Ethyl N-hydroxyacetimidate

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:

Data is from OECD QSAR toolbox version 3.3 and the QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox version 3.3.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (IUPAC name) : (E)-(ethyl N-hydroxyethenecarboximidate)
- Common name : Ethyl N-hydroxyacetimidate, Ethyl Acetohydroximate
- Molecular formula : C4H9NO2
- Molecular weight : 103.12 g/mol
- Smiles notation : C(=N/O)(\OCC)C
- InChl : 1S/C4H9NO2/c1-3-7-4(2)5-6/h6H,3H2,1-2H3
- Substance type : Organic
- Physical state : Liquid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Details on test organisms:

- Common name: Water flea

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Test temperature:

20°C

pH:

8±0.2

Dissolved oxygen:

> 2mg/L

Nominal and measured concentrations:

Estimated data

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

729.073 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

other: Intoxication

Remarks on result:

other: Nontoxic

Details on results:

No data available

Results with reference substance (positive control):

No data available

Reported statistics and error estimates:

No data available

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "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 "z" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Azomethine, aliphatic attach [-N=C] AND Hydroxy, nitrogen attach [-OH] AND Olefinic carbon [=CH- or =C<] AND Oxime, aliphatic attach [-CH=N-OH]  AND Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Schiff base formation by aldehyde formed after metabolic activation >> N-methylol 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 >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> N-Nitroso Compounds 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 metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation OR SN1 >> Nucleophilic attack after nitrenium and/or carbenium ion formation >> N-Nitroso Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds 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 >> Nitrobiphenyls and Bridged Nitrobiphenyls 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 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline 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: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas OR 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 >> Methylenedioxyphenyl OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Halogenated polarised alkenes OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

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, without OH or NH2 group OR Strong binder, NH2 group OR Weak binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "k"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Selennm Se OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acetoxy by Organic Functional groups

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Alcohol by Organic Functional groups

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Urea derivatives by Organic Functional groups

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Alkoxy AND Ether by Organic Functional groups

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Isopropyl by Organic Functional groups

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No functional group found by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Secondary aliphatic amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.72

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.92

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 729.034 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Daphnia magna for 48 hrs.
 

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on Daphnia magna predicted for (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2).The EC50 value was estimated to be 729.034 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Daphnia magna for 48 hrs.

 

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on Daphnia magna predicted for (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2).The EC50 value was estimated to be 729.034 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Daphnia magna for 48 hrs.

 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

729.034 mg/L

Additional information

Based on the various experimental data and prediction data for the target chemical study have been reviewed to determine the toxic nature of (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2) on the growth of invertebrates. The studies are as mentioned below:

In the first predicted study for the target chemical (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2) from QSAR toolbox 2017, study was carried out. Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the seven closest read across substances, toxicity on Daphnia magna predicted for (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2).The EC50 value was estimated to be 729.034 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Daphnia magna for 48 hrs. 

 

In second predicted study for the target chemical (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2) based on the prediction done by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of this program, the LC 50 value for short term toxicity to aquatic invertebrates was predicted to be 1055.510 mg/l for (E)-(ethyl N-hydroxyethenecarboximidate) in 48 hrs. Based on this value it can be concluded that the substance (E)-(ethyl N-hydroxyethenecarboximidate) is considered to be not toxic to aquatic environment and cannot be classified as per the criteria mentioned in CLP regulation.

 

Similarly in the third weight of evidence study for the second RA chemical 1,1-dimethyl propyl methyl ether (TAME) (994-05-8) (from Chemosphere, 1997) toxicity was measured. Study was conducted to determine the toxic nature of chemical 1,1-dimethyl propyl methyl ether (TAME) on the growth and mobility of daphnia magna. Test was conducted according to the standard test guideline 202. Immobility of daphnia magna was determined over a 48 h exposure period. Nominal 0.1, 1, 10 and 100 mg/l concentrations of TAME and a control (dilution water) were prepared. Completely filled, sealed flasks were used to prevent volatile losses of TAME. The highest exposure concentration (nominal 100 mg/l) was analysed by gas chromatography at the beginning and end of the exposure period. 20 Daphnia magna were placed in 4 flasks at 100 mg/l and the control level, and 10 D. magna were placed in 2 flask for the remaining treatment levels. Based on the immobility of daphnia magna due to the exposure of chemical 1,1-dimethyl propyl methyl ether (TAME), the EC50 was determine to be > 100 mg/l.

 

Similarly fourth weight of evidence study was conducted for the RA chemical (556-88-7) from ECTOX database, 2017. Study was conducted to determine the toxic nature of chemical 1-nitroguanidine on the growth of invertebrates (Ceriodaphnia dubia). Test was conducted in the static system for the total exposure period of 48hrs. <12 h old Neonate was used in the test as attest organism by providing proper conditions of temperature and pH. After the 48hrs of exposure lethal concentration to 50% of test organisms was detected. Based on the mortality of Ceriodaphnia dubia (Water Flea) due to the exposure of chemical 1-nitroguanidine for 48hrs, the LC50 was 2698 mg/l. Thus on the basis of LC50, chemical can be concluded as nontoxic.

 

Based on the data obtain from various predicted and experimental studies for the toxicity on invertebrates due to the exposure of (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2) it was concluded that the chemical (E)-(ethyl N-hydroxyethenecarboximidate) was consider as nontoxic and can be consider to be not classified as toxic to aquatic invertebrates as per CLP classification criteria.