Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.7 Hepatotoxicity 1381
to convert these agents to their respective toxic metabolites. 6,9 Among other mechanisms responsible
for the species differences are liver blood flow, protein binding, and the points of
binding intracellularly. Genetic factors in humans are of extreme importance. Genetic factors
are most-likely responsible for the various levels of adverse effects of alcohol in different
individuals due to induced activity of detoxification enzymes in the liver in some and
lack of those or reduced activity in others. Another important factor is age. The effect of age
on the susceptibility has been shown in experimental animals. For instance, the neonatal rats
are less susceptible to carbon tetrachloride and bromobenzene toxicity as compared to adult
animals. 9 In humans, liver necrosis after the administration of Halothane was rare in children,
but more common in more elderly patients. Factors such as sex and endocrine status
have also influence and different toxic effects of solvents in this case. Nutritional status is a
major factor in the effects of solvents on the liver. For instance, protein malnutrition leads to
reduced activity of cytochrome P450. Increasing the percentage of fat in the liver has been
shown to increase the susceptibility of toxicity to such agents as carbon tetrachloride. Several
studies have looked into the histopathological injury of some solvents and solvent-like
agents and the liver, and are shown in Table 20.7.1.
Table 20.7.1. Partial list of agents that produce hepatic necrosis in experimental
animals. [Adapted, by permission, from HJ Zimmerman, Hepatotoxicity, 1978]
Site of necrosis
Centrizonal Midzonal Peripheral Zone Massive Steatosis
Bromobenzene + (+)
Bromotrichloromethane + +
CCl4 + +
Chlorobenzenes + (+)?
Chloroform + +
Dichloropropane + +
Dinitrobenzene + (+) +
Dinitrotoluene + (+) +
Ethylene dichloride + +
Methylene chloride (+) (+) (+)
Naphthalene + +
The specific mechanism of hepatotoxicity of many solvents are unknown, however,
the knowledge have been gathered from experimental studies now available for the reader
for review. 10,11,12,13
Due to the lack of specific information for many solvents, I have decided to discuss in
this chapter some of the most typical ones which have been used in the past heavily, or are
used currently.