2-methylbutan-1-ol

Specific investigations: other studies

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

Reference

Reference 1

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 2

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

Test material information

Constituent 1

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