Pharmacokinetic study of p-chloronitrobenzene in rat

T Yoshida

Osaka Prefectural Institute of Public Health, Japan.

The pharmacokinetics of p-chloronitrobenzene (p-CNB) was evaluated in rats to propose an index for monitoring p-CNB exposure of humans exposed to it. After a single dose of 30, 100, or 333 mg/kg body weight, p-CNB was administered intraperitoneally to male Sprague-Dawley rats; blood and urine were collected periodically. p-CNB in plasma and its five major metabolites--2-chloro-5-nitrophenol, N-acetyl-S-(4- nitrophenyl)-L-cysteine,2,4-dichloroaniline,p-chloroanilin e, and 2- amino-5-chlorophenol--in urine were measured by reversed-phase HPLC methods. Pharmacokinetics was evaluated by moment analysis and compartment model analysis of the p-CNB concentration in plasma vs. time curves and of the urinary excretion rate of its metabolites vs. time curves. Urinary excretion was considered to be the most important pathway for disappearance of p-CNB, because the fraction of p-CNB metabolites excreted in urine was ca.2/3 of the dose level. N-Acetyl-S- (4-nitrophenyl)-L-cysteine was the most abundant urinary metabolite of p-CNB and comprised ca.1/2 of the total amount of the five metabolites excreted into the urine. The urinary excretion of N-acetyl-S-(4- nitrophenyl)-L-cysteine was considered to be proportional to the dose of p-CNB over a wide range of doses, because the process of metabolism of p-CNB to N-acetyl-S-(4-nitrophenyl)-L-cysteine was linear in the dose range studied. Consequently, urinary N-acetyl-S-(4-nitrophenyl)-L- cysteine was considered to be suitable as an index for monitoring p-CNB exposure.

Volume 22, Issue 2, pp. 275-280, 03/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics