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Description of key information

Skin sensitization:

The dermal irritation potential of 3-(bromomethyl)benzonitrile was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be corrosive to the skin of New Zealand White rabbits.

Based on the estimated results, 3-(bromomethyl)benzonitrile can be considered to be irritating to skin and can be classified under the category “ Category 1(corrosive) based on GHS criteria ” as per CLP regulation.

Eye irritation:

The ocular irritation potential of 3-(bromomethyl)benzonitrile was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be irritating to the eye of New Zealand White rabbits.

Based on the estimated results, 3-(bromomethyl)benzonitrile can be considered to be irritating to eye and can be classified under the category “ Category 2 (irritant) based on GHS criteria ” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of the test material: α-bromo-m-toluonitrile
- IUPAC name: 3-(bromomethyl)benzonitrile
- Molecular formula: C8H6BrN
- Molecular weight: 196.046 g/mol
- Smiles: N#Cc1cc(CBr)ccc1
- Inchi: 1S/C8H6BrN/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5H2
- Substance type: Organic
- Physical state : Solid crystalline powder (Off white)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
No data available
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
No data available
Duration of treatment / exposure:
No data available
Observation period:
No data available
Number of animals:
No data available
Details on study design:
No data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: Not specified
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
positive indication of irritation estimated

Estimation method: Takes mode value from the 6 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 ( not "j") )  )  and ("k" and "l" )  )

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 (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group All log Kow < -3.1 OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acetylenic Carbon [#C] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aromatic Carbon [C] AND Bromine, aliphatic attach [-Br] AND Cyano, aromatic attach [-C#N] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] by Organic functional groups (US EPA)

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.718

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.85

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
3-(bromomethyl)benzonitrile was considered to be skin irritant on New Zealand White Rabbit.
Executive summary:

The dermal irritation potential of 3-(bromomethyl)benzonitrile was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 3-(bromomethyl)benzonitrile can be considered to be irritating to skin and can be classified under the category “ Category 1B (corrosive) based on GHS criteria ” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
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 predicted using OECD QSAR toolbox version 3.3 and QMRF report has been attached
Qualifier:
according to
Guideline:
other: estimated data
Principles of method if other than guideline:
Prediction was done by using OECD QSAR toolbox v3.3
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of the test material: α-bromo-m-toluonitrile
- IUPAC name: 3-(bromomethyl)benzonitrile
- Molecular formula: C8H6BrN
- Molecular weight: 196.046 g/mol
- Smiles: N#Cc1cc(CBr)ccc1
- Inchi: 1S/C8H6BrN/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5H2
- Substance type: Organic
- Physical state : Solid crystalline powder (Off white)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data available
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
Not specified
Duration of treatment / exposure:
Not specified
Observation period (in vivo):
Not specified
Duration of post- treatment incubation (in vitro):
Not specified
Number of animals or in vitro replicates:
Not specified
Details on study design:
Not specified
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Reversibility:
not specified
Remarks on result:
positive indication of irritation

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((((((("a" or "b" or "c" or "d" or "e" )  and "f" )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and "p" )  and "q" )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

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 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: "c"

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: "d"

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: "e"

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: "f"

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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Halogens AND Non-Metals by Groups of elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Metalloids by Groups of elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Br AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 17 - Halogens Br AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkyl halide AND Aryl AND Benzyl AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alkyl halide AND Aryl AND Benzyl AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkyl halide AND Aryl AND Benzyl AND Nitrile by Organic Functional groups ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Benzyl AND Nitrile AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Benzyl AND Nitrile AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 4 g/kg AND (!Undefined)Group CNHal Lipid Solubility < 400 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Group CHal log Kow > 4.5 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> Nucleophilic substitution on benzilyc carbon atom AND SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as SN2 >> Nucleophilic subsitution at sp3- Carbon atom >> alpha, omega-Dihaloalkanes by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "y"

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: "z"

Referential boundary: The target chemical should be classified as SN2 >> Nucleophilic substitution after carbenium ion formation by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.01

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.14

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
3-(bromomethyl)benzonitrile was considered to be eye irritant on New Zealand White Rabbit.
Executive summary:

The ocular irritation potential of 3-(bromomethyl)benzonitrile was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be irritating to the eye of New Zealand White rabbits.

Based on the estimated results, 3-(bromomethyl)benzonitrile can be considered to be irritating to eye and can be classified under the category “ Category 2 (irritant) based on GHS criteria ” as per CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In different studies, 3-(bromomethyl)benzonitrile has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical

3-(bromomethyl)benzonitrile and its structurally similar read across substances Benzonitrile (CAS: 100-47-0) and Phenylacetonitrile (CAS: 140-29-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The dermal irritation potential of 3-(bromomethyl)benzonitrile was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 3-(bromomethyl)benzonitrile can be considered to be irritating to skin and can be classified under the category “ Category 2 (irritant) based on GHS criteria ” as per CLP regulation.

The above predicted data was supported by experimental data summarized in GESTIS - Substance Database (Information system on hazardous substances of the Benzonitrile ) 2017 for the structurally similar read across substance Benzonitrile (CAS: 100-47-0)

Benzonitrile was used as a test material to evaluate skin irritation potential on rabbits.

The test material was applied on the intact or scarified rabbit skin in undiluted concentration under occlusion for 24 hrs. Slight irritation reactions were observed. Hence, Benzonitrile was considered to be skin irritant.

 The above experimental result was further supported by experimental data summarized by Hazardous Substances Data Bank (HSDB) for phenylacetonitrile U.S National Library of Medicine 2017 and IUCLID dataset for phenylacetonitrile European Chemicals Bureau 2000 for the structurally similar read across substance Phenylacetonitrile (CAS: 140-29-4).

Phenylacetonitrile was used as a test material to evaluate its skin irritation potential on rabbits.

Phenylacetonitrile was applied onIntact or abraded skin ofrabbits under occlusion for 24 hrs .Positive skin reactions were observed .Hence,Phenylacetonitrile was considered to be slightly irritating.

Even though the predicted data for target 3-(bromomethyl)benzonitrile was stated as corrosive , based on the available data of closely related

structurally similar read across substance 3-(bromomethyl)benzonitrile may considered as irritating to skin

Based on the available data for the target 3-(bromomethyl)benzonitrile and read across substances and applying the weight of evidence approach,3-(bromomethyl)benzonitrilecan be considered to be irritating to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritant) based on GHS criteria”.

Eye irritation:

In different studies, 3-(bromomethyl)benzonitrile has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical

3-(bromomethyl)benzonitrile and its structurally similar read across substances Benzonitrile (CAS: 100-47-0) and Phenylacetonitrile (CAS: 140-29-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

The ocular irritation potential of 3-(bromomethyl)benzonitrile was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be irritating to the eye of New Zealand White rabbits.

Based on the estimated results, 3-(bromomethyl)benzonitrile can be considered to be irritating to eye and can be classified under the category “ Category 2 (irritant) based on GHS criteria ” as per CLP regulation.

The above predicted data was supported by experimental data summarized in GESTIS - Substance Database (Information system on hazardous substances of the Benzonitrile ) 2017 for structurally similar read across substance Benzonitrile (CAS: 100-47-0).

Benzonitrile was used as a test material to evaluate its ocular irritation potential on rabbits.

Benzonitrile when administrated on rabbit eye producedreddening of the conjunctiva, no irritation to the cornea and iris, minor vascular injection. These reactions were reversible after 10 days. Based on the ocular reactions Benzonitrile was considered to be slight eye irritant.

 The above experimental data was further supported by experimental data summarized in IUCLID dataset for phenylacetonitrile European Chemicals Bureau 2000 for the structurally similar read across substance Phenylacetonitrile (CAS: 140-29-4).

Phenylacetonitrile was used as a test material to evaluate its ocular irritation potential .

Phenylacetonitrile was subjected to rabbit eye which resulted intotransient hyperemia and lachrymation. On the Basis of above ocular reactions phenylacetonitrile was considered to be eye irritating.

Based on the available data for the target 3-(bromomethyl)benzonitrile and read across substances and applying the weight of evidence approach,3-(bromomethyl)benzonitrilecan be considered to be irritating to eye.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritant) based on GHS criteria”.

 

 

Justification for classification or non-classification

Even though the predicted data for target 3-(bromomethyl)benzonitrile was stated as corrosive , based on the available data of closely related

structurally similar read across substance 3-(bromomethyl)benzonitrile may considered as irritating to skin .

Based on the available data for the target 3-(bromomethyl)benzonitrile and read across substances and applying the weight of evidence approach,3-(bromomethyl)benzonitrilecan be considered to be irritating to skin and eye.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2 (irritant) based on GHS criteria”.