The fate of saccharin impurities: the metabolism and excretion of 3-amino [3-14C]benz[d]-isothiazole-1,1-dioxide and 5-chlorosaccharin in the rat.

1. 3-Amino[3-14C]benz[d]isothiazole-1, 1-dioxide was prepared from [3-14C]-saccharin. IT was well adsorbed on oral administration to rats (25 mg/kg) with only 2% of the 14C in the faeces. The absorbed material was rapidly eliminated with about 87% dose in the urine in 24 h and 91% in 4 days. Little 14C (0.5% of dose) was present in the carcass 4 days after dosing. Most of the 14C in the 0--24 h urine (99%) was present as unchanged 3-aminobenz[d]isothiazole-1,1-dioxide, the rest being an unidentified metabolite. 2. 5-Chlorosaccharin was excreted unchanged after oral administration to rats (80 mg/kg) with 76% dose in the urine in 24 h and 81% in 4 days. Only 4% was detected in the faeces. There was no significance hydrolysis (less than 0.5%) to 5-chloro-2-sulphamoylbenzoic acid. 3. The extent of metabolism of these and other compounds related to saccharin showed good agreement with the extent of their partitioning into organic solvents.