Potential tolerance against bromobenzene-induced acute hepatotoxicity due to prior subchronic exposure

Groups of adult male Sprague-Dawley rats were treated i.p. with 0, 0.3 and 0.5 mmole bromobenzene (BB)/kg per day in corn oil, 5 days a week for 4 weeks. Thereafter, one half of each of these groups was treated i.p. with a single acute toxic dose of 2.5 mmole BB/kg. Urines were then collected for 24 h and the animals were then sacrificed. The hepatotoxicity induced by an acute dose of BB was significantly reduced due to prior subchronic exposure to BB at 0.5 mmol/kg, but not so at 0.3 mmol/kg. These data indicate a potential tolerance against acute hepatotoxicity of BB due to prior subchronic exposure. A significant increase in the urinary excretion of thioethers or mercapturic acids of BB combined with a significant increase in the urinary level of p-bromocatechol due to prior subchronic treatment with 0.5 mmol BB/kg relative to those due to acute treatment alone was observed. Thus enhanced bromobenzene metabolism could partly explain such potential tolerance against its acute hepatotoxicity. Such protection may also be related to certain cellular events which might occur subsequent to metabolic activation of BB.