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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication which meets basic scientific principles

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The toxic and metabolic effects of 23 aliphatic alcohols in the isolated perfused rat liver
Author:
Strubelt O, Deters M, Pentz R, Siegers C-P and Younes M
Year:
1999
Bibliographic source:
Toxicological Sciences, 49(1), 133-142
Reference Type:
secondary source
Title:
No information
Author:
RIFM
Year:
2009
Bibliographic source:
RIFM database

Materials and methods

Principles of method if other than guideline:
Testing of acute toxic and metabolic effects in the isolated perfused rat liver
GLP compliance:
no
Type of method:
in vitro
Endpoint addressed:
not applicable

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methylbutan-1-ol
EC Number:
205-289-9
EC Name:
2-methylbutan-1-ol
Cas Number:
137-32-6
Molecular formula:
C5H12O
IUPAC Name:
2-methylbutan-1-ol
Details on test material:
- Name of test material (as cited in study report): 2-Methanol-1-pentanol
- Source: Merck-Schuchardt

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 320 - 380 g
- Diet (e.g. ad libitum): Altromin pellets
- Water (e.g. ad libitum): tap water

Administration / exposure

Route of administration:
other: ot applicable
Analytical verification of doses or concentrations:
not specified
Doses / concentrations
Remarks:
Doses / Concentrations:
65.1 mmol/l
Basis:
nominal conc.
No. of animals per sex per dose:
no data

Results and discussion

Details on results:
Together with 22 aliphatic alcohols 2-methyl-1-butanol was tested for acute toxic and metabolic effects in the isolated perfused rat liver at a concentration of 65.1 mmol/l (about 5742 mg 2-methyl-1-butanol/l). All alcohols under investigation (with the exception of methanol) increased the lactate/pyruvate ratio within the perfusates (increase in the lactate and a simultaneous decrease in the pyruvate concentrations). In comparison to the control (0.9% saline) 2-methyl-1-butanol led to a statistical significant increase in GPT, LDH and GLDH as well as to a statistical significant decrease in O2 consumption and bile and perfusion flow. Moreover a statistical significant decrease in the ATP concentration and a statistical significant increase in the GSSG concentration was observed. GSH and MDA concentrations were not significantly influenced.
The increase of LDH, GPT and GLDH indicates damage to the cell membranes, and in the case of GLDH of mitochondrial membrane damage. Decreases in oxygen consumption, bile secretion and perfusion flow are consistent with the hypothesis that the alcohols produce their hepatotoxic effects primarily by entering and disordering biological membranes. A decreased energy supply from mitochondrial respiration is obviously the cause for the decline in hepatic ATP concentrations. In conclusion, alcohol inuced hepatotoxicity is primarily due to membrane damage induced by the direct solvent properties of the alcohols
 

Any other information on results incl. tables

Results:

2-Methyl-1-pentanol (3 experiments) Control (9 experiments) Potency value compared to control
GPT (U/I) 1385 ± 142* 93.6 ± 27.8 14.8
LDH (U/I) 20521 ± 1087* 1109 ± 1.97 18.5
GLDH (U/I) 266.0 ± 52.8* 11.9 ± 1.97 22.4
O2consumption (µmol/g x min) 0.3 ± 0.03* 1.54 ± 0.07 0.19
Bile flow (µg/ g x min) 10.4 ± 7.3* 219.0 ± 95.8 0.05
Perfusion flow (µg/g x min) 20.0 ± 2.0* 55.0 ± 1.4 0.36
ATP (µmol/g) 0.1 ± 0.01* 1.25 ± 0.20
GSH (µmol/g) 1.33 ± 0.29 2.52 ± 0.29
GSSG (µmol/g) 0.24 ± 0.07* 0.06 ± 0.01
MDA (µmol/g) 14.4 ± 5.7 17.1 ± 1.4
Lactate (mmol/l) 3.21 ± 0.25* 1.16 ± 0.14
Pyruvate (µmol/l) 56.1 ± 8.8* 190.0 ± 15.2
Lactate/Pyruvate 60.0 ± 9.53* 6.01 ± 0.52

* p<0.05

GPT: glutamate-pyruvatetransaminase

LDH: lactate dehydrogenase

GLDH: glutamate dehydrogenase

GSH: reduced glutathione

GSSG: oxidized gluthatione

MDA: malondialdehyde

Applicant's summary and conclusion