N-ethyl-p-methoxy-α-methylphenethylamine

Endpoint summary

Description of key information

Skin Sensitization:

The skin sensitization potential of N-ethyl-p-methoxy-α-methylphenethylamine was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. N-ethyl-p-methoxy-α-methylphenethylamine was predicted to be sensitizing to the skin of male/female Dunkin - Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Type of study:

guinea pig maximisation test

Specific details on test material used for the study:

- Name of test material: N-ethyl-p-methoxy-α-methylphenethylamine
- IUPAC name: N-ethyl-1-(4-methoxyphenyl)propan-2-amine
- Molecular formula: C12H19NO
- Molecular weight: 193.2881 g/mole
- Smiles Notation: CCNC(C)Cc1ccc(OC)cc1
- InChl: 1S/C12H19NO/c1-4-13-10(2)9-11-5-7-12(14-3)8-6-11/h5-8,10,13H,4,9H2,1-3H3
- Substance type: Organic
- Physical state: Liquid (Colorless to pale yellow)

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

no data available

Route:

intradermal and epicutaneous

Vehicle:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

no data available

Reading:

1st reading

Group:

test chemical

Clinical observations:

signs of dermal sensitization observed

Remarks on result:

positive indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

Referential boundary: The target chemical should be classified as (!Undefined)Group C Surface Tension > 62 mN/m OR (!Undefined)Group CNHal Lipid Solubility < 4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR (!Undefined)Group CNS Surface Tension > 62 mN/m OR (N/A) OR Exclusion rules not met OR Group All log Kow < -3.1 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 Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CHal Melting Point > 65 C OR Group CN Aqueous Solubility < 0.0001 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN log Kow > 5.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Molecular Weight > 540 g/mol OR Group CN Vapour Pressure < 0.001 Pa OR Group CNHal Aqueous Solubility < 0.001 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNHal Molecular Weight > 380 g/mol OR Group CNS log Kow < 0.5 OR Group CNS log Kow < -2 OR Group CNS Melting Point > 120 C OR Group CNS Melting Point > 50 C by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Alkylalkanol-amines OR Ketones OR Phenols OR Primary and secondary aliphatic amines OR Sulfonic acids or their salts OR Tertiary aliphatic amine by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "i"

Similarity boundary:Target: CCNC(C)Cc1ccc(OC)cc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acetal OR Acrylate OR Alcohol by Organic Functional groups

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as AlkoxySilane by Organic Functional groups

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.2

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.26

Interpretation of results:

other: Positive

Conclusions:

N-ethyl-p-methoxy-α-methylphenethylamine was predicted to be sensitizing to the skin of male/female Dunkin - Hartley guinea pigs.

Executive summary:

The skin sensitization potential of N-ethyl-p-methoxy-α-methylphenethylamine was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. N-ethyl-p-methoxy-α-methylphenethylamine was predicted to be sensitizing to the skin of male/female Dunkin - Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin Sensitization:

Various studies have been investigated for assessing the dermal sensitization potential of N-ethyl-p-methoxy-α-methylphenethylamine to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs as well predicted data for target chemical and its structurally similar read across chemical. The predicted data has also been compared with the experimental data.

The skin sensitization potential of N-ethyl-p-methoxy-α-methylphenethylamine was estimated by SSS (2018) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor. N-ethyl-p-methoxy-α-methylphenethylamine was predicted to be sensitizing to the skin of male/female Dunkin - Hartley guinea pigs.

This is supported by the experimental data a guinea pig Maximization assay performed to determine the degree of dermal sensitization caused by the structurally similar read across chemical. 10 female Hartley guinea pigs were used for the study.

During the induction phase, the test chemical in Freund's Adjuvant was injected into the skin of guinea pigs, then 1% of the test material was applied onto the skin. Negative control was also used (name not specified). After few days, the induced guinea pigs were challenged with 1% test chemical and observed for signs of erythema.

5 animals showed slightly greater degree of erythema than control animals. Five of ten animals induced with the test material in Freund's Adjuvant responded to challenge with a slightly greater degree of erythema than seen in animals previously injected with Freund's Adjuvant only.

Based on these observations, the test chemical was considered to be sensitizing to guinea pig skin.

Based on the available data for the target as well as read across chemicals and applying the weight of evidence approach,N-ethyl-p-methoxy-α-methylphenethylamine was considered to sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available data for N-ethyl-p-methoxy-α-methylphenethylamine indicates that it is likely to cause dermal sensitization to skin.

N-ethyl-p-methoxy-α-methylphenethylamine can be considered to be sensitizer to skin.