2-methyl-2-butanol
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Pharmacokinetics
Half-life
Upon repeated exposure to 50 ppm, the material /2-methyl-2-butanol/ was cleared by rats (t1/2 = 47 min) and dogs (t1/2 = 69 min) in an apparent first-order manner.
Following repeated exposure to 1000 ppm the plasma clearance was more rapid in the mouse than in either the rat or the dog exposed to 50 ppm, the t1/2 times being 29, 47, and 69 min, respectively ... The data demonstrate that the kinetics of tert-amyl alcohol are highly species- and conc-dependent.
Absorption
Dog weighing 11 kg, when injected sc with dose of 0.1 mL of 2-methyl-2-butanol...exhaled 65% of it within 5.75 hr. Another dog given slightly larger dose of same alc iv exhaled 52% within 6 hr. Cats also exhaled large quantity unchanged.
When rabbits were injected with 2 levels of dosage ... they exhaled, in first instance 21% of alc in unchanged form within 4 hr, & in second, 22% within 3 hr. ... rat given 1 g/kg of same isomer eliminated 26.4% unchanged in expired air and 8.9% in the urine within 50 hr.
The rate of elimination of amyl alcohols from the blood of rats decreases in the order of primary, secondary, and tertiary. tert-Amyl alcohol did not disappear from the blood of rats until 50 hr following an ip dose of 1 g/kg.
Small amts of the primary and secondary alcohols, and appreciable amts of the tertiary isomer, are excreted unchanged in the respired air and urine. /Amyl alcohols/
... /The authors/ Found a conc of 12.5 mg percent of tert-amyl alcohol in the blood of rats 1 hr following an ip dose of 1.0 kg. They also found a conc of 191 mg percent in the jugular blood of rats at the time of death from respiratory failure. Conc in the plasma of rats about 0.6 hr after they had inhaled 150, 500, or 1500 ppm of tert-amyl alcohol for 6 hr were 9.6, 59.9, and 337 ug/mL, respectively.
Metabolism
... the biotransformation of tert-Amyl methyl ether (TAME) /was studied/ in rats and one human volunteer after inhalation of (12)C- or (13)C-labeled TAME. In addition, the biotransformation of [(13)C]-tert-amyl alcohol was studied in rats after gavage. ... Rats (two males and two females) were individually exposed to 2000 ppm [(12)C]- or [(13)C]TAME for 6 hr, and urine was collected for 48 hr. Free and glucuronidated 2-methyl-2,3-butanediol and a glucuronide of tert-amyl alcohol were identified ... as major urinary metabolites on the basis of the relative intensities of the (13)C NMR signals. The presence of several minor metabolites was also indicated by (13)C NMR; they were identified as tert-amyl alcohol, 2-hydroxy-2-methylbutyric acid, and 3-hydroxy-3-methylbutyric acid. One human volunteer was exposed to an initial concentration of 27,000 ppm [(13)C]TAME by inhalation for 4 min from a 2 L gas sampling bag, and metabolites of TAME excreted in urine were analyzed by (13)C NMR. All TAME metabolites identified in rats were also present in the human urine samples. To study tert-amyl alcohol biotransformation, male rats (n = 3) were treated with 250 mg/kg [(13)C]-tert-amyl alcohol dissolved in corn oil by gavage, and urine was collected for 48 hr. (13)C NMR of the urine samples showed the presence of metabolites identical to those in the urine of [(13)C]TAME-treated rats. Our results suggest that TAME is extensively metabolized by rats and humans to tert-amyl alcohol which may be further oxidized to diols and carboxylic acids. These reactions are likely mediated by cytochrome P450-dependent oxidations.
... The objective of this study was to use a physiologically-based pharmacokinetic (PBPK) model to describe the disposition of tert-amyl methyl ether (TAME) and its major metabolite, tert-amyl alcohol (TAA), in male Fischer-344 rats. The model compartments for TAME and TAA were flow-limited. The TAME physiological model had 6 compartments: lung, liver, rapidly perfused tissues, slowly perfused tissues, fat, and kidney. The TAA model had 3 compartments: lung, liver, and total-body water. The 2 models were linked through metabolism of TAME to TAA in the liver. Model simulations were compared with data on blood concentrations of TAME and TAA taken from male Fischer-344 rats during and after a 6-hour inhalation exposure to 2500, 500, or 100 ppm TAME. The PBPK model predicted TAME pharmacokinetics when 2 saturable pathways for TAME oxidation were included. The TAA model, which included pathways for oxidation and glucuronide conjugation of TAA, underpredicted the experimental data collected at later times postexposure. To account for biological processes occurring during this time, three hypotheses were developed: nonspecific binding of TAA, diffusion-limited transport of TAA, and enterohepatic circulation of TAA glucuronide. These hypotheses were tested using three different model structures. Visual inspection and statistical evaluation involving maximum likelihood techniques indicated that the model incorporating nonspecific binding of TAA provided the best fit to the data. ...
The biotransformation of ... tert-amyl methyl ether (TAME) was studied in humans and in rats after inhalation of 4 and 40 ppm of ... TAME ... for 4 hours, and the biotransformation of ... TAME was studied after ingestion exposure in humans to 5 and 15 mg in water. .../Following ingestion/ tert-Amyl alcohol (TAA), free and glucuronidated 2-methyl-2,3-butanediol (a glucuronide of TAA), 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3-methyl butyrate were found to be metabolites of TAME. After inhalation ... TAME /was/ rapidly taken up by both rats and humans; after termination of exposure, clearance from blood of the ethers by exhalation and biotransformation to urinary metabolites occurred with half-times of less than 7 hours in rats and humans. ... Biotransformation of TAME was qualitatively similar in rats and humans, but the metabolic pathways were different. In humans, 2-methyl-2,3-butanediol, 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3methyl butyrate were recovered as major urinary products. In rats, however, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine. After ingestion ... TAME /was/ ... rapidly absorbed from the gastrointestinal tract. Hepatic first-pass metabolism ... was not observed, and a significant part of the administered dose was transferred into blood and cleared by exhalation. Metabolic pathways for ... TAME and kinetics of excretion were identical after ingestion and inhalation exposures. ...
... Male mice of ICR strain were exposed to about 5% /isopentane/ for one hour while the oxygen in the environmental air was maintained at about 20%. Then their blood and liver tissue were collected and analyzed by means of GC and GC-MS. The metabolites thus obtained were ... 3-methyl-2-butanol, 2-methyl-2-butanol and 3-methyl-2-butanone were detected as the resultant metabolites. In the presence of the NADPH-generating system liver microsomes were made to react to the substrate of saturated ... isopentane aqueous solution at 37 degrees C for one hour. As a result, the same metabolites were produced as obtained in the exposure experiment. It was therefore suggested that ... isopentane /was/ metabolized chiefly by liver microsomes. Male mice of ICR strain were fed with 80 mg/kg b.w. of phenobarbital for consecutive four days and exposed to ... isopentane for one hour. This resulted in an increase in the amount of ... 2-methyl-2-butanol in the isopentane inhalation experiment. ...
For more Metabolism/Metabolites (Complete) data for 2-METHYL-2-BUTANOL (7 total), please visit the HSDB record page.
Tert-amyl alcohol is a known human metabolite of tert-amyl methyl ether.
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