Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.7 Hepatotoxicity 1385
toxicity of chloroform to the liver in humans. Chloroform was used years ago as an anesthetic,
and has been used successfully, however, due to its’ toxicity the use of it has been
abandoned. Acute exposure and toxicity has been associated with liver necrosis, liver
steatosis, and chronic exposure has been associated with liver cirrhosis. The mechanism of
injury most-likely is the result of metabolic changes of chloroform by the liver. Different effects
and level of toxicity between carbon tetrachloride and chloroform is most-likely the
result from the solubility in lipid and water, and the mechanisms by which these two agents
are metabolized and then cause liver toxicity. Table 20.7.5 summarizes liver damage described
in the literature as a result of halogenated aliphatic hydrocarbons.
Table 20.7.5. Lesions produced by halogenated aliphatic hydrocarbons. [Adapted, by
permission, from HJ Zimmerman, Hepatotoxicity, 1978]
Steatosis and centrizonal
Steatosis only Slight steatosis or no injury
necrosis
CCl 4
CI 4
CCl 3Br
CHCl 3
CHI 3
CHBr 3
CHCl 2CHCl 2
CH 2ClCH 2Cl
CH 2BrCH 2Br
CH 3CCl 3
CHCl 2CCl 3
CHCl=CCl 2
CH 3CHClCH 3
CH 3CHClCH 2Cl
CH 2ClBr
CH 2Cl 2
CHCl=CHCl (cis)
CCl 2=CCl 2
CH 3CH 2CHClCH 3
CH 3Cl
CH 3Br
CH 3I
CCl 2F 2
CHCl=CHCl (trans)
CH 3CH 2Cl
CH 3CH 2I
CH 3CH 2Br
CH 3CH 2CH 2CH 2Cl
20.7.3 NON-HALOGENATED SOLVENTS
While the halogenated hydrocarbons discussed here include carbon tetrachloride, chloroform,
1,1,1-trichloroethene, trichloroethylene are significantly hepatotoxic, the literature
on the toxicity of the non-halogenated hydrocarbons is a combination of positive and negative
studies. Several studies looking into the hepatotoxicity of both aliphatic solvents such
as kerosene, hexane and aromatics such as xylene, toluene and styrene have reported mixed
results. Xylene is an aromatic hydrocarbon which is used heavily in the industry, as well as
medical technology as a solvent.
Xylene commonly has been reported with impurities in varying amounts which include
ethyl benzene, prime ethyl benzene, phenol, benzene and toluene. 25 To evaluate the
effects of xylene in experimental animals, Toftgard et al. 26 studied rats who were exposed
for three days by inhalation to xylene and to a mix of xylene isomers. Hepatic cytochrome
P450 concentration increased as well as C reductase activity, and NADPH cytochrome C
reductase activity. Furthermore, xylene and its isomers were able to modify the metabolism
of other potentially toxic substances. In addition to these biochemical changes, the investigators
found that xylene increased liver body weight, most-likely secondary to proliferation
of the endoplastic reticulum. These studies show that at these levels xylene induced
cytochrome P450 activity and NADPH cytochrome C reductase activity, but was not associated
with significant pathological abnormalities. On the other hand, these same investiga-