Pharmacokinetics and Disposition of Methyl t-Butyl Ether in Fischer-344 Rats

✍ Scribed by Mary Jo Miller; Eckhardt S. Ferdinandi; Mark Klan; Larry S. Andrews; J. Fielding Douglas; John J. Kneiss

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 189 KB
• Volume: 17
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/(sici)1099-1263(199705)17:1+<s3::aid-jat405>3.0.co;2-8

✦ Synopsis

Methyl t-butyl ether (MTBE) is a commonly used octane booster in gasoline. This study examines the pharmacokinetics and disposition of MTBE in Fischer-344 rats after i.v., oral, dermal and inhalation routes of administration. Groups of male and female rats were given single i.v. (40 mg kg -1 ), oral (40 and 400 mg kg -1 ) and dermal (40 and 400 mg kg -1 in occluded chambers) doses of [ 14 C]MTBE. For inhalation studies, rats were exposed nose-only for 6 h to low (400 ppm), high (8000 ppm) and repeated daily 6-h low (400 ppm × 15 days) chamber concentrations of [ 14 C]MTBE. Blood, expired air, and excreta (urine and feces) were collected at selected times up to 7 days post-dose and quantified for 14 C content. Plasma concentrations of MTBE and t-butyl alcohol (TBA) were quantified and mean values used for pharmacokinetic analysis. The mean total recoveries of 14 C ranged from 91 to 105%. Methyl t-butyl ether was rapidly and completely absorbed after oral and inhalation exposures; dermal absorption was low. After all routes, MTBE was rapidly eliminated from blood (t . = 0.5 h) by exhalation and metabolism to TBA. At the high doses, metabolism was saturated and the proportion of renal 14 C excretion decreased relative to the pulmonary route. At 48 h post-exposure, virtually all of the 14 C was eliminated. The major metabolites recovered in urine were 2-methyl-1,2-propanediol and ␣hydroxyisobutyric acid. There were no significant gender or route-dependent differences in the pharmacokinetics and disposition of MTBE.