Toxicology of Industrial Compounds

Figure 3.2 Bioactivation of styrene.
Figure 3.3 Bioactivation of chloroform.
oxide, generated in vivo inside a cell is such a good substrate for the phase
2 enzymes, epoxide hydrolase and glutathione transferase, that virtually
immediately upon its synthesis, it is further metabolized. Thus, presumably
the build-up of an effective concentration in vivo is prevented. Whether
other toxicity of styrene in, for example, oesophagus, stomach or
forestomach is related to covalent binding of styrene oxide to protein thiol
groups in those tissues is unclear at present.
Styrene is an example of a compound of which the metabolism
completely goes through a reactive intermediate (the epoxide); yet it does
not cause the cancer that might be expected from its highly mutagenic
metabolite. Accumulation of enough of this epoxide inside the cells for a
detectable genotoxic effect may require a dose which is acutely toxic, and
therefore can never be tested.
Chloroform
G.J.MULDER 39
Chloroform is acutely toxic in the liver and the kidney. This is the result of
formation of a reactive intermediate (Figure 3.3), phosgene, which binds