Prop-2-yn-1-yl 1H-imidazole-1-carboxylate

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

(Q)SAR

Adequacy of study:

key study

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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
T.E.S.T (Toxcity Estimation Software Tool) 5.1.1

2. MODEL (incl. version number)
Consensus method
Hierarchical clustering
Single model
Nearest neighbor

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: C#CCOC(=O)N1C=CN=C1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please see attachment "TEST User's Guide_5.1.1"


5. APPLICABILITY DOMAIN
- General applicability domain:
In the Section 4.6 of the User’s Guide, it says that “salts, undefined isomeric mixtures, polymers, or mixtures were removed [from the training set]”. Therefore, those types of substances should not be predicted with T.E.S.T. However, the target chemical is not salt, undefined isomeric mixture, polymer, or mixture.

- Descriptor domain:
The overall pool of descriptors in the software contains 797 2-dimensional descriptors. For the Hierarchical and Single methods, 797 descriptors can be used in the model equation depending on the target chemical. These methods give a prediction only if the target chemical is within the ranges of descriptor values for the chemicals in the cluster (for the descriptors appearing in the cluster model).
Concerning the nearest neighbor method, the descriptor differences between the target chemical and its structural analogues are not accounted for by T.E.S.T.
Besides, the target chemical is within the ranges of log Kow and molecular weight of the compounds in the cluster (and of the three nearest neighbours).

- Structural domain:
The Hierarchical and Single methods give a prediction only if the compounds in the cluster have at least one example of each of the fragments contained in the target chemical.

- Mechanistic domain: N/A

- Similarity with analogues in the training set: Please see attachment of specific prediction report.

- Other considerations (as appropriate): N/A

6. ADEQUACY OF THE RESULT
For Hierarchical methods, the target chemical is falling into 7 cluster models's applicability domain (model 421, 427, 434, 440, 445, 448 and 452). And the predicted value matches the experimental values for similar chemicals in the external test and training set well, therefore the pridiction of Hierarchical methods seem to be reliable.

For Single methods, the target chemical is falling into the cluster model 452's applicability domain . And the predicted value matches the experimental values for similar chemicals in the external test and training set well, therefore the pridiction of Single methods seem to be reliable.

For Nearest neighbor methods, the predicted toxicity is the average of the toxicities of the three most similar chemicals (structural analogs) in the training set.

Data source

Reference

Reference Type:

other: QSAR

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Principles of method if other than guideline:

- Software tool(s) used including version: T.E.S.T (Toxcity Estimation Software Tool) 5.1.1

- Model(s) used:
Consensus method
Hierarchical clustering
Single model
Nearest neighbor

- Model description: Please see attachment "TEST User's Guide_5.1.1"

- Justification of QSAR prediction:
For Hierarchical methods, the target chemical is falling into 7 cluster models's applicability domain (model 421, 427, 434, 440, 445, 448 and 452). And the predicted value matches the experimental values for similar chemicals in the external test and training set well, therefore the pridiction of Hierarchical methods seem to be reliable.
For Single methods, the target chemical is falling into the cluster model 452's applicability domain . And the predicted value matches the experimental values for similar chemicals in the external test and training set well, therefore the pridiction of Single methods seem to be reliable.
For Nearest neighbor methods, the predicted toxicity is the average of the toxicities of the three most similar chemicals (structural analogs) in the training set.

Test material

Test material information

Constituent 1

Reference substance name:

prop-2-yn-1-yl 1H-imidazole-1-carboxylate

EC Number:

695-595-2

Cas Number:

83395-38-4

Molecular formula:

C7H6N2O2

IUPAC Name:

prop-2-yn-1-yl 1H-imidazole-1-carboxylate

Test material form:

solid

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Key result

Dose descriptor:

other: Prediction of reproductive and developmental toxicity by QSAR

Based on:

other: Prediction of reproductive and development toxicity by QSAR

Sex:

not specified

Basis for effect level:

reproductive performance

Remarks on result:

other: Prediction of reproductive and development toxicity by QSAR

Results: F1 generation

Effect levels (F1)

Key result

Dose descriptor:

other: Prediction of reproductive and developmental toxicity by QSAR

Generation:

F1

Based on:

other: Prediction of reproductive and development toxicity by QSAR

Sex:

not specified

Remarks on result:

other: Prediction of reproductive and development toxicity by QSAR

Overall reproductive toxicity

Key result

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

All predicted Developmental Toxicity for Prop -2-yn -1-yl 1H yl 1H -imidazole -1-carboxylate (CAS number: 83395-38-4) from Consensus, Hierarchical clustering, Single model and Nearest neighbor method is Developmental toxicant.

Executive summary:

Reliable predicted Developmental Toxicity obtained by Toxcity Estimation Software Tool using the Consensus, Hierarchical clustering, Single model and Nearest neighbor method. The pridiction fulfilling the OECD five criteria for validation of QSAR models. All predicted Developmental Toxicity for Prop -2-yn -1-yl 1H yl 1H -imidazole -1-carboxylate (CAS number: 83395-38-4) from Consensus, Hierarchical clustering, Single model and Nearest neighbor method is Developmental toxicant.