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

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: as mentioned below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.

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 : C7H9ClN2O3
- Molecular weight: 204.612 g/mol
- Substance type:Organic
- Physical state:Solid

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Test temperature:

20 degree C

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

478.57 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 5 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 "j" )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and "o" )  and "p" )  and ("q" and "r" )  )

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 OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives 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 AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene 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 >> N,N-Dialkyldithiocarbamate Derivatives 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 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) >> 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 reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroaniline Derivatives 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 after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups 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 OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Low reactive OR Low reactive >> N-substituted aromatic amides OR Moderate reactive OR Moderate reactive >> Five-membered heterocyclic urea by DPRA Cysteine peptide depletion

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

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"

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

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Similarity boundary:Target: CCN1CCN(C(=O)Cl)C(=O)C1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: CCN1CCN(C(=O)Cl)C(=O)C1=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.64

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.928

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on aquatic invertebrates was predicted for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no 59703-00-3) using the OECD QSAR toolbox version 3.3. EC50 value was estimated to be 478.57 mg/L on the basis of intoxication for Daphnia magna for 48 hrs duration.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no 59703-00-3). EC50 value was estimated to be 478.57 mg/L on the basis of intoxication for Daphnia magna for 48 hrs duration. Hence, 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no 59703-00-3) was considered being non hazardous to aquatic invertebrates at environmentally relevant concentrations and can be considered to be not classified as per the CLP regulations.

Description of key information

In the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no 59703-00-3). EC50 value was estimated to be 478.57 mg/L on the basis of intoxication for Daphnia magna for 48 hrs duration.

Hence, it can be considered that 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was likely to be non-toxic to aquatic invertebrates at environmentally relevant concentrations and can be considered to be not classified as per the criteria of CLP regulation.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

478.57 mg/L

Additional information

Short term toxicity to aquatic invertebrates

Short term toxicity to aquatic invertebrates was reviewed for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) with two predicted data and two experimental data for functionally similar read across Dimethylformamide (68-12-2) and Tetraacetylethylenediamine (10543-57-4) are as follows:

In the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (CAS no 59703-00-3). EC50 value was estimated to be 478.57 mg/L on the basis of intoxication for Daphnia magna for 48 hrs duration.

Another prediction on short-term toxicity of the substance to invertebrate was predicted using EPI suite, ECOSAR version 1.1, 2017, based on the effects observed in 48 hr exposure. The lethal concentration (LC50) for the 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was estimated to be 91580.016 mg/l.

Study was performed in read across Dimethylformamide (68-12-2) by Sebaughet. al, 1991 in Daphnia magna for 48 hrs in static test conditions. Less than 24 hrs daphnids were used for treatment from adults. The 250 ml beaker was used with 200 ml of test concentrations. Well water was the dilution water used for the test and test solution was not aerated during test. Test was conducted with 12 test concentrations and for test pH, dissolved oxygen, alkalinity, and hardness were monitor at the beginning and end of the test. Probit and logit model are the two parameter models which assume symmetry of response. After the experiment, EC 50 value for Dimethylformamide (68-12-2) was determined to be 13700 mg/l.

Another study on read across tetraacetylethylenediamine (10543-57-4) was performed in Daphnia magna for 24 and 48 hrs. After the period, the EC 50 value of Tetraacetylethylenediamine (10543-57-4) was determined to be >500 and >800 mg/l for 24 and 48 hrs.

Thus, based on the predicted results 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) and study from read across, it can be considered that all the above weight of evidences has value greater than 100 mg/l. Hence, it can be considered that 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) was likely to be non-toxic to aquatic invertebrates at environmentally relevant concentrations and can be considered to be not classified as per the criteria of CLP regulation.