Disposition of Orally and Intravenously Administered Methyltetrahydrofuran in Rats and Mice
| Autor: | Jacob D. McDonald, Kelly J. Dix, Dean Kracko, Rogene F. Henderson, Katayoon Ghanbari, Mark Gurule, Briana M. Hedtke-Weber |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Chemistry Health Toxicology and Mutagenesis Administration Oral Mice Inbred Strains Urine Absorption (skin) Pharmacology Toxicology Rats Inbred F344 Rats Excretion Mice Urinary excretion Injections Intravenous Toxicity Animals Environmental Pollutants Carbon Radioisotopes Dosing Furans Chromatography High Pressure Liquid Feces |
| Zdroj: | Journal of Toxicology and Environmental Health, Part A. 70:582-593 |
| ISSN: | 1087-2620 1528-7394 |
| Popis: | 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 with8% (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. |
| Databáze: | OpenAIRE |
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