The metabolic fate of the herbicide nitralin in the rat

Abstract

1. ¹⁴C-Nitralin (4-methylsulphonyl-2,6-dinitro-N,N-dipropyl-[¹⁴Claniline) was dosed orally to rats (50mg/kg). The radioactivity was quantitatively recovered (99′8%) between 0 and 72 h after dosing. Most of this was distributed equally between the urine and the faeces; about 1·5% was found in the carcass, skin and intestines.

2. Structural analysis of the urinary metabolites showed that the metabolism proceeded via a complex multistep series of biotransformations involving nitro-group reduction, side-chain oxidation and removal and the subsequent formation of a variety of heterocyclic ring structures.

3. A major metabolite was 7-amino-2-ethyl-5-methylsulphonyl-l-propylbenzimi-dazole; however, this accounted for only three—four per cent of the ingested radioactivity and was one of about five metabolites produced in this yield. Seven other metabolites were identified, none of which was derived from single-step biotransformation of nitralin.

4. The latter, simpler, metabolites were detected on the incubation of nitralin with rat-liver enzymes of the type used in microbial mutagenicity testing. Two pathways (nitro-reduction and N-dealkylation) were observed under aerobic conditions but the former greatly predominated under anaerobic conditions.