Bromobenzene is metabolized by the rat and guinea pig to 2-, 3- and
4-bromophenol.
3-Bromophenol is formed through the
sulfur-series pathway to
phenols. This route involves the enterohepatic circulation; the key intermediate is the S-(2-hydroxy-4-bromocyclohexa-3,5-dienyl)-L-cysteine derived from the 4-S-glutathione conjugate of the 3,4-oxide. A sulfonium ion
C-S lyase reaction is proposed in order to account for the
pyridoxal phosphate-dependent cleavage/aromatization step, and a C-S beta-
lyase reaction sequence is also proposed for the formation of bromodihydrobenzene thiolols. This route of
phenol formation may prove to be a general one for
aromatic hydrocarbons and closely related compounds that show arene
oxide conjugation with
glutathione.
2-Bromophenol is formed predominately by spontaneous isomerization of the 2,3-oxide.
4-Bromophenol is formed by the
sulfur-series route from the S-(2-hydroxy-5-bromocyclohexa-3,5-dienyl)-L-cysteine. Additional in vivo routes to 3- and
4-bromophenol involve
dehydration/aromatization of the 3,4-dihydro-3,4-diol, possibly by way of conjugates; these routes have transient ketonic intermediates. The pathways from
bromobenzene to
phenols and to
sulfur-containing metabolites derived from premercapturic
acids show species and dosage variation.