Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.8 Solvents and the liver 1399
curs after nonfatal exposures. 77 The mechanism of hepatotoxicity has not been elucidated in
humans but the reactive metabolites 1,1-dichloroacetyl chloride with binding to hepatic
macromolecules may play a role. 76 Metabolism of 1,1,2,2-tetrachloroethane is potentiated
by fasting and ethanol in rats. 79,80 There is little documentation of any precise inhalational
exposure levels necessary to cause hepatotoxicity.
20.8.2.7 Tetrachloroethylene and trichloroethylene
This widely used dry cleaning agent and degreasing agent is associated with hepatotoxic effects.
81,82 Cases of human hepatotoxicity to tetrachloroethylene at exposure levels greater
than 100 ppm have been reported in the literature. 83,84 Humans exposed to
tetrachloroethylene at dosages up to 150 ppm for durations of one to five 8 hour shifts had
no difference in hepatic enzyme levels from baseline levels. 85 Studies of workers chronically
exposed to concentrations of tetrachloroethylene less than 50 ppm showed no difference
in liver enzyme levels, relative to groups of workers who did not have the exposure. 82
However, dry cleaning workers chronically exposed to low levels of tetrachloroethylene at
less than 25 ppm had evidence of an alteration in hepatic echogenicity relative to non-exposed
workers. 80 This is suggestive evidence that steatosis may occur at levels below the
ACGIH TLV, without associated alterations in serum hepatic enzymes. The long term effects
of exposures have not been well characterized.
Wide spread use of trichloroethylene occurs in the dry cleaning industry and industrially
as a degreasing agent. Historical use as an anesthetic generally suggests little acute
hepatotoxicity. 86,87 Longer term exposures in an occupational setting are associated with elevations
in serum transaminases, with variable findings in epidemiologic studies. 88-90 Exposures
below the ACGIH TLV of 50 ppm in workers using trichloroethylene as a cleaning
agent found elevated levels of serum bile acids. 45,91 Hepatotoxicity is potentiated by alcohol,
92 isopropanol and acetone. 69 The long term effects of subclinical exposures are not
known.
20.8.2.8 Other halogenated hydrocarbons
Vinyl chloride, a gas at normal temperature and pressure, has solvent properties at high
pressures; its industrial use as a monomer in the manufacture of polyvinylchloride and
hepatotoxicity with chronic exposure make it an important public health risk. Vinyl chloride
is associated with angiosarcoma, 93,94 a rare highly malignant hepatic tumor, hepatic fibrosis,
6 hepatocellular injury 95 and hepatoportal sclerosis, a form of noncirrhotic portal
hypertension. 96,97 Appearance of angiosarcoma and hepatoportal sclerosis occurred in
workers after decade long exposures. 94,98 Measures to limit both occupational and environmental
exposures have been instituted to decrease potential hepatic outcomes, with effective
screening programs using indocyanine green clearance tests. 6
Haloalkanes other than the chloroalkanes, especially those with structural homology
to known hepatotoxic chloroalkanes, should be considered potentially hepatotoxic despite
little industrial use as solvents. 5,20 Case reports of bromoethane and hydrochlorofluorocarbon
poisonings with hepatotoxicity have been reported in the literature. 99-102
20.8.2.9 Styrene and aromatic hydrocarbons
Styrene is not only used as a monomer in the production of polystyrene but also as a reactive
solvent in the manufacture of unsaturated polyester resins. 103 The hepatic metabolism of
styrene involves the formation of the reactive intermediate styrene 7,8-oxide. 104 In rat models,
styrene 7,8-oxide binds to hepatic macromolecules and lipids causing hepatocellular in-