4''-Butoxy-4-ethyl-2',2'',3''-trifluoro-[1,1':4',1'']-terphenyl

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:

2014-11-11 to 2015-02-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

07-1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-butoxy-4'-(4-ethylphenyl)-2,3,3'-trifluoro-1,1'-biphenyl

EC Number:

812-028-8

Cas Number:

612543-60-9

Molecular formula:

C24H23F3O

IUPAC Name:

4-butoxy-4'-(4-ethylphenyl)-2,3,3'-trifluoro-1,1'-biphenyl

Test material form:

solid: bulk

Method

Target gene:

HIS operon (S. thyphimurium)

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 mix from Aroclor 1254-pretreated rats with standard co-factors

Test concentrations with justification for top dose:

1st series: 5, 16, 50, 160, 500, 1600 and 5000 µg/plate
2nd series: 8.192, 20.48, 51.2, 128, 320, 800, 2000 and 5000 µg/plate
In the two series with S9 mix, 10 % S9 in the S9 mix were used.

Vehicle / solvent:

dimethylformamide

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

Remarks:

without S9 mix

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

other: 2-aminoanthracene

Remarks:

with S9 mix

Details on test system and experimental conditions:

Acceptance Criteria
The assay was to be considered valid if all the following criteria were met:
The vehicle control counts fell within the laboratory’s historical control ranges.
The positive control chemicals induced increases in revertant numbers of >= 1.5-fold (in strain TA102), >= 2-fold (in strains TA98 and TA100) or >= 3-fold (in strains TA1535 and TA1537) the concurrent vehicle control confirming discrimination between different strains, and an active S-9 preparation.

Evaluation criteria:

For valid data, the test article was considered to be mutagenic if:
A concentration related increase in revertant numbers was >= 1.5-fold (in strain TA102), >= 2-fold (in strains TA98 or TA100) or >= 3-fold (in strains TA1535 or TA1537) the concurrent vehicle control values.
The positive trend/effects described above were reproducible.
The test article was considered positive in this assay if both of the above criteria were met.
The test article was considered negative in this assay if neither of the above criteria were met.
Results which only partially satisfied the above criteria were dealt with on a case-by-case basis. Biological relevance was taken into account, for example consistency of response within and between concentrations and (where applicable) between experiments.

Statistics:

n.a.

Results and discussion

Test results

Key result

Species / strain:

other: all tested strains

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

With and without addition of S9 mix as the external metabolizing system, the test material was not mutagenic under the experimental conditions described.

Executive summary:

Study design

The mutagenic potential of the test item was examined in a GLP study according to OECD GL 471 using Salmonella typhimurium tester strains TA 98, TA 100, TA 102, TA 1535 and TA 1537. The plate incorporation test with and without addition of liver S9 mix from Aroclor 1254-pretreated rats was used. Two independent experimental series were performed. In the two series with S9 mix, 10 % S9 in the S9 mix was used. The test item was dissolved in dimethylformamide and tested at concentrations ranging from 8.192 - 5000 μg/plate.

 

Results

In experiment 1, evidence of toxicity was observed at >= 1600 μg/plate in strain TA1535 in the absence of S9 and strain TA102 in the presence of S9. Precipitation was observed on the test plates at concentrations of >= 1600 μg/plate for all strains in the absence and presence of S9. In experiment 2, evidence of toxicity was observed at 5000 μg/plate in strains TA98, TA100 and TA1535 in the absence and presence of S9, strain TA1537 in the absence of S9 and strain TA102 in the presence of S9 and at >= 800 µg/plate in strain TA1537 in the presence of S9 only. Precipitation was observed on the test plates at concentrations of 800 or >= 2000 μg/plate in strains TA100, TA1535, TA1537 and TA102 in the absence of S9 and at 5000 μg/plate in strain TA98 in the absence and presence of S9. Each treatment with the test materials used as positive controls led to a clear increase in revertant colonies, thus, showing the expected reversion properties of all strains and good metabolic activity of the S9 mix used. Following test item treatments of all the test strains in the absence and presence of S9, no increases in revertant numbers were observed that were >= 1.5-fold (in strain TA102), >= 2-fold (in strains TA98 or TA100) or >= 3-fold (in strains TA1535 or TA1537) the concurrent vehicle control.

 

Conclusion

With and without addition of S9 mix as the extemal metabolizing system, the test item was not mutagenic under the experimental conditions described.