N-[3-(diethylamino)phenyl]acetamide

Endpoint summary

Description of key information

The skin sensitization potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) failed to induce skin sanitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

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 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:

not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material: N-[3-(diethylamino)phenyl]acetamide
- Molecular formula: C12H18N2O
- Molecular weight: 206.287 g/mol
- Smiles notation: O=C(Nc1cccc(N(CC)CC)c1)C
- InChl: 1S/C12H18N2O/c1-4-14(5-2)12-8-6-7-11(9-12)13-10(3)15/h6-9H,4-5H2,1-3H3,(H,13,15)
- Substance type: Organic
- Physical state:Solid

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: No data available

Route:

other: No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

skin sensitizing effects were ont observed.

Remarks on result:

no 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 6 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "e"

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 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-specific OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    OR Non-specific >> Incorporation into DNA/RNA, due to structural analogy with  nucleoside bases    >> Specific Imine and Thione Derivatives OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> 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 >> Fused-Ring Primary Aromatic Amines 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 >> Nitro Azoarenes 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 >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution on diazonium ions OR SN1 >> Nucleophilic substitution on diazonium ions >> Specific Imine and Thione Derivatives OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, 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, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 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: "f"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine 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 >> Formamides OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals 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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones 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  >> Ethylenediamines (including piperazine) OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Similarity boundary:Target: CCN(CC)c1cccc(NC(C)=O)c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.647

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.23

Interpretation of results:

other: not sensitizing

Conclusions:

The skin sensitization potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) failed to induce skin sanitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

Executive summary:

The skin sensitization potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) failed to induce skin sanitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) and its structurally similar read across substancesTrimellitic anhydride (CAS no: 552-30-7)andN, N-Diethylaniline (CAS No: 91-66-7).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

The skin sensitization potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) failed to induce skin sanitization effects on guinea pig skin and hence is considered to be not sensitizing to the skin.

 

 

The skin sensitization study was conducted by OECD (2005) onstructurally similar read across substanceTrimellitic anhydride (CAS no: 552-30-7) on ten male Hartley guinea pigs by mean of Modified Buehler Dermal Sensitization method under occlusive condition which supports the above result.About 300mg (0.3g) of TMA was applied to the backs of 10 guinea pigs once per week for three weeks. Dosing material was held in place using an elastic adhesive bandage. All wrappings were removed 6 hours after each application. Two weeks following the last induction phase animals were challenged at dose of 300mg (0.3g) to the backs of each ten treated and ten control animals. Test article was held in place for 6 hours. A second challenge dose was applied in the same manner 13 days later. Approximately 24 and 48 hours after removal of each challenge patch, the test sites were scored for edema and erythema according to the method of Draize. A reaction with a Draize erythema score of 2 or greater in the treated animals was considered a positive response. The amount of chemical used during the challenge phase was intended to produce a Draize erythema reaction of 1 or less in control animals.Since the Positive erythema reactions (score > 2) were not observed in any treated or sham animals following either challenge dose, the chemical Trimellitic anhydride (CAS no: 552-30-7) was considered to be not sensitizing to the skin ten male Hartley guinea pigs.

 

 

The above results were further supported by the experimental study conducted by the U.S. Environmental Protection Agency Hazard Characterization Document (2009) onstructurally similar read across substanceN, N-Diethylaniline (CAS No: 91-66-7) in guinea pigs.In this study, the test animals were treated dermally with 10% solution of N, N-diethylaniline during induction. After induction, treated animals were dermally exposed to challenge concentration of 1 or 2% solutions of N, N-diethylaniline. Since the chemical did not produce any cutaneous reaction at challenge concentrations, the test chemical N, N-Diethylaniline (CAS No: 91-66-7) was considered as not sensitizing to guinea pigs.

 

 

Based on the available data for thetarget chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) and its structurally similar read across substancesTrimellitic anhydride (CAS no: 552-30-7)andN, N-Diethylaniline (CAS No: 91-66-7),it can be concluded thatchemical N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is unable to cause skin sensitization and considered as non skin sensitizer.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

The skin sensitization potential of test substance N -[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) and its structurally similar read across substancesTrimellitic anhydride (CAS no: 552-30-7)andN, N-Diethylaniline (CAS No: 91-66-7)were observed in various studies. From the results obtained from these studies it is concluded that the chemical N -[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.