N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated to be not irritating to the skin of Himalayan rabbits. Based on the estimated result N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

 

Eye irritation:

The ocular irritation potential of N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated to be not irritating into the eyes of Himalayan rabbits. Based on the estimated result N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ 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 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 of test material: N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride
- Molecular formula: C37H29N3.ClH
- Molecular weight: 552.118 g/mol
- Smiles notation: C(\c1ccc(Nc2ccccc2)cc1)(c1ccc(Nc2ccccc2)cc1)=C1/C=C\C(=N/c2ccccc2)C=C1.Cl
- InChl: 1S/C37H29N3.ClH/c1-4-10-31(11-5-1)38-34-22-16-28(17-23-34)37(29-18-24-35(25-19-29)39-32-12-6-2-7-13-32)30-20-26-36(27-21-30)40-33-14-8-3-9-15-33;/h1-27,38-39H;1H
- Substance type: Organic
- Physical state: solid

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

72 hours

Observation period:

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 8 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Aromatic amine OR Aryl OR Azomethine OR Ketimine OR No functional group found by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Aromatic amine OR Aryl OR Azomethine OR Ketimine OR No functional group found OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Nitrogen, two or tree olefinic attach [>N-] OR No functional group found OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR No functional group found OR Secondary amine OR Secondary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found AND Non-specific AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as 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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Ketones OR Organic silicon halides by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "n"

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 AND Exclusion rules not met AND Group All log Kow > 9 AND Group All Melting Point > 200 C AND Group CN Aqueous Solubility < 0.0001 g/L AND Group CN Aqueous Solubility < 0.1 g/L AND Group CN log Kow > 4.5 AND Group CN log Kow > 5.5 AND Group CN Melting Point > 180 C AND Group CN Molecular Weight > 290 g/mol AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group C Surface Tension > 62 mN/m OR Group All log Kow < -3.1 OR Group C Aqueous Solubility < 0.0001 g/L OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CN Molecular Weight > 540 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Amorphous silica silicates OR Cadmium (oxide) OR Carbonate/Hydrocarbonate OR Chlorosilanes OR Chromates OR Copper metal and copper compounds OR Iron salts OR Mono and Di-butyltins OR Mono and Di-octyltins OR Nitrates OR Persulfates OR Sodium chlorite/Chlorine dioxide OR Soluble silicates by OECD HPV Chemical Categories

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as DSSTOX AND ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as (N/A) OR Canada DSL OR COSING OR HPVC OECD OR METI Japan by Inventory Affiliation

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Nitrogen, two or tree olefinic attach [>N-] AND No functional group found AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] AND Aliphatic Nitrogen, two aromatic attach [-N-] AND Aromatic Carbon [C] AND Nitrogen, two or tree olefinic attach [>N-] AND No functional group found AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.88

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 13.4

Interpretation of results:

other: not irritating

Conclusions:

The substance N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated to be not irritating to the skin of Himalayan rabbits.

Executive summary:

The dermal irritation potential of N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated to be not irritating to the skin of Himalayan rabbits. Based on the estimated result N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) 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:

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 of test material: N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride
- Molecular formula: C37H29N3.ClH
- Molecular weight: 552.118 g/mol
- Smiles notation: C(\c1ccc(Nc2ccccc2)cc1)(c1ccc(Nc2ccccc2)cc1)=C1/C=C\C(=N/c2ccccc2)C=C1.Cl
- InChl: 1S/C37H29N3.ClH/c1-4-10-31(11-5-1)38-34-22-16-28(17-23-34)37(29-18-24-35(25-19-29)39-32-12-6-2-7-13-32)30-20-26-36(27-21-30)40-33-14-8-3-9-15-33;/h1-27,38-39H;1H
- Substance type: Organic
- Physical state: solid

Species:

rabbit

Strain:

Himalayan

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:

72 hours

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

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 signs of eye irritation were seen in any animal.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkene OR Aromatic amine OR Aryl OR Azomethine OR Ketimine OR No functional group found by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkene OR Aromatic amine OR Aryl OR Azomethine OR Ketimine OR No functional group found OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Aromatic Carbon [C] OR Nitrogen, two or tree olefinic attach [>N-] OR No functional group found OR Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Amine OR Aromatic compound OR No functional group found OR Secondary amine OR Secondary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, MW>500 AND Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Aldehydes OR Organic silicon halides by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B OR Aliphatic/Alicyclic hydrocarbons (Alpha 2u-globulin nephropathy) Rank C OR Organophosphates (Neurotoxicity) Rank A OR Perhexiline (Hepatotoxicity) Alert OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not categorized by OECD HPV Chemical Categories

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alpha-olefins OR Amorphous silica silicates OR C14+Aliphatics hydrocarbon solvents (less than 2 percent aromatics) OR C9-13 Aliphatics hydrocarbon solvents (less than 2 percent aromatics) OR Cadmium (oxide) OR Carbonate/Hydrocarbonate OR Chlorosilanes OR Chromates OR Copper metal and copper compounds OR Higher olefins OR Iron salts OR Nitrates OR Persulfates OR Sodium chlorite/Chlorine dioxide OR Soluble silicates by OECD HPV Chemical Categories

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as DSSTOX AND ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as HPVC OECD by Inventory Affiliation

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as DSSTOX AND ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as METI Japan by Inventory Affiliation

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as DSSTOX AND ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as COSING by Inventory Affiliation

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as DSSTOX AND ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Canada DSL by Inventory Affiliation

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as DSSTOX AND ECHA PR AND EINECS AND NICNAS AND REACH ECB AND TSCA AND US HPV Challenge Program by Inventory Affiliation

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as (N/A) by Inventory Affiliation

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as (N/A) by Database Affiliation

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Phys-chem EPISUITE by Database Affiliation

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Not calculated by Biodeg BioHC half-life (Biowin) ONLY

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as No alert found AND Non-specific AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    AND Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives AND SN1 AND SN1 >> Nucleophilic substitution on diazonium ions AND SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "ae"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines by DNA binding by OASIS v.1.3

Domain logical expression index: "af"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND No functional group found AND Secondary amine AND Secondary aromatic amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.79

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 11

Interpretation of results:

other: not irritating

Conclusions:

The substance N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated to be not irritating to the eyes of Himalayan rabbits. Based on the estimated result N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) was estimated to be not irritating to the eyes of Himalayan rabbits. Based on the estimated result N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) 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 chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9)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 chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) and its structurally similar read across substancesBasic Violet 3 (CAS No: 548-62-9)and Hexamethylcyclotrisiloxane (CAS No: 541-05-9).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 skin irritation potential was estimated for test chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) .The chemical N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) is estimated to be not irritating to skin of Himalayan rabbits.

 

The dermal irritation potential ofstructurally similar read across substanceBasic Violet 3 was assessed (Haskell Laboratory for Toxicology and Industrial medicine, Sustainability Support Services (Europe) AB has letter of access, 1974) in rabbits. 6 male albino rabbits were clipped free of hair on the trunk and lateral areas and placed in a FDA- type stocks. One inch sqaures of test material were applied to intact skin under 1inch*1inch gauze squares (double thickness). Rubber sheeting was loosely wrapped around the trunk and secured with an adhesive tape. After 24 hours, the rabbits were removed from the stocks and reactions were graded. Observations were also made at 48 hours. The observations were graded according to the system of the regulations of the Federal Hazardous Substances Act. Basic Violet 3 (CAS No: 548-62-9) failed to produce any dermal reactions in the rabbits. Hence, Basic Violet 3 was considered to be not irritating to rabbit skin

The above results were supported by the experimental study reported by OECD SIDS (2008) forstructurally similar read across substanceHexamethylcyclotrisiloxane (CAS No: 541-05-9) on single rabbits to determine its skin irritation efficacy. The abdomen of the rabbit was prepared for testing by shaving the application site. One side of the abdomen was manually abraded while the skin on the opposite was not. During the test, the 500mg (0.5g) of undiluted Hexamethylcyclotrisiloxane was applied daily for 10 days (excluding weekends) to each side of the shaved abdomen under semi-occlusive condition and later observed for skin reactions. The test material produced slight redness only. The study did not provide the severity score for redness or the time of its onset and reversibility. Hence the Hexamethylcyclotrisiloxane (CAS No: 541-05-9) was considered to be not irritating to the rabbit skin.

Thus on the basis of available data for the target chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) and its structurally similar read across substancesBasic Violet 3 (CAS No: 548-62-9)and Hexamethylcyclotrisiloxane (CAS No: 541-05-9),it can be concluded thatchemical N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) 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 chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) 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 chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9)its structurally similar read across substances Octamethylcyclotetrasiloxane (CAS No: 556-67-2)and Hexamethylcyclotrisiloxane (CAS No: 541-05-9).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 chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) .The chemical N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) is estimated to be not irritating to eye of Himalayan rabbits.

 

The SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS (SCCP, 2005) a Draize test ofstructurally similar read across substanceOctamethylcyclotetrasiloxane (CAS No: 556-67-2) on One male and one female New Zealand White rabbits to assess the degree of irritancy caused by the chemical. In this test, 100 µl neat octamethyltetracyclosiloxane was instilled into the conjunctival sac of one eye of each of the two rabbits and the lids were gently held together for about one second. The eyes were not rinsed after treatment. The other eye served as control. Eyes were examined at 1, 24, 48, 72 h and 7 days after application. Apart from hyperaemic vessels in the conjunctivae of one rabbit eye at one hour after application, which were resolved by 24 hours. Since the observed effects were cleared within 24 hours, the chemical Octamethylcyclotetrasiloxane (CAS No: 556-67-2) was considered as not irritating to the eye of New Zealand White rabbits.

 

The above results were supported by the experimental studies reported by OECD SIDS (2008) forstructurally similar read across substanceHexamethylcyclotrisiloxane (CAS No: 541-05-9) on single rabbit to determine its eye irritation efficacy. In this test, 0.1 ml of of undiluted Hexamethylcyclotrisiloxane was installed in each eye. Following instillation, one eye was washed and the other was not. The eyes were observed for 1, 2, 24, 48 and 168 hours. Since no eye irritation was observed the Hexamethylcyclotrisiloxane (CAS No: 541-05-9) was considered to be not irritating to the rabbit's eye.

 

Thus on the basis of available data for thetarget chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) and its structurally similar read across substancesOctamethylcyclotetrasiloxane (CAS No: 556-67-2)and Hexamethylcyclotrisiloxane (CAS No: 541-05-9),it can be concluded thatchemical N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) 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 chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemicalN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride is unlikely to cause skin and eye irritation. HenceN-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS No: 2152-64-9)can be classified under the category “Not Classified” for skin and eye as per CLP.