4-phenylbenzophenone

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:

21 August 2017 - 07 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

July 21, 1997

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-phenylbenzophenone

EC Number:

218-345-2

EC Name:

4-phenylbenzophenone

Cas Number:

2128-93-0

Molecular formula:

C19H14O

IUPAC Name:

{[1,1'-biphenyl]-4-yl}(phenyl)methanone

Test material form:

solid

Specific details on test material used for the study:

Appearance: White to off-white crystalline powder
Batch: 20161118
Purity/Composition: 99.74%
Test item storage: At room temperature protected from light
Stable under storage conditions until: 17 November 2017 (expiry date)

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Rat liver microsomal enzymes (S9 homogenate) prepared from male Sprague Dawley rats that had been injected intraperitoneally with Aroclor 1254.

Test concentrations with justification for top dose:

Dose-range finding test with concentrations of 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 µg/plate.
Based on the results of the dose-range finding test, the following dose-range was selected for the mutation assay with the tester strains, TA1535, TA1537 and TA98 in the absence and presence of S9-mix: 17, 52, 164, 512, 1600 and 5000 μg/plate.

Vehicle / solvent:

Dimethyl sulfoxide

Controls

Untreated negative controls:

yes

Remarks:

DMSO

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

2-nitrofluorene

sodium azide

methylmethanesulfonate

other: a: ICR-191 b: 2-aminoanthracene

Evaluation criteria:

A Salmonella typhimurium reverse mutation assay and/or Escherichia coli reverse mutation assay is considered acceptable if it meets the following criteria:
a) The vehicle control and positive control plates from each tester strain (with or without S9-mix) must exhibit a characteristic number of revertant colonies when compared against relevant historical control data generated at Charles River Den Bosch.
b) The selected dose-range should include a clearly toxic concentration or should exhibit limited solubility as demonstrated by the preliminary toxicity range-finding test or should extend to 5 mg/plate.
c) No more than 5% of the plates are lost through contamination or some other unforeseen event.

Statistics:

Not applicable.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 7

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

In the absence of S9-mix, the substanced induced dose related increases in the number of revertant colonies in the tester strains TA1537 and TA98. The increases observed in tester strain TA1537 were above the laboratory historical control data range, and were up to 24-fold the concurrent vehicle control. The increases observed in tester strain TA98 were above the laboratory historical control data range and were up to 6.1-fold the concurrent vehicle control.
 
In the presence of S9-mix, the substance induced dose related increases in the number of revertant colonies in the tester strains TA1537 and TA98. The increases observed in tester strain TA1537 were above the laboratory historical control data range, and were up to 12-fold the concurrent vehicle control. The increases observed in tester strain TA98 were above the laboratory historical control data range and were up to 4.6-fold the concurrent vehicle control.

Applicant's summary and conclusion

Conclusions:

The substance is mutagenic in the tester strains TA1537 and TA98 of the Salmonella typhimurium reverse mutation assay. The substance is not mutagenic in the other Salmonella typhimurium tester strains (TA1535 and TA100) or in the Escherichia coli reverse mutation assay using strain WP2uvrA.

Executive summary:

The potential of the substance and/or its metabolites to induce reverse mutations at the histidine locus in several strains of Salmonellatyphimurium (S. typhimurium; TA98, TA100, TA1535, and TA1537), and at the tryptophan locus of Escherichia coli (E.coli) strain WP₂uvrA in the presence or absence of an exogenous mammalian metabolic activation system (S9) was investigated.  The test was performed in two independent experiments, at first a direct plate assay was performed and secondly a pre-incubation assay. In the first mutation experiment, the substance was tested up to concentrations of 5000 µg/plate in the strains TA1535, TA1537 and TA98.  In the second mutation experiment, the substance was tested up to concentrations of 5000 µg/plate in the tester strains TA1535, TA1537, TA98, TA100 and WP₂uvrA in the pre-incubation assay.  The substance was mutagenic in the tester strains TA1537 and TA98 of the Salmonella typhimurium reverse mutation assay.  The substance was not mutagenic in the other Salmonella typhimurium tester strains (TA1535 and TA100) or in the Escherichia coli reverse mutation assay using strain WP2uvrA.