Registration Dossier

Skin irritation:

The dermal irritation potential of 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6 ) was estimated to be irritating to the skin of New Zealand White rabbits. Based on the estimated result 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) can be considered as irritating to skin and can be classified under the category ˋCategory 2 (irritant)’ as per CLP regulation.

Eye irritation:

The ocular irritation potential of 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated to be irritating to the eye of New Zealand White rabbits. Based on the estimated result 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) can be considered as irritating to eye and can be classified under the category ˋCategory 2 (irritant)’ as per CLP regulation.

Reference

Endpoint:

skin irritation: 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

Specific details on test material used for the study:

- Name of test material: 6-Methoxy-2-naphthaldehyde
- Molecular formula: C12H10O2
- Molecular weight: 186.209 g/mol
- Smiles notation: COc1ccc2cc(ccc2c1)C=O
- InChl: 1S/C12H10O2/c1-14-12-5-4-10-6-9(8-13)2-3-11(10)7-12/h2-8H,1H3
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

24 hours

Observation period:

8 days

Number of animals:

6

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Signs of irritation observed

Estimation method: Takes 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 ( not "k") ) ) and ("l" and ( not "m") ) ) and "n" ) and ("o" and ( not "p") ) ) and ("q" and ( not "r") ) ) and ("s" and ( not "t") ) ) and "u" ) and "v" ) and "w" ) and "x" ) and "y" ) and "z" ) and "aa" ) and "ab" ) and ("ac" and "ad" ) )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aldehyde OR Aryl OR Ether OR Fused carbocyclic aromatic OR Naphtalene by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aldehyde OR Ether OR Fused carbocyclic aromatic OR Naphtalene OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aldehyde, aromatic attach [-CHO] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aldehyde OR Alkylarylether OR Aromatic compound OR Carbonyl compound OR Ether by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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 >> Schiff base formation >> Dicarbonyl compounds 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical 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 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters 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 cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards 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 OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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 to Quinones and Quinone-type Chemicals 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 Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

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 Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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 >> alpha,beta-Carbonyl compounds with polarized double bonds OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m AND Group C Melting Point > 55 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m AND Group C Melting Point > 55 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Group All log Kow > 9 OR Group All Melting Point > 200 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

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

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.21

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.02

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

6-Methoxy-2-naphthaldehyde was estimated to be irritating to the skin of New Zealand White rabbits.

Executive summary:

The dermal irritation potential of 6-Methoxy-2-naphthaldehyde was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

6-Methoxy-2-naphthaldehyde was estimated to be irritating to the skin of New Zealand White rabbits.

Based on the estimated results, 6-Methoxy-2-naphthaldehyde can be considered to be irritating to skin and can be classified under the category “Category 2” as per CLP regulation.

Endpoint conclusion:

adverse effect observed (irritating)

Reference

Endpoint:

eye irritation: 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

Specific details on test material used for the study:

- Name of test material: 6-Methoxy-2-naphthaldehyde
- Molecular formula: C12H10O2
- Molecular weight: 186.209 g/mol
- Smiles notation: COc1ccc2cc(ccc2c1)C=O
- InChl: 1S/C12H10O2/c1-14-12-5-4-10-6-9(8-13)2-3-11(10)7-12/h2-8H,1H3
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1g

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Signs of irritation were observed

Estimation method: Takes mode value from the 7 nearest neighbours
Domain logical expression:Result: In Domain

((((((((((((((((((("a" and ("b" and ( not "c") ) ) and ("d" and ( not "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 "q" ) and "r" ) and "s" ) and "t" ) and "u" ) and "v" ) and "w" ) and "x" ) and "y" ) and ("z" and ( not "aa") ) ) and ("ab" and "ac" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group C Melting Point > 55 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition, quinoid structures OR AN2 >> Michael-type addition, quinoid structures >> Quinones OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom 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) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones 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 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 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group C Melting Point > 55 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group All Molecular Weight > 650 g/mol OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Molecular Weight > 380 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CNHal Molecular Weight > 370 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aliphatic monoalcohols by Eye irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Ac-SN2 OR Ac-SN2 >> Acylation involving an activated (glucuronidated) ester group OR Ac-SN2 >> Acylation involving an activated (glucuronidated) ester group >> Arenecarboxylic Acid Esters 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 alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Phenols by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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 >> Anhydrides (sulphur analogues of anhydrides) OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters 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 >> alpha,beta-Carbonyl compounds with polarized double bonds OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Carboxylic acids (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.62

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.16

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

6-Methoxy-2-naphthaldehyde was estimated to be irritating to the eyes of New Zealand White rabbits.

Executive summary:

The ocular irritation potential of 6-Methoxy-2-naphthaldehyde was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor.

6-Methoxy-2-naphthaldehyde was estimated to be irritating to the eyes of New Zealand White rabbits.

Based on the estimated results, 6-Methoxy-2-naphthaldehyde can be considered to be irritating to eyes and can be classified under the category “Category 2” as per CLP regulation

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Skin irritation:

Various studieshas been investigated for the test chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substancesp-Anisaldehyde (CAS No: 123-11-5)and4-chloro-benzaldehyde (CAS No: 104-88-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) .The chemical 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)is estimated to be irritating to skin of New Zealand White rabbits.

The D. L. J. Opdyke (1979) conducted skin irritation study ofstructurally similar read across substancep-Anisaldehyde (CAS No: 123-11-5) on rabbits.Each rabbit received neatp-Anisaldehyde on intact and abraded skin for 24 hours under occlusive condition and later observed for skin lesions.Since the treated rabbits showed mild signs of irritation, the chemicalp-Anisaldehyde (CAS No: 123-11-5)was considered to be mildly irritating to theintact and abraded skin of rabbits.

The above results were further supported by the experimental study conducted by EUROPEAN COMMISSION – European Chemicals Bureau (2000) onstructurally similar read across substance4-chloro-benzaldehyde (CAS No: 104-88-1) in two rabbits to observe its irritation efficacy under semi-occlusive condition.In this study, the test chemical was applied to the skin of each rabbits for the exposure period of 8 and 24 hours and observed for 7 days.Slight signs of irritation were observed during 7 days observation period. Hence the test chemical4-chloro-benzaldehyde (CAS No: 104-88-1)was considered to be slightly irritating to the rabbit’s skin.

Based on the available data for the targetchemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substancesp-Anisaldehyde (CAS No: 123-11-5)and4-chloro-benzaldehyde (CAS No: 104-88-1),it can be concluded thatchemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)is able to cause skin irritation and considered as irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2(irritant)”.

Eye irritation

In different studies,the test chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) has been investigated for potential for ocular irritationto observe the potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substancesVanillin (CAS No: 121-33-5)and4-chloro-benzaldehyde (CAS No: 104-88-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) .The chemical 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)is estimated to be irritating to eye of New Zealand White rabbits.

The NTRL (National Technical Reports Library, 1991) and OECD SIDS (1996) reported an eye irritation study ofstructurally similar read across substanceVanillin (CAS No: 121-33-5) in six New Zealand White rabbits. The Vanillin was applied as finely ground powder at a dose equivalent to 55 mg (0.1 ml) for 24 hours and reactions were scored at 24 , 48 and 72 hours according to Federal Hazardous Substances Act (FHSA). Mild irritating effects were observed with the irritation score of 18.8 (out of maximum score of 110). All scored zero after 168 hours. Since the chemical caused slight discomfort and ocular lesions during the 72 hours observation period, the chemical Vanillin (CAS No: 121-33-5) was considered to be mildly irritating to the eyes of six New Zealand White rabbits

The above results were further supported by the experimental study conducted by EUROPEAN COMMISSION – European Chemicals Bureau (2000) onstructurally similar read across substance4-chloro-benzaldehyde (CAS No: 104-88-1) on rabbits. In this study, the test chemical was installed into the eyes of each rabbits and later ocular lesions were observed for 7 days. Slight signs of irritation were observed during 7 days observation period. Hence the chemical4-chloro-benzaldehyde (CAS No: 104-88-1) was considered to be slightly irritating to the rabbit’s eye.

Thus based on the available data for the targetchemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substancesVanillin (CAS No: 121-33-5)and4-chloro-benzaldehyde (CAS No: 104-88-1),it can be concluded thatchemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) is able to cause eye irritation and considered as irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2(irritant)”.

The skin and eye irritation potential of test chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the test chemical 6-Methoxy-2-naphthaldehydeis likely to cause skin and eye irritation. Hence 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)can be classified under the category “Category 2(irritant)” for skin and eye as per CLP.