di-tert-butyl (2S,3E)-3-[(dimethylamino)methylene]-4-oxopyrrolidine-1,2-dicarboxylate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2015

Materials and methods

Principles of method if other than guideline:

Carcinogenicity on rat (male, female) was estimated by using two predictors: Leadscope Model Applier and ACD/Percepta.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

di-tert-butyl (2S,3E)-3-[(dimethylamino)methylene]-4-oxopyrrolidine-1,2-dicarboxylate

EC Number:

942-146-6

Cas Number:

166410-06-6

Molecular formula:

C17H28N2O5

IUPAC Name:

di-tert-butyl (2S,3E)-3-[(dimethylamino)methylene]-4-oxopyrrolidine-1,2-dicarboxylate

Test animals

Species:

rat

Sex:

male/female

Results and discussion

Any other information on results incl. tables

Name	Model	ACD/Percepta	Leadscope	Consensus prediction
di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate	Rat male	OUT OF THE DOMAIN)	NEGATIVE (Borderline reliable)	NEGATIVE (Borderline reliable)
	Rat female	OUT OF THE DOMAIN	NEGATIVE (Borderline reliable)	NEGATIVE (Borderline reliable)

 

Leadscope FDA Model Applier prediction for carcinogenicity on rat (both males and females) resulted to be NEGATIVE, since the positive prediction probability was equal to 0.07 (male) and 0.18 (female). Since at least 11 features were found, it was concluded that di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate is represented by the models. The robustness of the prediction was further evaluated by examining compounds similar to the di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate from the training set. While this information does not take part to the prediction, it provides the complementary means to see how similar compounds were predicted and what the experimental values of similar compounds are. Two structures from the training set of Car Rat Male model and one structure from the training set of Car Rat Female model were identified as analogues to di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate (similarity > 30%), although characterized by little similarity (similarity < 0.5) and positive experimental data . Based on that, Leadscope predictions were assessed as borderline reliable.

Applicant's summary and conclusion

Conclusions:

Since ACD/Percepta predictions resulted to be out of the model domains, based on Leadscope predictions of carcinogenicity on rat male and female the target di-tert-butyl (2S,3E)-3-[(dimethylamino)methylidene]-4-oxopyrrolidine-1,2-dicarboxylate was predicted as NEGATIVE for rat carcinogenicity, and the predictions were assessed as borderline reliable.