[1,1'-Biphenyl]-2-carbonitrile, 4'-(bromomethyl)-

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:

From 2 September 1994 to 17 October 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The assay is based on the use of 5 Salmonella typhimurium tester strains that revert from histidine dependence (auxotrophy) to histidine independence (prototrophy) in the presence of a genotoxic agent, with or without metabolic activation system.
This study was carried out with the preincubation method.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4'-(bromomethyl)-[1,1'-biphenyl]-2-carbonitrile

EC Number:

601-327-7

Cas Number:

114772-54-2

Molecular formula:

C14H10BrN

IUPAC Name:

4'-(bromomethyl)-[1,1'-biphenyl]-2-carbonitrile

Test material form:

other: solution

Details on test material:

Test compound/batch: SR 48941/ batch 4 SNP 006.
SR 48941 was extemporaneously dissolved and diluted in dimethyl sulfoxide (Merck, 99.8 % purity) in order to obtain the following concentrations: 1, 5, 10, 25, 50, 100, 250, 500, 1000 and 2500 µg/plate.

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other: TA1535 and TA 1537: rfa uvrB; TA 98 and TA100: rfa uvrB with R factor plasmid pKM 101, TA102: rfa with the R factor plasmid pKM101 and pAQ1.

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix (2.5%) from Aroclor 1254-induced rat liver

Test concentrations with justification for top dose:

Preliminary study (TA100)
Preincubation method: 0, 10, 50, 100, 250, 500, 1000 and 2500 µg/plate on TA100

Main study(TA98, TA100, TA102, TA1535, TA1537)
Plate incorporation method: 0, 10, 50, 100, 250, 500 and 1000 µg/plate

Additional assay on TA1537: 0, 1, 5, 10, 50, 100 and 250 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl sulfoxide

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

other: 2-aminoanthracene, Danthron

Remarks:

Further information on positive controls under section 'Any other information on materials and methods incl. tables".

Details on test system and experimental conditions:

Main study method: preincubation
Numbers od replications: 3
Exposure duration: 48 hours for TA98, TA100, TA1535, TA1537; 72 hours for TA102
The bacterial suspension used for each test was obtained from a bacterial inoculum grown in nutrient broth in a shaking incubator for approximately 7 hours at 37°C. The bacterial density ranged from 1 to 2 x 10^9 bacteria/ml.

Evaluation criteria:

Criteria for bacterial toxicity are:
- reduced number of revertant colonies/plate,
- sparsity of the bacterial background lawn when compared with control plates

The compound is considered genotoxic:
- if the increase in the number of revertants is concentration-related, or
- if, at one concentration tested (at least), the induction factor is equal to or higher than 2 with TA98, TA100 and TA102 and higher than 3 with TA1535 and TA1537 and,
- if the positive response is reproducible in an independent assay.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

From 250 µg/plate upwards

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

A significant increase in the number of His+ revertant colonies/plate was seen.

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

From 250 µg/plate upwards with S-9 mix and from 500 µg/plate upwards without S9- mix

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

A significant increase in the number of His+ revertant colonies/plate was seen.

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

From 500 µg/plate upwards

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 1000 µg/plate with S-9 mix

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

A significant increase in the number of His+ revertant colonies/plate was seen.

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

In conclusion, SR 48941 was genotoxic in the Ames test, with or without metabolic activation.