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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information

Basic toxicokinetics

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Administrative data

basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Meets generally accepted scientific standards and is described in sufficient detail. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

Data source

Reference Type:
Report date:

Materials and methods

Objective of study:
Test guideline
no guideline available
Principles of method if other than guideline:
Examination of the mitochondrial and peroxisomal fatty acid metabolism in the isolated perfused rat liver and in-vivo
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
-Source: Sigma Chemical Co., St. Louis, MO

Test animals


Administration / exposure

Route of administration:
other: in-vitro: isolated perfused rat liver; in-vivo: i.p. injection

Results and discussion

Any other information on results incl. tables

(1) From experiments with perfused livers from starved rats it is concluded 
(a) 2-ethylhexanol is oxidized via two independent pathways:
(i) in the peroxisomes by phenobarbital-inducible pathways via omega and 
omega-1 oxidation to metabolites which do not inhibit ketogenesis; 
(ii) in mitochondria via beta-oxidation
(b) that ethylhexanol inhibits beta-oxidation of fatty acids in mitochondria 
but not in peroxisomes. 

(2) Treatment of rats with ethylhexanol (0.32 g/kg i.p.) decreased plasma 
ketone bodies from 1.6 to 0.8 mM, increased hepatic triglycerides and increased 
lipid predominantly in periportal regions of the liver lobule.

As to the mechanism of the inhibition of ß-oxidation, the authors discussed:

(1) inhibition of acyl-Coenzyme A formation was regarded to be unlikely; reasons remain unclear

(2) inhibition of mitochondrial ß-oxidation system was regarded to be unlikely; reason: hexanoate metabolism was not affected by 2 -EH

(3) inhibition of long chain fatty acid transport into mitochondria was regarded to be likely; supporting observations include:

- valproic acid forms conjugates with carnitine; carnitine is, however, needed for the mitochondrial transporter

- accumulation of total lipids and triglycerides in-vivo after treatment with 2-EH

Applicant's summary and conclusion

2-EH inhibits the fatty acid ß-oxidation in rat liver mitochondria, but not in peroxisomes.