2,3,3-trimethyl-3H-indole-5-carboxylic acid

Boiling point

Link to relevant study record(s)

Reference

Endpoint:

boiling point

Type of information:

(Q)SAR

Adequacy of study:

other information

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
Individual model MPBPWIN included in the Estimation Programs Interface (EPI) Suite.

2. MODEL (incl. version number)
MPBPWIN v1.43 included in EPISuite v 4.11, 2000 - 2012
The adapted Stein and Brown method

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
A SMILES NOTATION was entered in the initial data entry screen. In the structure window, the molecular weight, structural formula and the structure of the input SMILES notation is shown. If available, experimental determined values of melting point are taken for input.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
a. Defined endpoint: boiling point
b. Unambigous algorithm: MPBPWIN estimates boiling point (BP) by an adaption of the Stein and Brown (1994) method which is an extension and refinement of the Joback method. The Stein and Brown (1994) method is a group contribution QSAR (quantitative structure activity relationship) method that calculates boiling point (Tb) of a compound by adding group increment values according to the relationship:
Tb = 198.2 + Σ( ni * gi )
where gi is a group increment value and ni is the number of times the group occurs in the compound. The resulting Tb (deg K) is then corrected by one of the following equations:
Tb (corr) = Tb - 94.84 + 0.5577 Tb - 0.0007705 (Tb)2 [Tb <= 700 K]
Tb (corr) = Tb + 282.7 - 0.5209 Tb [Tb > 700 K]
MPBPWIN incorporates additional extensions to Stein and Brown Method such as (1) new group contributions missing from Brown and Stein (e.g. thiophosphorus [P=S], quaternary ammonium) and (2) correction factors for specific types of compounds (e.g. amino acids, various aromatic nitrogen rings, and phosphates).
c. Descriptor selection: As the program requires only a chemical structure to estimate a boiling point, MPBPWIN initially separates a molecule into distinct atom/fragments for calculating the melting point and the boiling point. MPBPWIN estimates boiling point (BP) by an adaption of the Stein and Brown (1994) method which is an extension and refinement of the Joback method. The Stein and Brown (1994) method is a group contribution QSAR (quantitative structure activity relationship) method that calculates boiling point (Tb) of a compound by adding group increment values according to the relationship. The BP and MP coefficients are based on organic group fragments like e.g. -CH3, -OH, -NH2, also including some inorganic groups (metals). Appendix F of the MPBPWIN help file contains a complete list the group descriptors and coefficient values used by MPBPWIN to estimate boiling point.
d. Applicability domain: With a molecular weight of 203.24 g/mol the substance is within the applicable range of 16 - 959 g/mol. Regarding the structure, the fragment descriptors used by the program for the estimation of the boiling point are complete and listed in Appendix F of the MPBPWIN help file.
e. Statistical characteristics: Correlation coefficient of the total test set is r2= 0.935.
f. Mechanistic interpretation: MPBPWIN estimates the normal boiling point using an adaptation of the Stein & Brown method. This method is a group contribution QSAR (quantitative structure activity relationship) method that calculates the boiling point of a compound by adding group increment values.
g. The uncertainty of the prediction (OECD principle 4):
2,3,3-Trimethyl-3H-indole-5-carboxylic acid is not highly complex and the rules applied for the substance appear appropriate. An individual uncertainty for the investigated substance is not available.

5. APPLICABILITY DOMAIN
a.Domains:
i. Molecular weight: With a molecular weight of 203.24 g/mol 2,3,3-trimethyl-3H-indole-5-carbolxylic acid is within the range of the training set (16 -– 959 g/mol).
ii. Structural fragment domain: Regarding the structure, the fragment descriptors used by the program for the estimation of the boiling point are complete and listed in Appendix F of the MPBPWIN help file.
iii. Mechanism domain: NO INFORMATION AVAILABLE
iv. Metabolic domain, if relevant: NOT RELEVANT
b. Structural analogues: NO INFORMATION AVAILABLE
c. Considerations on structural analogues: NO INFORMATION AVAILABLE

6. ADEQUACY OF THE RESULT
a. Regulatory purpose: The data may be used under any regulatory purpose.
b. Approach for regulatory interpretation of the model result: If no experimental data are available the estimated value may be used to fill data gaps needed for hazard and risk assessment. Further the value can be used for other calculations.
c. Outcome: The prediction of boiling point yields a useful result for further evaluation.
d. Adequacy of prediction: The result for 2,3,3-trimethyl-3H-indole-5-carboxylic acid falls within the applicability domain described above and the estimation rules applied for the substance appear appropriate. Therefore the predicted value can be considered reliable yielding a useful result for further assessment.
e. Conclusion: The result is considered as useful for regulatory purposes.

Guideline:

other: REACH guidance on QSARs R.6, May 2008

Principles of method if other than guideline:

The Estimation Program Interface (EPI) Suite v4.11 includes the model MPBPWIN for estimating the vapour pressure of organic compounds. The Estimation Programs Interface was developed by the US Environmental Agency's Office of Pollution Prevention and Toxics and Syracuse Research Corporation (SRC). © 2000 - 2012 U.S. Environmental Protection Agency for EPI SuiteTM. Published online in November 2012.

GLP compliance:

no

Type of method:

other: QSAR-estimation

Boiling pt.:

342 °C

Atm. press.:

1 013 Pa

Validity of the model:

1. Defined Endpoint: boiling point

2. Unamigous algorithm: The Stein and Brown (1994) method is a group contribution QSAR (quantitative structure activity relationship) method that calculates boiling point (Tb) of a compound by adding group increment values according to the relationship: Tb  =  198.2  + Σ( ni * gi ) where  gi  is a group increment value and  ni  is the number of times the group occurs in the compound. MPBPWIN incorporates additional extensions to Stein and Brown Method such as (1) new group contributions missing from Brown and Stein (e.g. thiophosphorus [P=S], quaternary ammonium) and (2) correction factors for specific types of compounds (e.g. amino acids, various aromatic nitrogen rings, and phosphates).

The following groups were applied: methyl group, carbon (ring), carboxylic group, nitrogen (ring), carbon (aromatic) and an equation constant. The number of times of the groups that occur in the structure of the substance applied by the program is verified.

3. Applicability domain: With a molecular weight of 203.24 g/mol the substance is within the range of the training set (16 - 959 g/mol). Regarding the structure of 2,3,3-trimethyl-3H-indole-5-carboxylic acid the fragment descriptors found by the program are complete.

4. Statistical characteristics: Correlation coefficient of the total test set is r²= 0.935.

5. Mechanistic interpretation: The structural fragments used as descriptors reflect the fugacity of the substances, and so the boiling point.

6. Adequacy of prediction: The result for 2,3,3-trimethyl-3H-indole-5-carboxylic acid falls within the applicability domain described above and the estimation rules applied for the substance appears appropriate. Therefore the predicted value can be considered reliable yielding a useful result for further assessment.

Conclusions:

The QSAR determination of the boiling point for 2,3,3-trimethyl-3H-indole-5-carboxylic acid using the model MPBPWIN included in the Estimation Program Interface (EPI) Suite v4.11 revealed a boiling point of 342 °C at 1013 Pa. The predicted value can be considered reliable yielding a useful result for further assessment.

Executive summary:

The boiling point for 2,3,3-trimethyl-3H-indole-5-carboxylic acid was predicted using the QSAR calculation of the Estimation Programm Interface (EPI) Suite v4.11. The boiling point was estimated to be 342 °C. The pressure is assumed as 1013 Pa.

The predicted value can be considered reliable yielding a useful result for further assessment.

Description of key information

The boiling point for 2,3,3-trimethyl-3H-indole-5-carboxylic acid was predicted using the QSAR calculation of the Estimation Programm Interface (EPI) Suite v4.11. The boiling point was estimated to be 342 °C. The pressure is assumed as 1013 Pa.

The predicted value can be considered reliable yielding a useful result for further assessment.

Key value for chemical safety assessment

Boiling point at 101 325 Pa:

342 °C