Ethyl N-hydroxyacetimidate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Hardness:

No data available

Test temperature:

23 +/- 2°C

pH:

7.6 - 8.3

Dissolved oxygen:

No data available

Salinity:

No data available

Conductivity:

No data available

Nominal and measured concentrations:

Estimated data

Details on test conditions:

No data available

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

296.406 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

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 ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and "v" )  and ("w" and "x" )  )

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 OECD

Domain logical expression index: "f"

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 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 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 >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) 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 >> Tertiary (unsaturated) heterocyclic amine  by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic Amine, primary by Organic Functional groups

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as N-Hydroxylamine derivatives by Organic Functional groups

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Aliphatic Amine, secondary by Organic Functional groups

Domain logical expression index: "v"

Similarity boundary:Target: CCOC(C)=NO
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.00301

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.01

Validity criteria fulfilled:

not specified

Conclusions:

The EC50 value was estimated to be 296.405 mg/l when(E)-(ethyl N-hydroxyethenecarboximidate) exposed to Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) for 72hrs.

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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2).The EC50 value was estimated to be 296.405 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) for 72hrs.

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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2).The EC50 value was estimated to be 296.405 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) for 72hrs.

Key value for chemical safety assessment

EC50 for freshwater algae:

296.405 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 algae. 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 five closest read across substances, toxicity on Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) was predicted for (E)-(ethyl N-hydroxyethenecarboximidate) (10576-12-2).The EC50 value was estimated to be 296.405 mg/l when (E)-(ethyl N-hydroxyethenecarboximidate) exposed to Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum) for 72hrs. 

 

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 1.10, the short term toxicity on green algae was predicted for test substance (E)-(ethyl N-hydroxyethenecarboximidate) (10576 -12 -2). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 432.880 mg/l for green algae for 72 hrs duration. Based on this value, it can be concluded that the test chemical (E)-(ethyl N-hydroxyethenecarboximidate) can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria. 

 

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 of algae Selenastrum capricornutum. Test was conducted according to the standard test guideline 201. Growth inhibition of liquid cultures of Selenastrum capricornutum (green alga) was determined over a 72 h exposure period. Nominal test concentrations were 0, 6.25, 12.5, 25, 50 and 100 mg/l. completely filled, sealed flasks were used to prevent volatile losses of TAME. The initial inoculum concentration was 1 x 10⁴cells/ml. Nominal concentrations were confirmed by gas chromatography at the beginning and end of the exposure period. The cell concentration in the stock cultures were determined by an electronic cell counter. After the exposure of chemical, EC50 was measured based on the average specific growth rate and area under the growth curves. The NOEC levels were determined to exceed 100 mg/l (p = 0.05). Based on the growth inhibition of Selenastrum capricornutum (green alga) due to the exposure of chemical 1,1-dimethyl propyl methyl ether (TAME), the EbC50 and ErC50 was > 100 mg/l based on the area under the growth curves and average specific growth rate.  

 

Similarly in the fourth weight of evidence study for the read across chemical (111-76-2) from j-check, 2017, Study was conducted for determination of nature of chemical 1-Butoxy-2-hydroxyethan on the growth and other activity of test animal green algae. Test performed under the static system for the total exposure period of 72hrs. After the exposure of chemical 1-Butoxy-2-hydroxyethan, effect concentration was measured at which 50% growth inhibited by the chemical. Based on the growth rate inhibition of green algae, the EC50 and NOEC was > 1000 and 130 MG/L. And on the basis of area under the growth curve and biomass rate the EC50 and NOEC was 630 mg/l and 63 mg/l. Thus the chemical was concluded as nontoxic and can be consider to be not classified as per the CLP classification criteria.

 

 

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 algae as per CLP classification criteria.