1-Propanone, 2-hydroxy-2-methyl-, 1-(4-C10-13-alkylphenyl) derivs.

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:

9 July - 17 November, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

In the second test, no concentration was tested at with precipitation was observed.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1-(4-dodecylphenyl)-2-hydroxy-2-methylpropan-1-one

EC Number:

274-071-3

EC Name:

1-(4-dodecylphenyl)-2-hydroxy-2-methylpropan-1-one

Cas Number:

69673-80-9

IUPAC Name:

1-(4-dodecylphenyl)-2-hydroxy-2-methylpropan-1-one

Constituent 2

Reference substance name:

1-Propanone, 1-(4-dodecylphenyl)-2-hydroxy-2-methyl-

IUPAC Name:

1-Propanone, 1-(4-dodecylphenyl)-2-hydroxy-2-methyl-

Constituent 3

Reference substance name:

1-(4-Dodecylphenyl)-2-hydroxy-2-methylpropan-1-on

IUPAC Name:

1-(4-Dodecylphenyl)-2-hydroxy-2-methylpropan-1-on

Method

Target gene:

Histidine gene in S. typhimurium

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver post-mitochondrial fraction (S9)

Test concentrations with justification for top dose:

First test: 313 - 625 - 1250 - 2500 - 5000 µg/plate
Second test: 125 - 250 - 500 - 750 - 1000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: not indicated

Controls

Controls 1

Positive controls:

yes

Remarks:

without S9

Positive control substance:

sodium azide

Remarks:

For strains TA 100 and TA 1535

Migrated to IUCLID6: 2 µg/plate (both strains)

Controls 2

Positive controls:

yes

Remarks:

without S9

Positive control substance:

9-aminoacridine

Remarks:

For strain TA 1537

Migrated to IUCLID6: 35 µg/plate

Controls 3

Positive controls:

yes

Remarks:

without S9

Positive control substance:

2-nitrofluorene

Remarks:

For strain TA 98

Migrated to IUCLID6: 4 µg/plate

Controls 4

Positive controls:

yes

Remarks:

with S9

Positive control substance:

other: 2-aminoanthracene at 2, 2, 7 and 10 µg/plate

Remarks:

For strain TA 1535, TA 100, TA 1537 and TA 102, respectively

Controls 5

Positive controls:

yes

Remarks:

with S9

Positive control substance:

benzo(a)pyrene

Remarks:

For strain TA 98

Migrated to IUCLID6: 30 µg/plate

Controls 6

Positive controls:

yes

Remarks:

without S9

Positive control substance:

mitomycin C

Remarks:

For strain TA 102

Migrated to IUCLID6: 0.5 µg/plate

Controls 7

Untreated negative controls:

yes

Remarks:

DMSO, with and without S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: at least 48 h

NUMBER OF REPLICATIONS: doses of the test substance were tested in triplicate in each strain. Negative control was tested six fold. Two independent experiments were conducted.

DETERMINATION OF CYTOTOXICITY
- Method: toxicity to the background lawn and colonies of his+ revertants

Evaluation criteria:

If the number of revertants is at least twice the spontaneous reversion rate in one of the strains and if there is a concentration related increasing number of revertants over the range tested then a biological relevant response is observed and the test substance is considered mutagenic.

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: observed at concentrations of 1250 µg/plate and higher in the first test. No precipitation was observed in the second test up to concentrations of 1000 µg/plate.

COMPARISON WITH HISTORICAL CONTROL DATA: negative controls were in the historical ranges

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The negative controls were within the historical ranges and the positive controls all induced large increases in the revertant numbers. The strain characteristics of the bacteria have been confirmed. The study was therefore accepted as valid.
Compared to the negative control group the test substance does not indicate an elevation of the revertant colonies neither in the absence nor in the presence of S9-mix. It was concluded that the test substance did not induce mutation in five strains of Salmonella typhimurium and is not toxic when tested under the conditions employed for this study.

Executive summary:

The potential of the substance to induce mutations was assessed in a bacterial reverse mutation assay. The study was conducted in accordance with OECD Guideline 471. The assay was performed in two independent experiments. Both took place as a plate incorporation test using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102. All experiments were in the absence and in the presence of a metabolic activation by an Aroclor 1254 induced rat liover post mitochondrial fraction (S9). Five concentrations were tested in each experiment using 0.1 ml for each plate. No mutagenic effects occurred with or without metabolic activation in experiment 1 (313, 625, 1250, 2500 and 5000 µg/plate). Precipitation was observed at a concentration >= 1250 µg/plate at all tester strains. In experiment 2 (125, 250, 500, 750, 1000 µg/plate) no mutagenic or toxic effects occurred. Precipitation was not observed at any concentration.

It can be concluded that the test substance did not induce gene mutations by base pair substitution or frame shifts in the genom of the used strains. Therefore the test substance is considered to be non mutagenic in the bacterial reverse mutation assay.