3-hydroxy-2-methyl-4-pyrone

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Validity of study confirmed by EFSA (FGE.213), Only tested strains TA98 and TA100, Quercetin and sterigmatocystin were used as positive controls. Max dose tested 2 mg/plate.

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of 1,2-dicarbonyl compounds: Maltol, Kojic Acid, Diacetyl and related substances

Author:

Bjeldanes L.F. and Chew H.

Year:

1979

Bibliographic source:

Mutation Research, 67 (1979) 367-371

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Ames, B.N., J. McCann and E. Yamasaki, Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test, Mutation Res., 31 (1975) 347-364.

Deviations:

yes

Remarks:

Only tested strains TA98 and TA100, Quercetin and sterigmatocystin were used as positive controls. Max dose tested 3 mg/plate.

GLP compliance:

no

Remarks:

pre-GLP

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-hydroxy-2-methyl-4-pyrone

EC Number:

204-271-8

EC Name:

3-hydroxy-2-methyl-4-pyrone

Cas Number:

118-71-8

Molecular formula:

C6H6O3

IUPAC Name:

3-hydroxy-2-methyl-4H-pyran-4-one

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: Chemical Division, Pfizer, New York, NY

Method

Target gene:

hisG46/hisD3052

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 98

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: Provided by B.N. Ames
- Suitability of cells: commonly used strain to detect frameshift reverse mutation

Additional strain / cell type characteristics:

other: R factor plasmid, pKM101, deep rough coat mutation and uvrB deletion

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

CELLS USED
- Source of cells: Provided by B.N. Ames
- Suitability of cells: commonly used strain to detect base-pair substitution reverse mutation

Additional strain / cell type characteristics:

other: R factor plasmid, pKM101, deep rough coat mutation and uvrB deletion

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital -induced rat liver S9

Test concentrations with justification for top dose:

Initial study: 10 µg, 100 µg, 1 mg, 10 mg/plate
Main study: 0.5, 1, 1.5, 2 and 3 mg/plate

Vehicle / solvent:

Filter sterilised water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

other: Quercetin, Sterigmatocystin

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation)

DURATION
- Exposure duration: 48h

DETERMINATION OF CYTOTOXICITY
- Method: not specified

NUMBER OF REPLICATIONS:
- Number of cultures per concentration (single, duplicate, triplicate): 3

Rationale for test conditions:

As described by Ames et al. (1975)

Evaluation criteria:

Not specified

Statistics:

The mean number of revertant colonies is calculated from triplicate runs, and the number of spontaneous revertants is subtracted from each value.
Further statistics were not specified.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

max dose tested 3 mg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

max dose tested 3 mg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: the publication did not mention precipitation, also not at the highest dose tested 3 mg/plate

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Cytotoxicity was not observed for maltol up to the highest concentration tested (3 mg/plate).

Applicant's summary and conclusion

Conclusions:

Under the conditions of this test, a dose related mutagenic effect was observed for Maltol against tester strain TA100 but not in strain TA98. Based on this result, the test substance is considered mutagenic.

Executive summary:

In a reverse gene mutation assay in bacteria (Bjeldanes and Chew, 1979), strains of S. typhimurium TA 98 and TA 100 were exposed to Maltol at concentrations of 0.5, 1, 1.5, 2 and 3 mg/plate (plate incorporation) in the presence and absence of mammalian metabolic activation (Phenobarbital-induced rat liver S9). Quercetin, sterigmatocystin and benzo[a]pyrene were used as positive controls. The study was judged to be valid by the EFSA (FGE.213) and rated Klimisch 2.

The substance induced a dose-related increase in the number of revertant colonies in S. typhimurium TA100, both in the absence and presence of S9 metabolic activation. No mutagenicity was observed in strain TA98. Under the conditions of this study, the test substance is considered mutagenic.

EFSA Journal 2015;13(9):4244