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>.

环丁砜（Sulfolane）已被证实为炼油厂周边地下水的污染物。本研究针对单次经口染毒（剂量分别为30、100或300 mg/kg）与皮肤染毒（剂量为100 mg/kg）后，[¹⁴C]环丁砜（[¹⁴C]Sulfolane）在大鼠与小鼠体内的体外（in vitro）肝清除率及体内（in vivo）处置过程进行了探究。经口染毒的雄性大鼠对[¹⁴C]环丁砜吸收良好，且药物经尿液大量排泄（排泄率≥93%）。染毒后24小时与48小时，组织内总放射性残留分别约为7%与<2%。在100 mg/kg经口染毒剂量下，雌性大鼠与雌雄小鼠的药物处置模式相似。皮肤给药（给药部位被遮盖，剂量100 mg/kg）时，雌雄大鼠对[¹⁴C]环丁砜的吸收均较差（雄性约16%，雌性约19%）；当雄性大鼠的给药部位未被遮盖时，吸收比例升至59%，提示药物可能通过大鼠舔舐给药部位经口摄入。皮肤给药（剂量100 mg/kg，给药部位被遮盖）时，雌雄小鼠对[¹⁴C]环丁砜的吸收均良好（雄性约70%，雌性约80%）。不同给药途径、物种与性别间的尿液放射性化学成分谱相似；尿液中的主要分析物为环丁砜与3-羟基环丁砜。啮齿类与人类的肝细胞无法清除环丁砜，提示体内环丁砜的代谢可能存在肝脏以外的其他途径。
环丁砜（Sulfolane）已被证实为炼油厂周边地下水的污染物。本研究针对单次经口染毒（剂量分别为30、100或300 mg/kg）与皮肤染毒（剂量为100 mg/kg）后，[¹⁴C]环丁砜（[¹⁴C]Sulfolane）在大鼠与小鼠体内的体外（in vitro）肝清除率及体内（in vivo）处置过程进行了探究。经口染毒的雄性大鼠对[¹⁴C]环丁砜吸收良好，且药物经尿液大量排泄（排泄率≥93%）。染毒后24小时与48小时，组织内总放射性残留分别约为7%与<2%。在100 mg/kg经口染毒剂量下，雌性大鼠与雌雄小鼠的药物处置模式相似。皮肤给药（给药部位被遮盖，剂量100 mg/kg）时，雌雄大鼠对[¹⁴C]环丁砜的吸收均较差（雄性约16%，雌性约19%）；当雄性大鼠的给药部位未被遮盖时，吸收比例升至59%，提示药物可能通过大鼠舔舐给药部位经口摄入。皮肤给药（剂量100 mg/kg，给药部位被遮盖）时，雌雄小鼠对[¹⁴C]环丁砜的吸收均良好（雄性约70%，雌性约80%）。不同给药途径、物种与性别间的尿液放射性化学成分谱相似；尿液中的主要分析物为环丁砜与3-羟基环丁砜。啮齿类与人类的肝细胞无法清除环丁砜，提示体内环丁砜的代谢可能存在肝脏以外的其他途径。