4-aminonaphthalene-1,8-dicarboximide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test compound 4-Amino-1,8-naphthalimide is not likely to be a gene mutant in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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 database

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 102

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation system

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

No data

Evaluation criteria:

Increase in the number of revertants

Statistics:

No data

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

No data

Remarks on result:

other: strain/cell type:

Remarks:

Migrated from field 'Test system'.

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" or "e" or "f" )  and "g" )  and ("h" and ( not "i") )  )  and ("j" and ( not "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" )  )

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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Conjugated keto(scy) - 1,5-H shift OR Conjugated keto(scy) - 1,7-H shift OR Conjugated ketoamine(scy) - 1,5-H shift OR Enol form OR Keto form (5-membered heteroarenes) - 1,3-H shift by Tautomers unstable

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR 4,4'-Methylenedianilines/benzidines (Hepatobiliary toxicity) Rank B  OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Dantrolene (Hepatotoxicity) Alert OR Fialuridine (Hepatotoxicity) Alert OR Nitrobenzenes (Hemolytic anemia with methemoglobinemia) Rank A OR Nitrobenzenes (Hepatotoxicity) Rank C OR Nitrosamines (Hepatotoxicity) No rank OR o-/ p-Aminophenols (Hemolytic anemia with methemoglobinemia) Rank B by Repeated dose (HESS)

Domain logical expression index: "p"

Similarity boundary:Target: Nc1ccc2c3c1cccc3C(=O)NC2=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group OR Acylation >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amides OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carboxylic Acid Amides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha, beta - Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Carboxylic Acid Amides OR AN2 >> Michael addition to the quinoid type structures >> Hydroxylated Phenols OR AN2 >> Michael addition to the quinoid type structures >> N-Subsituted Aromatic Amines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines OR AN2 >> Michael addition to the quinoid type structures >> Substituted Phenols OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines OR AN2 >> Michael-type addition to activated double bonds in vinyl pyridines >> Ethenyl Pyridines OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as alpha,beta-unsaturated carbonyls OR Aromatic N-acyl amine OR Coumarins and Furocoumarins OR Hydrazine OR Nitro-aromatic OR No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.728

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.26

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation

The test compound 4-Amino-1,8-naphthalimide failed to induce mutation in the Salmonella typhimurium strain TA102 in the presence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Executive summary:

Gene mutation toxicity was predicted for the test compound 4-Amino-1,8-naphthalimide using SSS QSAR prediction database. The study assumed the use of Salmonella typhimurium strain TA102 in the presence of S9 metabolic activation system. The test compound 4-Amino-1,8-naphthalimide failed to induce mutation in the Salmonella typhimurium strain TA102 in the presence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Gene toxicity in vitro:

Prediction model based estimation and data from read across have been summarized to determine the mutagenic nature of the test compound 4-Amino-1,8-naphthalimide.

Gene mutation toxicity was predicted for the test compound 4-Amino-1,8-naphthalimide (CAS no 1742-95-6) using SSS QSAR prediction database (2016). The study assumed the use of Salmonella typhimurium strain TA102 in the presence of S9 metabolic activation system. The test compound 4-Amino-1,8-naphthalimide failed to induce mutation in the Salmonella typhimurium strain TA100 in the presence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

 

In a similar predictionusing SSS QSAR prediction database (2016),Gene mutation toxicity was predicted for the test compound 4-Amino-1,8-naphthalimide (CAS no 1742-95-6). The study assumed the use of Salmonella typhimurium strain TA1535 in the absence of S9 metabolic activation system. The test compound 4-Amino-1,8-naphthalimide failed to induce mutation in the Salmonella typhimurium strain TA1535 in the absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

 

In a study for RA CAS no 85-41-6 , Bacterial reverse mutation assay was performed for the test chemical phthalimide using Salmonella typhimurium strain TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA (Authorities of The Law, Ministry of Health, Labour and Welfare, Ministry Of Economy, Trade and Industry, and Ministry of the Environment, 2016). The study was performed using the preincubation protocol at dose levels of 0, 313, 625, 1250, 2500 or 5000 μg / plate with in incubation period of 48 hrs in the presence and absence of S9 mix.Dose range finding study was performed at dose levels of 5000, 1250, 313, 78.1, 19.5, 4.88, 1.22 μg / plate. No mutagenic response was noted for the test compound in the preliminary dose range finding study and the main study performed.The test compound pthalimide failed to induce mutation in the Salmonella typhimurium strain TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA with and without S9 mix and hence is not likely to classify for gene mutation in vitro.

In another study for RA CAS no 2835 -95 -2 conducted by Seifried et al (2006), The Ames salmonella typhimurium mutagenicity test was conducted for chemical 5-Amino-o-cresol. The study was performed using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 in the presence and absence of S9 metabolic activation system. Plate incorporation study was conducted at five dose levels from 100-10000 µg/plate during 48hrs exposure period. The test compound 5-Amino-o-cresol failed to induce mutation in the Salmonella typhimurium strains and hence is not likely to classify as a gene mutant in vitro.

Based on the weight of evidence data summarized, the test chemical 4-Amino-1,8-naphthalimide (CAS no 1742 -95 -6) is not likely to classify as a gene mutant in vitro.

Justification for selection of genetic toxicity endpoint

Data is from predicted database

Justification for classification or non-classification

Based on the weight of evidence data summarized, the test chemical 4-Amino-1,8-naphthalimide is not likely to classify as a gene mutant in vitro.

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