3,4-dimethoxyphenethylamine

Endpoint summary

Description of key information

The skin sensitization 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 guinea pigs and humans for target chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) and its functionally similar read across substanceAnisic alcohol (CAS No: 105-13-5)andstructurally similar read across substanceVanillin (CAS No: 121-33-5). The predicted data usingQSAR toolbox and Danish QASR Toolbox databasehas 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 unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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 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

Type of study:

other: Modified draize test

Justification for non-LLNA method:

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:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: No data available

Adequacy of induction:

not specified

No.:

#1

Route:

other: No data available

No. of animals per dose:

20

Details on study design:

No data available

Reading:

1st reading

Group:

test chemical

Dose level:

No data available

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No skin sensitization was observed in treated guinea pigs.

Remarks on result:

no indication of skin sensitisation

Cellular proliferation data / Observations:

No skin sensitization was observed in treated guinea pigs.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
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 ("o" and "p" )  )

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 >> 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, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 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 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: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR No alert found OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes 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 >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic amine  OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 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 Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "n"

Similarity boundary:Target: COc1ccc(CCN)cc1OC
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.699

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.15

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated to be not sensitizing to the guinea pigs. Based on the estimated result 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Executive summary:

The skin sensitization potential of 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated using OECD QSAR toolbox version 3.3 with log Pow 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 not sensitizing to the guinea pigs. Based on the estimated result 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) failed to induce skin sanitization effects and hence is considered to be not sensitizing to guinea pigs and can be classified under the category ˋ Not Classified’ as per CLP regulation. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

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 skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) and its functionally similar read across substanceAnisic alcohol (CAS No: 105-13-5)andstructurally similar read across substanceVanillin (CAS No: 121-33-5).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

According to Danish QSAR database , the skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) . Based on estimation, no skin sensitization reactions were observed in guinea Pig and Human. Therefore, 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was considered to be not sensitizing.

 

The skin sensitization potential of 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) failed to induce skin sanitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

 

The D.W. SHARP {Toxicology, 9 (1978) 261-271} conducted skin sensitization study of read across chemical Anisic alcohol (CAS No: 105-13-5) in 10 Inbred Hartley strain albino the guinea pigs of to determine its sensitization potential according modified Draize sensitization test. The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration (ICC) and application challenge concentration(ACC) ]. In the induction phase,the total dose was administered on one occasion as 4 intradermal injections, each 2.5 times the ICC (2.5X 0.25). Fourteen days later each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC (0.25 and 10 respectively). Twenty-four hours later the reactions were observed. In the absence of sensitization reactions at first challenge the induction and challenge procedures were repeated, and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included. Based upon the second challenge, it can be concluded that the Anisic alcohol (CAS No: 105-13-5) was considered to be non-sensitizing to the skin of albino Hartley guinea pigs at 0.25% ICC and 10% ACC concentrations.

 

 The above results were further supported by the Mouse Local Lymphnode Assay conducted by Gerberick GF {Dermatitis, 2005 Dec; 16(4):157-202} for read across chemical Vanillin (CAS No: 121-33-5) by using the Mouse Local Lymphnode Assay. The LLNA was conducted on groups of CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute.  An SI was calculated as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer, if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3) .The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value. The relative potency index of Vanillin (CAS No: 121-33-5) was not calculated but on the basis of classification system it was considered to be >100. Thus the chemical Vanillin (CAS No: 121-33-5) was considered as non-skin sensitizer.

 

Based on the available data for thetarget2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) and its functionally similar read across substanceAnisic alcohol (CAS No: 105-13-5)andstructurally similar read across substanceVanillin (CAS No: 121-33-5),it can be concluded thatchemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) is unable to cause skin sensitization and considered as non-skin sensitizer.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) and its functionally similar read across substanceAnisic alcohol (CAS No: 105-13-5)andstructurally similar read across substanceVanillin (CAS No: 121-33-5) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine; 3,4-dimethoxyphenethylamine (CAS No: 120-20-7) is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.