Background. The objective of this investigation was to determine the efficacy of routinely available biochemical tests of hepatic function in relation to ultrasonographic methods for detecting evidence of early hepatic injury in workers exposed to mixed hydrocarbon solvents. Methods. A cross-sectional investigation of 102 workers with a range of cumulative career exposures to organic solvents, including carpenters (low exposure), millwrights (intermediate exposure), and industrial painters (high exposure) was conducted. Data collection included an interview-administered questionnaire used to determine a semi-quantitative cumulative exposure index to mixed hydrocarbon solvents, obtained simultaneously with a venous sample collection for hepatic biochemical tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], direct/total bilirubin), and hepatic ultrasonography. Sonograms were interpreted as normal, mild, or moderate to severe parenchymal change by three radiologists blinded to exposure status. Multiple linear regression analyses were used to assess hepatic biochemical levels (lU/L) and ultrasonographic parenchymal changes, respectively, as a function of cumulative exposure to mixed organic solvents (both by work type and semi-quantitative index), adjusting for the confounding variables of age, gender, alcohol intake, body mass index, and serologic evidence of prior Hepatitis B/C infection. Results. A significant increase in the hepatic cholestatic enzyme gamma glutamyl transpeptidase (GGT) was observed in painters, with a mean level of 41 IU/L, compared with carpenters and millwrights (27 IU/L; p<0.05). A significant exposure-response relationship for GGT and semi-quantitative index to mixed solvents was observed in multivariate analyses controlling for age, gender, alcohol, body mass index, and evidence of prior Hepatitis B/C (p<0.05). Along with changes in GGT; a concomitant trend towards increased sonographic parenchymal changes in relation to mixed solvent exposure (p=0.07) was also observed. No significant changes or trends were observed for AST, ALT, AP, or bilirubin in relation to solvent exposure. Conclusions. The significant exposure-response relationship between gamma glutamyl transpeptidase (GGT) levels and cumulative exposure to mixed organic solvents supports a primary cholestatic effect of hydrocarbon mixtures, providing a useful biomarker of effect among exposed workers. The efficacy of GGT in surveillance of workers exposed to mixed organic solvent compounds is further supported by the consistent trend in sonographic hepatic parenchymal changes observed in relation to solvent exposure in this investigation.
University of Washington, Occupational and Environmental Medicine Program, Harborview Medical Center, Seattle, WA 98104