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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
Scientific Opinion on Safety and efficacy of saturated and unsaturated aliphatic secondary alcohols, ketones and esters with esters containing secondary alcohols belonging to chemical group 5 when used as flavourings for all animal species
Author:
European Food Safety Authority
Year:
2015
Bibliographic source:
European Food Safety Authority EFSA Journal, 10 November 2015

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
according to guideline
Guideline:
other: No data
Principles of method if other than guideline:
Absorption, distribution, metabolism and excretion (ADME) of octan-2-one
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Octan-2-one
EC Number:
203-837-1
EC Name:
Octan-2-one
Cas Number:
111-13-7
Molecular formula:
C8H16O
IUPAC Name:
octan-2-one
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
CAS No: 111-13-7
Chemical Name: Octan-2-one
Nature of chemical: Organic
Specific details on test material used for the study:
- Name of test material: 2-octanone
- IUPAC name: octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.2134 g/mole
- Substance type: Organic
- Physical state: Liquid
Radiolabelling:
not specified

Test animals

Species:
other: Mammals (not specified)
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
other: No data
Vehicle:
not specified
Duration and frequency of treatment / exposure:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
No data
No. of animals per sex per dose / concentration:
No data
Control animals:
not specified

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
The chemical is rapidly absorbed in the gastrointestinal tract since the chemical is a flavoring substance.
Type:
distribution
Results:
No specific data, but since the chemical is extensively metabolized distribution in the liver is expected.
Type:
metabolism
Results:
The chemical is reported to be extensively metabolized in mammals.
Type:
excretion
Results:
Excretion occurs in the urine or bile.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The potential metabolic reactions involved in the biotransformation are (i) conjugation of secondary alcohols with glucuronic acid followed by excretion in the urine or bile; (ii) oxidation of secondary alcohols to the corresponding ketone (iii) reduction of ketones to the corresponding secondary alcohol with subsequent excretion as conjugate of glucuronic acid; (iv) omega oxidation of short-chain ketones (carbon atoms < 5) or oxidation of the terminal methyl group and subsequent oxidation to yield an alpha-ketocarboxylic acid; (v) oxidation of double bonds; (vi) hydrolysis of esters via carboxylesterases followed by excretion of the secondary alcohol as glucuronide-conjugate and metabolism of the linear carboxylic acid by beta-oxidation in the fatty acid pathway and citric acid cycle.

Applicant's summary and conclusion

Conclusions:
The in-vivo absorption and metabolism of the chemical Octan-2-one suggests rapid absorption of the chemical in the gastrointestinal tract, followed by extensive metabolism involving reduction of ketones to the corresponding secondary alcohol with subsequent excretion as conjugate of glucuronic acid or oxidation of the terminal methyl group and subsequent oxidation to yield an alpha-ketocarboxylic acid; and metabolism of the linear carboxylic acid by beta-oxidation in the fatty acid pathway and citric acid cycle. Excretion is reported to occur in the urine or bile. Thus, the chemical is expected to have low bio-accumulaton potential based on the study results.
Executive summary:

Available data pertaining to the in-vivo absorption and metabolism of the chemical Octan-2-one suggests rapid absorption of the chemical in the gastrointestinal tract, followed by extensive metabolism involving reduction of ketones to the corresponding secondary alcohol with subsequent excretion as conjugate of glucuronic acid or oxidation of the terminal methyl group and subsequent oxidation to yield an alpha-ketocarboxylic acid; and metabolism of the linear carboxylic acid by beta-oxidation in the fatty acid pathway and citric acid cycle. Excretion is reported to occur in the urine or bile.

Thus, there is no evidence that they or their metabolites would accumulate in tissues and cause a concern for consumer safety. Hence it is concluded that Octan-2-one is likely to exhibit low bio-accumulation potential based on study results.