1,3,5-Triazin-2-amine, 4-methoxy-6-(trifluoromethyl)-

Density

Administrative data

Endpoint:

relative density

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

10 MAR 2022

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 QSAR v5.1

2. MODEL (incl. version number)
Consensus

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
COc1nc(N)nc(n1)C(F)(F)F

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The data set for this endpoint was obtained from the density data contained in LookChem (Lookchem.com 2011). The data set was restricted to chemicals with boiling points greater than 25°C (or the boiling point was unavailable). The data set was further restricted to chemical with densities greater than 0.5 and less than 5 g/cm3. The final dataset consisted of 8909 chemicals. The data in lookchem.com is not peer reviewed but the set is very large and thus provides a large degree of structural diversity.

Hierarchical R^2: 0.972
Group contribution R^2: 0.872
Nearest neighbor R^2: 0.858
Consensus R^2: 0.938

For this property, the hierarchical clustering and FDA methods gave a slightly higher R2 value than the consensus method. However, the consensus method yielded a near 100% prediction coverage.

5. APPLICABILITY DOMAIN
The applicability domain is defined using several different constraints. The first constraint, the model ellipsoid constraint, checks if the test chemical is within the multidimensional ellipsoid defined by the ranges of descriptor values for the chemicals in the cluster (for the descriptors appearing the cluster model). The model ellipsoid constraint is satisfied if the leverage of the test compound (h00) is less than the maximum leverage value for all the compounds used in the model (Montgomery 1982). The second constraint, the Rmax constraint, checks if the distance from the test chemical to the centroid of the cluster is less than the maximum distance for any chemical in the cluster to the cluster centroid. The distance is defined in terms of the entire pool of descriptors (instead of just the descriptors appearing in the model): distance i = sum(j=i; d) [(Xij - Cj)^2] where distancei is the distance of chemical i to the centroid of the cluster. The last constraint, the fragment constraint, is that the compounds in the cluster have to have at least one example of each of the fragments contained in the test chemical.

Data source

Reference

Reference Type:

other: QSAR calculation

Title:

T.E.S.T (Toxicity Estimation Software Tool), V5.1

Author:

US EPA

Year:

2020

Bibliographic source:

U.S. Environmental Protection Agency

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs Chapter R.6

Version / remarks:

May 2008

Principles of method if other than guideline:

Software tool(s) used including version: T.E.S.T QSAR v5.1
- Model(s) used: Consensus
- Model description: 3 models (Hierarchical, group, nearest neighbor method) were used to draw the value of consensus method
Hierarchical method – The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm-based technique is used to generate models for each cluster. The models are generated prior to runtime.
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). The regression model is generated prior to runtime.
Nearest neighbor method – The predicted toxicity is estimated by taking an average of the three chemicals in the training set that are most similar to the test chemical.
Consensus method – The predicted toxicity is estimated by taking an average of the predicted toxicities from each of the above QSAR methodologies. If only a single QSAR methodology can make a prediction, the predicted value is deemed unreliable and not used. This method typically provides the highest prediction accuracy since errant predictions are dampened by the predictions from the other methods. In addition this method provides the highest prediction coverage because several methods with slightly different applicability domains are used to make a prediction.
- Justification of QSAR prediction: see field 'Justification for type of information'.

Test material

Test material information

Constituent 1

Reference substance name:

4-methoxy-6-(trifluoromethyl)-1,3,5-triazin-2-amine

EC Number:

610-962-9

Cas Number:

5311-05-7

Molecular formula:

C5H5F3N4O

IUPAC Name:

4-methoxy-6-(trifluoromethyl)-1,3,5-triazin-2-amine

Specific details on test material used for the study:

COc1nc(N)nc(n1)C(F)(F)F

Results and discussion

Density

Density 1

Key result

Type:

relative density

Density:

1.44 other: no unit for relative density

Remarks on result:

other: to water at 4 °C

Density 2

Type:

density

Density:

1.44 g/cm³

Remarks on result:

other: no details about temperature given in the QSAR calculation

Any other information on results incl. tables

Method	Predicted value (g/cm^3 )
Hierarchical clustering	1.43
Group contribution	1.49
Nearest neighbor	1.39

Based on these 3 models predicted value, consensus method drew the value of 1.44 g/cm³ .

Applicant's summary and conclusion

Conclusions:

The density of the test item was calculated to be 1.44 g/cm³ using the US- EPA software T.E.S.T consensus method.

Executive summary:

The density of the test item was calculated to be 1.44 g/cm³ using the US- EPA software T.E.S.T consensus method. The relative density of the test item was calculated to be 1.44 (to water at 4 ^oC). The prediction was in the applicability domain of the model.