Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.8 Solvents and the liver 1393
20.8 SOLVENTS AND THE LIVER
David K. Bonauto
Occupational Medicine, University of Washington
Seattle, Washington, USA
C. Andrew Brodkin
Department of Internal Medicine and Department of Environmental Health,
University of Washington, Seattle, Washington, USA
William O. Robertson
Washington Poison Center, University of Washington
Seattle, Washington, USA
The toxic effects of organic solvent compounds on the liver are dependent on the intensity
and duration of exposure, route of exposure, the intrinsic toxicity of the specific compound,
as well as individual susceptibility factors. 1 There are a number of pathologic manifestations
of solvent induced hepatotoxicity, including inflammation, fat accumulation in the
liver (steatosis), hepatocellular necrosis and carcinogenesis. Functional disturbances in
liver physiology have also been associated with solvent exposure.
The purpose of this chapter is to review the known hepatotoxicity of commonly used
industrial solvents. 2 A brief review of normal anatomic and physiologic function of the
liver will be provided as a background for understanding histopathologic and biochemical
changes associated with solvent toxicity. The final segment includes a discussion of solvents
known to cause liver injury with a review of the available medical evidence suggestive
of human hepatotoxicity of solvents at present day exposure levels. Solvent induced
hepatotoxicity is almost exclusively encountered in an occupational setting and thus this review
will focus on evidence culled from that setting.
20.8.1 NORMAL ANATOMIC AND PHYSIOLOGIC FUNCTION OF THE LIVER
The liver is the largest internal organ and is involved in many physiologic processes including
nutrient homeostasis, synthesis and excretion of bile, lipid metabolism and lipoprotein
and protein synthesis. 3 Most importantly for purposes of this chapter, the liver is the site of
the biotransformation of a wide variety of endogenous and exogenous toxins. 4 The ability of
the liver to biotransform various chemicals is due to the multiple different enzyme systems
contained within the hepatocytes. 3,5 One such enzyme system is the cytochrome p 450 enzyme
system. It consists of a large group of enzymes which biotransform many different
substances by either oxidation or reduction to facilitate excretion from the body. Specifically
different members of the cytochrome p 450 family catalyze reactions involving aromatic
and aliphatic hydroxylation, epoxidation, dehalogenation, dealkylation, N-, Soxidation
as well as O-, N-, S- dealkylation reactions. 3,5
The diverse metabolic activities of the liver make it susceptible to solvent induced injury,
particularly from reactive intermediates which damage cellular macromolecules. The
microscopic anatomy of the liver provides an explanation for this susceptibility. The basic
unit of the liver is the hepatic lobule which consists of a central vein surrounded radially by
sinusoids of liver cells (hepatocytes). Portal triads consisting of a hepatic artery, a hepatic
vein and a bile canniliculus are located at the periphery. Liver cells closest to the vascular