3,4-dimethoxyphenethylamine

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was assessedin various experimental studies which were conducted on rabbits and guinea pigs for target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  and its functionally similar read across substancesAnisic alcohol (CAS No: 105-13-5)andveratrole (CAS No: 91-16-7). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) is able to cause severe skin irritation and thus considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 2”.

 

Eye irritation

An ocular irritation potential of target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  was assessedin various experimental studies which were conducted on rabbits for target chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  and its functionally similar read across substances2-Methoxybenzyl alcohol (CAS no: 612-16-8) and 4-MethoxyphenyIacetic Acid (MPAA) (CAS No: 104-01-8). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) is able to cause severe eye damage and thus can be considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 2”.

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:

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 version 3.3 and QMRF report has been attached

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 the test material (IUPAC name): 2-(3,4-dimethoxyphenyl)ethan-1-amine
- Common name: 3,4-dimethoxyphenethylamine
- Molecular weight: 181.2335 g/mole
- Molecular formula: C10H15NO2
- Smiles: COc1ccc(CCN)cc1OC
- Inchl: 1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not fully reversible within:

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

skin irritation was observed.

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Primary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

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 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 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 SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR 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, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "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 Moderate binder, NH2 group OR 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, NH2 group OR Strong binder, OH group OR Weak binder, NH2 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 ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA) by Protein binding potency

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 CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as (!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 Melting Point > 200 C OR Group C Melting Point > 55 C 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 CNHal log Kow > 3.8 OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion 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 CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m 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 Non-Metals by Groups of elements

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Similarity boundary:Target: COc1ccc(CCN)cc1OC
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

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 Aliphatic amines (Mucous membrane irritation) Rank C OR Oximes (Hemolytic anemia with methemoglobinemia) Rank B by Repeated dose (HESS)

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Alkylarylether AND Amine AND Aromatic compound AND Ether AND Primary aliphatic amine AND Primary amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Alkylarylether AND Amine AND Aromatic compound AND Ether AND Primary aliphatic amine AND Primary amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Alkylarylether AND Amine AND Aromatic compound AND Ether AND Primary aliphatic amine AND Primary amine by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary AND Aryl AND Ether by Organic Functional groups ONLY

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.148

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.45

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated to be highly irritating to the skin of rabbits. Based on the estimated results, 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) can be considered to be severely irritating to skin.

Executive summary:

The dermal irritation potential of 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor. The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated to be highly irritating to the skin of rabbits. Based on the estimated results, 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) can be considered to be severely 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:

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 version 3.3 and QMRF report has been attached

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 the test material (IUPAC name): 2-(3,4-dimethoxyphenyl)ethan-1-amine
- Common name: 3,4-dimethoxyphenethylamine
- Molecular weight: 181.2335 g/mole
- Molecular formula: C10H15NO2
- Smiles: COc1ccc(CCN)cc1OC
- Inchl: 1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not fully reversible within:

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

severe eye irritation was observed in treated rabbits.

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 "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and ( not "x") )  )  and ("y" and "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Primary amines by OECD HPV Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals AND Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Narcotic Amine by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

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 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 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 SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR 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 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "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 Moderate binder, NH2 group OR 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, NH2 group OR Strong binder, OH group OR Weak binder, NH2 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 ONLY

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group CN Lipid Solubility < 0.4 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as (!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 Melting Point > 200 C OR Group C Melting Point > 55 C 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 CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNS Aqueous Solubility < 0.006 g/l OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Derivatives of alpha amino benzene by Eye 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 CN Lipid Solubility < 0.4 g/kg by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m 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 Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Similarity boundary:Target: COc1ccc(CCN)cc1OC
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Oximes (Hemolytic anemia with methemoglobinemia) Rank B by Repeated dose (HESS)

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.399

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.89

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated to be severely irritating to the eyes of rabbits.Based on the estimated results, 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) can be considered to be irritating to eyes and can be classified under the category “Category 2” as per CLP regulation.

Executive summary:

The ocular irritation potential of 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)was estimated using OECD QSAR toolbox v3.3 with logPow as the primary descriptor. The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)was estimated to be severely irritating to the eyes of rabbits. Based on the estimated results, 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)can be considered to be irritating to eyes 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 chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  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-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) and its functionally similar read across substancesAnisic alcohol (CAS No: 105-13-5)andveratrole (CAS No: 91-16-7).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 chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) .The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  is estimated to be irritating to skin of rabbits.

 

The Sustainability Support Service (Europe) AB with access rights from Givaudan UK Ltd. (1978) conducted a skin irritation study of read across chemical Anisic alcohol (CAS No: 105-13-5) in guinea pigs via Open Epicutaneous test (OET) that supported the above mentioned results of target chemical. The 0.025ml of chemical was applied at different concentrations (60, 30, 10 and 3 %) to an area measuring 2cm2previously marked with a circular stamp on the clipped flanks in of 6 to 8 animals under non-occlusive condition. Skin reactions were evaluated after 24 hours of application and on day 7, 14 and 21. A single application of Anisyl alcohol (4-methoxybenzyl alcohol) 3% in acetone is well tolerated. Repeated applications cause very slight skin irritation only. The highest concentration of the preparation used for this treatment was 60%. Hence the chemical 4-methoxybenzyl alcohol / Anisic alcohol (CAS No: 105-13-5) was considered as irritating to the skin on guinea pigs.

 

The above results were further supported by dermal irritation study of read across chemical veratrole (CAS No: 91-16-7) reported by S Gangolli (The dictionary of substances and their effects second edition 1999) which was conducted on guinea pigs. When veratrole (CAS No: 91-16-7) was applied dermally on guinea pigs at a dose of 40% in olive oil, slight to moderate irritation was observed. Hence the chemical veratrole (CAS No: 91-16-7) was considered as irritating to the skin of guinea pigs.

 

Thus based on the available data for the target as well as read across substances and applying the weight of evidence approach,it can be concluded thatchemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) is able to cause severe 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,the test chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  its functionally similar read across substances2-Methoxybenzyl alcohol (CAS no: 612-16-8) and 4-MethoxyphenyIacetic Acid (MPAA) (CAS No: 104-01-8).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 ocular irritation potential was estimated for test chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7).The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  is estimated to be severely irritating to eye of rabbits.

 

The D. Belsito et.al, (Food and Chemical Toxicology, Vol. 50, Pg. no. S52-S99, 2012) conducted an eye irritation study of read across chemical 2-Methoxybenzyl alcohol (CAS no: 612-16-8) on three rabbits. The chemical was installed into the eye of each subjects at a dose of 0.1ml and later observed for ocular lesions. Each treated rabbit showed definite conjunctival irritation which persisted until day 7. Hence, the chemical 2-Methoxybenzyl alcohol (CAS no: 612-16-8) was considered to be irritating to the rabbits’ eye.

 

 

The above results were further supported by the ocular irritation study reported by National Technical Information Service {National Technical Information Service, OTS0530656-1 (1991)} on read across chemical 4-methoxyphenylacetic acid in rabbits according to the Draize method. The test was conducted on New Zealand White rabbits. The test was first performed on one rabbit with 0.1gm of test substance, the treated eye showed moderate irritation, Thereafter 8 additional animals were tested and subjected to rinsing with normal saline after 30 seconds of administration .Ocular lesions were scored approx 1 hr, 1 day upto 21 days. Even 21 days after treatment, un-rinsed eyes in 5/6 treated animals displayed corneaI opacity, iritis and conjunctival irritation. The maximum mean irritation score was 71.2 (of 110 possible maximum) which occurred on day 3, the rinsed eyes showed milder effects; however, serious adverse effects persisted to day 21. 4-MethoxyphenyIacetic Acid (MPAA) was considered to be a very severe irritant to the eye of albino rabbits under the conditions of these studies causing effects which were not reversed within 21 days of treatment. Immediate washing of the eyes resulted in reduced irritation and more rapid recovery. 4-MethoxyphenyIacetic Acid (MPAA) (CAS No: 104-01-8) can be considered as irritating to the eyes.

 

Thus based on the available data for the target as well as read across substances and applying the weight of evidence approach,it can be concluded thatchemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) is able to cause severe 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 chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  and its functionally similar read across substanceswere observed in various studies. The results obtained from these studies indicates that the chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  is likely to cause severe skin and eye irritation. Hence 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7)  can be classified under the category “Category 2” for skin and eye as per CLP.