Possible metabolic interaction between hexane and other solvents co-exposed at sub-occupational exposure limit levels

Objective: To investigate whether metabolic interactions exist between hexane (HEX) and other solvents when co-exposed at the levels below occupational exposure limits. Methods: Workers, 219 men in ten workshops in total, volunteered to participate in the study. They were occupationally exposed to mixtures of HEX and one or more of toluene (TOL), ethyl acetate (EA) and acetone (ACE). Time-weighted average intensity of vapor exposures was monitored by diffusive personal sampling. 'Free'- and 'total'-2, 5-hexanedione (HD) levels in the end-of-shift urine samples were determined by gas chromatography (GC) before and after acid hydrolysis of urine, respectively, and expressed as observed (HDob) or after correction for creatinine concentration (HDcr) or urine specific gravity (HDsg). Possible interaction was examined by multiple regression analysis (MRA), taking either free- or total-HD as a dependent variable, and the four solvent concentrations as independent variables. Results: In most cases, exposure intensity did not exceed the current occupational exposure limits even when additiveness was assumed. In addition that HEX was the most influential independent variable in all cases as expected, the MRA showed that, in cases of free-HD, ACE was also influential to HDob although weakly, but not to HDcr or HDsg. With regard to total-HD, ACE was weakly influential to HDob and HDsg, and EA also weakly to HDcr. The effect of ACE on free- or total-HD was not detected, however, when 22 men exposed only to HEX and ACE were subjected to the same analysis. Similarly, the effect of EA on total-HD was not observed among the remaining 197 men exposed to HEX, TOL and EA only. Conclusions: When the exposures were below occupational exposure limits, the free-HD levels in urine after HEX exposure will not be modified by co-exposures to TOL, EA or ACE.