Fatty acids, C12-16 (even numbered) and C18 unsatd., Me esters

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 based on grouping of substances (category approach)

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Relevant methodological deficiencies (purity of test substance is not specified; test substance was only tested in combination with the mutagen busulfan, test dose was only 100 mg/kg bw).

Data source

Reference

Reference Type:

publication

Title:

The anticlastogenic potential of fatty acid methyl esters.

Author:

Renner, H.W.

Year:

1986

Bibliographic source:

Mutat Res 172: 265-269, 1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

: purity of test substance is not specified; test substance was only tested in combination with the mutagen busulfan, test dose was only 100 mg/kg bw

Principles of method if other than guideline:

The anticlastogenic effects of different methyl esters of fatty acids (C6 - C20) were examined on busulfan in Chinese hamster bone-marrow cells using the chromosome aberration test. Only one dose of 100 mg/kg bw of the test substance and only in combination with the mutagen busulfan was tested.

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

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 laurate

Details on test material:

- Name of test material (as cited in study report): methyl ester of lauric acid
- Analytical purity: no data

Test animals

Species:

hamster, Chinese

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: inhouse-bred
- Age at study initiation: 12 - 18 weeks
- Weight at study initiation: 30 - 40 g
- Diet: laboratory chow (Herilan MRH, Eggersmann, Rinteln), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: liquid paraffin
- Justification for choice of solvent/vehicle: the solvent used had to be the same for the fatty acid esters as for the mutagen, to avoid differences in resorption and biological availability
- Amount of vehicle (if gavage or dermal): 0.15 mL/animal (corresponding to 5 mL/kg)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: the busulfan solution was prepared in an ultrasonic bath

Duration of treatment / exposure:

two consecutive treatments (test substance, immediately followed by busulfan)

Frequency of treatment:

single treatment

Post exposure period:

30 hours after treatment

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg bw fatty acid methyl esters
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
50 mg/kg bw busulfan
Basis:
actual ingested

No. of animals per sex per dose:

3

Control animals:

other: yes, concurrent no treatment and concurrent vehicle

Examinations

Tissues and cell types examined:

Tissue: bone marrow
Cell type: bone marrow cells

Details of tissue and slide preparation:

OTHER:
- Colchicine was used at 1 mg/kg and injected subcutaneously 2 h before femora cells were flashed out
- 100 metaphases/animal were evaluated

Statistics:

t-test was used for comparison of fatty acid methyl ester effects on busulfan induced aberrant metaphases

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

other: the test substnace did act anticlastinogenically

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Table1: Examination of the anticlastogenic activity of Fatty Acid Methyl Esters (100 mg/kg p.o.) on Busulfan (50 mg/kg p.o.) induced aberrations

Number of C-atoms in the acid	Methyl ester of the fatty acid + busulfan	Aberrant metaphases (excluding gaps)% ± SD
C12	caprylic acid	3.2 ± 0.8*
untreated control	without ester an busulfan	0.4
positive control	only busulfan	9.4 ± 1.0
control	with solvent (paraffin)	0.2

* p<0.001 (t-test) in comparison to the positive control

Applicant's summary and conclusion

Conclusions:

The test substance did show anticlastogenic potential to busulfan induced aberrations.