Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. residues

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is from literature, no information about GLP and not enough information to assess the study following an official and validated method, but the study is well conducted and scientifically valid

Data source

Reference

Reference Type:

publication

Title:

The anticlastogenic potential of fatty acid methyl esters

Author:

Renner H.W.

Year:

1986

Bibliographic source:

Mutation Research/Genetic Toxicology Volume 172, Issue 3, December 1986, Pages 265-269

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

not specified

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Methyl oleate

EC Number:

203-992-5

EC Name:

Methyl oleate

Cas Number:

112-62-9

Molecular formula:

C19H36O2

IUPAC Name:

Methyl (Z)-octadec-9-enoate

Constituent 2

Reference substance name:

Methyl stearate

EC Number:

203-990-4

EC Name:

Methyl stearate

Cas Number:

112-61-8

Molecular formula:

C19H38O2

IUPAC Name:

Methyl Octadecanoate

Constituent 3

Reference substance name:

Methyl palmitate

EC Number:

203-966-3

EC Name:

Methyl palmitate

Cas Number:

112-39-0

Molecular formula:

C17H34O2

IUPAC Name:

Mehtyl Hexadecanoate

Constituent 4

Reference substance name:

Methyl linoleate

EC Number:

203-993-0

EC Name:

Methyl linoleate

Cas Number:

112-63-0

Molecular formula:

C19H34O2

IUPAC Name:

methyl (9Z,12Z)-octadeca-9,12-dienoate

Constituent 5

Reference substance name:

Methyl (9Z,12Z,15Z)-9,12,15-octadecatrienoate

EC Number:

206-102-3

EC Name:

Methyl (9Z,12Z,15Z)-9,12,15-octadecatrienoate

Cas Number:

301-00-8

Molecular formula:

C19H32O2

IUPAC Name:

methyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate

Constituent 6

Reference substance name:

Methyl laurate

EC Number:

203-911-3

EC Name:

Methyl laurate

Cas Number:

111-82-0

Molecular formula:

C13H26O2

IUPAC Name:

Methyl dodecanoate

Test material form:

liquid

Details on test material:

NO DATA AVAILABLE IN THE PUBLISHED LITERATURE

Specific details on test material used for the study:

Analytical grade, obtained from Serva (heidelberg)

Test animals

Species:

hamster, Chinese

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

6 male + 6 female
12 -18 weeks old
weighing 30-40 g
Animal were in-house bred and had free access to laboratory chow and tap water
Animals were kept in temperature controlled rooms (21+/- 1°C) on a 12h light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Liquid paraffin

Frequency of treatment:

Singel treatment

Post exposure period:

24 h
30 h
48 h

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1 mg/Kg
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
10 mg/Kg
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
100 mg/Kg
Basis:
nominal conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
500 mg/Kg
Basis:
nominal conc.

Doses / concentrations 5

Remarks:

Doses / Concentrations:
5000 mg/Kg
Basis:
nominal conc.

No. of animals per sex per dose:

6 animals per sex per dose

Control animals:

yes

Positive control(s):

Yes, with busulfan

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Methyl ester of fatty acids in chain lenght from C6 to C20 doesn't show chromosomal aberration on Chinese Hamster bone-marrow cells until a concentration of 5000 mg/Kg

Executive summary:

To test for possible anticlastogenic effects of fatty acids, the methyl esters of fatty acids — short-chain to long-chain — were examined on busulfan in Chinese hamster bone-marrow cells using the chromosome aberration test. When the experimental animals were treated with fatty acid esters and the mutagen, the chromosome-breaking actions of busulfan were not modulated by the short-chain fatty acids, but the fatty acids from lauric acid (C₁₂) up to nonadecanoic acid (C₁₉) reduced the rate of aberrant metaphases from 9.4 to about 3% at doses of 100 mg/kg and less. Other chemical properties of the fatty acids (saturated or not, number of double bonds, even- or odd-numbered) had no influence on the anticlastogenic effects. The only exceptions to this rule were arachidonic acid, which had no effect, and γ-linolenic acid, which had no consistent effect on the action of busulfan