Influence of various mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats

Abstract

The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20-30%) and methylhippuric acids (4-40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190-240%; xylene, 340-650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats.