4-hydroxy-2,5-dimethylfuran-2(3H)-one

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 June to 3 July 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study, evaluation criteria, historical control data not reported

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

evaluation criteria, historical control data not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Remarks:

pre-GLP but considered to be equivalent to GLP standard

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxy-2,5-dimethylfuran-2(3H)-one

EC Number:

222-908-8

EC Name:

4-hydroxy-2,5-dimethylfuran-2(3H)-one

Cas Number:

3658-77-3

Molecular formula:

C6H8O3

IUPAC Name:

4-hydroxy-2,5-dimethylfuran-3(2H)-one

Test material form:

solid

Remarks:

Powder

Details on test material:

- Description: Beige coloured powder
- Storage condition of test material: Stored in the drak, under nitrogen and in a dessicator at ambient room temperature (ca 18°C)..

Method

Target gene:

Histidine and tryptophan gene for Salmonella typhimurium and Escherichia coli, respectively.

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

10 % S9 mix; S9 from liver of SD rats induced with Aroclor 1254

Test concentrations with justification for top dose:

- Test: 10, 33.3, 100.0, 333.3, 1000 and 3300 µg/plate in S. typhimurium strains TA 1535, TA 1537, TA 1538, TA 98, TA 100 and in E.coli WP2 uvrA-, with and without S9-mix
- Retest (at higher dose levels): 1000, 2000, 4000, 6000 and 8000 µg/plate in S. typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100, with and without S9-mix
- Test to deduce if exposure to air, light and humidity affect the mutagenic activity of test item: 100, 500, 1000, 2000, 4000 and 6000 µg/plate in S. typhimurium strain TA 100, with and without S9-mix

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: The test compound was dissolved and diluted in Dimethylsulphoxide (DMSO)

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

with and without S9-mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: Two days at 37 °C

NUMBER OF REPLICATIONS: 3 plates/dose

DETERMINATION OF CYTOTOXICITY
- Method: Evaluation of the toxicity was performed on the basis of microcolony growth.

OTHERS:
- After two days incubation at 37 °C the colonies counted using a New Brunswick Inc. (New Brunswick, N.J.) Biotran II automated counter set for maximum sensitivity (colonies of 0.1 mm or more in diameter counted). The plates were also examined for precipitates and, microscopically, for microcolony growth.

Evaluation criteria:

No data

Statistics:

No data

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 1538, TA 98 and TA 100

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

Test results 2

Key result

Species / strain:

E. coli WP2 uvr A

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

Additional information on results:

Cytotoxicity: no cytotoxicity.

Results of mutagenicity:
The substance was mutagenic in strain TA 100 both with activation at a lowest effective dose of 3300 µg/plate and without activation at a lowest effective dose of 1000 µg/plate. The compound was not mutagenic in E. coli WP2 uvrA. Exposure to air, light and humidity did not affect its mutagenic activity in strain TA 100

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the test condition, the test item is mutagenic in S. typhimurium TA 100 with and without metabolic activation.

Executive summary:

In a reverse gene mutation assay, strains of Salmonella typhimurium (TA 1535, TA 1537, TA 1538, TA 98 and TA 100) and Escherichia coliWP2 uvrA- were exposed to the test item at 10, 33.3, 100.0, 333.3, 1000 and 3300 µg/plate. The compound was also tested at 1000, 2000, 4000, 6000 and 8000 µg/plate to obtain a mutagenic dose response and at 100, 500, 1000, 2000, 4000 and 6000 µg/plate to assess the effect of air, light and humidity.

 

The substance was mutagenic in S. typhimurium TA 100 at a lowest effective dose of 1000 µg/plate in the absence of the activation system and 3300 µg/plate in the presence of the activation system. Even though the compound was known to decompose in the presence of air and humidity, exposure of the compound to these effects did not alter its mutagenic activity. The compound was not mutagenic in E. coli WP2 uVrA-.

 

The vehicle control plates gave counts of revertant colonies within the normal range. Positive control induced marked increases in the frequency of revertant colonies indicating the validity of the study. 

 

Under the test condition, the test item is mutagenic in S. typhimurium TA 100 with and without metabolic activation.