N-[3-(diethylamino)phenyl]acetamide

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

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

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Test temperature:

21 deg.C

pH:

7.9

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

151.18 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 7 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 ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and "q" )  )

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 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones 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 >> Quinones 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 >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Polynitroarenes 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) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroaniline Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Specific Imine and Thione Derivatives OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers 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 >> Nitroaniline Derivatives 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 >> Polynitroarenes 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, 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 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 >> Haloalkanes Containing Heteroatom 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 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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 Very fast by Bioaccumulation - metabolism half-lives 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 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 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 Aliphatic nitriles (Hepatotoxicity) Rank B OR Anilines (Hemolytic anemia with methemoglobinemia) Rank A OR Anilines (Hepatotoxicity) Rank C OR Hydrazines (Hepatotoxicity) Rank C OR Oxyphenistain (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Pro-Michael Addition OR Pro-Michael Addition >> Pro-quinone and related OR Pro-Michael Addition >> Pro-quinone and related >> Aminophenols by Respiratory sensitisation

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.658

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.48

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on Daphnia magna (aquatic invertebrates) was predicted for N-[3-(diethylamino)phenyl]acetamide using OECD QSAR toolbox version 3.3 and EC50 value was estimated to be 151.18 mg/l on Daphnia magna for 48 hrs duration considering Intoxication effects.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8). Effect concentration i.e EC50 value was estimated to be 151.18 mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) was non toxic to aquatic invertebrates, hence it can be considered to be not classified  as per the CLP classification criteria for aquatic environment.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8). Effect concentration i.e EC50 value was estimated to be 151.18 mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) was non toxic to aquatic invertebrates, hence it can be considered to be not classified  as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

151.18 mg/L

Additional information

Five studies including predicted data from validated tools and experimental data from peer reviewed journal and authorative database for short term aquatic invertebrate’s endpoint of test chemical N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) with relevant read across which is close to target using log Kow as primary descriptor were summarised as follows:

 

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, which indicate the short term toxicity on aquatic invertebrates was predicted for N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) and the Effect concentration i.e EC50 value was estimated to be 151.18 mg/l for Daphnia magna for 48 hrs duration.

 

Above predicted result of target assist by experimental result of peer reviewed journal Ecotoxicology 21(7): 2031-2050 for read across chemical Erythromycin (Cas no. 114-07-8) indicate In acute toxicity to aquatic invertebrates species Moina macrocopa (Water Flea) the effective concentrations (EC50) of erythromycin was estimated using probit model. Experiment performs in static fresh water with 25 deg.Test temp. and Moderately Hard condition. Experimental result suggests the effect concentration (EC50) at 48 hrs exposure period for chemical Erythromycin (Cas no. 114-07-8) was observed to be 135.52 mg/l with confidence limit 116.01 - 155.02.

And from ECOTOX database for another read across Methyl 4-acetamido-2-ethoxybenzoate (Cas no. 59-06-3) indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <1 d age.Test in fresh water media with static condition. During the experiment, the EC50 value for Methyl 4-acetamido-2-ethoxybenzoate i.e Ethopabate (Cas no. 59 -06 -3) was determined to be 170 mg/l on the basis of mobility.

Same data source (ECOTOX database) for another read across chemical methyl (2S)-2-[N-(2,6-dimethylphenyl)-2-methoxyacetamido]propanoate (Cas no. 57837-19-1) indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <1 d age.Test in fresh water media with static condition. During the experiment, the EC50 value for methyl (2S)-2-[N-(2,6-dimethylphenyl)-2-methoxyacetamido]propanoate (Cas no. 57837-19-1) was determined to be 121 mg/l on the basis of mobility.

Last study also from same data source (ECOTOX database) for read across Methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate (Cas no. 70630-17-0) also assist all above aquatic effect range such as short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <=24 h (Neonate)age. Test in fresh water media with static condition. During the experiment, the EC50 value for Methyl N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-DL-alaninate (Cas no. 70630-17-0) was determined to be 128.26 mg/l on the basis of Mortality.

Thus based on the all available effect concentrations which is in the range of 135.52 to 170 mg/l for target and read across chemicals give the conclusion that test substance N-[3-(diethylamino)phenyl]acetamide (Cas no. 6375-46-8) was likely to be non toxic to aquatic invertebrates as it not meet the classification criteria, hence it can be considered to be not classified as per the CLP regulation.