4-methylpentan-2-one

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:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Reference 2

Reference Type:

publication

Title:

Mutagenicity studies on ketone solvents: methyl ethyl ketone, methyl isobutyl ketone and isophorone

Author:

O'donoghue JL, Haworth SR, Curren RD, Kirby PE., Lawlor T et al.

Year:

1988

Bibliographic source:

Mutat. Res., 206, 149-161

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

- missing S. typhimurium strain TA102 or E. coli strain WP2 uvrA, and 2-aminoanthracene was the only compound used to test the efficacy of the S9 fraction for all strains

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-methylpentan-2-one

EC Number:

203-550-1

EC Name:

4-methylpentan-2-one

Cas Number:

108-10-1

Molecular formula:

C6H12O

IUPAC Name:

4-methylpentan-2-one

Details on test material:

- Name of test material (as cited in study report): Methyl isobutyl Ketone
- Physical state: Clear, non-viscous liquid
- Analytical purity: Not reported
- Lot/batch No.: MA #T1827
- Stability under test conditions: Not reported
- Storage condition of test material: Not reported

Method

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-1254 induced rodent liver microsomes

Test concentrations with justification for top dose:

Preliminary toxicity assay: 0.015, 0.05, 0.15, 0.5, 1.7, 5.2, 17, 50, 100, or 150 µL/plate (± S9)
Ames assay: 0.04, 0.1, 0.4, 1, or 4 µL/plate (± S9)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: See Table 1

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 37 ºC for 20 minutes

NUMBER OF REPLICATIONS: Triplicate (no independent repeat)

Evaluation criteria:

Revertant colonies for a given tester strain within a given test article dilution series were counted either entirely by automated colony counter or entirely by hand. Plates with sufficient test article precipitate to interfere with automated colony counting were counted manually. The condition of the background bacterial lawn was evaluated for evidence of test article toxicity by using a dissecting microscope. This toxicity was scored relative to the solvent control plate and recorded along with the revertant count for that plate on the individual strain data forms a code system.

For a test article to be considered positive, it must cause at least a doubling in the mean revertants/plate of at least one tester strain. This increase in the mean number of revertants/plate must be accompanied by a dose response to increasing concentrations of the test article. In those cases where the observed dose-responsive increase in TA1537 or TA1538 revertants/plate is less than three-fold, the response must be reproducible.

Statistics:

For all replicates plated, an average and standard deviation were calculated. No statistics conducted (revertant colonies counted).

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In the preliminary toxicity test, doses of 5.2 µL/plate and above, the microcolony lawn was slightly-to-moderately reduced. The background lawn was absent at doses of 17 µL/plate and above.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In the preliminary toxicity test, doses of 5.2 µL/plate and above, the microcolony lawn was slightly-to-moderately reduced. The background lawn was absent at doses of 17 µL/plate and above.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In the preliminary toxicity test, doses of 5.2 µL/plate and above, the microcolony lawn was slightly-to-moderately reduced. The background lawn was absent at doses of 17 µL/plate and above.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In the preliminary toxicity test, doses of 5.2 µL/plate and above, the microcolony lawn was slightly-to-moderately reduced. The background lawn was absent at doses of 17 µL/plate and above.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In the preliminary toxicity test, doses of 5.2 µL/plate and above, the microcolony lawn was slightly-to-moderately reduced. The background lawn was absent at doses of 17 µL/plate and above.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

negative

Executive summary:

In a bacterial reverse mutation assay (equivalent to OECD guideline 471), MIBK was tested at doses of 0, 0.04, 0.1, 0.4, 1.0, or 4.0 µL/plate in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 both in the presence and absence of exogenous metabolic activation (Aroclor 1254-induced rat liver S9).  The experiment was conducted in triplicate; however, an independent repeat experiment was not performed. Dimethyl sulfoxide (DMSO) was used as the vehicle and positive controls were included in all incubations. No cytotoxicity was observed and noincrease in the reverse mutation rate was observedat any MIBK concentration either in the presence or absence of metabolic activation. Incubation with positive control substances in the presence or absence of metabolic activation resulted in anticipated increases inreverse mutation rates.