Pharmacokinetics and disposition of methyl t-butyl ether in Fischer-344 rats.
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 [14C]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 x 15 days) chamber concentrations of [14C]MTBE. Blood, expired air, and excreta (urine and feces) were collected at selected times up to 7 days post-dose and quantified for 14C content. Plasma concentrations of MTBE and t-butyl alcohol (TBA) were quantified and mean values used for pharmacokinetic analysis. The mean total recoveries of 14C 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 (ti = 0.5 h) by exhalation and metabolism to TBA. At the high doses, metabolism was saturated and the proportion of renal 14C excretion decreased relative to the pulmonary route. At 48 h post-exposure, virtually all of the 14C was eliminated. The major metabolites recovered in urine were 2-methyl-1,2-propanediol and alpha-hydroxyisobutyric acid. There were no significant gender or route-dependent differences in the pharmacokinetics and disposition of MTBE.
Miller
M J
MJ
Exxon Biomedical Science, Inc., East Millstone, NJ 08875, USA.
Ferdinandi
E S
ES
Klan
M
M
Andrews
L S
LS
Douglas
J F
JF
Kneiss
J J
JJ
D000042:Absorption; D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000284:Administration, Oral; D000393:Air Pollutants / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000393:Air Pollutants; D008738:Methyl Ethers; C043243:methyl tert-butyl ether