2-hydroxy-2-methylpropiophenone

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:

From Jun. 12, 1980 to Sep. 9, 1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

2-aminoanthracene was the only compound used to test the efficacy of the S9 fraction

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-2-methylpropiophenone

EC Number:

231-272-0

EC Name:

2-hydroxy-2-methylpropiophenone

Cas Number:

7473-98-5

Molecular formula:

C10H12O2

IUPAC Name:

2-hydroxy-2-methyl-1-phenylpropan-1-one

Method

Target gene:

Histidine (his- to his+) and tryptophan (tryp- to tryp+) genes in Salmonella typhimurium and Escherichia coli respectively

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Additional strain / cell type characteristics:

not applicable

Species / strain 3

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9

Test concentrations with justification for top dose:

Plate incorporation (TA98, TA100, TA1535, TA1537 and TA1538) conc. range in tests: 0.4, 4.4, 44.3, 443.3, 4433 and 22167 µg/plate
Pre-incubation (WP2 uvrA) conc. range in tests: 0.3, 3.3, 32.8, 328.44, 3283.7 and 16420 µg/ml

Vehicle / solvent:

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

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

methylmethanesulfonate

other: daunomycin, 4-nitr-1,2-phenylenediamine

Remarks:

without S9 mix

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2 -aminoanthracene

Remarks:

with S9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION:
TA98, TA100, TA1535, TA1537 and TA1538: in agar (plate incorporation)
WP2 uvrA: preincubation

DURATION
- Preincubation period: 0.5 hours at 37°C
- Exposure duration: 48 hours at 37°C

NUMBER OF REPLICATIONS: 4 plates per compound or concentration
-Independent repeat experiment was conducted.

Statistics:

Revertant colony numbers were calculated as average and standard deviation. No statistical analysis test was performed.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

22167 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

22167 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

22167 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

22167 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

22167 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 6

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

22167 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Toxic effect was observed in all experiments macroscopically or during the routinely conducted microscopical examination of the plates, in some cases already at 4433 µg/plate, in all cases at 22167 µg/plate.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Under the experimental conditions of this study the test item did not show any mutagenic activity in the concentration range used with and without addition of a postmitochondrial liver homogenate (S-9) as metabolizing system.

Executive summary:

In this guideline (OECD 471) study conducted with GLP certification, the test material (EC xxx-xxx-x) was determined not to be mutagenic. The reverse mutagenicity study was conducted in S. typhimurium (TA98, TA 100, TA 1535, TA 1537, & TA1538) and E. coli (WP2 uvr A) with and without metabolic acitvation. Cytotoxicity was observed at the highest tested concentration (22167 µg/l). The results of the study indicate that the test material does not meet the criteria to be considered mutagenic under the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008).