3,4-dicyanoaniline

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) was assessedin various experimental studies which were conducted on rabbits for target chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) and its structurally similar read across substances2,5-Diaminotoluene (CAS no:95-70-5) and 2-Chloro-1,4-phenylenediamine (CAS No: 615-66-7). The predicted data usingQSAR toolbox and Danish QSAR databasehas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

An ocular irritation potential of target chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) was assessedin various experimental studies which were conducted on rabbits for target chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) and its structurally similar read across substancessubstance2,5-Diaminotoluene (CAS no:95-70-5)anditsfunctionallysimilar read across substancebenzonitrile (CAS No: 100-47-0). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) is unable to cause eye damage and thus can be considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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 from 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 is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

Name: 4-aminobenzene-1,2-dicarbonitrile
SMILES:Nc1ccc(C#N)c(C#N)c1
InChI: 1S/C8H5N3/c9-4-6-1-2-8(11)3-7(6)5-10/h1-3H,11H2
Mol. formula: C8H5N3
Molecular Weight: 143.148 g/mole

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

4 hours

Observation period:

24/48/72 hours

Number of animals:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation was observed.

Estimation method: Takes mode value from the 12 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Phthalonitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Aminobiphenyl Analogs OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> p-Aminobiphenyl Analogs OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Primary aromatic amine,hydroxyl amine and its derived esters by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All Melting Point > 200 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.238

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.22

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)can be considered to be not irritating to skin.

Executive summary:

The dermal irritation potential of 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

Prediction is done using QSAR Toolbox version 3.3

Qualifier:

according to guideline

Guideline:

other: estimated below

Principles of method if other than guideline:

OECD QSAR toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 4-aminobenzene-1,2-dicarbonitrile
- Common name : 3,4-dicyanoaniline
- Molecular formula : C8H5N3
- Molecular weight : 143.148 g/mol
- Smiles notation : N#Cc1c(C#N)ccc(N)c1
- InChl : 1S/C8H5N3/c9-4-6-1-2-8(11)3-7(6)5-10/h1-3H,11H2
- Substance type : Organic
- Physical state : Solid

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:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed.

Estimation method: Takes mode value from the 9 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Phthalonitriles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens by Groups of elements

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  by Repeated dose (HESS)

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Ester, aliphatic attach [-C(=O)O] by Organic functional groups (US EPA)

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.408

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.97

Interpretation of results:

other: not irritating

Conclusions:

The chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) and its structurally similar read across substances2,5-Diaminotoluene (CAS no:95-70-5) and 2-Chloro-1,4-phenylenediamine (CAS No: 615-66-7).The predicted data using the OECD QSAR toolbox andDanish QSAR databasehas also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) .The chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)is estimated to be not irritating to skin of New Zealand White rabbits.

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8). Based on estimation, no skin irritation reactions were observed in rabbits. Therefore, 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) was considered to be not irritating.

 

TheCosmetic Ingredient Review Expert Panel {International Journal of Toxicology; 2010 May;29(3 Suppl):61S-83S}conducted skin irritation study of read across chemical2,5-Diaminotoluene (CAS no:95-70-5) on New Zealand White rabbits that supports above mentioned results.When thetest material was applied at a dose of 2.5% on intact and abraded skin of three rabbit,slight erythema and edema were observed at intact sites of all the animals and one rabbit ha very slight erythema at the abraded site. No signs of irritation were observed after 72 hours. The primary irritation index was estimated to be 0.3.Since all the observed effects were not persisted after 72 hours, the chemical2,5-Diaminotoluene (CAS no:95-70-5) was considered to be not irritating to the New Zealand White rabbits’ eye.

 

The above results were further supported by the another skin irritation study conducted byCosmetic Ingredient Review Expert Panel{JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY Volume 11, Number 4,1992} for read across chemical 2-Chloro-1,4-phenylenediamine (CAS No: 615-66-7) on 3 albino rabbits. The test material was applied on the clipped hair free skin of albino rabbits on one abraded and one intact site on each animal. The test material was used in the concentration0.5 ml of 2.5% w/v in distilled water for 24 hours exposure. The patches were removed and the test sites scored on a scale of 0 to 4 Sites were scored again 72 h after the application. No skin irritation reactions were observed. Hence,2-Chloro-1,4-phenylenediamine was considered to be not irritating to rabbit skin .

 

Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) is unable to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

Eye irritation:

In different studies,the test chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8) andits structurally similar read across substancessubstance2,5-Diaminotoluene (CAS no:95-70-5)anditsfunctionallysimilar read across substancebenzonitrile (CAS No: 100-47-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8).The chemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)is estimated to be not irritating to eye of New Zealand White rabbits.

 

 

The Cosmetic Ingredient Review Expert Panel {International Journal of Toxicology; 2010 May;29(3 Suppl):61S-83S}conducted an ocularirritation study of read across chemical2,5-Diaminotoluene (CAS no:95-70-5)of read across chemical2,5-Diaminotoluene (CAS no:95-70-5). During the test, the test material was installed onto the eyes of rabbits in the concentration 0.1 mL of a 2.5% w/v in aqueous sodium sulphite (pH 7.0) for 10 sec. After 10 seconds the eye was rinsed with 50 mL of lukewarm water. The treatedeyes were evaluated and scored by Draize scoring system at 1 hour and then at Days 1, 2, 3, 4, and 7. Since none of the treated rabbit produced any ocular lesions, the chemical2,5-Diaminotoluene (CAS no:95-70-5) was considered to be not irritating to the rabbits’ eye.

 

 

The above results were further supported by the experimental study reported by BG Chemie {BG Chemie InfoCenter, TOXIKOLOGISCHE BEWERTUNGEN; TOXICOLOGICAL EVALUATION last updated: 06/2000} of read across chemical benzonitrile (CAS No: 100-47-0) in rabbits according to FDA method. In this test, 6 New Zealand white rabbits had 0.1 ml of the test chemical instilled into the conjunctival sac. The untreated eye served as the control. The findings were assessed 24, 48 and 72 hours as well as 7 days after instillation. After 24, 48 and 72 hours, reddening of the conjunctivae was observed in 6, 4 and 4 of the 6 animals, respectively (irritation index 1 from a maximum score of 3). Chemosis occurred in 2 of the 6 animals 24 hours after instillation (irritation index 1 from a maximum score of 4). The cornea and iris were without findings. Slight Irritation was observed, which cleared completely after 7 days. Conjunctivae score – 1; chemosis score – 1; cornea score -0, iris score- 0. Based on these findings and the FDA criteria, benzonitrile was evaluated as not irritating to rabbit eyes.

 

 

Thus on the basis of available data for thetarget chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)and its structurally similar read across substancesits structurally similar read across substancessubstance2,5-Diaminotoluene (CAS no:95-70-5)anditsfunctionallysimilar read across substancebenzonitrile (CAS No: 100-47-0),it can be concluded thatchemical 4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)is unable to cause eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical4-aminobenzene-1,2-dicarbonitrileis unlikely to cause skin and eye irritation. Hence4-aminobenzene-1,2-dicarbonitrile (CAS No: 56765-79-8)can be classified under the category “Not Classified” for skin and eye as per CLP.