2-methylanisole

Endpoint summary

Description of key information

The skin sensitization potential of 1-methoxy-2-methylbenzene(578-58-5)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-methoxy-2-methylbenzene(578-58-5)was predicted to be not sensitizing to the skin of guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

- Name of test material: 2-methylanisole
- IUPAC name: 1-methoxy-2-methylbenzene
- Molecular formula: C8H10O
- Molecular weight: 122.166 g/mole
- Smiles : COc1ccccc1C
- Inchl: 1S/C8H10O/c1-7-5-3-4-6-8(7)9-2/h3-6H,1-2H3
- Substance type: Organic
- Physical state: Liquid (Colorless)

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Statistics:

No data available

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

No skin sensitization reaction was observed

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation","A B C"
Estimation method: Takes highest 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 ( 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 Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Aryl OR Ether by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkyl arenes OR Ether OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] 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 Alkylarylether OR Aromatic 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 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Michael addition on conjugated systems with electron withdrawing group OR AN2 >> Michael addition on conjugated systems with electron withdrawing group >> Thiadiazoledioxide derivatives 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 >> 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 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 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 >> 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) >> Geminal Polyhaloalkane Derivatives 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 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN2 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 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 >> 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 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 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 >> 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 Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Alpha-beta-dicarbonyl 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 >> Secondary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes 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 >> Ring opening acylation OR Acylation >> Ring opening acylation >> Cyclopropenones  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 >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes 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 >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  by Protein binding by OASIS v1.3

Domain logical expression index: "n"

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 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 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 CHal Molecular Weight > 370 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as Ethylenglycolethers OR Ketones by Skin irritation/corrosion Inclusion 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 Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical 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 Chlorphentermine (Hepatotoxicity) Alert 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 No alert found by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as 1,3-dialkoxy-benzene OR alpha,beta-unsaturated aliphatic alkoxy group OR H-acceptor-path3-H-acceptor OR Oxolane by in vivo mutagenicity (Micronucleus) alerts by ISS

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 Low (Class I) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

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

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.73

Interpretation of results:

other: not sensitizing

Conclusions:

The skin sensitization potential of 1-methoxy-2-methylbenzene (578-58-5) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-methoxy-2-methylbenzene (578-58-5) was predicted to be not sensitizing to the skin of guinea pig.

Executive summary:

The skin sensitization potential of 1-methoxy-2-methylbenzene(578-58-5)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-methoxy-2-methylbenzene(578-58-5)was predicted to be not sensitizing to the skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, 1-methoxy-2-methylbenzene (578-58-5) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical 1-methoxy-2-methylbenzene(578-58-5)and its structurally similar read across substances2-methoxynaphthalene (93-04-9)and1 Methoxy 4 methylbenzene (104-93-8) the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 1-methoxy-2-methylbenzene (578-58-5)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances 1-methoxy-2-methylbenzene(578-58-5)was predicted to be not sensitizing to the skin of guinea pig.

Prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for estimated 1-methoxy-2-methylbenzene(578-58-5)Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 1-methoxy-2-methylbenzene(578-58-5) estimated to be not sensitizing when applied to human and guinea pig skin.

The experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology. Vol. 13, Pg. 885, 1975)to evaluate the skin sensitizing potential of 2-methoxynaphthalene (93-04-9) in human. In skin sensitization study, 26 volunteers were tested by maximization test at a concentration of 4% in petrolatum. No skin sensitization reaction was observed in treated volunteer.Therefore, the 2-methoxynaphthalene (93-04-9) was considered to be not sensitizing to humans.

Supported by experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology. Vol. 12, Pg. 393, 1974) to evaluate the skin sensitizing potential of read across substance 1 Methoxy 4 methylbenzene (104-93-8) in human. In skin sensitization study, 25 volunteers were tested by maximization test at a concentration of 2% in petrolatum. No skin sensitization reaction was observed in treated volunteer.Therefore, the 1 Methoxy 4 methylbenzene (104-93-8) was considered to be not sensitizing to humans.

Thus based on the above predictions on 1-methoxy-2-methylbenzene (578-58-5) as well as its read across and applying weight of evidence, it can be concluded that 1-methoxy-2-methylbenzene (578-58-5) is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 1-methoxy-2-methylbenzene (578-58-5) can be considered as not classified for skin sensitization.

 

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, 1-methoxy-2-methylbenzene (578-58-5) can be considered as not classified for skin sensitization.