4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride

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:

equivalent or similar 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 (as cited in study report): 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride
- Molecular formula (if other than submission substance): C7H9ClN2O3
- Molecular weight (if other than submission substance): 204.612 g/mol
- Smiles notation (if other than submission substance): N1(C(C(=O)N(CC1)CC)=O)C(=O)Cl
- InChI: 1S/C7H9ClN2O3/c1-2-9-3-4-10(7(8)13)6(12)5(9)11/h2-4H2,1H3
- Substance type: Organic
- Physical state: Solid

Oxygen conditions:

aerobic

Inoculum or test system:

other: Microorganisms

Duration of test (contact time):

28 d

Parameter followed for biodegradation estimation:

other: BOD

Key result

Parameter:

other: BOD

Value:

31.54

Sampling time:

28 d

Remarks on result:

other: Other details not known

Details on results:

Test substance undergoes 31.54% 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 "g" )  and "h" )  and "i" )  and "j" )  and "k" )  and ("l" and "m" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Alkyl carbamyl halides OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD ONLY

Domain logical expression index: "b"

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 >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.3 ONLY

Domain logical expression index: "c"

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 >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Dialkyl carbamoylhalides by Protein binding by OECD ONLY

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 >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> N,N-Dialkyldithiocarbamate Derivatives 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) >> 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, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides 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 >> 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 days - weeks by Biodeg primary (Biowin 4) ONLY

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Does NOT Biodegrade Fast by Biodeg probability (Biowin 5) ONLY

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 135 Da

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 252 Da

Validity criteria fulfilled:

not specified

Interpretation of results:

not readily biodegradable

Conclusions:

The test chemical 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride was estimated to be not readily biodegradable in water.

Executive summary:

Biodegradability of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride is predicted using QSAR toolbox version 3.3 with logKow as the primary descriptor. Test substance undergoes 31.54% degradation by BOD in 28 days.Thus, based on percentage degradation, the test chemical 4 -ethyl-2,3 -dioxopiperazine-1 -carbonyl chloride was estimated to be not readily biodegradable in water.

Description of key information

Biodegradability of 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride is predicted using QSAR toolbox version 3.3 with logKow as the primary descriptor (2017). Test substance undergoes 31.54% degradation by BOD in 28 days.Thus, based on percentage degradation, the test chemical 4 -ethyl-2,3 -dioxopiperazine-1 -carbonyl chloride 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

2 predicted data for the target compound 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no. 59703-00-3) and the total 3 weight of evidence studies (from authoritative database) 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 QSAR toolbox version 3.3 with logKow as the primary descriptor, percentage biodegradability of test chemical 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no. 59703-00-3) was estimated. Test substance undergoes 31.54% degradation by BOD in 28 days. Thus, based on percentage degradation, the test chemical 4 -ethyl-2,3 -dioxopiperazine-1 -carbonyl chloride 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 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no. 59703-00-3) 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 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride is expected to be not readily biodegradable.

 

In a weight of evidence study from authoritative database (J-CHECK, 2016) for read across substance 5,5 -Diphenyl-2,4 -Imidazolidinedione (CAS no. 57-41-0), biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of read across substance 5,5 -Diphenyl-2,4 -Imidazolidinedione. 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 test substance was determined to1 and 2% by BOD and HPLC parameter in 28 days. Thus, based on percentage degradation, 5,5 -Diphenyl-2,4 -Imidazolidinedione is considered to be not readily biodegradable in nature.

 

Another supporting weight of evidence study of biodegradation was conducted for 14 days for evaluating the percentage biodegradability of read across substance sodium p-acetylaminobenzenesulfonate (CAS no. 6034-54-4) (J-CHECK). 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 test substance was determined to 2 and 0% by BOD, TOC removal and HPLC parameter in 14 days.Thus, based on percentage degradation, sodium p-acetylaminobenzenesulfonate is considered to be not readily biodegradable in nature.

 

In an additional studyof read acrosssubstance N-Methylacetanilide (CAS no. 579-10-2) from authoritative database (J-CHECK, 2016), biodegradation experiment was conducted for 28 days for evaluating the percentage biodegradability of test substance N-Methylacetanilide. Concentration of inoculum i.e, sludge used was 30 mg/l and initial test substance conc. used in the study was 100 mg/l. The percentage degradation of test substance was determined to be 1% by BOD and 0% by both TOC removal and HPLC parameter in 28 days. Thus, the substance N-Methylacetanilide is considered to be not readily biodegradable in water.

 

On the basis of above results for target chemical4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (from OECD QSAR toolbox version 3.3 and EPI Suite) and for its read across substance (from authoritative database J-CHECK), it can be concluded that the test substance 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride can be expected to be not readily biodegradable in nature.