2-ethylhexanoic acid, monoester with propane-1,2-diol

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

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxypropyl 2-ethylhexanoate

EC Number:

261-499-0

EC Name:

2-hydroxypropyl 2-ethylhexanoate

Cas Number:

58921-10-1

Molecular formula:

C11H22O3

IUPAC Name:

2-hydroxypropyl 2-ethylhexanoate

Constituent 2

Reference substance name:

1-hydroxypropan-2-yl 2-ethylhexanoate

Molecular formula:

C11H22O3

IUPAC Name:

1-hydroxypropan-2-yl 2-ethylhexanoate

impurity 1

Reference substance name:

Monoesters of 2-ethylhexanoic acid and dipropyleneglycol

IUPAC Name:

Monoesters of 2-ethylhexanoic acid and dipropyleneglycol

impurity 2

Reference substance name:

1-methylethylene 2-ethylhexanoate

EC Number:

301-185-3

EC Name:

1-methylethylene 2-ethylhexanoate

Cas Number:

93981-97-6

Molecular formula:

C19H36O4

IUPAC Name:

propane-1,2-diyl bis(2-ethylhexanoate)

impurity 3

Reference substance name:

2-ethylhexanoic acid

EC Number:

205-743-6

EC Name:

2-ethylhexanoic acid

Cas Number:

149-57-5

Molecular formula:

C8H16O2

IUPAC Name:

2-ethylhexanoic acid

impurity 4

Reference substance name:

Propane-1,2-diol, propoxylated

EC Number:

500-039-8

EC Name:

Propane-1,2-diol, propoxylated

Cas Number:

25322-69-4

IUPAC Name:

Propane-1,2-diol, propoxylated

impurity 5

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Water

Test material form:

liquid: viscous

Method

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

S9 microsomal fraction from male rats which has been induced with phenobarbital/beta-naphthoflavone.

Test concentrations with justification for top dose:

0, 25, 50, 100, 200, 300, 400, 450, 500 - Expt 1 (-S9)
0, 50, 100, 200, 300, 400, 450, 500, 550 - Expt 1 (+S9)
0, 6.25, 12.5, 25, 50, 100, 150, 200, 250 - Expt 2 (-S9)
0, 50, 100, 200, 300, 350, 400, 450, 500 - Expt 2 (+S9)
The purity of the test item was 94.8% and was therefore accounted for when formulating the dosing solutions in the preliminary toxicity and mutagenicity tests.

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

ethylmethanesulphonate

Evaluation criteria:

For a test item 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. Following discussions at an International Workshop on Genotoxicity Test Procedures in Plymouth, UK, 2002 (Moore et al 2003) it was felt that the IMF must exceed some value based on the global background MF for each method (agar or microwell). This Global Evaluation Factor (GEF) value was set following a further meeting of the International Workshop in Aberdeen, Scotland, 2003 (Moore et al 2006) at 126 x 10-6 for the microwell method. Therefore, any test item dose level that has a mutation frequency value that is greater than the corresponding vehicle control by the GEF of 126 x 10-6 and demonstrates a positive linear trend will be considered positive. However, if a test item produces a modest increase in mutant frequency, which
only marginally exceeds the GEF value and is not reproducible or part of a dose-related response, then it may be considered to have no toxicological significance. Conversely, when a test item induces modest reproducible increases in the mutation frequencies that do not exceed the GEF value then scientific judgement will be applied. If the reproducible responses are significantly dose-related and include increases in the absolute numbers of mutant colonies then they may be considered to be toxicologically significant.

Statistics:

The experimental data was analysed using a dedicated computer program, Mutant 240C by York Electronic Research, which follows the statistical guidelines recommended by the UKEMS (Robinson W D et al, 1989).

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

The substance was considered to be non-mutagenic to mouse lymphoma cells in vitro.