Temporal and dose-response features of XXXX hepatotoxicity in rats.

@entity1447 @entity308 @entity30170 @entity8600 @entity39 @entity2041 @entity35326 @entity2197 @entity99 @entity493
Time- and dose-dependent correlations of @entity30170 (CB) hepatotoxic effects were studied in view of (1) assumed mechanistic similarities to @entity35326 (BB), (2) the paucity of these data for CB, and (3) the relatively greater environmental importance of CB compared with BB. An ip dosage of 9.8 mmol/kg CB (approximately equal to LD10) produced evidence of @entity99 over a 72-hr time course. @entity8600 (BSP) retention was maximized 3-16 hr post-treatment and normalized after 72 hr, whereas plasma @entity493 aminotransferase activity (ALT) and morphological evidence of damage were maximized about 48 hr after dosing. Maximal covalent binding to liver protein (3.07 nmol/mg) had occurred by 24 hr and approximately 36% of the administered dose had appeared in the urine by 48 hr. Liver and plasma CB concentrations were proportionally increased over the dosage range 2.0-14.7 mmol/kg but marked centrolobular @entity39 and ALT elevations were seen only at the two highest dosages (9.8 and 14.7 mmol/kg). On the other hand, all doses @entity308 hepatic @entity2041 ( @entity2197 ) to between 30 and 40% of control by 4 hr. Evidence of rapid recovery was evident at 2.0 and 4.9 mmol/kg but @entity2197 levels remained low through 8 hr after 9.8 or 14.7 mmol/kg. Liver/body weight ratios were increased to a similar extent at all dosages when measured 24 hr post-treatment. Urinary excretion ranged from 59% at the low dosage to only 19% at the highest dosage by 24 hr. Dose-related covalent binding to liver protein at 24 hr occurred up to 9.8 mmol/kg but the binding associated with 14.7 mmol/kg was equivalent to that seen with the 4.9 mmol/kg dosage (1.6 nmol/mg protein). @entity1447 levels were @entity308 to between 50 and 80% of control 24 hr post-treatment with no clear dose relationship. While the hepatotoxic effects of CB and BB appear similar, these data suggest that some mechanistic differences are involved.
