N-[3-(diethylamino)phenyl]acetamide

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: screening tests

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:

OECD Guideline 301 C (Ready Biodegradability: Modified MITI Test (I))

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

Oxygen conditions:

aerobic

Inoculum or test system:

other: Microorganisms

Duration of test (contact time):

28 d

Based on:

not specified

Parameter followed for biodegradation estimation:

other: BOD

Key result

Parameter:

other: BOD

Value:

0.38

Sampling time:

28 d

Remarks on result:

other: Other details not known

Details on results:

Test substance undergoes 0.37% degradation by BOD in 28 days.

The prediction was based on dataset comprised from the following descriptors: BOD
Estimation method: Takes average value from the 5 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 ( not "i") )  )  and "j" )  and ("k" and "l" )  )

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 >> Amino Anthraquinones 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 Radical 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones 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) >> Quinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones 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 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, 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 >> 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 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 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 >> 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 SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo by DNA binding by OECD

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, MW>500 OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 121 Da

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 304 Da

Validity criteria fulfilled:

not specified

Interpretation of results:

under test conditions no biodegradation observed

Conclusions:

The test chemical N-[3-(diethylamino)phenyl]acetamide was estimated to be not readily biodegradable in water.

Executive summary:

Biodegradability of N-[3-(diethylamino)phenyl]acetamide (CAS no. 6375 -46 -8) is predicted using QSAR toolbox version 3.3 with logKow as the primary descriptor. Test substance undergoes 0.37% degradation by BOD in 28 days.Thus, based on percentage degradation, the test chemical N-[3-(diethylamino)phenyl]acetamide was estimated to be not readily biodegradable in water.

Description of key information

Biodegradability of N-[3-(diethylamino)phenyl]acetamide (CAS no. 6375 -46 -8) is predicted using QSAR toolbox version 3.3 (2017) with logKow as the primary descriptor. Test substance undergoes 0.37% degradation by BOD in 28 days.Thus, based on percentage degradation, the test chemical N-[3-(diethylamino)phenyl]acetamide was estimated to be not readily biodegradable in water.

Key value for chemical safety assessment

Biodegradation in water:

under test conditions no biodegradation observed

Additional information

Various predicted data for the target compound N-[3-(diethylamino)phenyl]acetamide (CAS No. 6375-46-8) and supporting weight of evidence studies for its closest read across substance with logKow as the primary descriptor were reviewed for the biodegradation end point which are summarized as below:

 

In a prediction done by SSS (2017) using OECD QSAR toolbox version 3.3 with logKow as the primary descriptor, percentage biodegradability of test chemical N-[3-(diethylamino)phenyl]acetamide(CAS No. 6375-46-8) was estimated.Test substance undergoes 0.37% degradation by BOD in 28 days.Thus, based on percentage degradation, the test chemical N-[3-(diethylamino)phenyl]acetamide was estimated to be not readily biodegradable in water.

 

In another prediction using the Estimation Programs Interface Suite (EPI suite, 2017), the biodegradation potential of the test compound N-[3-(diethylamino)phenyl] acetamide(CAS No. 6375-46-8) in the presence of mixed populations of environmental microorganisms was estimated. The biodegradability of the substance was calculated using seven different models such as Linear Model, Non-Linear Model, Ultimate Biodegradation Timeframe, Primary Biodegradation Timeframe, MITI Linear Model, MITI Non-Linear Model and Anaerobic Model (called as Biowin 1-7, respectively) of the BIOWIN v4.10 software. The results indicate that chemical N-[3-(diethylamino)phenyl]acetamide is expected to be not readily biodegradable.

 

In a supporting weight of evidence study from authoritative database (J-CHECK, 2017 and Envichem, 2014) for the read across chemical N-methyl-N-phenylacetamide (CAS no. 579-10-2),biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of read across substance N-methyl-N-phenyl acetamide. Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l, respectively. The percentage degradation of substance N-methyl-N-phenylacetamide was determined to be 1 and 0% degradation by BOD, TOC removal and HPLC parameter in 28 days. Thus, based on percentage degradation, N-methyl-N-phenylacetamide is considered to be not readily biodegradable in nature.

 

Additional biodegradation study was conducted for 5 days for evaluating the percentage biodegradability of another read across substance N, N-diethylaniline (CAS no. 91-66-7) (H. Heukelekian and M. C. Rand, 1955) using standard dilution method at a temperature of 20°C. Sewage was used as a test inoculum. The 5 day BOD value of chemical N, N-diethylaniline was determined to be 0 g/g. Thus, based on this value, N, N-diethylaniline is considered to be not readily biodegradable in nature.

 

For the same read across chemical N,N-diethylaniline (CAS no. 91-66-7) from authoritative database (HSDB, 2017), biodegradation study was conducted for 5 days for evaluating the percentage biodegradability of read across substance N, N-diethylaniline. Sewage sludge was used as a test inoculum. The percentage degradation of substance N, N-diethylaniline was determined to be 5% by BOD parameter in 5 days. Thus, based on percentage degradation, N, N-diethylaniline is considered to be not readily biodegradable in nature.

 

In a supporting weight of evidence study from authoritative database (J-CHECK, 2017) for the read across chemical N, N-dimethylaniline (CAS no. 121-69-7), biodegradation experiment was conducted for 14 days for evaluating the percentage biodegradability of read across substance N, N-dimethylaniline. Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l, respectively. The percentage degradation of substance N, N-dimethylaniline was determined to be1.9, 12.3 and 0% by BOD, TOC removal and GC parameter in 14 days. Thus, based on percentage degradation, N, N-dimethylaniline is considered to be not readily biodegradable in nature.

 

On the basis of above results for target chemicalN-[3-(diethylamino)phenyl]acetamide(from OECD QSAR toolbox version 3.3 and EPI suite, 2017) and for its read across substance (from authoritative database J-CHECK, Envichem, HSDB and peer reviewed journal), it can be concluded that the test substance N-[3 -(diethylamino)phenyl] acetamide can be expected to be not readily biodegradable in nature.