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Toxicological information

Genetic toxicity: in vitro

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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.