Pentane-2,4-dione

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-04-03 to 1985-12-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conduction and documentation of study very acceptable. Study report available.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

Test performed according to standard protocols by inclusion of a metabolic activation system (S9-Mix from livers of Sprague-Dawley rats pretreated with Aroclor 1254).

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pentane-2,4-dione

EC Number:

204-634-0

EC Name:

Pentane-2,4-dione

Cas Number:

123-54-6

Molecular formula:

C5H8O2

IUPAC Name:

pentane-2,4-dione

Details on test material:

- Name of test material (as cited in study report): 2,4-Pentanedione
- Physical state: liquid
- Expiration date of the lot/batch: not reported
- Stability under test conditions: stable

Method

Target gene:

not applicable

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with

Metabolic activation system:

S9-Mix

Test concentrations with justification for top dose:

0.3 - 30mg/plate

Vehicle / solvent:

water

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4 -nitro-o-phenylenediamine

Remarks:

TA98 and TA1538 without S9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA100 without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA1537 without S9

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

all strains with S9

Details on test system and experimental conditions:

METHOD OF APPLICATION:in agar (plate incorporation)


DURATION
- Exposure duration: 24 and 48 h



NUMBER OF REPLICATIONS:3



DETERMINATION OF CYTOTOXICITY
- Method: growth inhibition

Evaluation criteria:

Test chemicals which produce at least a 2-fold and dose-related increase in mutant colonies over the concurrent solvent control value are considered to be bacterial mutagens and suspect mammalian mutagens.

Statistics:

not reported

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

97.8 mg/plate produced significant cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: none reported
- Effects of osmolality: none reported
- Evaporation from medium: none reported
- Water solubility: soluble
- Precipitation: none reported
- Other confounding effects: none reported


RANGE-FINDING/SCREENING STUDIES: yes, outside GLP


COMPARISON WITH HISTORICAL CONTROL DATA: yes, compliant

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: S. typhimurium, TA 98, 100, 1535, 1537, 1538

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

From the results it is concluded that 2,4-pentanedione is not mutagenic under the conditions of the assay.

Executive summary:

2,4-pentanedione (99.2% pure) was tested for potential mutagenic activity using the Salmonella/microsome bacterial mutagenicity assay (Ames test).

The test was performed according to standard protocols by inclusion of a metabolic activation system (S9-Mix from livers of Sprague-Dawley rats pretreated with Aroclor 1254). In preliminary trials with strain TA 100 only, a concentration of 97.4 mg/plate proved to completely inhibit bacterial growth. The next lower concentration of 30 mg/plate showed some toxic effects. Accordingly, doses selected on the basis of these trials were 0.3, 1.0, 3.0, 10.0 and 30.0 mg/plate. Incubations were run in triplicate at 37°C for 24 to 48 hours. Plates were examined for the condition of their background lawns and growth was recorded as either confluent (non-toxic), sparse (moderately toxic) or absent (toxic). The solvents of choice was water. Concurrent solvent and positive controls were run in each test. Positive control substances were without S9-mix 0.01 mg 4 -nitro-ophenylenediamine/ plate for TA98 and TA1538, 0.01 mg sodium azide for TA100, 0.06 mg 9-aminoacrididine/plate for TA1537 and with S9-mix 0.01 mg 2-aminoanthracene for all strains.

2,4-pentanedione did not produce a doubling or a dose-response relationship of the number of revertants/plate in the Salmonella typhimurium strains used neither in the absence nor in the presence of a metabolic activation system. Dose selection appeared to be in a suitable range, because in tests both with and without metabolic activation, bacteriotoxicty was observe d at 30 mg/plate (highest dose tested) with all strains. Well proven positive controls did produce mutagenic effects demonstrating the functionality of the test system. It can therefore be concluded that 2,4-pentanedione is not mutagenic under the conditions of the assay.