N-[3-(diethylamino)phenyl]acetamide

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to the skin of rabbits. Based on the estimated result N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) can be considered to be highly irritating to skin and can be classified under the category “Category 2 (irritant)” as per CLP regulation

Eye irritation:

The ocular irritation potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to the eye of rabbits. Based on the estimated result N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) can be considered to be highly irritating to eye and can be classified under the category “Category 2 (irritant)” as per CLP regulation

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: as mentioned below

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 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:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period:

No data available

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

severe skin irritating reactions were observed.

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: Out of 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" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and ("ac" and ( not "ad") )  )  and ("ae" and ( not "af") )  )  and ("ag" and "ah" )  )

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 Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group 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 Very strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 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-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) >> Geminal Polyhaloalkane Derivatives 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) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes 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 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids 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, 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 >> 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: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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: "m"

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

Domain logical expression index: "n"

Similarity boundary:Target: CCN(CC)c1cccc(NC(C)=O)c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "o"

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 AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Group All log Kow < -3.1 by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

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 AND 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 Group C Molecular Weight > 350 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "s"

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 AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Group CN Aqueous Solubility < 0.1 g/L by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

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 AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "w"

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 AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "y"

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 AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "aa"

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 AND Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "ab"

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

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "ad"

Referential boundary: The target chemical should be classified as Acylation >> Ring opening acylation >> Active cyclic agents  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "ae"

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: "af"

Referential boundary: The target chemical should be classified as Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  by Protein binding by OASIS v1.3

Domain logical expression index: "ag"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.3

Domain logical expression index: "ah"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.27

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Migrated information

Conclusions:

he substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to the skin of rabbits. Based on the estimated result N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) can be considered to be highly irritating to skin.

Executive summary:

The dermal irritation potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to the skin of rabbits. Based on the estimated result N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) can be considered to be highly irritating to skin and can be classified under the category “Category 2 (irritant)” 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 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:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

No data available

Observation period (in vivo):

No data available

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

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

severe ocular lesions were observed.

Estimation method: Takes 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 ("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 ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and "y" )  and "z" )  and "aa" )  and ("ab" and ( not "ac") )  )  and "ad" )  and ("ae" and "af" )  )

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 Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as 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 Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

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 Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At OR Group 17 - Halogens I by Chemical elements

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Dantrolene (Hepatotoxicity) Alert OR Perhexiline (Hepatotoxicity) Alert OR Tamoxifen (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Ac-SN2 OR Ac-SN2 >> Acylation involving an activated (glucuronidated) carboxamide group OR Ac-SN2 >> Acylation involving an activated (glucuronidated) carboxamide group >> Carboxylic Acid Amines OR Ac-SN2 >> Direct acylation involving a leaving group OR Ac-SN2 >> Direct acylation involving a leaving group >> Carboxylic Acid Amines OR Ac-SN2 >> Ring opening acylation reaction OR Ac-SN2 >> Ring opening acylation reaction >> Carboxylic acid Anhydrides OR AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha, beta - Unsaturated Carbonyls and Related Compounds OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems OR AN2 >> Michael addition to activated double bonds in heterocyclic ring systems >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters OR AN2 >> Michael type addition to activated double bond of pyrimidine bases OR AN2 >> Michael type addition to activated double bond of pyrimidine bases >> Pyrimidines and Purines OR AN2 >> Michael-type addition to quinoid structures OR AN2 >> Michael-type addition to quinoid structures >> Carboxylic Acid Amines OR AN2 >> Shiff base formation with carbonyl compounds OR AN2 >> Shiff base formation with carbonyl compounds >> Pyrazolone and Pyrazolidine Derivatives OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases OR AN2 >> Shiff base formation with carbonyl group of pyrimidine or purine bases >> Pyrimidines and Purines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as High gene expression OR High gene expression >> N-Acylamides OR Very high gene expression OR Very high gene expression >> Epoxyethers by Keratinocyte gene expression

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alpha aryloxy substituted acetic acid (9c) OR Bicyclic compounds with aryl fused O-containing heterocycle-coumarin-related (14a ) OR Known precedent reproductive and developmental toxic potential OR NO2-alkyl/NO2-benzene derivatives (8b) OR Steroid derivatives OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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: "s"

Referential boundary: The target chemical should be classified as Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR No alert found OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo by Protein binding by OECD

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Kb, pH 8)(Hydrowin) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Unsaturated acid anhydrides OR Low reactive OR Low reactive >> Saturated acid anhydrides by DPRA Cysteine peptide depletion

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as AN2 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 SN2 OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones by DNA binding by OASIS v.1.3

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 7) ONLY

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 2) ONLY

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as days - weeks by Biodeg primary (Biowin 4) ONLY

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "ac"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "ad"

Similarity boundary:Target: CCN(CC)c1cccc(NC(C)=O)c1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ae"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.678

Domain logical expression index: "af"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.6

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

he substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to the eye of rabbits. Based on the estimated result N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) can be considered to be highly irritating to eye.

Executive summary:

The ocular irritation potential of N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to the eye of rabbits. Based on the estimated result N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) can be considered to be highly irritating to eye and can be classified under the category “Category 2 (irritant)” 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 chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8)to observe the potential for dermal irritation 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)andMaleic anhydride (CAS no: 108-31-6) .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 chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) .The chemical N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to skin of rabbits.

 

 

The OECD SIDS (2004) carried out skin irritation study ofstructurally similar read across substanceMaleic anhydride (CAS no: 108-31-6) on six New Zealand White rabbits toassess the irritationefficacy which supports the above result.In this study, 500mg (0.5g) was applied to two intact skin locations on the backs of six rabbits for four hours and skin reactions were observed for 7 days.Severe skin irritation was present in both treated areas of most rabbits for the entire 7-day observation period. Eschar formation with epidermal regenerationwas present in all of the sections. At 24 hours, the Draize scores for erythema and edema for site 1 (site 2) were 4.0 (3.7) and 4.0 (3.7), respectively. At 48 hours, the scores for erythema and edema were 4.0 (4.0) and 3.8 (3.5), respectively. At 72 hours, the erythema and edema scores were 4.0 (4.0) and 3.7 (3.0), respectively. At 7 days, the erythema and edema scores were 4.0 (4.0) and 3.7 (3.0), respectively.Sever signs of irritation were observed during 7 days observation period. Hence theMaleic anhydride (CAS no: 108-31-6) was considered to be highly irritating to theNew Zealand Whiterabbit’s skin.

 

 

The above results were further supported by Primary Skin irritation study conducted by OECD (2005) onstructurally similar read across substanceTrimellitic anhydride (CAS no: 552-30-7) was conducted on six New Zealand White rabbits in order to examine the degree of skin irritation caused by the chemical according to OECD Guideline 404 (Acute Dermal Irritancy/Corrosivity Study).Eachrabbit received 500mg of undilutedTrimellitic anhydride on shaved, pre-moistened (with water) backs for 4 hours under occlusive condition.The application site was covered with an adhesive dressing. After 4 hours the dressings were removed, the application site was rinsed with a light mineral oil and rubbed gently with a paper towel to remove residual test article. The skinof the animal was scored for irritation at 30-60 minutes, 24, 48, and 72 hours and 7 and 14 days following removal of the wrappings according to the Draize method.The dermal irritation score ranged from 4.3/8.0 at 30-60 minutes following unwrapping to 0.0/8.0 at 14 days. The primary dermal irritation score (PDIS) for trimellitic anhydride was observed o be 1.7. The primary dermal irritation score (PDIS) for trimellitic anhydride was observed o be 1.7.Thus chemicalTrimellitic anhydride (CAS no: 552-30-7) was considered to be moderately irritating to the skin ofNew Zealand Whiterabbits.

 

 

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)andMaleic anhydride (CAS no: 108-31-6),it can be concluded thatchemical N-[3-(diethylamino)phenyl]acetamide is able to cause skin irritation and considered as severely irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 2 (irritant)”.

 

 

Eye irritation:

In different studies,the test chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) 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 chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) and its structurally similar read across substancesTrimellitic anhydride (CAS no: 552-30-7)andMaleic anhydride (CAS no: 108-31-6).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 eye irritation potential was estimated for test chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8.The chemical N-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) is estimated to be highly irritating to eye of rabbits.

 

 

The OECD SIDS (2004) carried out skin irritation study ofstructurally similar read across substanceMaleic anhydride (CAS no: 108-31-6) on six New Zealand albino rabbits to observe its irritation potential according to guideline 405 which supports the above result.In this study, the undiluted 100mg ofMaleic anhydride was installed intotheeye of each rabbits whilethe untreatedeye served as control.The treated eye of each rabbit was examined 1, 24, and 48 hours following test article administration.The mean conjunctival erythema scores at 24 and 48 hours were 2.0 and 3.0, respectively. The mean conjunctival chemosis scores at 24 and 48 hours were 4.0 and 4.0, respectively. The corneal opacity scores at 24 and 48 hours were 3.8 and 3.8, respectively. The iridial lesions scores at 24 and 48 hours were 2.0 and 2.0, respectively.The observed maximum eye irritation score was 106.7 (out of a maximum of 110).No deaths occurred during the study .However, due to signs of severe ocular irritation, the study was terminated following the 48-hour.Since Sever signs of eye irritation were observed, theMaleic anhydride (CAS no: 108-31-6) was considered to be highly irritating to theeye ofNew Zealand albino rabbits.

 

 

 

The above results were further supported by an ocular irritation study conducted by OECD (2005) onstructurally similar read across substanceTrimellitic anhydride (CAS no: 552-30-7) on one New Zealand albino rabbits in order to examine the degree of eye irritation caused by the chemical. It was anticipated that TMA might be a severe eye irritant. Therefore, out of concern for animal pain and discomfort, only one rabbit was used initially as a test subject. TMA was administered undiluted at a dose of 100mg (0.1mg) into one eye with the other eye serving as the untreated control. The treated eye was scored for irritation at 1, 2, 3, 4, 7, and 14 days following test article administration. Irritation was scored using the Draize method. A reaction was considered positive if at any observation period, the test article produced ulceration or opacity of the cornea (cornea score > than 0), inflammation or slight circumcorneal injection of blood vessels of the iris (iris score > 0), any obvious conjunctival swelling with partial eversion of the lids (chemosis score 2 or greater), or conjunctival erythema of diffuse crimson red (erythema score 2 or g greater) with individual vessels not easily discernable. Signs of ocular irritation were maximum (i.e. Draize score 110/110) at the 24 hour examination and the study was terminated immediately thereafter with no dosing of any additional animals. The maximum eye irritation score of 110/110 was obtained 1 day after administration of Trimellitic anhydride.Thus chemicalTrimellitic anhydride (CAS no: 552-30-7) was considered to be severely irritating to theeyeofNew Zealand albinorabbit.

 

 

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)andMaleic anhydride (CAS no: 108-31-6),it can be concluded thatchemical N-[3-(diethylamino)phenyl]acetamide is able to cause ocular lesions and considered as severely irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category“Category 2 (irritant)”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8) and its structurally similar read across substancesTrimellitic anhydride (CAS no: 552-30-7)andMaleic anhydride (CAS no: 108-31-6)were observed in various studies. The results obtained from these studies indicates that the chemicalN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8)is likely to cause skin and eye irritation. HenceN-[3-(diethylamino)phenyl]acetamide (CAS No: 6375-46-8)can be classified under the category“Category 2 (irritant)”for skin and eye as per CLP.