Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
March 30th, 2018
Reliability:
1 (reliable without restriction)
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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6 (QSPR model adapted specifically from OECD test guidelines 107 and 123)
Principles of method if other than guideline:
Principle:
This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) in as much as this is possible for this model and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 107, or 123.
In the majority of cases data were obtained from shake flask experiments although when available, for higher log KOW values, the slow-stir method was preferred. This reduced the risk of error due to adsorption and emulsification which is known to occur at higher log KOW in the shake-flask study potentially causing errors in log KOW values for experiemental data at log KOW >4.

Methodology:
The iSafeRat® HA-QSAR predicts log KOW using the chemical structure as an input.
The method is termed as “the Core-Centered Substitution Method” (C2SM) and is based on a substitution-based approach, a methodology which has been commonly implemented for the estimation of log KOW and is readily found in the literature (Hansch and Leo, 1979). Typically, with the C2SM, the molecular structure is splitted into a core and substituents. The core and each substituent are associated with a log KOW contribution which can be positive or negative depending on the impact of the fragment on the hydrophobicity on the molecule. For example, a hydroxyl substituent will have a negative contribution because it contributes to decrease the hydrophobicity of a molecule. For a given chemical structure, the contribution values of all its relevant structural fragments are added together by substitution to obtain a high accuracy log Kow prediction. The intrinsic error for each substituent is depending on the quality of the log KOW data used.
The log KOW calculation is carried out in three steps:
a. The core is identified within the target substance (i.e. the substance to be predicted) as the largest core which can be considered among three different kids of core among : alkane chain, cycloalkane and benzene.
b. The remaining fragments of the molecule are identified as substituents and their hydrophobic contribution are added to the contribution of the core.
c. The C2SM is then finalised by taking into account potential effect of interaction between the fragments considered (e.g. electronic delocalistion)
GLP compliance:
no
Type of method:
other: QSPR model adapted specifically from OECD test guidelines 107 and 123
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Smiles: CCCCCCCCCCCCCCCCCCOCC(O)CO

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
ca. 7.8
Temp.:
25 °C
Remarks on result:
other: no pH was measured since this is a QSAR calculation.

Applicant's summary and conclusion

Executive summary:

The purpose of the in silico study was to determine the log KOW of 3-OCTADECOXYPROPANE-1,2-DIOL.

The determination was performed using a core-centred substitution method (C2SM) in which the molecule is divided a core and substituents and each fragment is related to a specific contribution of log KOW which may be positive or negative. The final log KOW is determined by simple addition of the fragments. The predicted log KOW values have been validated against high quality experimental studies generally using the shake-flask method but slow-stir values have been used when available. The results are considered to be as accurate as those from a good quality OECD 107 or 123 study.

The results below is the anticipated log KOW value further to a study following OECD Guideline No. 107 or 123.

The log KOW is calculated as follows: 7.8 at 25°C.