Registration Dossier

Administrative data

Endpoint:
boiling point
Type of information:
(Q)SAR
Adequacy of study:
key study
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 limited documentation / justification
Justification for type of information:
1. SOFTWARE
EPI v.4.11 (MPBPWIN v1.43), US EPA

2. MODEL (incl. version number)
MPBPWIN v1.43 (Adaptation of the Stein and Brown (1994))

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)(C)NC[C@H](O)CO

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
MPBPWIN estimates the normal boiling point using an adaptation of the Stein and Brown (1994) method which is an extension and refinement of the Joback method (Joback, 1982; Reid et al, 1987).
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]
The Stein and Brown (1994) method was developed using a training dataset of boiling points for 4426 diverse organic compounds collected from the Aldrich Handbook (Aldrich, 1990).
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).
Estimation Accuracy
The Stein and Brown method was derived from a training set of 4426 diverse organic compounds with following reported statistical accuracy (Stein and Brown, 1994):
Average absolute error = 15.5 deg Kelvin
Standard deviation = 24.6 deg Kelvin
Average error = 3.2%

It was then validated on a dataset of 6584 compounds collected from HODOC (1990) (compounds not used in the training set) with the following statistical accuracy (Stein and Brown, 1994):
Average absolute error = 20.4 deg Kelvin
Standard deviation = 38.1 deg Kelvin
Average error = 4.3%

The training and validation sets were not available. However, a test set of 5890 compounds with available normal boiling points was collected from the PHYSPROP Database that is included with the EPI Suite. Various compounds having boiling points were excluded (most inorganic compounds, compounds using reduced pressures).

5. APPLICABILITY DOMAIN
Currently there is no universally accepted definition of model domain. However property estimates are less accurate for compounds outside the Molecular Weight range of the training set compounds (Molecular Weight range: 16.04 – 959.17), and/or that have more instances of a given fragment than the maximum for all training set compounds.
The complete training sets for MPBPWIN's estimation methodology are not available. Therefore, describing a precise estimation domain for this methodology is not possible. The number of compounds used to derive each of the Stein and Brown descriptors is shown in Appendix F of MPBPWIN User’s Guide, but the maximum number of each descriptor that occurs in each compound is not available.
The current applicability of the MPBPWIN methodology is best described by its accuracy in predicting boiling point as described above in the Accuracy section.

6. ADEQUACY OF THE RESULT
The estimate value has been generated by a valid model. The model is applicable to the substance with the necessary level of reliability and is sufficiently relevant for the regulatory purpose.

Data source

Reference
Reference Type:
other: calculation
Title:
MPBVP 1.43
Author:
US EPA
Year:
2014
Bibliographic source:
EPI Suite v4.11

Materials and methods

Principles of method if other than guideline:
Predicted data. Adapted Stein & Brown method
GLP compliance:
no
Type of method:
other: predicted data

Test material

Reference
Name:
Unnamed
Test material form:
solid: particulate/powder

Results and discussion

Boiling point
Key result
Boiling pt.:
250.86 °C
Remarks on result:
other: Pressure not available

Applicant's summary and conclusion

Conclusions:
Predicted Boiling point (EPI v4.11 - Adapted Stein & Brown method): 250.86 °C