Disposition and metabolism of sulfolane in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans

Abstract

Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the in vitro hepatic clearance and in vivo disposition of [C-14]sulfolane in rats and mice following a single oral administration (30, 100, or 300 mg/kg) and dermal application (100 mg/kg). [C-14]Sulfolane was well-absorbed in male rats following oral administration and excreted extensively in urine (>= 93%). Total radioactivity in tissues at 24 and 48 h was similar to 7% and Dermally applied [C-14]Sulfolane (covered dose site, 100 mg/kg) was poorly absorbed in male (similar to 16%) and female (similar to 19%) rats; absorption increased to 59% when the dose site was uncovered in male rats suggesting ingestion of dose via grooming of the dose site. Dermally applied [C-14]sulfolane (100 mg/kg, covered dose site) was well absorbed in male (similar to 70%) and female (similar to 80%) mice. Urinary radiochemical profiles were similar between routes, species, and sexes; the main analytes present in urine were sulfolane and 3-hydroxysulfolane. Sulfolane was not cleared in hepatocytes from rodents or human suggesting sites other than liver might be involved in metabolism of sulfolane in vivo.