2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone is estimated to be non-mutagenic in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 as well as Chinese hamster Ovary (CHO) in the presence or abscence of metabolic activation.

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)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

The prediction is done using QSAR toolbox version 3.3 with lo Kow as the primary discriptor

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

No data available

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9

Test concentrations with justification for top dose:

no data

Vehicle / solvent:

DMSO

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

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

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

Remarks on result:

other: all strains/cell types tested

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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Hydrazines and Related Compounds by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Fused carbocyclic aromatic AND Naphtalene AND Phenol by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Overlapping groups AND Phenol by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alcohol, olefinic attach [-OH] AND Aromatic Carbon [C] AND Hydrazine [>N-N<] AND Hydroxy, aromatic attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aromatic compound AND Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider (checkmol)

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 of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 >> 5-alkoxyindoles 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 Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl 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 amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Carbenium Ion Formation >> Diazoalkanes OR SN1 >> Carbenium Ion Formation >> Hydrazine OR SN1 >> Carbenium Ion Formation >> N-Nitroso (alkylation) OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Carbenium Ion Formation >> Triazenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic nitroso OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN1 >> Nitrosation-SN1 OR SN1 >> Nitrosation-SN1 >> N-Nitroso-SN1 OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Nitrosation-SN2 OR SN2 >> Nitrosation-SN2 >> Nitroso-SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides 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 No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Flavonoids OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> Hydroxamic Acids OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Anthrones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Flavonoids OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 >> Acyclic Triazenes OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines 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 SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Fused-Ring Nitroaromatics OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Polynitroarenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Hydroxamic Acids OR SN2 >> Acylation >> Specific Acetate Esters 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins 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 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.6

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.37

Conclusions:

Interpretation of results (migrated information):negativeThe substance 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone is estimated to be non-mutagenic in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 in the presence or abscence of metabolic activation in an bacterial reverse mutation assay.

Executive summary:

The mutagenicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone is estimated using QSAR toolbox 3.3.

The substance 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone is estimated to be non-mutagenic in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 in the presence or abscence of metabolic activation in an bacterial reverse mutation assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Genetic toxicity in vitro:

The mutagenicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy naphthyl)methylene]hydrazone (CAS no 2387-03-3) was estimated using QSAR toolbox 3.3 (2016). The substance 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1 naphthyl)methylene]hydrazone is estimated to be non-mutagenic in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 in the presence or abscence of metabolic activation in an bacterial reverse mutation assay.

The mutagenicity of 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone (CAS no 2387-03-3) was estimated using QSAR toolbox 3.3 (2016). The substance 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy-1-naphthyl)methylene]hydrazone is estimated to be non-mutagenic in Chinese hamster Ovary (CHO) in the presence or abscence of metabolic activation in an in vitro mammalian chromosome aberration test.

The mutagenic potency of test substanceYellow 101(CAS no 2387-03-3)was estimatedby four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database, 2016.The ames test was performed using theSalmonella typhimuriumstrains. Based on the four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database, it was found that the test compound induces mutation in the Salmonella typhimurium strains. Thus, the test was found to be positive.

The mutagenic potency of test substanceYellow 101(CAS no 2387-03-3)was estimatedby four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database, 2016.In vitro Chromosome Aberration assay in Chinese Hamster Lung (CHL) cells was performed.Based on the four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database, it was found that thetest compound induces chromosomal mutation/aberrations in the Chinese Hamster Lung (CHL) cells. Thus, the test was found to be positive.

In the Ames bioassay (Sustainability Support Services, 1983) no 2-tert-butylhydroquinone (TBHQ) (RA CAS no 1948-33-0) related increases in revertants were noted in any test strain either with or without S-9 liver enzymes. 2-tert-butylhydroquinone (TBHQ) was negative when tested in the standard Ames test in five strains of Salmonella typhimurium both with and without rat liver S-9 microsomal activation.

2-tert-butylhydroquinone(RA CAS no 1948-33-0)showed negative results for Salmonella typhimurium TA97, TA100, TA102, TA104 with and without metabolic activation. At dose level of 100 μg/plate and higher, 2-tert-butylhydroquinone was found to show cytotoxic effect on the test bacterial strains (Hageman et al, 1988).

2-tert-butylhydroquinone is non-mutagenic to E. coli strain IC203, deficient in OxyR, and its oxyR+ parent WP2 uvrA/pKM101 in the presence of rat liver S9 activation at a test concentration of 150 µg/plate. Mutagenesis by 2-tert-butylhydroquinone was inhibited by catalase present in rat liver S9 (Hageman et al, 1988).

An in vitro mammalian cell gene mutation study (Sustainability Support Services (Europe) AB, 2015) was designed and conducted to determine the genotoxicity profile of 4, 4'-methylenedi-2,6-xylenol (CAS No. 5384-21-4) when administered to Chinese Hamster Ovary (CHO) cells.In the genotoxicity test, 4,4'-methylenedi-2,6-xylenol was administered to CHO cells for 3 hrs at the dose levels of 0, 12.5, 25.0, 50.0 or 100.0µM and in the absence or presence of exogenous metabolic activation.4,4'-methylenedi-2,6-xylenol does not give rise to gene mutations when exposed to the test chemical at ≤ 100.0µM for 3 hrs or more, in the presence or absence of metabolic activation.

 

Genetic toxicity in vivo:

The mutagenic potency of test substance Yellow 101 was estimated by four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database (2016).Sex Linked Recessive Lethal (SLRL) Testwas performed usingDrosophila melanogasteras the test animal.Based on the four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database, it was found that the test compound Yellow 101 induces no gene mutation in Drosophila melanogaster.Thus, the test was found to be negative.

 

The mutagenic potency of test substance Yellow 101 was estimatedby four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database (2016).In vivo dominant lethal mutation assaywas performed using the rodents as the test animal.Based on the four different models i.e, Battery, CASE Ultra, Leadscope and SciQSAR used within Danish QSAR database, it was found that the test compound Yellow 101 induces no chromosomal aberration in rodents.Thus, the test was found to be negative. As per the CLP classification, the test material Yellow 101 is not likely to classify for gene mutation in vitro and in vivo. The test material Basic yellow 57 is not likely to be classified as a gene mutant in vitro and in vivo.

Based on the information observed for the test chemical and its various read across, it is summarized that 2-hydroxynaphthalene-1-carbaldehyde [(2-hydroxy naphthyl)methylene] hydrazone (CAS no 2387-03-3) is not likely to exhibit genetic toxicity. Thus, the chemical is not classified as a genetic toxicant.

Justification for selection of genetic toxicity endpoint
The data is obtained using prediction model.

Justification for classification or non-classification

On the basis of the available data, the substance Basic yellow 57 can be considered to be non-mutagenic and hence can be classified as non-genotoxic in vitro and in vivo as per the CLP criteria.