4,4'-dihydroxybenzophenone

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

(i) the stability and achieved concentration of the test substance in the vehicle used were not determined by analysis. (ii) certified purity of the test substance is not available. GLP assessed not to affect the integrity of the study or conclusions.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-dihydroxybenzophenone

EC Number:

210-288-1

EC Name:

4,4'-dihydroxybenzophenone

Cas Number:

611-99-4

Molecular formula:

C13H10O3

IUPAC Name:

4,4'-dihydroxybenzophenone

Test material form:

solid: particulate/powder

Details on test material:

Purity >99.5%w/w

Specific details on test material used for the study:

Name: 4,4'-Dihydroxybenzophenone
Source: ICI Measurement Science Group
Colour: Yellowish
Physical state: Solid
Batch reference: PML Ref 199.02; 050808
Purity: 100%

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Remarks:

WP2 uvrA (pKM101)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

in the presence and absence of a rat liver - derived metabolic activation system (S9-mix).

Test concentrations with justification for top dose:

Individual stock solutions of the test substance were prepared at a suitable concentration for each experiment in DMSO and serial dilutions were carried out as required in each case.
The positive control substances were prepared as solutions in the solvents detailed in the table above.
All test and positive control substance dosing preparations were prepared as close to the time of culture treatment as possible and were dosed at a dosing volume of 100gl/plate (apart from in the pre-incubation experiment, where the volume was reduced to 20gl/plate).

Vehicle / solvent:

dried dimethylsulphoxide (DMSO: CTL test substance reference number Y 00876/020)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: Daunorubicin HCI (DR) N-Ethyl-; Acridine Mutagen ICR191 (ICR); 2-Aminoanthracene (2AA)

Rationale for test conditions:

The bacterial mutation assay was used as it is a well-established assay, designed to detect reversion to amino acid independence (his- to his for S.typhimurium, [rp- to trp for E.coli strains) induced by chemicals which cause base changes or frameshift mutations in the genome of these organisms. The use of strains TAl 535, TAl 537, TA98, TA 100 and WP2 uvrA (pKM101) is in accordance with the current scientific recommendations for the conduct of this assay

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The numbers of revertant colonies per plate observed in the four Salmonella lyphimurium tester strains (TAl 535, TA 1537, TA98 and TA 100) and one Escherichia coli strain (WP2 uvrA (pKMl 01)), when exposed to 4,4'-Dihydroxybenzophenone and the various positive and solvent control substances are shown in Tables 1-5. All derived values in the results tables are expressed, where appropriate, to one decimal place: values of 0.05+ have been rounded up to 0.1. In at least two separate assays with each strain, the test substance did not induce any significant, reproducible increases in the observed number of revertant colonies, either in the presence or absence of S9-mix
The positive controls for each experiment induced the expected responses, indicating the strains were responding satisfactorily in each case.

Any other information on results incl. tables

In at least two separate assays with each strain, the test substance did not induce any significant, reproducible increases in the observed number of revertant colonies, either in the presence or absence of S9-mix.

The positive controls for each experiment induced the expected responses, indicating the strains were responding satisfactorily in each case.

Applicant's summary and conclusion

Conclusions:

It is concluded that, under the conditions of this assay, 4,4'-Dihydroxybenzophenone gave a negative, i.e. non-mutagenic, response in S.lyphimurium strains TAl 535, TAl 537, TA98 and TAIOO and E.coli strain WP2 uvrA (pKM101) in both the presence and absence of S9-mix.