α-bromo-m-toluonitrile

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 3-(bromomethyl)benzonitrile. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 3-(bromomethyl)benzonitrile was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

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 OECD QSAR Toolbox version 3.3 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of the test material: 3-(bromomethyl)benzonitrile
- IUPAC name: 3-(bromomethyl)benzonitrile
- Molecular formula: C8H6BrN
- Molecular weight: 196.046 g/mol
- Substance type: Organic
- Smiles: N#Cc1cc(CBr)ccc1
- Inchi: 1S/C8H6BrN/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5H2

Target gene:

Histidine

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

No data

Rationale for test conditions:

No data

Evaluation criteria:

Prediction is done considering a dose dependent increase in the number of revertants/plate

Statistics:

No data

Species / strain:

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

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

No data

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 13 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" or "e" )  and "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and "l" )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Benzyl Halides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) by Protein binding by OECD ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR SN2 OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Shiff base formation for aldehydes AND AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen AND SN2 AND SN2 >> Acylation involving a leaving group  AND SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution at sp3 carbon atom AND SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  AND SN2 >> Nucleophilic substitution on benzilyc carbon atom AND SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Shiff base formation for aldehydes AND AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen AND SN2 AND SN2 >> Acylation involving a leaving group  AND SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom AND SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.34

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.77

Conclusions:

3-(bromomethyl)benzonitrile was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 3-(bromomethyl)benzonitrile. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 3-(bromomethyl)benzonitrile was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Gene mutation in vitro:

Prediction model based estimation for the target chemical and data from read across chemicals were reviewed to determine the mutagenic nature of 3-(bromomethyl)benzonitrile. The studies are as mentioned below:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 3-(bromomethyl)benzonitrile. The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 3-(bromomethyl)benzonitrile was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Gene mutation toxicity was predicted for 3-(bromomethyl)benzonitrile using the battery approach from Danish QSAR database (2017). The study assumed the use of Salmonella typhimurium bacteria in the Ames test. The end point for gene mutation has been modeled in the Danish QSAR using the three software systems Leadscope, CASE Ultra and SciQSAR. Based on predictions from these three systems, a fourth and overall battery prediction is made. The battery prediction is made using the so called Battery algorithm. With the battery approach it is in many cases possible to reduce “noise” from the individual model estimates and thereby improve accuracy and/or broaden the applicability domain. Gene mutation toxicity study as predicted by Danish QSAR for3-(bromomethyl)benzonitrileis negative and hence the chemical is predicted to not classify as a gene mutant in vitro.

The predicted data is further supported by the data form read across chemicals as mentioned below:

Gene mutation toxicity study was performed by Ball et al (Mutation Research, 1984) to determine the mutagenic nature of structurally and functionally similar read across chemical p-Cyanobenzyl chloride (RA CAS no 874 -86 -2; IUPAC name: 4-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.

Another gene mutation study was performed by Juneja et al (Mutation Research, 1995). Gene mutation toxicity study was performed to determine the mutagenic nature of structurally and functionally similar read across chemical 3-Nitrobenzyl bromide (RA CAS no 3958 -57 -4; IUPAC name: 3-Nitrobenzyl Bromide). The study was performed as per the Salmonella plate incorporation assay with preincubation modification using Salmonella typhimurium strains TA100 (with and without S9) and TA98 (without S9). The test chemical was dissolved in suitable solvent and used at dose levels of 0, 50, 250 or 500 nmol/plate. Concurrent solvent and positive control chemicals were also included in the study. The chemical that induced dose dependent increase of more than twice the number of spontaneous revertants was considered mutagenic. 3-Nitrobenzyl bromide did not induce gene mutation in Salmonella typhimurium strain TA100 (with and without S9) and TA98 (Without S9) and hence it is not likely to classify as a gene mutant in vitro.

Based on the data available for the target chemical and its read across, 3-(bromomethyl)benzonitrile is not likely to exhibit gene mutation in vitro. Hence it is not likely to classify as a gene mutant.

Justification for classification or non-classification

Based on the data available for the target chemical and its read across, 3-(bromomethyl)benzonitrile (CAS no 28188-41-2) is not likely to exhibit gene mutation in vitro. Hence it is not likely to classify as a gene mutant.