Solvents have become a ubiquitous work place exposure involving millions of workers, with use in painting, dry-cleaning, de-greasing, and printing industries. The clinical assessment of hepatic status in exposed workers has been limited by the need for non-invasive surveillance techniques, with increasing evidence that routinely used biochemical test do not adequately correlate with parenchyma changes, underestimating solvent induced hepatic injury. To establish a scientific basis for surveillance of hepatic effects in solvent-exposed workers, we propose conducting a cross-sectional study investigating 100 industrial painters at the Hanford Nuclear Reservation, exposed sub-acutely and chronically to a variety of solvent mixtures over their working careers, compared to a referent group of 100 non-exposed carpenters, matched by age, gender and race. The proposed study will examine the hypothesis that solvent-related hepatic injury is characterized by parenchyma changes of steatosis and fibrosis, without associated necrotic changes detectable by transaminases, and will address a priority research area posed by the National Occupational Research Agenda for development of effective surveillance methods. The proposed study's specific aims will address the following research questions:
AIM#1 : Are there ultrasonographic abnormalities in hepatic parenchyma echogenicity in painters compared to carpenters, and are such abnormalities associated with elevations in hepatic transaminase levels? AIM#2: Are there elevations in pro-collagen biomarkers of fibrosis in painters compared to referents, and are these correlated with hepatic transaminase levels? AIM#3: Is there evidence of diminished hepatic clearance of conjugated serum bile acids in painters compared with the referent group, in the absence of other biochemical changes? AIM#4: Are there dose-response relationships between cumulative and/or sub-acute exposure to mixed solvent chemicals, and abnormalities in parenchyma echogenicity on ultrasound, biomarkers, of hepatic fibrosis, or serum bile acids levels?
Luderer, Ulrike; Bushley, Abigail; Stover, Bert D et al. (2004) Effects of occupational solvent exposure on reproductive hormone concentrations and fecundability in men. Am J Ind Med 46:614-26 |