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Toxicity to reproduction: other studies

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toxicity to reproduction: other studies
Type of information:
Adequacy of study:
weight of evidence
Study period:
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

Referenceopen allclose all

Reference Type:
The Toxicity Estimation Software Tool (T.E.S.T.).
Bibliographic source:
Presented at New England Green Chemistry Networking Forum , Boston, MA, December 16, 2010.
Reference Type:
Evaluation of different statistical approaches for the validation of quantitative structure-activity relationships.
Gramatica, P., and Pilutti, P.
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
not applicable to QSAR models
Type of method:
other: QSAR

Test material

Constituent 1
Reference substance name:
Constituent 2
Reference substance name:
structure formula
structure formula

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).

- Group contribution method (Predictions are made using a multilinear regression model that is fit to the training set (using molecular fragment counts as independent variables).

- 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

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

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