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

Endpoint summary

Description of key information

Acute oral toxicity: 

LD50 was considered to be 23902 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride.

Acute Inhalation toxicity: 

LC50 was considered to be 59.7 mg/L in air when WAG/RijCrlBR male rats were exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by inhalation.

Acute Dermal toxicity: 

LD50 was considered to be 8191 mg/kg bw, when Crj: CD(SD) male and female rats were treated with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by dermal application.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

23902 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

23 902 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Not categorized by US-EPA New Chemical Categories ONLY

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters by DNA binding by OECD

Domain logical expression index: "h"

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: "i"

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: "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 Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> 3-Alken-2-ones (MA) by Protein binding potency

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Inorganic chemical AND Not covered by current version of the decision tree AND Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Metals (1a) OR Multi-halogenated alkyl ethers (23b) OR Organophosphorus compounds (1b) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkyl (C<5) or benzyl ester of sulphonic or phosphonic acid OR H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds AND Halogenated Cycloalkane Type Compounds by Oncologic Primary Classification

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Siloxane Type Compounds by Oncologic Primary Classification

Domain logical expression index: "t"

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: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Group 14 - Metalloids Si,Ge OR Group 15 - Metalloids As,Sb OR Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.02

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.8

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 23902 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride. The LD50 was estimated to be 23902 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

23 902 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Hazardous Substances Data Bank

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

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:

rat

Strain:

other: WAG/RijCrlBR

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

8 h

Remarks on duration:

not specified

Concentrations:

not specified

No. of animals per sex per dose:

8

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LC50

Effect level:

59.7 mg/L air

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average 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(not "l")) ) and("m" and(not "n")) ) and("o" and(not "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 >> 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 SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 SN1 OR SN1 >> Nitrenium Ion formation OR 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 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, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes by Protein binding by OASIS v1.3

Domain logical expression index: "m"

Referential boundary:The target chemical should be classified as Inorganic chemical AND Not covered by current version of the decision tree AND Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "n"

Referential boundary:The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Miscellaneous non-cyclic chemicals (20) OR Multi-halogenated alkyl ethers (23b) by DART scheme v.1.0

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary:The target chemical should be classified as Group 16 - Oxygen O OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F by Chemical elements

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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 Perhexiline (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "u"

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: "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 >= 4.06

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.77

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was estimated to be 59.7 mg/L in air when WAG/RijCrlBR male rats were exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by inhalation.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride. The LC50 was estimated to be 59.7 mg/L in air when WAG/RijCrlBR male rats were exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by inahaltion.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

59 700 mg/m³

Quality of whole database:

Data is Klimisch 2 and from Hazardous Substances Data Bank

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

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:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

8191 mg/kg bw

No. of animals per sex per dose:

Total = 10 (male/female)

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8 191 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "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 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 Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Vinyl pyridines OR Low reactive OR Low reactive >> alpha-alkyl cinnamaldehyde derivatives OR Moderate reactive OR Moderate reactive >> 1,2-Dicarbonyl compounds OR Moderate reactive >> Glycidyl ether epoxides OR Moderate reactive >> Phenyl substituted cinnamaldehydes OR Moderate reactive >> Saturated aldehydes by DPRA Cysteine peptide depletion

Domain logical expression index: "g"

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: "h"

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 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 >> ROS formation after GSH depletion 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 SN2 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 by DNA binding by OASIS v.1.3

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, without OH or NH2 group OR Weak binder, 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 No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acyl halides OR Alkyl (C<5) or benzyl ester of sulphonic or phosphonic acid 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 vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

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 Alkali Earth OR Alkaline Earth OR Metalloids OR Metals OR Transition Metals by Groups of elements

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Oxygen O OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.202

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.8

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 8191 mg/kg bw, when Crj: CD(SD) male and female rats were treated with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by dermal application.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride. The LD50 was estimated to be 8191 mg/kg bw, when Crj: CD(SD) male and female rats were treated with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 191 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Hazardous Substances Data Bank

Additional information

Acute oral toxicity:

In different studies, N-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 acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and mice for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride along with the study available on structurally similar read across substance Isododecane (CAS no 13475-82-6) and 2,2,4,4,6,8,8-Heptamethylnonane (CAS no 4390-04-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride. The LD50 was estimated to be 23902 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride.

In experimental study done on Isododecane by Wilbur et al. (International Journal of Toxicology, vol. 31, suppl 3 : pp. 269S-295S, 2012), the acute oral toxicity study was conducted by using Isododecane in 5 mice in the concentration of 2000 mg/kg bw orally in 10%Olive oil. No mortality was observed at 2000 mg/kg bw. Therefore, LD50 was considered to be > 2000 mg/kg when mice were treated with Isododecane orally.

In another experimental study supported by Ministry of Health, Labour and Welfare, Ministry of the Environment and National Institute of Technology and Evaluation (J-CHECK Japan Chemicals Collaborative Knowledge database, 2010), in a acute oral toxicity study, Sprague-Dawley (Crj: CD) male and female rats were treated with 2, 2, 4, 4, 6, 8, 8, 8-heptamethylnonane in the concentration of 0 and 2000 mg/kg bw orally by gavage in corn oil 25.6% (v / v) and observed for 14 days. No mortality was observed at 2000 mg/kg bw treated rat. Transient diarrhea stools or loose stools were excreted from about 30 minutes to 4 hours after administration in all cases of male and female in the solvent control group, 3 out of 5 females in the 2000 mg / kg administration group and 5 males 4 of them were admitted. However, in both cases, it became a normal flight after that, and there was no abnormality in general condition until the end of the observation. No increase in body weight was observed in any of the administration groups, and body weight gain during the observation period was smooth. No macroscopic changes were observed in both solvent control group and 2000 mg / kg administration group in both sexes. Therefore, LD50 was considered to be > 2000 mg/kg when rats were treated with 2, 2, 4, 4, 6, 8, 8, 8-heptamethylnonane orally.

Thus, based on the above studies and prediction on N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS no 2152-64-9) and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride can be classified as category V of acute oral toxicity.

Acute Inhalation toxicity: 

In different studies, N-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 acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and mice for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride along with the study available on structurally similar read across substance Decane (CAS no: 124-18-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride. The LC50 was estimated to be 59.7 mg/L in air when WAG/RijCrlBR male rats were exposed with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by inahaltion.

In another experimental study supported by U.S. National Library of Medicine (ChemIDplus) and Nilsen et al. (Pharmacology and Toxicology Vol. 62, Pg. 259, 1988), the acute inhalation toxicity study was conducted by using Decane in Sprague Dawley rats at the concentration of1369000 mg/m3. 50% mortality was observed at 1369000 mg/m3 when exposed for 8 hours. Therefore, LC50 was considered to be1369000 mg/m3 when rats were treated with Decane by inahaltion for 8 hours.

Also these results are further supported by U.S. National Library of Medicine (ChemIDplus), the acute inhalation toxicity study was conducted by using Decane in mouse in the concentration of 72300mg/m3. 50% mortality was observed at 72300mg/m3 when exposed for 2 hours. Therefore, LC50 was considered to be72300mg/m3 when mice were treated with Decane by inahaltion for 2 hours.

Thus, based on the above studies and prediction on N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS no 2152-64-9) and its read across substances, it can be concluded that LC50 value is greater than 20000 ppm. Thus, comparing this value with the criteria of CLP regulation, N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity:

In different studies, N-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 acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and rabbits for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride along with the study available on structurally similar read across substance Isooctane (CAS no 540-84-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride. The LD50 was estimated to be 8191 mg/kg bw, when Crj: CD(SD) male and female rats were treated with N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride by dermal application.

In experimental study done on 7-methyloctyl acetate by Wilbur et al. (International Journal of Toxicology, vol. 31, suppl 3 : pp. 269S-295S, 2012), the acute dermal toxicity study was conducted by using Isooctane in Rabbit. Groups of 4 New Zealand White Rabbits were taken for the dermal study. The given test material Isooctane was applied to abraded abdominal skin of rabbits at 3160 mg/kg. No mortality was observed at 3160 mg/kg bw. The dark livers and mottled kidneys were observed in Necropsy observation. Therefore, LD50 was considered to be > 3160 mg/kg when rabbits were treated with Isooctane by dermal application to abraded abdominal skin.

In another experimental study supported by Wilbur et al. (International Journal of Toxicology, vol. 31, suppl 3 : pp. 269S-295S, 2012), the acute dermal toxicity study was conducted by using Isooctane in Rabbit. The given test material Isooctane was applied to skin of rabbits at 2000 mg/kg. No mortality was observed at 2000 mg/kg bw. Therefore, LD50 was considered to be > 2000 mg/kg when rabbits were treated with Isooctane by dermal application.

Thus, based on the above studies and prediction on N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS no 2152-64-9) and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Thus, comparing these values with the criteria of CLP regulation, N-phenyl-4-[[4-(phenylamino)phenyl][4-(phenylimino)cyclohexa-2,5-dien-1-ylidene]methyl]aniline monohydrochloride (CAS no 2152-64-9) can be “Not classified” for acute oral, Inhalation and dermal toxicity.