2-methylpropan-1-ol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Zur Pharmakokinetik der hoeheren aliphatischen Alkohole

Author:

Rüdell E, Bonte W, Sprung R, Kuhnholz B

Year:

1983

Bibliographic source:

Beitr. Gerichtl. Med., Vol. 41: 211-218

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

In an effort to understand the elimination kinetics of aliphatic alcohols found in alcoholic beverages, research was conducted with human subjects.
Test subjects consumed isobutanol in an ethanol/water vehicle over a two hour time period. Blood and urine samples were collected prior to consumption, at the end of the two-hour consumption period, at one, two, eight (urine only), and nine hours after the end of the exposure period.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpropan-1-ol

EC Number:

201-148-0

EC Name:

2-methylpropan-1-ol

Cas Number:

78-83-1

Molecular formula:

C4H10O

IUPAC Name:

2-methylpropan-1-ol

Specific details on test material used for the study:

- Name of test material (as cited in study report): Isobutanol

Test animals

Species:

human

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

other: orange juice

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Orange juice was prepared containing 40 % (v/v) ethan-1-ol and 3.75 mg/l 2-methylpropan-1-ol

Duration and frequency of treatment / exposure:

2 hours followed by 9 hours of post exposure

Doses / concentrations

No. of animals per sex per dose / concentration:

not specified

Control animals:

not specified

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

isobutyraldehyde and isobutyric acid

Any other information on results incl. tables

The blood concentrations of isobutanol, isobutyraldehyde, and isobutyric acid were approximately 4, 4, and 17 µmol/L at the end of the consumption period, clearly demonstrating that isobutyric acid was the major metabolite of isobutanol metabolism. While the addition of ethanol to the test beverage definitely altered the rate of isobutanol metabolism (via a competition for metabolic enzymes), the presence of ethanol did not affect how isobutanol was metabolized. Blood levels of isobutanol decreased over the next two hours while the isobutyraldehyde levels slowly increased in the blood. Isobutyric acid levels also decreased after the end of the consumption period. Urinary concentrations of isobutanol peaked at the one-hour postexposure time point. Urinary levels of isobutyraldehyde peaked at the eight hour post-exposure time point. Urinary levels of isobutyric acid peaked at the end of the two-hour exposure period. Urinary levels of propionaldehyde roughly followed those for isobutyraldehyde with peak levels of approximately 8 µmol/L. Urinary levels of propionic acid rose after the exposure period ended with plateau levels between 2 and 8 hours of approximately 60 µmol/L. Urinary levels of succinic acid roughly followed the propionic acid urinary elimination curve with peak levels of approximately 30 µmol/L. A diagram was provided in the paper describing the further metabolism of isobutyric acid, ending with propionic acid. The formation of succinic acid from propionic acid is proposed based on the known intermediate metabolism of propionic acid via the citric acid cycle.