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

Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the <i>in vitro</i> hepatic clearance and <i>in vivo</i> disposition of [¹⁴C]sulfolane in rats and mice following a single oral administration (30, 100, or 300 mg/kg) and dermal application (100 mg/kg).[¹⁴C]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 ∼7% and &lt;2%. Disposition pattern was similar in female rats and male and female mice at 100 mg/kg oral dose.Dermally applied [¹⁴C]Sulfolane (covered dose site, 100 mg/kg) was poorly absorbed in male (∼16%) and female (∼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 [¹⁴C]sulfolane (100 mg/kg, covered dose site) was well absorbed in male (∼70%) and female (∼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 <i>in vivo</i>. Sulfolane has been found as a ground water contaminant near refining sites. These studies investigated the <i>in vitro</i> hepatic clearance and <i>in vivo</i> disposition of [¹⁴C]sulfolane in rats and mice following a single oral administration (30, 100, or 300 mg/kg) and dermal application (100 mg/kg). [¹⁴C]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 ∼7% and &lt;2%. Disposition pattern was similar in female rats and male and female mice at 100 mg/kg oral dose. Dermally applied [¹⁴C]Sulfolane (covered dose site, 100 mg/kg) was poorly absorbed in male (∼16%) and female (∼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 [¹⁴C]sulfolane (100 mg/kg, covered dose site) was well absorbed in male (∼70%) and female (∼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 <i>in vivo</i>.