9β,11β-epoxy-6α-fluoro-17,21-dihydroxypregna-1,4-diene-3,20-dione 17,21-di(acetate)

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2014

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: US EPA Toxicity Estimation Software Tool (TEST) v.4.1, accepted QSAR method for organic chemicals properties assessment.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The Toxicity Estimation Software Tool (T.E.S.T.).

Author:

YOUNG, D. M.

Year:

2010

Bibliographic source:

Presented at New England Green Chemistry Networking Forum , Boston, MA, December 16, 2010.

Reference 2

Reference Type:

publication

Title:

Evaluation of different statistical approaches for the validation of quantitative structure-activity relationships.

Author:

Gramatica, P., and Pilutti, P.

Year:

2004

Bibliographic source:

Ispra, Italy: The European Commission - Joint Research Centre, Institute for Health & Consumer Protection - ECVAM.

Materials and methods

Principles of method if other than guideline:

QSAR approach

GLP compliance:

not specified

Remarks:

not applicable to QSAR models

Type of method:

other: QSAR

Test material

Test material information

Constituent 1

Reference substance name:

9β,11β-epoxy-6α-fluoro-17,21-dihydroxypregna-1,4-diene-3,20-dione 17,21-di(acetate)

EC Number:

276-705-4

EC Name:

9β,11β-epoxy-6α-fluoro-17,21-dihydroxypregna-1,4-diene-3,20-dione 17,21-di(acetate)

Cas Number:

72498-89-6

Molecular formula:

C25H29FO7

IUPAC Name:

2-[(1S,2S,8S,10S,11S,14R,15S,17S)-14-(acetyloxy)-8-fluoro-2,15-dimethyl-5-oxo-18-oxapentacyclo[8.8.0.0^{1,17}.0^{2,7}.0^{11,15}]octadeca-3,6-dien-14-yl]-2-oxoethyl acetate

Results and discussion

Observed effects

Substance has been predicted as Developmental toxicant

Any other information on results incl. tables

Developmental toxicity includes any effect interfering with normal development, both before and after birth. A dataset of 293 chemicals was created by Arena and Coworkers (Arena et al. 2004; Sussman et al. 2003) by combining data from the Teratogen Information System (TERIS) (Briggs et al. 1990) and the FDA guidelines (Shepard 1992). The developmental toxicity values were taken from the revised binary toxicity values developed for the CAESAR project (CAESAR 2009). The final dataset consists of 285 chemicals (after removing salts, mixtures, and ambiguous compounds).

The predicted value is estimated by taking an average of the predicted values from the following QSAR methods (provided the predictions are within the respective applicability domains):

- Hierarchical method (The toxicity for a given query compound is estimated using the weighted average of the predictions from several different cluster models).

- Single model (The model is generated using techniques and constraints similar to those for the hierarchical method (except that the training cluster contains the entire training set).

- FDA method (The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime).

- Nearest neighbor method (The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical).

Statistical External Validation

The prediction results for the Ames mutagenicity were as follows:

Method	Concordance	Sensitivity	Specificity	Coverage
Hierarchical	0.724	0.829	0.471	1.000
Single Model	0.732	0.850	0.438	0.966
FDA	0.724	0.780	0.588	1.000
Nearest neighbor	0.759	0.844	0.667	0.759
Consensus	0.793	0.902	0.529	1.000

Applicant's summary and conclusion

Conclusions:

Substance has been predicted as developmental toxicant by T.E.S.T.