Various pharmacokinetic parameters in relation to enzyme-inducing abilities of 1,2,4-trichlorobenzene and 1,2,4-tribromobenzene.

1,2,4-Trichlorobenzene (TCB) and 1,2,4-tribromobenzene (TBB) were administered for 7 d to rats at a dose of 1 mmol/kg.d. The animals were sacrificed at various times to observe the decline in enzyme induction. Carbon 14-labeled TCB and TBB were administered and the disposition of the radioactivity was determined. The influence of starvation and phenobarbital on the inductive effects of TCB and TBB was observed. p-Nitroanisole demethylation and EPN (O-ethyl O-p-nitrophenyl phenylphosphonothionate) detoxification increases declined with time but were still elevated 16 d after the last dose of TBB. Cytochorme P-450 and NADPH-cytochrome c reductase were alsoinduced. Tissue analysis showed greater retention of TBB than of TCB, with highest levels in the fats. More TCB than TBB was excreted in the urine, and fecal excretion was only 5-10% of the dose. The highest enzyme levels were found after 4 d of starvation following the 7 d of treatment and 6 d of recovery. Starvation resulted in increased plasma, fat, and liver concentrations and increased urinary excretion of 14C after TBB dosing. Phenobarbital treatment decreased the levels of induction by the halogenated benzenes. The results demonstrate that, on an equimolar basis, TBB leads to higher levels of induction that are maintained for longer periods than does TCB. Treatments, such as starvation and phenobarbital, that after storage in fat of these materials change the decline with time of the level of induction.