Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
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:
Unnamed
Year:
1993

Materials and methods

Objective of study:
absorption
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study investigated the metabolism of the individual isomers of 2,3-butanediol (2R,3R-, 2S,3S-, meso-2,3-butanediol and racemic 2,3-butanediol) in perfused livers from fed rats.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(R,R)-(-)-butane-2,3-diol
EC Number:
246-186-9
EC Name:
(R,R)-(-)-butane-2,3-diol
Cas Number:
24347-58-8
Molecular formula:
C4H10O2
IUPAC Name:
(R,R)-(-)-butane-2,3-diol
Test material form:
liquid
Specific details on test material used for the study:
- 2R,3R (levo) and 2S,3S (dextro) 2,3-butanediol were obtained from Aldrich Chemical Co.
- Racemic 2,3-butanediol was purchased from Pfaltz and Bauer, Waterbury, CN.
- Meso-2,3-butanediol was obtained from Fluka Chemical Corp., Ronkonkoma, NY.
Radiolabelling:
yes
Remarks:
2H, 14C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
For liver perfusion experiments:
Male Sprague-Dawley rats (Charles River Laboratories) were fed ad libitum with Purina rat chow. For the series of liver perfusions with unlabelled isomers of butanediol, the rats weighed 210-300 g. For the series of perfusions with radio labelled butanediols, the rats weighed 160-210 g.

Administration / exposure

Route of administration:
other: ex vivo (liver perfusion)
Statistics:
Data were analysed by one-way ANOVA, followed by the Bonferroni test to identify significant differences between groups. Perfusions with labelled 2,3-butanediol were analysed separately from perfusions with unlabelled 2,3-butanediol because of the difference in weights of rats. Significance level was set to p < 0.05.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Uptake of the 2,3-butanediol isomers decrease in the order: levo > meso > dextro.
Type:
metabolism
Results:
Levo and meso 2,3-butanediol metabolise to acetate, R-3-hydroxybutyrate and CO2, suggesting that 2,3- butanediol is oxidized to acetyl-coA via acetoin.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Analysis of control liver perfusates from fed rats indicated that any endogenous production of 2,3-butanediol or acetoin was below LOD of the assay (1 µM). In a preliminary perfusion experiment with 20 mM ethanol, neither acetoin nor butane-2,3-diol was produced during the first hour. However, when 5 mM pyruvate was added, acetoin and 2,3-butanediol accumulated up to 15 µM over the second hour. Presence or absence of butane-2,3-diol isomers did not affect the uptake rate of any individual isomer.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
Differences were observed in the metabolism of individual 2,3-butanediol isomers in perfused rat liver. Interconversion of isomers and oxidation to acetoin was observed with levo and meso, but not with dextro 2,3-butanediol.
In liver perfusions with either levo or meso (radiolabelled) 2,3-butanediol, the substrates were converted to labelled acetate, R-3-hydroxybutyrate and CO2, suggesting that 2,3-butanediol was oxidized to acetyl-CoA via acetoin. Production of radio-labelled CO2, acetate, ketone bodies, acetoin, and other isomers of butane-2,3-diol accounted for approximately one-third of the label uptake.


Applicant's summary and conclusion

Conclusions:
Absorption: Uptake of 2,3-butanediol isomers decrease in the order: levo > meso > dextro.
Metabolism: Levo and meso 2,3-butanediol metabolise to acetate, R-3-hydroxybutyrate and CO2, suggesting that 2,3- butanediol is oxidized to acetyl-coA via acetoin.
Executive summary:

Montgomery et al. 1993 investigated the metabolism of the individual isomers of 2,3 -butanediol (levo (2R,3R), dextro (2S,3S), meso 2,3 -butanediol and racemic 2,3 -butanediol) in perfused livers from fed rats. Differences were observed in the metabolism of individual 2,3-butanediol isomers in perfused rat liver. Interconversion of isomers and oxidation to acetoin was observed with the levo and meso forms, but not with dextro 2,3-butanediol. In liver perfusions with either levo or meso (radio-labelled) 2,3-butanediol, the substrates were converted to labelled acetate, R-3-hydroxybutyrate and CO2, suggesting that 2,3-butanediol was oxidized to acetyl-CoA via acetoin.