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J Toxicol Environ Health A

Title:		Disposition of orally and intravenously administered methyltetrahydrofuran in rats and mice
Author(s):		Henderson RF; Gurule M; Hedtke-Weber BM; Ghanbari K; McDonald JD; Kracko DA; Dix KJ;
Address:		"Lovelace Respiratory Research Institute. Albuquerque, New Mexico 87108, USA. rhenders@LRRI.org"
Journal Title:		J Toxicol Environ Health A
Year:		2007
Volume:		70
Issue:		7
Page Number:		582 - 593
DOI:		10.1080/10937400600882848
ISSN/ISBN:		1528-7394 (Print) 0098-4108 (Linking)
Abstract:		"The disposition of [14C]methyltetrahydrofuran (14C-MTHF) in rats and mice was determined by following changes in the radioactivity in tissue and excreta with time after dosing. MTHF administered orally (1, 10, or 100 mg/kg) or intravenously (1 mg/kg) to either rats or mice was rapidly metabolized and excreted with <8% (mice) or 8-22% (rats) of the dose remaining in the body after 24 h (1 and 10 mg/kg doses) or 72 h (100 mg/kg dose). Based on recovery of radioactivity in excreta (other than feces) and tissues (other than the gastrointestinal [GI] tract), absorption of orally administered MTHF was essentially complete (93-100%). There were no overt signs of toxicity observed at any dose studied. The major route of excretion in mice was in urine followed by exhaled CO2. In rats the major route of excretion was exhaled CO2 followed by urinary excretion. The excretion of exhaled volatile organic compounds (VOC) was dose-dependent in both species; at lower doses exhaled VOC represented 1-5% of dose, but at the highest dose (100 mg/kg) this proportion rose to 14% (mice) and 27% (rats). Analysis of the VOCs exhaled at the high dose indicated that the increase was due to exhalation of the parent compound, 14C-MTHF. Analysis of urine showed three highly polar peaks in the mouse urine and two polar peaks in the rat urine. Because the 14C label in MTHF was in the methyl group, the polar metabolites were considered likely due to the one-carbon unit getting into the metabolic pool and labeling intermediate dietary metabolites"
Keywords:		"Administration, Oral Animals Carbon Radioisotopes Chromatography, High Pressure Liquid Environmental Pollutants/*pharmacokinetics Furans/*pharmacokinetics Injections, Intravenous Male Mice Mice, Inbred Strains Rats Rats, Inbred F344;"
Notes:		"MedlineHenderson, Rogene F Gurule, Mark Hedtke-Weber, Briana M Ghanbari, Katayoon McDonald, Jacob D Kracko, Dean A Dix, Kelly J eng N01-ES-25483/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural England 2007/03/17 J Toxicol Environ Health A. 2007 Apr 1; 70(7):582-93. doi: 10.1080/10937400600882848"