4-(α,α-dimethylbenzyl)phenol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-10-24 to 1988-12-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-(α,α-dimethylbenzyl)phenol

EC Number:

209-968-0

EC Name:

4-(α,α-dimethylbenzyl)phenol

Cas Number:

599-64-4

Molecular formula:

C15H16O

IUPAC Name:

4-(α,α-dimethylbenzyl)phenol

Constituent 2

Reference substance name:

290-968-0

IUPAC Name:

290-968-0

Details on test material:

- Name of test material: p-Cumylphenol
- Physical state: white crystalline powder

Method

Target gene:

Histidine locus (S. typhimurium) and tryptophan locus (E. coli)

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:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

liver microsomal S9 from rats

Test concentrations with justification for top dose:

12.5. 25, 50, 100 and 200 µg/plate

Vehicle / solvent:

dimethyl sulphoxide (DMSO)

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-Methyl –N’-nitro-N-nitrosoguanidine (MNNG) 2 ug/plate for TA1535 and TA100, 9-Aminoacridine (9AA) 100 ug/plate for TA1537, 4-Nitro-0-phenylenediamine (4NOPD) 10 ug/plate for TA98, 4-Nitroquinoline N-oxide (4NQ0) 3.3 ug/plate for WP2uvrA-.

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

SELECTION AGENT: Histidine (S. typhimurium) and tryptophan (E. coli)

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: thinning of the background lawn

Evaluation criteria:

Five concentrations of the test material were assayed in triplicate against each tester strain in accordance with the standards for mutagenicity tests using microorganisms. For a substance to be considered positive in this test system, it should have induced a dose-related and statistically significant increase in mutation rate (of at least twice the spontaneous reversion rate) in one or more strains of bacteria in the presence and/or absence of the S-9 microsomal enzymes in both experiments. To be considered negative the number of induced revertants compared to spontaneous revertants should be less than twofold at each dose level employed, the intervals of which should be between 2 and 5 fold and extend to the limits imposed by toxicity or solubility or up to the maximum recommended dose of 5000 µg/plate. In this study the limiting factor was toxicity.

Results and discussion

Test results

Test results 1

Key result

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:

cytotoxicity

Remarks:

at doses at and above 200 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at doses at and above 200 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: The dose range determined in a preliminary toxicity assay was 0.32 to 200 µg/plate. p-Cumylphenol caused a reduction in the growth of the bacterial lawn at dose levels between 200 and 5000 µg/plate both with and without metabolic activation. p-Cumylphenol was therefore tested up to the toxic dose limit of 200 µg/plate.

ADDITIONAL INFORMATION ON CYTOTOXICITY: A toxic effect was observed with p-cumylphenol treatment but the response varied with the strains used. Generally a weakening of the background lawn was observed with doses of p-cumylphenol at and above 200 µg/plate.

INFORMATION ON CONTROLS AND S-9: The solvent control plates gave counts of revertant colonies within the normal range. The positive control substances all produced marked increases in the number of revertant colonies and the activity of the S-9 fraction was found to be satisfactory.

Applicant's summary and conclusion

Conclusions:

p-Cumylphenol was determined to be non-mutagenic.

Executive summary:

The genotoxic potential of the substance was investigated in an in vitro bacterial reverse mutation assay (Ames test) conducted using methodology similar/equivalent to OECD guideline 471.

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A- were exposed to the test material in DMSO at concentrations of 12.5. 25, 50, 100 and 200 µg/plate using the plate incorporation method both with and without S9.

Under the conditions of this study, no significant increase in the numbers of revertant colonies was recorded for any of the bacterial strains with any dose of p-cumylphenol, either with or without metabolic activation. p-Cumylphenol was determined to be non-mutagenic.