α-bromo-m-toluonitrile

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity studies of p-substituted benzyl derivatives in the Ames Salmonella plate-incorporation assay

Author:

James C. Ball, Susan Foxall-VanAken and Trescott E. Jensen

Year:

1984

Bibliographic source:

Mutation Research, 138 (1984) 145-151

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Ames assay was performed to determine the mutagenic nature of p-Cyanobenzyl chloride

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-(Chloromethyl)benzonitrile

Cas Number:

874-86-2

Molecular formula:

C8H6ClN

IUPAC Name:

4-(Chloromethyl)benzonitrile

Details on test material:

- Name of test material: p-Cyanobenzyl chloride
- IUPAC name: 4-(Chloromethyl)benzonitrile
- Molecular formula: C8H6ClN
- Molecular weight: 151.595 g/mol
- Substance type: Organic

Specific details on test material used for the study:

- Name of test material: p-Cyanobenzyl chloride
- IUPAC name: 4-(Chloromethyl)benzonitrile
- Molecular formula: C8H6ClN
- Molecular weight: 151.595 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

not specified

Metabolic activation system:

No data

Test concentrations with justification for top dose:

0, 20, 50, 200, 500 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Dry DMSO
- Justification for choice of solvent/vehicle: The test chemical was soluble in dry DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

dry DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: No data
- Exposure duration: No data
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: Duplicate

NUMBER OF CELLS EVALUATED: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: No data

Rationale for test conditions:

No data

Evaluation criteria:

A compound was considered to be mutagenic if the number of revertants/plate exceeded the 99.9% confidence limit and a concentration-dependent increase in the mutagenicity was observed. The 99.9% confidence limit was 99 revertants above spontaneous revertant levels for TA100 (spontaneous revertants = 196 ± 29 revertants/plate) and 40 revertants above spontaneous revertants for TA98 (spontaneous revertants = 40 ± 12 revertants/plate).

Statistics:

The number of induced mutants//µmole was calculated from the linear portion of the concentration-mutagenicity curve. When the results were not mutagenic an upper limit for the potential mutagenicity was estimated by dividing a significant mutagenic response that would have been observed (> 99 revertants above the spontaneous background, 99.9% confidence limit) by the highest non-toxic concentration.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 100

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

No data

Remarks on result:

other: No mutagenic potential

Applicant's summary and conclusion

Conclusions:

p-Cyanobenzyl chloride did not induce gene mutation in Salmonella typhimurium strain TA100 and hence it is not likely to classify as a gene mutant in vitro.

Executive summary:

Gene mutation toxicity study was performed to determine the mutagenic nature of p-Cyanobenzyl chloride. The study was performed as per the Ames plate incorporation assay using Salmonella typhimurium strain TA100. The test chemical was dissolved in dry DMSO and used at dose levels of 0, 20, 50, 200, 500µg/plate. p-Cyanobenzyl chloride did not induce gene mutation in Salmonella typhimurium strain TA100 and hence it is not likely to classify as a gene mutant in vitro.