Student Research: Guy William Silvey

, , 1994
Faculty Advisor: David A Kalman

Investigation of In-Vitro Individual Blood/Air Partition Coefficients for the Perdeuterated and Nondeuterated Isomers of Xylene and Toluene


Abstract

Blood/air partition coefficients (KB/A) describe the molecular behavior that influences the pulmonary exchange of volatile chemicals and therefore are important parameters in physiologically based pharmacokinetic models that predict the uptake, distribution, and elimination of volatile chemicals in humans following environmental or occupational exposures. The KB/A is defined as the ratio between the concentration of a chemical in blood and in air, as determined at equilibrium.

Very little data have been published which report the in-vitro xylene and toluene KB/A values for individuals; the population variation of KB/A for xylene and toluene isomers in humand; or the within-person variation of KB/A values in humans. In this study, in-vitro KB/A values have been determined for the perdeuterated and nondeuterated isomers of xylene and toluene. Also determined were the within=person variation, and correlations among the KB/A values of structurally similar compounds. The KB/A parameter was determined using the equilibrium partition in closed systems (EPICS) method. This constant volume method that compares the measured solute concentrations in the gas phases of two vials: one containing a reference atmosphere of the contaminant being tested; the other containing the same atmosphere plus the condensed phase being tested. The KB/A was determined by measurement of the relative headspace concentrations of the two vials after equilibrium was acheived.

The unitless KB/A values measured in 35 independent experiments using human blood for the following compounds were: d0-toluene, 18.3 + 2.0; dg-toluene, 18.2 + 1.9; d0-m-xylene, 31.9 + 3.0; d10-m-xylene, 31.6 + 2.9; d0-o-xylene, 35.2 + 3.5; d10-o-xylene, 35.1 + 3.5; d0-p-xylene, 39.0 + 3.3; d10-p-xylene, 38.4 + 3.3; (geometric mean + standard error). Correlation analysis comparing the perdeuterated and nondeuteratred isomers of p-xylene resulted in a correlation coefficient of 0.96 (N=35). Likewise, corellation analysis of the other perdeuterated and nondeuterated pairs gave high correlations.

This study shows that a strong relationship exists between in-vitro perdeuterated and nondeuterated toluene and xylene KB/A values and between structurally similar compounds. Furthermore, the within-person KB/A values did not vary significantly throughout time. Based on analysis of variance, I conclude that blood/air partition coefficients measured in-vitro for the perdueterated analogs are better predictors of KB/A for the nondeuterated agent in that person at that time than are either in-vitro measurements of KB/A using an individual's blood taken at a different time, or KB/A values measured from other individuals or populations.