Registration Dossier

Skin irritation:

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to skin of rabbits.

Eye irritation:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to eye of rabbits.

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 predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached
Qualifier:: according to guideline
Guideline:: other: estimated data
Principles of method if other than guideline:: Prediction was done by using OECD QSAR toolbox v3.4
GLP compliance:: not specified
Specific details on test material used for the study:: - Name of test material (IUPAC name): 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one
- Common name: 7-Methoxy-2-tetralone
- Molecular formula: C11H12O2
- Molecular weight: 176.214 g/mol
- Smiles notation: c12c(CCC(C1)=O)ccc(c2)OC
- InChl: 1S/C11H12O2/c1-13-11-5-3-8-2-4-10(12)6-9(8)7-11/h3,5,7H,2,4,6H2,1H3
Physical state: Liquid (Light yellow to yellow)
- Substance type: Organic
Species:: rabbit
Strain:: not specified
Details on test animals or test system and environmental conditions:: No data available
Type of coverage:: not specified
Preparation of test site:: not specified
Vehicle:: not specified
Controls:: not specified
Amount / concentration applied:: No data available
Duration of treatment / exposure:: No data available
Observation period:: No data available
Number of animals:: No data available
Details on study design:: No data available
Irritation parameter:: overall irritation score
Basis:: mean
Time point:: other: not specified
Reversibility:: not specified
Remarks on result:: no indication of irritation
Interpretation of results:: other: Not irritating
Conclusions:: 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was considered to be not skin irritating on rabbit skin.
Executive summary:: In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to skin of rabbits.

Endpoint conclusion:

no adverse effect observed (not 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 adequate and reliable documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name): 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one
- Common name: 7-Methoxy-2-tetralone
- Molecular formula: C11H12O2
- Molecular weight: 176.214 g/mol
- Smiles notation: c12c(CCC(C1)=O)ccc(c2)OC
- InChl: 1S/C11H12O2/c1-13-11-5-3-8-2-4-10(12)6-9(8)7-11/h3,5,7H,2,4,6H2,1H3
- Substance type: Organic
Physical state: Liquid (Light yellow to yellow)

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period (in vivo):

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: not specified

Reversibility:

not specified

Remarks on result:

no indication of irritation

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

(((((((((((("a" or "b" ) and ("c" and ( not "d") ) ) and ("e" and ( not "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" ) and "q" ) and "r" ) and ("s" and "t" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nucleophilic addition AND Nucleophilic addition >> Addition to carbon-hetero double bonds AND Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives 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 >> Fused-Ring Nitroaromatics OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives 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) >> Fused-Ring Nitroaromatics OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide 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 nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes 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 and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes 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 >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes 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 OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 >> 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 >> 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 esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR High reactive >> Vinyl pyridines OR Low reactive OR Low reactive >> Alicyclic ketones by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "j"

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 Strong binder, OH group OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Group All Melting Point > 200 C OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 4-Alkylchlorobenzenes OR Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "o"

Similarity boundary:Target: COc1ccc2CCC(=O)Cc2c1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: COc1ccc2CCC(=O)Cc2c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Similarity boundary:Target: COc1ccc2CCC(=O)Cc2c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.49

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.39

Interpretation of results:

other: not irritating

Conclusions:

7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was considered to be non irritant to rabbit eye.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to eye of rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation:

In different studies, 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one and its structurally similar read across substances 4-(p-methoxyphenyl)butan-2-one(104-20-1) and p- methoxyphenylacetone (122-84-2) . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to skin of rabbits.

The above estimation was further supported by another prediction done by using Danish QSAR database

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one. Based on estimation, no severe skin irritation effects were known when 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was exposed to rabbit skin.Hence, 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one can be considered not irritating to skin.

The above predicted data were supported by experimental result of study conducted by Food and Cosmetics Toxicology. 12, 929, 1974 for the structurally similar read across substance 4-(p-methoxyphenyl)butan-2-one(104-20-1)

4-(p-methoxyphenyl) butan-2-one was used as a test material to evaluate its skin irritation potential .4-(p-methoxyphenyl) butan-2-one was used in the concentration of 5% in petrolatum for 48hrs in a closed patch test on human subjects. The substance 4-(p-methoxyphenyl) butan-2-one produced no skin reaction when applied on human skin. 4-(p-methoxyphenyl) butan-2-one was considered to be not irritant to human skin.

The above experimental result was further supported by Food and cosmetics toxicology volume 17, supplement ,Pages 695-923 (December 1979) forstructurally similar read across substance p- methoxyphenylacetone (122-84-2)

p-methoxyphenylacetone was used as a test material to evaluate its skin irritation potential. p-methoxyphenylacetone was tested on human subjects in a closed patch test method in the concentration 4% in petrolatum for 48 hrs. p-methoxyphenylacetone produced no skin reaction. Hence,itwas considered as not irritating to human skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,7-methoxy-1,2,3,4-tetrahydronaphthalen-2-onewas not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Eye irritation:

In different studies, 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one and its closely related read across substances 4-methylanisole (104-93-8) and Methyl Benzoylformate (15206-55-0) . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to eye of rabbits.

The above predicted data was further supported by experimental study conducted by IUCLID Dataset - 4-Methylanisole European Chemicals Bureau (ECB) 2000 for theclosely related read across substance 4-methylanisole (104-93-8)

4-methylanisole was used as test material for evaluation of its ocular irritation potential on rabbits , according toOECD Guide–line 405 "Acute Eye Irritation/Corrosion"4-methylanisole was evaluated for its eye irritation potential on rabbits. 4-methylanisole produced no ocular reactions were noted . 4-methylanisole is considered to be not irritating to rabbit eye.

The above experimental report was further supported by experimental study conducted by IUCLID Dataset - Methyl Benzoylformate European Chemicals Bureau (ECB) 2000

Methyl benzoylformate was used as test material for evaluation of its ocular irritation potential on rabbits , according toOECD Guide–line 405 "Acute Eye Irritation/Corrosion" methyl benzoylformatewas evaluated for its eye irritation potential on rabbits. methyl benzoylformateproduced no ocular reactions were noted . 4-methylanisole is considered to be not irritating to rabbit eye.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,7-methoxy-1,2,3,4-tetrahydronaphthalen-2-onewas not irritating to eye.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,7-methoxy-1,2,3,4-tetrahydronaphthalen-2-onewas not irritating to skin and eye.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.