The fate of diphenyl sulphide, diphenyl sulphoxide and diphenyl sulphone in the rat.

Radiolabelled [UL-14C]-diphenyl sulphide, [UL-14C]-diphenyl sulphoxide and [UL-14C]-diphenyl sulphone were administered by gavage (1.0 mmol/kg body weight) to adult male Wistar rats following an overnight fast. For all compounds, faeces were the major route of excretion of radioactivity (50%). Urinary elimination (40%) was similar during the first (19%) and second (16%) days and a small amount of radioactivity (6%) was found within the carcass after four days. From urinary and faecal data, metabolism occurred via ring hydroxylation with subsequent conjugate formation. Oxidation of the sulphur to form the sulphoxide and sulphone also took place; a small amount of sulphoxide reduction was apparent but no sulphone reduction was found. No evidence for exclusion of the sulphur was obtained, and it appeared unlikely that extensive cleavage of the ring structures occurred.

Rôle of bile in the elimination of dipropyl sulphone from the male rat.

Following oral administration of [35S]-dipropyl sulphone to male Wistar rats (4.24 mmol/kg body wt), the only radioactive component subsequently found in the blood and bile was the sulphone. Biliary excretion played an important rôle in the elimination of this compound, with 16% of the dose excreted during the first twenty-four hours and 33% passing through the bile duct over a two day period. Bile/plasma concentration ratios remained constant during the first day (c. 46-fold), suggesting that a concentration process was taking place and that active transport of this low molecular weight compound (150 Da) into the bile was occurring.

Fate of dipropyl sulphone in rat.

1. Dipropyl [35S]-sulphone was administered by gavage (4.24 mmol/4 ml/kg body weight) to the adult male Wistar rat following an overnight fast. 2. Urine was the major route of excretion (83%) with more radioactivity appearing during the second day (47%) than the first (28%). Only small amounts were found in the faeces (10%). Biliary excretion played an important role with substantial amounts of the dose (33%) passing through the bile duct during 0-48 h. A near total recovery was achieved suggesting that only small amounts (2%) may have been lost as volatile components. 3. Metabolism was limited, the majority (> or = 98%) of the sulphone being recovered unchanged. Oxidation of the sulphur with the formation of inorganic sulphate was the only pathway observed.

Distribution of dipropyl [35S]-sulphoxide in the rat.

Dipropyl [35S]-sulphoxide was administered by gavage (4.24 mmol/kg body weight) to adult male Wistar rats and the placement of radioactivity about the animal examined at 4, 8 and 12 hours post-dosing. Widespread and diffuse distribution throughout soft tissues was observed with the largest amounts of radioactivity being found within the liver (3.2% dose at 4 h) and kidney (1.3% dose at 4 h). Activity levels declined over the 12 hour experimental period. This distribution pattern is discussed and compared with results previously reported for dimethyl sulphoxide.

Fate of dipropyl sulphide and dipropyl sulphoxide in rat.

1. Dipropyl [35S]-sulphide and dipropyl [35S]-sulphoxide were administered by gavage (4.24 mM/4 ml/kg body wt) to adult male Wistar rats following an overnight fast. 2. Urine was the major route of excretion for both compounds, with more radioactivity appearing during the second day (c. 43%) than the first (c. 26%). Only small amounts were found in the faeces (c. 5%). Biliary excretion played an important role with substantial amounts of the dose (c. 25%) passing through the bile duct during 0-48 h. Following ingestion of the sulphide large quantities of radioactivity (18%) were detected in exhaled air. Near total recoveries were achieved for both compounds, although 13% of the radioactivity remained within the carcass 3 days after administration of the sulphoxide. 3. Absorption and elimination half-lives were in the region of 5 and 8 h, respectively, for both compounds, with the sulphoxide plasma profile showing a prolonged plateau region. 4. Metabolism was limited to oxidation of the sulphur with the formation of the sulphoxide and sulphone, and trace amounts of inorganic sulphate.