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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the overall internal quality check in VEGA v1.1.3 indicates that the prediction is reliable with a Klimisch score of 2.
Justification for type of information:
1. SOFTWARE
VEGA version 1.1.3

2. MODEL (incl. version number)
ALogP Model v. 1.0.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: VEGA v1.1.3
- Model(s) used: ALogP Model version 1.0.0
The model is based on the Ghose-Crippen-Viswanadhan LogP (ALogP) and consists of a regression equation based on the hydrophobicity contribution of 120 atom types as described in: A.K. Ghose and G.M. Crippen, J. Comput. Chem. 1986, 7, 565-577; V.N. Viswanadhan et al., J. Comput. Chem. 1993, 14, 1019-1026; A.K. Ghose, V.N. Viswanadhan, J.J. Wendoloski, J. Phys. Chem. A 1998, 102, 3762-3772. For the purpose of applicability domain assessment, the training set of the Meylan LogP model (9,961 compounds) has been considered, setting all molecules as belonging to the test set.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
7.05
Remarks on result:
other: QSAR result, no information on temperature and pH available.

For detailed information on the results please refer to the attached report.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the overall internal quality check in VEGA v1.1.3 indicates that the prediction is reliable with a Klimisch score of 2.
Justification for type of information:
1. SOFTWARE
VEGA version 1.1.3

2. MODEL (incl. version number)
Meylan/Kowwin v. 1.1.4

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Any other information on results incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: VEGA v1.1.3
- Model(s) used: Meylan/Kowwin LogP Model version 1.1.4
The model is based on the Atom/Fragment Contribution (AFC) method from the work of Meylan and Howard (W.M. Meylan and P.H. Howard, Atom/fragment contribution method for estimating octanol-water partition coefficients, 1995, J. Pharm. Sci. 84: 83-92.), as implemented in the EPI Suite KOWWIN module (http://www.epa.gov/oppt/exposure/pubs/episuite.htm). The calculated model has a lower bound of -5.0 log units (all predictions lower than this value are set to -5.0). A dataset of compounds with experimental logP values has been built starting from the original dataset provided in EPI suite. The set has been processed and cleared from compounds that were replicated or that had problems with the provided molecule structure. The final dataset has 9,961 compounds.
- Model description: see field 'Justification for non-standard information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'
GLP compliance:
no
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
7.7
Remarks on result:
other: QSAR result, no information on temperature and pH available.

For detailed information on the results please refer to the attached report.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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
ARChem SPARC. version 4.6

2. MODEL
Properties - Partition coefficient (Distribution)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables".

5. APPLICABILITY DOMAIN
See information provided in "Any other information of materials and methods incl. tables".

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
Calculation based on SPARC version v4.6, "Properties" calculation type
- Software tool(s) used including version: SPARC v4.6
- Model(s) used: Properties - Partition coefficient (Log)
SPARC calculates the liquid-liquid partition constant by combining the calculated activities at infinite dilution of the molecular species of interest in each of the liquid phases, as described by Hilal et al. 2004. For the complete method's description see field 'Any other information on materials and methods incl. tables'.
The datasets used for the model development (623 molecules) and for the external validation (698 molecules) are described in the field 'Any other information on materials and methods incl. tables'.
- Model description: see field 'Any other information on materials and methods incl. tables'.
- Justification of QSAR prediction: see field 'Justification for type of information' and 'overall remarks'.
GLP compliance:
no
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
8.03
Temp.:
20 °C
Remarks on result:
other: QSAR result, no information on pH available.

QSAR result. For detailed description of the model and its applicability, see "Any other information of materials and methods incl. tables".

Description of key information

Log Pow = 7.6 (QSAR, VEGA v1.1.3 - two models: Meylan/Kowwin v1.1.4, ALogP v1.0.0; SPARC v4.6)

Key value for chemical safety assessment

Log Kow (Log Pow):
7.6
at the temperature of:
20 °C

Additional information

Overall results

The Log Pow values as estimated by the VEGA/ALogP, VEGA/Meylan-KOWWIN and SPARC/physico-chemical models are reported in the following table. The two most similar substances identified by VEGA are also included (using their CAS number), together with their similarity degree with the target component, experimental Log Pow values and the predictions obtained by the QSAR models.

Molecule / CAS

Similarity degree

Experimental Log Pow

VEGA / ALogP

VEGA / Meylan-KOWWIN

SPARC

Target

-

n.a.

7.05

7.7

8.03

20292-08-4

0.892

8.03

7.81

8.648

-

1120-28-1

0.87

9.3

8.443

9.213

-

 

Discussion

The applicability domain (AD) evaluation performed by the VEGA software suggests that the evaluated substance could be out of the models’ AD. According to the VEGA reports, the result obtained with the Meylan-KOWWIN model was slightly more reliable.

The result obtained with the SPARC model supports a slightly higher Log Pow, closer to the estimation obtained by Meylan-KOWWIN. Currently, there is no universally accepted definition of model domain; SPARC has been designed and parameterized to be applicable to any organic chemical structure. The partition coefficient model validation, performed on a dataset of 698 molecules, proved that the model can be used to provide reliable estimations.

 

Conclusion

Considering the obtained results, an average Log Pow value of 7.6 can be considered as a reasonable estimation for the whole substance.