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

Xenobiotica. 2020 Apr;50(4):442-453. doi: 10.1080/00498254.2019.1630786. Epub 2019 Jul 5.

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 [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 <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 in vivo.

Keywords: Sulfolane; absorption; distribution; excretion; metabolism.

MeSH terms

  • Administration, Oral
  • Animals
  • Female
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Rats
  • Rats, Sprague-Dawley
  • Thiophenes / metabolism*
  • Water Pollutants, Chemical / metabolism*

Substances

  • Thiophenes
  • Water Pollutants, Chemical
  • sulfolane