CHARACTERIZATION OF RAT HEPATIC CYTOCHROME-P-450 ACTIVITIES FOLLOWINGINHALATION EXPOSURE TO P-CHLOROBENZOTRIFLUORIDE

p-Chlorobenzotrifluoride (PCBTF), an intermediate in the synthesis of some herbicides, is currently being evaluated as an industrial solvent . The neurotoxicity of PCBTF was evaluated in a 90-day inhalation stud y in male and female Sprague-Dawley rats exposed for 6 h/day to target concentrations of 0, 10, 50, and 250 ppm PCBTF. Following exposure fo r 90 days, the livers were weighed, frozen, and microsomal fractions p repared to assess cytochrome P-450 (CYP450) content and activities. A significant increase in liver weight and CYP450 content in female rats was observed in the high exposure group (250 ppm), while the increase in males was not found to be statistically significant. 7-Ethyoxyreso rufin O-deethylase (EROD), a measure of CYP1A1 activity, and acetanili de and phenacetin metabolism, a measure of CYP1A2 activity were increa sed about twofold in both males and females at the high exposure level (250 ppm). Pentoxyresorufin O-dealkylase (PROD) and benzyloxyresorufi n O-dealkylase (BROD), a measure of CYP2B activity, were increased app roximately fivefold in males at 250 ppm; however, the increase in fema les at 250 ppm was only twofold. Relatively small changes were observe d in chlorzoxazone hydroxylation (CYP2E1) in the male high exposure gr oup, while there were no differences in the females. Conversely, nifed ipine oxidation (CYP3A1/3A2) showed a small increase in the females at 250 ppm and no change in males. Western blots of protein levels corre lated generally well with increases in enzyme activity (control vs. hi gh exposure level) for CYP1A2, CYP2B, and CYP2E1. The relatively modes t induction of a wide range of hepatic CYP450 activities was limited t o rats exposed to the 250 ppm dose of PCBTF, supporting the NOEL of 50 ppm. In addition, the results suggest that there are gender differenc es associated with the induction of CYP450 activities.