Ethyl 2-cyano-3-ethoxyacrylate

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The source experimental data for the model originate from different labs and different experiment series, as they are represented in the US EPA database, adding to uncertainty, however, careful data analysis, previous (and present) successful modeling add to the consistence of the data. The significant dataset size (~300) statistical quality (RMS, correlation coefficients etc.) of the model supports reliable predictions within the margins of the experimental error. The similarity of the analogues together with the correct estimates supports potential prediction consistency.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Principles of method if other than guideline:

Nonlinear ANN QSAR Model 3.3.8 for Acute toxicity for Daphnia magna-LC50(48h) - Version 2010-10-10
Backpropagation Neural Network (Multilayer Perceptron) regression

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 2-cyano-3-ethoxyacrylate

EC Number:

202-299-5

EC Name:

Ethyl 2-cyano-3-ethoxyacrylate

Cas Number:

94-05-3

Molecular formula:

C8H11NO3

IUPAC Name:

ethyl 2-cyano-3-ethoxyacrylate

Test organisms

Test organisms (species):

Daphnia magna

Study design

Total exposure duration:

48 h

Results and discussion

Effect concentrations

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

98.4 mg/L

Basis for effect:

mobility

Details on results:

log(LC50) = -3.24

Any other information on results incl. tables

Domains:

i. descriptor domain All descriptor values for ethyl 2-cyano-3-ethoxyacrylate fall in the applicability domain (training set value ±30%).

ii. structural fragment domain Ethyl 2-cyano-3-ethoxyacrylate is structurally relatively similar to the model compounds, the model contains compounds featuring short alkyl chains; unsaturated CN (including cyano groups) and CC bonds, ether and ester functionalities. The training set contains compounds of similar size to the studied molecule.

iii. mechanism domain Ethyl 2-cyano-3-ethoxyacrylate is considered to be in the same mechanistic domain as the molecules in the training set as it is structurally similar to the model compounds.

iv. metabolic domain, if relevant Ethyl 2-cyano-3-ethoxyacrylate is considered to be in the same metabolic domain as the molecules in the training set of the model due to the structural similarity.

Structural analogues:

CAS	smiles	source	log (EC50) exp / pred
105 -37 -3	C(OCC)(CC)=O	training	-2.78	-3.16
5160 -58 -1	c1(ccc(cc1)Cl)C(C(O C(c1cccc(c1)Oc1cccc c1)C#N)=O)C(C)C	training	-8.13	-8.34
107 -13 -1	C(C#N)=C	training	-3.78	-3.64

The experimental acute toxicity values for compounds of similar functionalities (unsaturated esters, cyano compounds) are somewhat scattered in the toxicity scales depending on the molecular size and other functionalities. The structural analogues are relatively similar to the studied compound, covering all the chemical features. The model also contains several other cyano-, ester- etc compounds but with additional functionalities. The descriptor values of the analogues are close to those of the studied compound. The analogues are considered to be within the same mechanistic domain. All the analogues are very well estimated within the model. The mechanistic picture of the model is complicated due to the nature of the endpoint and the nonlinear modeling technique - ANN (artificial neural network). Nevertheless, the nature of the descriptors present in the model indicates that molecular size and shape have the largest impact on the endpoint. Some of the advanced topological descriptors also take into account the presence of heteroatoms, as is needed for the potential hydrogen bonding capability consideration. While a number of different modes of actions are known, it is generally known that LC50 for Daphnia Magna of organic compounds is strongly related to hydrogen bonding, as well as membrane transport (reflected by the shape and size descriptors) but also the polarizability. Most of the descriptors are related to the structural complexity of the molecules as well as their geometrical and surface properties. Regarding the most significant descriptor Kier&Hall index (order 3) it can be noted that it has negative correlation with the property. It suggests that with the increase of the descriptor, the property would decrease. The same holds for the Molecular surface, Gravitational index and polarizability descriptors.

Applicant's summary and conclusion

Conclusions:

The LC50 value of the substance, using a Nonlinear ANN QSAR Model 3.3.8 for Acute toxicity for Daphnia magna-LC50(48h), was predicted to be 98.4 mg/l.