Esterification products of glycerol with docosanoic acid, icosanedioic acid and 16-methylheptadecanoic acid

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

August 2017

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

Justification for type of information:

1. SOFTWARE

EPIWEB 4.1

2. MODEL (incl. version number)

KOWWIN v1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(COC(=O)CCCCCCCCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCCCCCCCC

CC(C)CCCCCCCCCCCCCCC(O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)OC(=O)CCCCCCCCCCCCCCC(C)C

OC(CCCCCCCCCCCCCCCCCCC(O)=O)OCC(COC(=O)CCCCCCCCCCCCCCCCCCC(O)=O)OC(=O)CCCCCCCCCCCCCCCCCCC(O)=O

CCCCCCCCCCCCCCCCCCCCCC(O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)OC(=O)CCCCCCCCCCCCCCCCCCCCC

CCCCCCCCCCCCCCCCCCCCCC(=O)OC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)COC(=O)CCCCCCCCCCCCCCCCCCCC

CCCCCCCCCCCCCCCCCCCCCC(O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)OC(=O)CCCCCCCCCCCCCCC(C)C

CC(C)CCCCCCCCCCCCCCC(=O)OCC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)OC(=O)CCCCCCCCCCCCCCC(C)C

CCCCCCCCCCCCCCCCCCCCCC(=O)OC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)COC(=O)CCCCCCCCCCCCCCCCCCC(O)=O

CC(C)CCCCCCCCCCCCCCC(=O)OCC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)OC(=O)CCCCCCCCCCCCCCCCCCC(O)=O

CCCCCCCCCCCCCCCCCCCCCC(=O)OC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)COC(=O)CCCCCCCCCCCCCCC(C)C




4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint: KOWWIN (the Log Octanol-Water Partition Coefficient Program) estimates the logarithmic octanol-water partition coefficient (log P) of organic compounds.
- Unambiguous algorithm: described in Meylan, W.M. and P.H. Howard.  1995.  Atom/fragment contribution method for estimating octanol-water partition coefficients.  J. Pharm. Sci. 84: 83-92.
- Defined domain of applicability: Training Set Molecular Weights:
Minimum MW:  18.02
Maximum MW:  719.92
Average MW:  199.98
Validation Molecular Weights:
Minimum MW:  27.03
Maximum MW:  991.15
Average MW:  258.98
- Appropriate measures of goodness-of-fit and robustness and predictivity:
Total Training Set Statistics:
  number in dataset      = 2447
  correlation coef (r2)  = 0.982
  standard deviation     = 0.217
  absolute deviation     = 0.159
  avg Molecular Weight   = 199.98
- Mechanistic interpretation: KOWWIN uses a "fragment constant" methodology to predict log P

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
The structures used for calculation of LogPow exhibit only fragments, which are covered by the Model: -CH3, -CH2-, -CH, -C(=O)O.
The molecular weight of the majority of structures used for calculation is slighly above the Molecular weights of compounds of Trainign and Validation set.

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
The predicted Endpoint is the LogPow and is identical to the endpoint for which information is required

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR calculation using the Software Epiweb 4.1

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

As calculation is performed, no specific details apply.

Key result

Type:

log Pow

Partition coefficient:

> 21.23

Temp.:

20 °C

pH:

ca. 7

Details on results:

The presented value represents the lowest log Pow, calculated for the compound with 1 Glycerol and 3 Eicosandioate and having a molecular weight of 1067 g/mol.

Table of compounds with calculated log Pow

MW	smiles	calculated Log Pow (KOWWIN v1.68)
1059,825	CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(COC(=O)CCCCCCCCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCCCCCCCC	29,83
893,517	CC(C)CCCCCCCCCCCCCCC(O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)OC(=O)CCCCCCCCCCCCCCC(C)C	22,36
1067,625	OC(CCCCCCCCCCCCCCCCCCC(O)=O)OCC(COC(=O)CCCCCCCCCCCCCCCCCCC(O)=O)OC(=O)CCCCCCCCCCCCCCCCCCC(O)=O	21,23
1005,733	CCCCCCCCCCCCCCCCCCCCCC(O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)OC(=O)CCCCCCCCCCCCCCCCCCCCC	26,44
1049,742	CCCCCCCCCCCCCCCCCCCCCC(=O)OC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)COC(=O)CCCCCCCCCCCCCCCCCCCC	25,77
949,625	CCCCCCCCCCCCCCCCCCCCCC(O)OCC(COC(=O)CCCCCCCCCCCCCCC(C)C)OC(=O)CCCCCCCCCCCCCCC(C)C	24,4
951,553	CC(C)CCCCCCCCCCCCCCC(=O)OCC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)OC(=O)CCCCCCCCCCCCCCC(C)C	22,18
1065,697	CCCCCCCCCCCCCCCCCCCCCC(=O)OC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)COC(=O)CCCCCCCCCCCCCCCCCCC(O)=O	23,45
1009,589	CC(C)CCCCCCCCCCCCCCC(=O)OCC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)OC(=O)CCCCCCCCCCCCCCCCCCC(O)=O	21,41
1007,661	CCCCCCCCCCCCCCCCCCCCCC(=O)OC(COC(O)CCCCCCCCCCCCCCCCCCC(O)=O)COC(=O)CCCCCCCCCCCCCCC(C)C	24,22

Conclusions:

The log Pow of Nomcort SG was calculated, based on selected compounds, to be at least 21.

Executive summary:

The log Pow of Nomcort SG was determined by using the QSAR Tool Kowwin 1.68. provided by the software Epiweb 4.1.

Compounds of Nomcort SG were used, which make up 70% of the substance, and can be generally described as being constituted of

1 Glycerol residue with 3 residues of either Behenate, Isostearate or Eicosandioate.

The smiles notation was generated for all of these compounds and used to calculate the log Pow.

The lowest log Pow (21.23) was resulted for the compound Glycerol with 3 Eicosandioate residues

Description of key information

QSAR calculation for the lower molecular weight compounds of Nomcort SG.

The key value represents the lowest value obtained.

Key value for chemical safety assessment

Log Kow (Log Pow):

21.23

at the temperature of:

20 °C