Octadecanedioic acid, 1,18-dimethyl ester

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 December 2011 to 24 January 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection 2011-07-19 to 2011-07-21; Date of signature 2011-08-31

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

methyl 9-decenoate

EC Number:

662-772-0

Cas Number:

25601-41-6

Molecular formula:

C11H20O2

IUPAC Name:

methyl 9-decenoate

Details on test material:

- Name of test material (as cited in study report): 9-decenoic acid, methyl ester (9DAME)
- Physical state: clear colourless liquid
- Analytical purity: > 99 %
- Lot/batch No.: 184-109
- Date received: 2011-04-01
- Storage condition of test material: room temperature, under nitrogen, in the dark

Method

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

S9 microsomal enzyme fraction

Test concentrations with justification for top dose:

Preliminary toxicity test: 0, 7.19, 14.38, 28.75, 57.5, 115, 230, 460, 920 and 1840 µg/mL

Experiment 1 (without S-9 mix): 0, 1.25, 2.5, 5, 10, 20, 40, 50 and 60 µg/mL
Experiment 1 (with S-9 mix): 0, 5, 10, 20, 40, 60, 80, 100 and 120 µg/mL

Experiment 2 (without S-9 mix): 0, 2.5, 5, 10, 20, 40, 50, 60 and 80 µg/mL
Experiment 2 (with S-9 mix): 0, 10, 20, 40, 60, 80, 100, 120 and 140 µg/mL

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl sulphoxide

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Remarks:

Experiment 1: 400 µg/mL; Experiment 2: 150 µg/mL; without metabolic activation

Controls 2

Positive control substance:

cyclophosphamide

Remarks:

2 µg/mL; with metabolic activation

Evaluation criteria:

The normal range for mutant frequency per survivor is 50-200 x 10E-06 for the TK+/- locus in L5178Y cells. Vehicle control results should ideally be within this range.
Positive control chemicals should induce at least 3 to 5 fold increases in mutant frequency greater than the corresponding vehicle control.
For a test material to demonstrate a mutagenic response it must produce a statistically significant increase in the induced mutant frequency (IMF) over the concurrent vehicle mutant frequency value.

Results and discussion

Test results

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

The test item, 9-decenoic acid, methyl ester (9DAME) did not induce any toxicologically significant increases in the mutant frequency at the TK +/- locus in L5178Y cells and is therefore considered to be non-mutagenic under the conditions of the test.

Executive summary:

An in vitro study was conducted to investigate the potential of test item to induce gene mutations at the HPRT locus in mouse lymphoma L5178Y cells, according to OECD Guideline 476, in compliance with GLP. The assay was performed in the presence and absence of metabolic activation (S9). The test item did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in either the first or second experiment. 9-decenoic acid, methyl ester (9-DAME) was therefore considered to be non mutagenic to L5178Y cells under the conditions of the test (Harlan Laboratories Ltd, 2012).