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Toxicological information

Genetic toxicity: in vivo

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg bw fatty acid methyl esters
Basis:
actual ingested
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.