Ethyl acetate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

This study is well reported. The lack of replicates is compensated for by the fact that this is s screening test of 46 chemicals, all with individual controls and all reported in detail. Only significant shortcoming is that it is not to GLP and deviates from the OECD 473 protocol.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

yes

Remarks:

single doses used and not all doses in duplicate

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

- Supplier: Litton Bionetics, Kentucky, MD. Used at 5th pasage level after cloning
- Periodically checked for karyotype stability: yes, by not using after 15th passage.
- Periodically checked for Mycoplasma contamination: yes

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 from SD rats treated with Aroclor 1254.

Test concentrations with justification for top dose:

500, 1510, 5000ug/ml without activation. 500, 1510, 5010ug/ml and 3010, 4020, 5020ug/ml with activation.

Vehicle / solvent:

DMSO

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2115 (without metabolic activation)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1831 (with metabolic activation)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: Cultures initiated for 24hrs prior to substance addition. With metabolic activation, substance pretreated for 2hrs with S9 before exposure with cells.
- Exposure duration: 8hrs.
- Expression time (cells in growth medium):
- Selection time (if incubation with a selection agent):
- Fixation time with spindle inhibitor up to harvest of cells: 2hrs

SPINDLE INHIBITOR (cytogenetic assays): colecemid
STAIN (for cytogenetic assays): Slides were stained with 5% Giesma for 5 minutes.

NUMBER OF REPLICATIONS: no data

NUMBER OF CELLS EVALUATED: Selection of cells for scoring was based on well spread chromosomes with good morphology and a chromosome number of 21±2. All cells except the positive control were scored by a single technician. 200 metaphase cells per dose were scored.

DETERMINATION OF CYTOTOXICITY
- Cytotoxicity not observed.

Evaluation criteria:

Abberations scored included chromatid gap, break, fragment, deletions, double minutes, all defined as 'simple', and interstitial deletions

Statistics:

All categories of aberrations combined for statistical analysis. The percent of cells with aberrations was used for analysis rather than the

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

Ethyl acetate was not toxic at the highest dose tested

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

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

Ethyl acetate was not toxic at the highest dose tested, with and without activation. Test with activation was negative even at delayed harvest time (> 14 h); S9 from Aroclor -1254 induced rats.

Executive summary:

The frequency of chromosome aberrations was evaluated in Chinese Hamster Ovary cells exposed to ethyl acetate concentrations up to 1500 ug/ml in a well reported study that was similar to guideline. Results were negative with and without metabolic activation up to the highest dose tested of 15mg/ml.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint
best available data