[4-[[4-anilino-1-naphthyl][4-(dimethylamino)phenyl]methylene]cyclohexa-2,5-dien-1-ylidene]dimethylammonium acetate

Endpoint summary

Description of key information

The skin sensitization potential ofN-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate(83803-79-6)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.N-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)was predicted to be non sensitizing to the skin of male and femaleHartleyguinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3.

GLP compliance:

not specified

Type of study:

other: Estimated data

Justification for non-LLNA method:

Not specified.

Specific details on test material used for the study:

- Name of test material : N-(4-((4-(dimethylamino)phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate- Molecular formula: C33H32N3C2H3O2- Molecular weight : 529.68 g/mol- Smiles notation : [N+](=C1/C=CC(\C=C1)=C(\c1ccc(c2ccccc12)Nc1ccccc1)c1ccc(cc1)N(C)C)(\C)C.C(C)(=O)[O-]- InChl : 1S/C33H31N3.C2H4O2/c1-35(2)27-18-14-24(15-19-27)33(25-16-20-28(21-17-25)36(3)4)31-22-23-32(30-13-9-8-12-29(30)31)34-26-10-6-5-7-11-26;1-2(3)4/h5-23H,1-4H3;1H3,(H,3,4)- Substance type: Organic- Physical state: Liquid

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

No data available.

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

Test group-20

Details on study design:

No data available.

Challenge controls:

No data available.

Positive control substance(s):

not specified

Statistics:

No data available.

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization effect were observed.

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 7 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 "m" )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acetoxy OR Alkene OR Ammonium salt OR Aromatic amine OR Aryl OR Carboxylic acid OR Fused carbocyclic aromatic OR Naphtalene by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acetoxy OR Alkene OR Ammonium salt OR Aromatic amine OR Aryl OR Fused carbocyclic aromatic OR Naphtalene OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aliphatic Nitrogen, one aromatic attach [-N] OR Aliphatic Nitrogen, two aromatic attach [-N-] OR Amino, aliphatic attach [-N<] OR Aromatic Carbon [C] OR Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Nitrogen, two or tree olefinic attach [>N-] 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 Anion OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Carboxylic acid salt OR Cation OR Secondary amine OR Secondary aromatic amine OR Tertiary amine OR Tertiary mixed 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 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 AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) 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 >> Quinone methides OR SN1 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 carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines 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 >> 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 >> Nucleophilic substitution at sp3 Carbon atom 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 by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 SN1 OR SN1 >> Carbenium ion formation (enzymatic) OR SN1 >> Carbenium ion formation (enzymatic) >> Carbenium ion by Protein binding by OASIS v1.3

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "l"

Similarity boundary:Target: CC(=O)O{-}.N{+}(C)(C)=C1C=CC(=C(c2ccc(N(C)C)cc2)c2ccc(Nc3ccccc3)c3ccccc23)C=C1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as months and longer by Biodeg ultimate (Biowin 3) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 5) ONLY

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.49

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 16.6

Interpretation of results:

other: not sensitising

Conclusions:

The skin sensitization potential of N-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate(83803-79-6) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. N-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6) was predicted to be non sensitizing to the skin of male and female Hartley guinea pig.

Executive summary:

The skin sensitization potential ofN-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate(83803-79-6)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.N-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)was predicted to be non sensitizing to the skin of male and female Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

In different studiesN-(4-((4-(dimethylamino) phenyl) (4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)has been investigated for potential for dermal sensitization to a greater or lesser extent. The prediction are based on in vivo experiments in guinea pig for target chemicalN-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)and its structurally similar read across substancesZinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate (CAS No: 2215–35–2). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential ofN-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate(83803-79-6)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.N-(4-((4-(dimethylamino) phenyl)(4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)was predicted to be non sensitizing to the skin of male and femaleHartleyguinea pig.

 It is supported by experimental data conducted by European Chemicals Bureau (IUCLID DATABSE- EUROPEAN COMMISSION – European Chemicals Bureau–2000) on structurally similar read across substance Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate (CAS No: 2215–35–2)on guinea pigs.The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on skin sensitization from the analogue substance. The skin sensitization study of Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate (CAS No: 2215–35–2) was performed in 10 guinea pigs to observed its sensitizing potential according to Guinea pig maximisation test.The material was tested on guinea pigs skin at a concentration 5% w/w dilution of the test article in white mineral oil which did not produce any sensitization reactions in any of 10 test animals.Therefore based upon study, it can be concluded that the Zinc bis (O, O-bis (1, 3-dimethylbutyl) dithiophosphate(CAS No: 2215–35–2) is not sensitizing to guinea pigs.

 

Thus based on the above predictions on N-(4-((4-(dimethylamino) phenyl) (4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)as well as its read across substances and applying weight of evidence, it can be concluded thatN-(4-((4-(dimethylamino) phenyl) (4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation,N-(4-((4-(dimethylamino) phenyl) (4-(phenylamino)naphthalen-1-yl)methylene)cyclohexa-2,5-dienylidene)-N-methylmethanaminium acetate (83803-79-6)can be considered as not classified for skin sensitization effects.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation,N-(4-((4-(dimethylamino) phenyl) (4-(phenylamino)naphthalen-1-yl) methylene)cyclohexa-2,5-dienylidene) -N-methylmethanaminium acetate (83803-79-6)can be considered as not classified for skin sensitization effects.