Bromobenzene, at doses greater than 5.7 mmol/kg, produced renal proximal tubular
necrosis and renal functional changes in mice.
p-Bromophenol and
o-bromophenol were the major urinary phenolic
bromobenzene metabolites although m-bromophenol and
4-bromocatechol were also excreted in detectable quantities. With the exception of
o-bromophenol, urinary metabolites were excreted primarily as conjugates.
4-Bromocatechol and the 3 bromophenol isomers were nephrotoxicants (measured as increased blood
urea nitrogen and decreased accumulation of organic
anions by renal cortical slices) but not hepatotoxicants (measured as serum glutamic
pyruvate transaminase) in vivo at 0.56 mmol/kg (i.v.). Preincubation of renal cortical slices with each of these
bromobenzene metabolites for 90 min resulted in dose-dependent decreases in the accumulation of
p-aminohippurate and
tetraethylammonium.
At 10 mumol/preincubation (2.4 mM), organic ion accumulation was decreased maximally by all
bromobenzene metabolites examined while equimolar amounts of
bromobenzene were without effect.
4-Bromocatechol was the most potent nephrotoxicant in vitro. Administration of 0.53-2.12 mmol/kg (i.v.)
4-bromocatechol to mice resulted in a dose-dependent decrease in renal function while hepatic function was altered only slightly at the higher doses. The
renal cortical necrosis produced by in vivo administration of
4-bromocatechol could not be distinguished histologically from that induced by
bromobenzene. These results demonstrate that
4-bromocatechol and the 3 bromophenol isomers are nephrotoxicants that can be generated from
bromobenzene in mice.