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Administrative data

Endpoint:
acute toxicity: oral
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, adding to uncertainty, however, previous (and present) successful modeling add to the consistence of the data. The significant 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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Type of model: Nonlinear ANN QSAR Model for acute oral toxicity - toxic class method (rat) Version 2010-12-19 .Backpropagation Neural Network (Multilayer Perceptron) regression.
The source experimental data for the model originate from different labs and different experiment series, adding to uncertainty, however, previous (and present) successful modeling add to the consistence of the data. The significant 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.
GLP compliance:
no
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
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
Details on test material:
- Name of test material (as cited in study report): ethyl-2-cyano-3-ethoxyprop-2-enoate

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
not specified

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
1 780 mg/kg bw

Any other information on results incl. tables

Log(LD50) = 1.02

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(LC5) exp. / pred      
110-40-7  C(C)OC(=O)CCCCCCCCC(= O)OCC  validation  1.748  0.8672
 115-02-6  O(CC(C(=O)O)N)C(C=[N]= N)=O   training -0.009   0.3115
 107-13-1 C(C#N)=C  validation  0.188 0.459 
 7085-85-0  O=C(OCC)/C=C/C#N  external*  **  0.55

* HSE. Risk assessment document Vol:EH72/13 (2000) 67 p; MSDS Krazy glue, Elmer's Products, Inc, 2006; MSDS SolidBond, British United Industries Pty Ltd., 2007;

** LD50 (oral, rat) range from ~5 mg to >5000 mg/kg

The experimental acute oral toxicity values for compounds of similar functionalities (unsaturated esters, cyano compounds) fall mostly to the Category 4- No category region, with obvious dependence on the particular structural features. 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 relatively 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, it can be concluded that model descriptors are related to the overall polarity -polarizability, reactivity, electrostatic and hydrogen donor/acceptor ability of the compounds stressing the role of heteroatoms.

The nature of ANN does not show direct quantitative relations between descriptor and endpoint values, rather the combinations of descriptor values are important. This makes analysis based on the trends of the descriptor values difficult, as most descriptors will have very diverse values for both highly toxic and less toxic compounds. Overall, there is strong qualitative agreement with the generally accepted scientific understanding. According to that and the present model, the acute oral toxicity is strongly dependent on the stability and reactivity of chemicals, in particular the presence of heteroatoms like oxygen, nitrogen, phosphorus, and halogenides in the structures, represented by the charge distribution descriptors in the model (LUMO+1 energy (AM1), Tot molecular 1-center E-N attraction (AM1), RNCG Relative negative charge (QMNEG/QTMINUS) (Zefirov)) – describing the availability of

The prediction reliability in terms of ATE Category is estimated as 84 %.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
On the basis of the predicted LD50 value of 1780 mg/kg, according to Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP Regulation), the substance is classified as harmful if swallowed.