Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.7 Hepatotoxicity 1387
early potential hepatotoxicity from mixed organic solvents. From a clinical point of view
this study suggests that exposure to mixture of solvents in an industrial setting may cause
liver damage which is subclinical and initially undetected, unless liver enzymes and bile acids
are measured. It seems likely that this initial stage of liver damage in patients exposed to
solvent mixtures is commonly missed.
20.7.5 TRICHLOROETHYLENE
The liver is a target organ toxicity for trichloroethylene in experimental animals. Data in humans
are limited. 34 Case reports describe trichloroethylene induced hepatitis and liver necrosis.
35 Guzelian et al. described both hepatic necrosis and fatty metamorphasis. 36 As early
as 1962, the hepatotoxicity of trichloroethylene has been studied in humans. Trichloroethylene
has been found to cause liver damage after both acute and chronic exposures. 37,38,39,40,41
Several studies reported a history of pathological changes including individual or focal necrosis
after treatment of experimental animals with trichloroethylene. 42 In addition to these
histopathological changes Berman also found a dose response relationship to the
histopathological changes. Since trichloroethylene is commonly present as a contaminant in
ground water (from degreasing, paint thinning and plastic metal processes) Barton has evaluated
risks assessment of trichloroethylene and liver toxicity, 43 and showed that exposure
was associated with continuous response in the form of liver toxicity. There was a connection
between increased liver weight over body weight and liver toxicity, this effect also appears
to be a sensitive indicator of liver toxicity. The authors concluded that
trichloroethylene is toxic to the liver, based on their analysis of their findings, and that the
use of liver enzymes by themselves may miss the early signs of toxicity to the liver by trichloroethylene.
From these studies on trichloroethylene, and the studies on solvent mixtures
described above, it seems reasonable to conclude that the early subclinical stages of
solvent hepatotoxicity are commonly missed. When patients present to the doctor they will
already be in more advanced stages such as liver steatosis and/or chronic hepatitis, and at
times liver fibrosis.
The toxicity of trichloroethylene is dependent upon metabolism and induction of
cytochrome P450. Trichloroethylene is metabolized through chloral hydrate to compounds
including trichloroacetic acid and dichloroacetic acid which alter intercellular communication,
induce peroxisome proliferation and may promote tumor production. 44 Significant
variability in trichloroethylene metabolism in 23 human haptic microsomal samples was reported
by Lipscomb et al. 44 It was also demonstrated that the trichloroethylene metabolism
is dependent on enzymatic activities of the cytochrome system, and they conclude that their
data indicates that humans are not uniform in their capacity for CPY dependent metabolism
of trichloroethylene and increased activity may increase susceptibility to trichloroethylene
induced toxicity in humans. These observations are compatible with the variability reaction
which is depending on nutritional factors, enzyme induction factors, hormonal factors and
interaction with other environmental chemicals, prescription medications and general
health conditions, and explains the variable reports as far as trichloroethylene and level of
liver toxicity in the various individuals studied.
In a predisposed individual (for example, a patient who is on medications or alcohol) it
is highly likely that exposure to trichloroethylene will be a substantial factor in the genesis
of a wide variety of liver diseases.