/air partition coefficient values for specific solvents that very by a factor of 2.5. Values determined by Bergerova and Sato for toluene were 10.3 and 15.6. Ackerlund observed a variation for toluene that spanned from 4 to 15 depending on the air concentration. An in vivo study by campbell et a. observed a variation in the partition coefficient value from 26.7 to 44.6 for venous blood that was dependent on the toluene concentration in the blood.
The goal of this research was to further investigate the variation in partition coefficient values for background and occupational exposures for toluene. Any variation in partition coefficient behavior due to changes in airborne solvent vapor concentration would have significantly undermined assumptions used for predicting exposures in both industrial hygiene and risk assessment applications. Our interest in testing the validity of the observed variation of blood/air partitioning with concentration was further heightened by the lack of a satisfying physical explanation for the positive variation of Kb/a with contaminant level. The experimental method of Ackerlund was repeated and the report trend in Kb/a with concentration was once again confirmed. To eliminate any measurement of method artifact, a new method utilizing 14C toluene was developed using liquid scintillation oounting (LSC). The 14C method provided the ability to quantify the blood phase in addition to the headspace phase, with 2 orders of magnitude greater sensitivity. Partition coefficient value determinations were made using both the blood to headspace toluene concentration ratio method developed in this study and the Equilibrium Partitioning In Closed Systems method of Sato.
Characterizations of Kb/a for a range of contaminant levels revealed no variation in blood partition coefficient. The partition coefficient value for toluene at 37 C at an equilibirium headspace concentration of 2 ppm was 12.46 using the Standard method (95% CI = 11.50 to 13.49). The EPICS value from the same test was 11.84 (95% CI = 11.20 to 12.49). At 40 ppm the standard method value was 13.42 (95% CI = 12.58 to 14.32). The EPICS value for the same test was 11.45 (95% CI = 10.15 to 12.84). Additional testes were conducted at concentration ranging from 0.1 to 200 ppm. No variation in Kb/a was observed at any of these concentrations. The same method was used to test the Henry's Constant of toluene in water. The Henry's Constant value was 2.75 and consistent between concentrations.