Toxicokinetics, metabolism, and microsomal studies of chlorpropham in rats

Abstract

A study on the toxicokinetic behavior, metabolism of chlorpropham, and its effect on cytochrome P450 from liver microsomes was carried out in albino rats after a single and consecutive oral administration at 500 mg kg−1 body weight for 10 and 20 days. Chlorpropham was detected in the blood at 0.08 h (11.43 ± 1.72 µg mL−1) reaching a maximum concentration at 2 h (30.90 ± 2.55 µg mL−1) and a minimum at 48 h (1.95 ± 0.20 µg mL−1) after a single oral administration of 500 mg kg−1. The absorption rate constant (K a) was 0.66 ± 0.48 h−1. The Vd area (18.01 ± 2.78 L kg−1) and t 1/2 β (12.23 ± 1.96 h) values suggested a wide distribution and long persistence of the compound in the body, respectively. The higher ClR (0.82 ± 0.00 L kg−1 h−1) compared to ClH (0.18 ± 0.02 L kg−1 h−1) value indicated that a major portion of chlorpropham was excreted through the urine (30%) compared to the faeces (2.81%). Chlorpropham residue was detected in all tissues of rat at 0.25 h while its metabolite, meta-chloroaniline was detected in liver, kidney, heart, lung, and spleen tissue at 0.25 h. Meta-chloroaniline was not detected in skeletal muscle, brain, fat, and stomach tissue at any time of the observation period. Maximum concentrations of chlorpropham and meta-chloroaniline were detected at 2 h (except in the spleen), and minimum concentrations of chlorpropham at 24 (heart, lung, spleen, skeletal muscle, and stomach) and 48 h (liver, kidney, brain, and fat tissue) respectively; and meta-chloroaniline at 24 h (except heart and spleen). The tissue half-life of chlorpropham in rat varied from 3.80 to 11.60 h. Repeated oral administration of chlorpropham at 500 mg kg−1 for 10 and 20 days caused an induction of the liver microsomal pellet of rat.