o-anisic acid

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated to be irritating to the skin of rabbits. Based on the estimated result 2-methoxybenzoic acid (CAS No: 579-75-9) can be considered as irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Eye Irritation:

The ocular irritation potential of 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated to be irritating to the eyes of rabbits. Based on the estimated result 2-methoxybenzoic acid (CAS No: 579-75-9) can be considered as irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

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:

other: Predicted data

Justification for type of information:

Data is from OECD QSAR Toolbox 3.3

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-methoxybenzoic acid (2-MBA)
- Molecular formula: C8H8O3
- Molecular weight: 152.1482 g/mol
- Smiles notation: COc1ccccc1C(=O)O
- InChl:1S/C8H8O3/c1-11-7-5-3-2-4-6(7)8(9)10/h2-5H,1H3,(H,9,10)
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

not specified

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

no data

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Details on study design:

no data

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:

Skin irritating effects were observed in treated animals.

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 ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and "aa" )  and "ab" )  and ("ac" and "ad" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Ether by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Ether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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: "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 >> 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 AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups 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 >> 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) >> Geminal Polyhaloalkane Derivatives 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 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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 >> Haloalkenes with Electron-Withdrawing Groups 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 >> Monohaloalkanes OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes 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.1.3

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 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 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 SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 >> Secondary 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: "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 Moderate binder, OH grooup OR 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: "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 >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Michael Addition 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 SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Ethylenglycolethers OR Hydrazines,hydrazonium salts OR Ketones OR Primary and secondary aliphatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal log Kow > 4.5 OR Group CHal Melting Point > 65 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 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: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic/Alicyclic hydrocarbons (Alpha 2u-globulin nephropathy) Rank C OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Perhexiline (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Lactone Type Reactive Functional Groups by Oncologic Primary Classification

Domain logical expression index: "y"

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: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 6) 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 <= 2.07

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The dermal irritation potential of 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated to be irritating to the skin of rabbits.

Executive summary:

The dermal irritation potential of 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated to be irritating to the skin of rabbits. Based on the estimated result 2-methoxybenzoic acid (CAS No: 579-75-9) can be considered as irritating to skin and can be classified under the category “Category 2”as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

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:

other: Predicted data

Justification for type of information:

Data is from OECD QSAR toolbox version 3.3

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-methoxybenzoic acid (2-MBA)
- Molecular formula: C8H8O3
- Molecular weight: 152.1482 g/mol
- Smiles notation: COc1ccccc1C(=O)O
- InChl:1S/C8H8O3/c1-11-7-5-3-2-4-6(7)8(9)10/h2-5H,1H3,(H,9,10)
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

no data

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

no data

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Eye irritating effects were observed in treated animals.

Estimation method: Takes mode value from the 6 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 ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Ether by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative AND Ether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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: "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 Acylation OR Acylation >> P450 Mediated Activation to Acyl Halides OR Acylation >> P450 Mediated Activation to Acyl Halides >> 1,1-Dihaloalkanes OR 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 ketones OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 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 >> Secondary aromatic amine OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> 1,2-Dihaloalkanes 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: "h"

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

Domain logical expression index: "i"

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: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Michael Addition 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 SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Aliphatic/Alicyclic hydrocarbons (Alpha 2u-globulin nephropathy) Rank C OR Aromatic hydrocarbons (Liver enzyme induction) Rank C OR Perhexiline (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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: "v"

Referential boundary: The target chemical should be classified as Group All Melting Point > 200 C OR Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.85

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The ocular irritation potential of 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated to be irritating to the eyes of rabbits

Executive summary:

The ocular irritation potential of 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 2-methoxybenzoic acid (CAS No: 579-75-9) was estimated to be irritating to the eyes of rabbits. Based on the estimated result 2-methoxybenzoic acid (CAS No: 579-75-9) can be considered as irritating to eye and can be classified under the category “Category 2”as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemical 2-methoxybenzoic acid (CAS No: 579-75-9) to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and guinea pigs for target chemical2-methoxybenzoic acid (CAS No: 579-75-9) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3),Methyl 2 hydroxybenzoate (CAS No: 119-36-8)and4-methoxyphenol (CAS No: 150-76-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are 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 chemical 2-methoxybenzoic acid (CAS No: 579-75-9).The test substance2-methoxybenzoic acid (CAS No: 579-75-9) is estimated to be irritating to skin of Rabbits when applied dermally.

Becker LC, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler D, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Andersen FA. performed Skin irritation study ofstructurally similar read across substanceMethylbenzoate (CAS No: 93-58-3) in 14male New Zealand albino rabbits. In this study, the undiluted test material was applied to the clipped dorsum (0.5mL) and external surface of the outer ear (0.2mL) of each rabbits for 6 observation period. On the dorsum there were marked cellular reactions and dermal edema beginning on day 2 followed by dermal hemorrhage, desquamated crust, and thickening of the malpighian stratum beginning on day 5 were observed and on the inner ear, there was slight hyperkeratosis on day 6.  Since the test chemical was rated as grade 1, Methylbenzoate (CAS No: 93-58-3) was considered to be irritating to the clipped dorsum and external surface of the outer ear of male New Zealand albino rabbits.

The above results were supported by experimental skin irritation study conducted by A. Lapczynski *, L. Jones, D. McGinty, S.P. Bhatia, C.S. Letizia, A.M. Api (2007) on anotherstructurally similar read across substanceMethyl 2 hydroxybenzoate (CAS No: 119-36-8) as a part of the acute dermal LD50 in 9 rabbits. The single application of undiluted test sample was applied dermally at concentration of 5000mg/kg and observations were made.Slight (2/9 rabbits) to moderate (7/9 rabbits) erythema and edema was observed.As the test chemical showed skin irritating effects in treated animals,Methyl 2 hydroxybenzoate (CAS No: 119-36-8) was considered to be irritating to the rabbits skin.

TheCosmetic Ingredient Review (1985) reported skin irritation study of another structurallysimilar read across substance4-methoxyphenol (CAS No: 150-76-5) on 2 guinea pigs which further supports the above results. A patch containing 40 % 4-methoxyphenolin an acetone/olive oil mixture (92:8) was applied for 24 hours in a single 10 or 20 ml/kg dose to the clipped and depilated skin of 2 guinea pigs (1 animal/dose) and skin reactions were observed.Slight to moderate skin irritation was observed after application of test chemical. Hence the test chemical4-methoxyphenol (CAS No: 150-76-5)was considered to be irritating to theguinea pigs’skin.

Based on the available data for the target substance 2-methoxybenzoic acid (CAS No: 579-75-9) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3),Methyl 2 hydroxybenzoate (CAS No: 119-36-8)and4-methoxyphenol (CAS No: 150-76-5),it can be concluded thatchemical 2-methoxybenzoic acid (CAS No: 579-75-9) 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”.

Eye irritation:

In different studies,test chemical2-methoxybenzoic acid (CAS No: 579-75-9) has been investigated for potential for ocular irritation to a greater or lesser extent.The studies are based on in vivo experiments in rabbits for target chemical2-methoxybenzoic acid (CAS No: 579-75-9) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3),Methyl 2 hydroxybenzoate (CAS No: 119-36-8)and4-methoxyphenol (CAS No: 150-76-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data which are 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 chemical 2-methoxybenzoic acid (CAS No: 579-75-9).The test substance2-methoxybenzoic acid (CAS No: 579-75-9) is estimated to be irritating to eye of Rabbits.

 

The above result was supported by an ocular irritation study conducted in rabbits by Becker LC, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler D, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Andersen FA onstructurally similar read across substanceMethylbenzoate (CAS No: 93-58-3). In this study,neat (100%) methyl benzoate was applied to the center of the cornea while the lids were retracted. One minute later the lids were released. The eyes were examined 18–24 h later in strong diffuse daylight and then stained with fluorescein.Methyl benzoate was given a grade 1 (iritis and slight internal congestion) after 24 hours of observation. Based on this rating, methyl benzoate can be considered as an eye irritant.

A. Lapczynski *, L. Jones, D. McGinty, S.P. Bhatia, C.S. Letizia, A.M. Api (2007) on anotherstructurally similar read across substanceMethyl 2 hydroxybenzoate (CAS No: 119-36-8) performed two eye irritation studies in rabbits for anotherstructurally similar read across substanceas follows;

The first eye irritation test was conducted in 5 healthy albino rabbits to assess the irritation potency ofMethyl 2 hydroxybenzoate (CAS No: 119-36-8). A 0.005 ml aliquot of neatMethyl 2 hydroxybenzoate (CAS No: 119-36-8)was applied to the center of the cornea while the lids were retracted. One minute later the lids were released. The eyes were examined 18–24 h later in strong diffuse daylight and then stained with fluorescein.Methyl 2 hydroxybenzoate (CAS No: 119-36-8)was assigned grade 3 – necrosis since 13–37% of the cornea was visible after fluorescein staining. Therefore,Methyl 2 hydroxybenzoate (CAS No: 119-36-8)can be considered to be irritating to rabbit eyes

The next eye irritation test was conducted in albino rabbit. Normal albino rabbit eyes were selected on the basis of absence of grossly visible staining by a 5-percent aqueous solution of fluorescein sodium, flushed with distilled water 20 seconds after application. A 2 hour interval was given so that the eye could return back to normal condition. Then, 0.005 ml of the undiluted test material was applied to the center of the cornea while the lids were retracted. About one minute later, the lids were released. This procedure is necessary to prevent the removal of a portion of the dose by the very efficient wiping system of the lids before intimate contact has been made with the eye. 18 to 24 hours later, the eyes were examined in strong diffuse daylight, and then stained with fluorescein, and the injury was scored.Methyl 2 hydroxybenzoate (CAS No: 119-36-8)was grouped under Grade 3 injury (0.1 ml undiluted gives injury of up to 5 points (0.5 ml gives over 5)) and Grade 9 injury (Excess of 1% solution gives injury up to 5 points (5% gives over 5)) when rabbit eyes were observed for injuries.Methyl 2 hydroxybenzoate (CAS No: 119-36-8)was known to have caused loss of vision or very slowly healing corneal burns. Based on these grades, it can be inferred thatMethyl 2 hydroxybenzoate (CAS No: 119-36-8)was irritating to rabbit eyes.

The Cosmetic Ingredient Review (1985) reported skin irritation study of another structurallysimilar read across substance4-methoxyphenol (CAS No: 150-76-5) in New Zealand rabbits according to the procedures used were a modified version of the test methods outlined by Draize. The undiluted test substance was installed into the eyes of 3 to 6 (exact number not specified) rabbits and ocular lesions were observed over a period of 7 days. The average corneal, iridic, and conjunctival irritation scores 1 hour postinstillation were as follows: (1) cornea: score, 20 (max, 80); (2) iris: score, 5 (max, 10); (3) conjunctivae: score, 4 (max, 20). Average ocular irritation scores for the undiluted chemical 7 days postinstillation were 80, 10, and 14 for cornea, iris, and conjunctiva, respectively, indicating severe ocular irritation.The Corneal and iridial lesions have not cleared by the seventh day. Hence thetestchemical4-methoxyphenol (CAS No: 150-76-5)was considered as severe irritant to New Zealand rabbits’ eye.

Based on the available data for the target substance 2-methoxybenzoic acid (CAS No: 579-75-9) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3),Methyl 2 hydroxybenzoate (CAS No: 119-36-8)and4-methoxyphenol (CAS No: 150-76-5),it can be concluded thatchemical 2-methoxybenzoic acid (CAS No: 579-75-9) 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”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical2-methoxybenzoic acid (CAS No: 579-75-9) and its structurally similar read across substancesMethylbenzoate (CAS No: 93-58-3),Methyl 2 hydroxybenzoate (CAS No: 119-36-8)and4-methoxyphenol (CAS No: 150-76-5), were observed in various studies. The results obtained from these studies indicates that the test chemical 2-methoxybenzoic acid (CAS No: 579-75-9)is likely to cause skin and eye irritation. Hence2-methoxybenzoic acid (CAS No: 579-75-9) can be classified under the category “Category 2” for skin and eye as per CLP