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Xenobiotica
the fate of foreign compounds in biological systems
Volume 50, 2020 - Issue 4
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Animal Pharmacokinetics and Metabolism

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

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Pages 442-453 | Received 06 May 2019, Accepted 08 Jun 2019, Published online: 05 Jul 2019
 

Abstract

  1. 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).

  2. [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.

  3. 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.

  4. Urinary radiochemical profiles were similar between routes, species, and sexes; the main analytes present in urine were sulfolane and 3-hydroxysulfolane.

  5. Sulfolane was not cleared in hepatocytes from rodents or human suggesting sites other than liver might be involved in metabolism of sulfolane in vivo.

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgements

The authors are grateful to Drs. Esra Mutlu and Kristen Ryan for their review of this manuscript, and would like to acknowledge the late Dr. Jason Burgess for conducting the NMR analysis. This work was performed by RTI International for the National Toxicology program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract No. N01-ES-75563 (HHSN29120077563).

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