Butanoic acid, 3-oxo-, 1,1'-[2-[(1,3-dioxobutoxy)methyl]-2-ethyl-1,3-propanediyl] ester

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

422-630-9

EC Name:

-

Cas Number:

22208-25-9

Molecular formula:

C18H26O9

IUPAC Name:

2,2-bis({[(3-oxobutanoyl)oxy]methyl})butyl 3-oxobutanoate

Test material form:

liquid

Method

Species / strain

Species / strain / cell type:

lymphocytes: Human

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-1254 induced rat liver S9-mix

Test concentrations with justification for top dose:

Concentration range in the first main test (with metabolic activation): 1000 - 5000 µg/ml
Concentration range in the second main test (with metabolic activation): 333 - 3330 µg/ml
Concentration range in the first main test (without metabolic activation): 1000 - 2400 µg/ml
Concentration range in the second main test (without metabolic activation): 100 - 1800 µg/ml
Concentration range in the second main test (without metabolic activation): 100 - 560 µg/ml

Vehicle / solvent:

Dimethylsulfoxide

Details on test system and experimental conditions:

Exposure period (with metabolic activation): 3 hours
Exposure period (without metabolic activation): 3 hours
Fixation time:
First test with metabolic activation: 24 h fixation time.
Second test with metabolic activation: 48 h fixation time.
First test without metabolic activation: 24 h fixation time.
Second test without metabolic activation: 24 h fixation up to 560 ug/ml and 48 h fixation up to 1800 ug/ml.

Results and discussion

Test results

Key result

Species / strain:

lymphocytes: Human

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

cytotoxicity 1st experiment (3h exposure, 24h fixation): with and without S9 mix: 1000 µg/mL 2nd experiment (3h exposure, 48h fixation): with S9 mix: 1000 µg/mL; without S9 mix: 333 µg/mL 2nd experiment (3h exposure, 24h fixation): without S9 mix: 1000 µg

Additional information on results:

The test substance did not induce a statistically or biologically significant increase in the number of cells with chromosome aberrations in the absence and in the presence of S9-mix, in two independently repeated experiments.
In the absence and presence of S9-mix the 48h fixation time in the second experiment an increase in the number of polypoploid cells was observed.
It is concluded that the test substance is not clastogenic in human lymphocytes under the experimental conditions.

Applicant's summary and conclusion

Conclusions:

The substance was determined to be negative with and without metabolic activation system.

Executive summary:

A chromosome aberration test was conducted according to B.10 (GLP study).  The human lymphocytes cell line were treated with and without metabolic activation. The substance was solubilized in Dimethylsulphoxide and evaluated at a concentration ranging from 100 to 5000 µg/mL according to the test conditions. The substance was determined to be negative with and without metabolic activation.