α-bromo-m-toluonitrile

Endpoint summary

Description of key information

Skin sensitization:

The skin sensitization potential of3-(bromomethyl)benzonitrilewas estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

3-(bromomethyl)benzonitrile was estimated to be not sensitizing to the skin of guinea pigs.

Based on the estimated results,3-(bromomethyl)benzonitrilecan be considered to be Not sensitizing to skin and can be classified under the category “Not classified” as per CLP regulation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

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

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

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

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:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of induction:

not specified

No.:

#1

Route:

other: Not specified

Vehicle:

not specified

Concentration / amount:

Not specified

Day(s)/duration:

Not specified

Adequacy of challenge:

not specified

No. of animals per dose:

Not specified

Details on study design:

Not specified

Challenge controls:

Not specified

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

Not specified

No. with + reactions:

0

Clinical observations:

No skin reaction estimated

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin reaction estimated

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 8 nearest neighbours
Domain  logical expression:Result: Out of 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 ( not "l") )  )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

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 SN2 AND SN2 >> SN2 at an sp3 Carbon atom AND SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD 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 All Melting Point > 200 C OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol 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 Alkyl bromide AND Alkyl halide AND Aromatic compound AND Halogen derivative AND Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkyl bromide AND Alkyl halide AND Aromatic compound AND Halogen derivative AND Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Aromatic compound OR Aryl chloride by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkyl bromide AND Alkyl halide AND Aromatic compound AND Halogen derivative AND Nitrile by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "o"

Similarity boundary:Target: N#Cc1cccc(CBr)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Organophosphates (Neurotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.3

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.56

Interpretation of results:

other: Not sensitizing

Conclusions:

3-(bromomethyl)benzonitrile was considered to be not skin sensitizing.

Executive summary:

The skin sensitization 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 not sensitizing to the skin of guinea pigs.

Based on the estimated results,3-(bromomethyl)benzonitrilecan be considered to be Not sensitizing to skin and can be classified under the category “Not classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

In different studies, 3-(bromomethyl)benzonitrile has been investigated for potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical Benzimidazole 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 skin sensitization 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 not sensitizing to the skin of guinea pigs.

Based on the estimated results,3-(bromomethyl)benzonitrilecan be considered to be Not sensitizing to skin and can be classified under the category “Not classified” 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 skin sensitization potential on 35 human volunteers.The test material when applied in the concentration 2% in petrolatum for 48 hrs in occlusive patch test produced no noticeable skin reactions. Hence, Benzonitrile was considered to be not sensitizing to human skin.

The above experimental result was further supported by experimental data summarized in The Scientific Committee on Cosmetic Products and Non-Food Products (SCCNFP) 2000 for structurally similar read across substance and Phenylacetonitrile (CAS: 140-29-4).

The skin sensitization study of Phenylacetonitrile was performed in 27 volunteers to determine its sensitization potential by human maximization test. 2% in petrolatum of test chemical was applied on 27 volunteers and observations were made. No irritation was observed. Therefore the test material Phenylacetonitrile was found to be non sensitizing to 27 volunteers.

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 not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not classified ”.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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 not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not classified ”.