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

Flash point

Administrative data

Endpoint:

flash point, other

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
A dataset of 8362 chemicals was compiled from LookChem. Chemicals with flash points greater than 1000°C were omitted from the data set.
Hierarchical R^2: 0.870
Group contribution R^2: 0.834
Nearest neighbor R^2: 0.801
Consensus R^2: 0.873
For this property, the consensus method produces the best results in terms of prediction accuracy and 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. As consensus method gives predictions for the test chemical and for the most similar chemicals in the external test set. Thus it is considered to be in the applicability domain of this model.

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: Consensus model draw a result based on below 3 different method values.
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.
In the consensus method, the predicted toxicity is simply the average of the predicted toxicities from the other QSAR methodologies (taking into account the applicability domain of each method)(Zhu et al. 2008). 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', 'Attached justification'

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

Flash point

Flash point:

115.34 °C

Remarks on result:

other: no pressure details given in the QSAR calculation

Any other information on results incl. tables

Method	Predicted value °C
Hierarchical clustering	132.83
Group contribution	134.64
Nearest neighbor	78.57

In the consensus method, the predicted toxicity is simply the average of the predicted toxicities from
the other QSAR methodologies(above table). The predicted value of flash point is calculated 115.34 °C.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The flash point of the test item was calculated to be 115.34 °C using the US- EPA software T.E.S.T consensus method.

Executive summary:

The flash point of the test item was calculated to be 115.34 °C using the US- EPA software T.E.S.T consensus method. The prediction was in the applicability domain of the model.