3,4-dimethoxyphenethylamine

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) was predicted based on OECD QSAR toolbox 963 mg/kg bw and different studies available for the structurally similar read across substances 1,2-dimethoxy-benzene (91-16-7) 890 mg/kg bw; and 4-methoxybenzyl alcohol (105-13-5)1200 mg/kg bw. All these studies concluded that the LD50 is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine can be classified as “Category 4” for acute oral toxicity.

Acute Inhalation toxicity: 

Acute Inhalation toxicity dose (LC50) for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) was predicted based on OECD QSAR toolbox 13.5 mg/L (13500 mg/m3); based on experimental study conducted by Jay A. Brown (Haz-Map®: Information on Hazardous Chemicals and Occupational Diseases, U.S. National Library of Medicine, October 2017)>5500 mg/m3; and different study available for the structurally similar read across substance 2-Methoxyphenol (90-05-1) 7570 mg/m³. All these studies concluded that the LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine cannot be classified for acute Inhalation toxicity.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) was predicted based on OECD QSAR toolbox 2100 mg/kg bw and different studies available for the structurally similar read across substances 4-Methoxyphenylacetone (122-84-9) >5000 mg/kg bw; and 4-methoxybenzyl alcohol (105-13-5)3000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting 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

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name: 2-(3,4-dimethoxyphenyl)ethan-1-amine
- InChI:1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Smiles:COc1ccc(CCN)cc1OC
- Name of test material: Homoveratrylamine
- Molecular formula :C10H15NO2
- Molecular weight :181.2335 g/mol
- Substance type:organic

Species:

rat

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

963 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

963 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 "n" )  and "o" )  and ("p" and "q" )  )

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 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: "g"

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 Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides 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 >> Aromatic nitro 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 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Aziridines OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Arylethanamine-like derivatives (11a) AND Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) by DART scheme v.1.0

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "l"

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: "m"

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: "n"

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: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.59

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

LD50 was estimated to be 963 mg/kg bw, when 5 male albino rats were treated with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) via oral gavage route.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7). The LD50 was estimated to be 963 mg/kg bw, when 5 male albino rats were treated with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) via oral gavage route.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

963 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting 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

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name: 2-(3,4-dimethoxyphenyl)ethan-1-amine
- InChI:1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Smiles:COc1ccc(CCN)cc1OC
- Name of test material: Homoveratrylamine
- Molecular formula :C10H15NO2
- Molecular weight :181.2335 g/mol
- Substance type:organic

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

13.5 mg/L

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

13.5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average 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 ("k" and "l" )  )

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 SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 No alert found by DNA binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.037

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.99

Interpretation of results:

other: Not classified

Conclusions:

LC50 was estimated to be 13.5 mg/L (13500 mg/m3), when 10 male and female Sprague-Dawley rats were exposed with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) via inhalation route to whole body exposure for 4 h.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7). The LC50 was estimated to be 13.5 mg/L (13500 mg/m3), when 10 male and female Sprague-Dawley rats were exposed with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) via inhalation route to whole body exposure for 4 h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

13 500 mg/m³

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.3 and the supporting 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

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name: 2-(3,4-dimethoxyphenyl)ethan-1-amine
- InChI:1S/C10H15NO2/c1-12-9-4-3-8(5-6-11)7-10(9)13-2/h3-4,7H,5-6,11H2,1-2H3
- Smiles:COc1ccc(CCN)cc1OC
- Name of test material: Homoveratrylamine
- Molecular formula :C10H15NO2
- Molecular weight :181.2335 g/mol
- Substance type:organic

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

24 hours

Doses:

2100 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 100 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((((("a" or "b" or "c" or "d" or "e" )  and "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and "s" )  and "t" )  and ("u" and "v" )  )

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 Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR Exclusion rules not met 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 Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Respiratory sensitisation

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Polarised alkenes OR Michael Addition >> Polarised alkenes >> Acrylates OR Pro-Schiff base formation OR Pro-Schiff base formation >> Pro-cross linking Schiff base OR Pro-Schiff base formation >> Pro-cross linking Schiff base >> Ethanolamines OR Pro-Schiff base formation >> Pro-cross linking Schiff base >> Ethylenediamines by Respiratory sensitisation

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic nitriles (Hepatotoxicity) Rank B by Repeated dose (HESS)

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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: "s"

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: "t"

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

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.69

Interpretation of results:

other: Not classified

Conclusions:

LD50 was estimated to be 2100 mg/kg bw, when 5 male and female New Zealand White rabbits were treated with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) for 24 hours by dermal application occlusively.

Executive summary:

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7). The LD50 was estimated to be 2100 mg/kg bw, when 5 male and female New Zealand White rabbits were treated with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) for 24 hours by dermal application occlusively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 100 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from QSAR toolbox 3.3.

Additional information

Acute oral toxicity:

In different studies, 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for 2-(3,4-dimethoxyphenyl)ethan-1-amine along with the study available on structurally similar read across substances 1,2-dimethoxy-benzene (91-16-7) and 4-methoxybenzyl alcohol (105-13-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7). The LD50 was estimated to be 963 mg/kg bw, when 5 male albino rats were treated with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) via oral gavage route.

This study is supported by U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 1,2-dimethoxy-benzene (91-16-7). The acute oral toxicity study was conducted in rat at the concentration of 890 mg/kg. 50% mortality was observed at 890 mg/kg bw. Therefore, LD50 was considered to be 890 mg/kg bw, when rat was treated with 1,2-dimethoxy-benzene via oral route.

These studies are further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 825), Draize et al.(Journal of Pharmacology and Experimental Therapeutics May 1948, 93 (1) 26-39), Scognamiglio et al.(Food and Chemical Toxicology 50 (2012) S134–S139),Richard J. Lewis, Sr.(Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set,2012) and MaryAdele J’o Neil (The Merck Index, 14th Edition, 2006), for the structurally similar read across substance 4-methoxybenzyl alcohol (105-13-5). The acute oral toxicity study was conducted in rat at the concentration of 1200 mg/kg. 50% mortality was observed at 1200 mg/kg bw. Clinical signs like severe depression and dyspnoea were reported prior to death. Therefore, LD50 was considered to be 1200 mg/kg bw, when rat was treated with 4-methoxybenzyl alcohol via oral route.

Thus, based on the above prediction on 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) and it’s read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine can be classified as “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity:

In different studies, 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) has been investigated for acute Inhalation toxicity to a greater or lesser extent. Often are the

studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for 2-(3,4-dimethoxyphenyl)ethan-1-amine along with the study available on structurally similar read across substance2-Methoxyphenol (90-05-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7). The LC50 was estimated to be 13.5 mg/L (13500 mg/m3), when 10 male and female Sprague-Dawley rats were exposed with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) via inhalation route to whole body exposure for 4 h.

This study is supported by experimental study conducted by Jay A. Brown (Haz-Map®: Information on Hazardous Chemicals and Occupational Diseases, U.S. National Library of Medicine, October 2017) for the target chemical 2-(3,4-dimethoxyphenyl)ethan-1-amine (120-20-7). The acute inhalation toxicity study was conducted in rats at concentration of 5500 mg/m3. No mortality was observed at 5500 mg/m3. Therefore, LC50 was considered to be >5500 mg/m3, when rats were exposed with2-(3,4-dimethoxyphenyl)ethan-1-amineby inhalation route for 4 hours.

The above prediction and experimental study is further supported by D. L. J. Opdyke(Food and Chemical Toxicology, Volume 20, Issue 6, 1982, Pages 637-852), IFA GESTIS (GESTIS SUBSTANCE Database, 2017) and Jay A. Brown (Haz-Map®: Information on Hazardous Chemicals and Occupational Diseases, U.S. National Library of Medicine, October 2017), for the structurally similar read across substance2-Methoxyphenol (90-05-1). The acute inhalation toxicity study was conducted in mice at the concentration range between 2,000 and 17,000 mg/m³. Animals were observed for mortality and clinical signs. Necropsy was performed. 50% mortality was observed in treated mice at 7570 mg/m³ when exposed for 2 hours. Initially all animals exhibited slight inflammations of the eyes and the respiratory tract as well as agitation, followed by a loss of activity. After exposures to values up to 4,000 mg/m³ these symptoms were reversible after the termination of the exposure. Higher concentrations caused further CNS and neuromuscular symptoms (weak reflexes, unsteady gait, respiratory disorders, and tonic-clonic spasms). The dissection revealed injuries in several organs (vascularisation, bleeding, dystrophic changes). Therefore, LC50 was considered to be 7570 mg/m³, when mice were exposed to 2-Methoxyphenol (90-05-1) via inhalation by vapor for 2 hour exposure.

Thus, based on the above studies on 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) and it’s read across substance, it can be concluded that LC50 value is >5 mg/L air. Thus, comparing this value with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine cannot be classified for acute Inhalation toxicity.

Acute Dermal toxicity:

In different studies, 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbit for 2-(3,4-dimethoxyphenyl)ethan-1-amine along with the study available on the structurally similar read across substances 4-Methoxyphenylacetone (122-84-9)and 4-methoxybenzyl alcohol (105-13-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

 

In a prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7). The LD50 was estimated to be 2100 mg/kg bw, when 5 male and female New Zealand White rabbits were treated with 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) for 24 hours by dermal application occlusively.

The above study is supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 17, Supplement, Pages 695-923, December 1979), U.S. National Library of Medicine (ChemIDplus, 2017) and RTECS (registry of toxic effect of chemical substance database, 2017), for the structurally similar read across substance 4-Methoxyphenylacetone (122-84-9). The acute dermal toxicity study was conducted in rabbits at the concentration of 5000 mg/kg bw by dermal application. No mortality was observed in treated rabbits at dose 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with 4-Methoxyphenylacetone (122-84-9) by dermal application.

This study is supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Page 825), IFA GESTIS (GESTIS SUBSTANCE Database, 2017), Scognamiglio et al.(Food and Chemical Toxicology 50 (2012) S134–S139) and RTECS (registry of toxic effect of chemical substance data base, 2018), for the structurally similar read across substance 4-methoxybenzyl alcohol (105-13-5). The acute dermal toxicity study was conducted in rabbit at the concentration of 1250, 2500, and 5000 mg/kg bw. Animals were observed for clinical signs. Mortalities included 1 rabbit from the 2500 g/kg group on day 1, and all 4 rabbits from the 5000 mg/kg group by day 6. Clinical signs of toxicity included loss of coordination and muscle tone in 2 animals at 5000 mg/kg and 1 animal at 2500 mg/kg. Slight to moderate erythema and edema was also observed in all animals. Therefore, LD50 was considered to be 3000 mg/kg with 95% confidential limit of 1940-4060 mg/kg bw, when rabbit was treated with 4-methoxybenzyl alcohol by dermal application.

Thus, based on the above studies on 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) and it’s read across substance, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on 2-(3,4-dimethoxyphenyl)ethan-1-amine (CAS no: 120-20-7) and it’s read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral toxicity; >2000 mg/kg bw for acute dermal toxicity; and LC50 value is >5 mg/L air for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, 2-(3,4-dimethoxyphenyl)ethan-1-amine can be classified as “Category 4” for acute oral toxicity and cannot be classified for acute dermal and inhalation toxicity.