4-aminonaphthalene-1,8-dicarboximide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vitro

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from predicted data

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Type of study:

other: Dendritic cell activity (h-CLAT)

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Route:

other: no data

Concentration / amount:

no data

Route:

other: no data

Concentration / amount:

no data

No. of animals per dose:

no data

Details on study design:

no data

Challenge controls:

no data

Positive control substance(s):

not specified

Parameter:

other: Dendritic cell activity (h-CLAT)

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

positive indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: CD86,CD54
Estimation method: Takes highest mode value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain AND Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation AND SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

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: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides AND AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "g"

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: "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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Stable form by Tautomers unstable

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Enamine-imine form - 1,5-H shift by Tautomers unstable

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.392

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.8

Interpretation of results:

sensitising

Conclusions:

The substance 4-Amino-1,8-naphthalimide is estimated to be sensitizing according to in vitro Dendritic cell activity (h-CLAT) study in guinea pigs.

Executive summary:

The skin sensitization potential for 4-Amino-1,8-naphthalimide is estimated using OECD QSAR toolbox version 3.4 The test substance 4-Amino-1, 8- (CAS No: 1742-95-6) is estimated to be sensitizing to guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization

Skin sensitization potential of test compound4-Amino-1, 8-naphthalimide (CAS No: 1742-95-6) have been summarized by using data from prediction model based estimation and its read across substances.

Skin sensitization reactions were estimated by OECD QSAR toolbox version 3.4 for test chemical 4-Amino-1, 8-naphthalimide(CAS No: 1742-95-6) in guinea pigs by in vitro Dendritic cell activity (h-CLAT) study. According to this prediction model the test chemical 4-Amino-1, 8-naphthalimide (CAS No: 1742-95-6) is estimated to be sensitizing to guinea pigs.

 

Another prediction model (The Danish (Q) SAR Database) estimated the skin sensitization effects of 4-Amino-1, 8-naphthalimide on guinea pig and human. Based on the QSAR prediction done using the Danish (Q) SAR Database, the substance 4-Amino-1, 8-naphthalimide has positive skin sensitization effect. Thus it can be concluded that the substance 4-Amino-1, 8-naphthalimide is a skin sensitizer.

In the study reported by IFA (GESTIS), the skin sensitization effects were observed for read across substance1, 5-Naphthalenediamine (CAS No:-2243-62-1) in guinea pigs (guinea pig maximisation test) and humans. Since the chemical producedpotential contact allergy, it is considered to be skin sensitizing in guinea pigs and humans.

Skin sensitization study was conducted byEuropean Commission – European Chemicals Bureau 2000(IUCLID Dataset), for similar read across substance 1, 5-Naphthalenediamine (CAS No:-2243-62-1)in guinea pigs. The study was performed according to OECDGuide–line 406 ‘Skin Sensitization’in which the chemical1, 5-Naphthalenediamine (CAS No:-2243-62-1)was applied on guinea pigs during induction phase atintradermal inductionconcentrationof 2.5 % and dermal inductionconcentration of 50 %. The first challenge was performed with 50% concentration. After induction, test animals were challenged with 5 and 25 % of 1, 5-Naphthalenediamine.On the basis of sensitization potential of test 1, 5-Naphthalenediamine (CAS No: - 2243-62-1) on guinea pigs, it can be concluded as skin sensitizer.

 

European Commission – European Chemicals Bureau 2000(IUCLID Dataset), reported the cutaneous reaction observed for another read across substance1-Naphthylamine (CAS No: - 134–32–7) in guinea pigs according toOECDGuide–line 406 ‘Skin Sensitization’. The chemical was able to produced skin sensitization reactions in guinea pig. Hence the test material 1-Naphthylamine (CAS No: - 134–32–7) reported to be sensitizing to guinea pigs.

Therefore based upon the available data for target substance as well as for read across substance and applying weight of evidence approach, the test chemical 4-Amino-1, 8-naphthalimide (CAS No: 1742-95-6) can be classified as skin sensitizer.

Migrated from Short description of key information:

Skin sensitization reactions were estimated by OECD QSAR toolbox version 3.4 for test chemical 4-Amino-1, 8-naphthalimide(CAS No: 1742-95-6) in guinea pigs by in vitro Dendritic cell activity (h-CLAT) study. According to this prediction model the test chemical 4-Amino-1, 8-naphthalimide (CAS No: 1742-95-6) is estimated to be sensitizing to guinea pigs.

Justification for selection of skin sensitisation endpoint:

Skin sensitization reactions were estimated by OECD QSAR toolbox version 3.4 for test chemical 4-Amino-1, 8-naphthalimide(CAS No: 1742-95-6) in guinea pigs by in vitro Dendritic cell activity (h-CLAT) study. According to this prediction model the test chemical 4-Amino-1, 8-naphthalimide (CAS No: 1742-95-6) is estimated to be sensitizing to guinea pigs.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test chemical4-Amino-1, 8- (CAS No: 1742-95-6) was observed in various studies. From the results obtained from these studies it is concluded that the chemical4-Amino-1, 8- (CAS No: 1742-95-6) is likely to cause skin sensitization and can be classified as skin sensitizer.