INDUCTION OF RAT-LIVER MICROSOMAL CYTOCHROME-P-450 BY THE PENTABROMO DIPHENYL ETHER BROMKAL-70 AND HALF-LIVES OF ITS COMPONENTS IN THE ADIPOSE-TISSUE

Pentabromo diphenyl ether (Bromkal® 70) was investigated for its half-life in perirenal fat of male and female Wistar rats following a single 300 mg/kg p.o. dose. Half-lives of five individual component fractions following extraction and separation with HPLC were between 30 and 91 days in female rats and between 19 and 119 days in male rats. Induction experiments in male and female Wistar rats with long-term (50 mg/kg daily for 28 days) and short-term administration (300 mg/kg once or 100 mg/kg daily for 4 days) resulted in a 2.3-3.9-fold increase on the cytochrome P-450c, an up to 2-fold increase of benzphetamine N-demethylation activity, a 2.2-5.3-fold increase of the benzo[a]pyrene oxidation activity, and an increase of the ethoxyresorufin O-deethylation activity to between 4.1 and 16.6 nmol/min mg microsomal protein. All variation of enzymatic activities were dependent on the animals' sex or on the administration schedule of the pentabromo diphenyl ether. The threshold for induction of the ethoxyresorufin O-deethylation or benzo[a]pyrene oxidation was between 3 and 10 mg/kg. In conclusion, with regard to the induction of cytochrome P-450 types pentabrominated diphenyl ethers behave as mixed-type inducers. © 1990.