Disposition and metabolism of sulfolane in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans
Waidyanatha S, Black S, Blystone C, Patel P,Watson S, Snyder R, Fennell T
DOI:
https://doi.org/10.22427/NTP-DATA-002-03276-0014-0000-5
Publication
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 h 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 (100mg/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.
ADME Data
Data Summary - Male Rats
- Dermal Single Dose (100 mg/kg, Covered, Study Duration 48 hours) (55 KB)
- Dermal Single Dose (100 mg/kg, Uncovered, Study Duration 48 hours) (58 KB)
- Dermal Single Dose (100 mg/kg, with Breath Traps, Covered, Study Duration 48 hours) (42 KB)
- Gavage Single Dose (30 mg/kg, Study Duration 72 hours) (61 KB)
- Gavage Single Dose (100 mg/kg, Study Duration 24 hours) (48 KB)
- Gavage Single Dose (100 mg/kg, Study Duration 48 hours) (50 KB)
- Gavage Single Dose (300 mg/kg, Study Duration 72 hours) (62 KB)
- IV Single Dose (100 mg/kg, Study Duration 48 hours) (50 KB)
Data Summary - Female Rats
- Dermal Single Dose (100 mg/kg, Covered, Study Duration 48 hours) (55 KB)
- Gavage Single Dose (100 mg/kg, Study Duration 48 hours) (50 KB)
Data Summary - Male Mice
- Dermal Single Dose (100 mg/kg, Covered, Study Duration 48 hours) (57 KB)
- IV Single Dose (100 mg/kg, Study Duration 48 hours) (50 KB)