Reaction Mass of 3,8-dimethyl-5-(prop-1-en-2-yl)-1,2,3,3a,4,5,6,7-octahydroazulene and 4,8a,9,9-octamethyldecahydro-1,6-methanonaphthalen-1-ol

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

22 February - 01 March 2018

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:

iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship (HA-QSAR) based on a holistic approach for predicting physicochemical and ecotoxicological endpoints: Octanol-water partition coefficient

1. SOFTWARE
iSafeRat® HA-QSAR toolbox v2.4

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.8

3. IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES codes of the constituents (see attached QPRF of each constituent)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

yes

Remarks:

QSAR model

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Deviations:

yes

Remarks:

QSAR model

Principles of method if other than guideline:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the n-octanol/water partition coefficients of the consituents of the test item (a Natural Complex Substance). This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) 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, "Partition Coeficient (n-octanol/water): Shake Flask Method" and No. 123 "Partition Coeficient (n-octanol/water): Slow Stirring Method”. The criterion predicted was the log KOW (also known as log POW).

The determination was performed using a core-centred substitution method (C2SM) in which the molecule is divided into 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.

GLP compliance:

no

Type of method:

other: QSAR

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

4.7

Temp.:

25 °C

Remarks on result:

other: constituent 1

Key result

Type:

log Pow

Partition coefficient:

6.6

Temp.:

25 °C

Remarks on result:

other: constituent 2

Key result

Type:

log Pow

Partition coefficient:

4.7

Temp.:

25 °C

Remarks on result:

other: constituent 3

Key result

Type:

log Pow

Partition coefficient:

1.26

Temp.:

25 °C

Remarks on result:

other: constituent 4

Key result

Type:

log Pow

Partition coefficient:

3.7

Temp.:

25 °C

Remarks on result:

other: constituent 5

Key result

Type:

log Pow

Partition coefficient:

4

Temp.:

25 °C

Remarks on result:

other: constituent 6

Conclusions:

The logKOW of 6 constituents of the test item were determined as follows (based on valid QSAR estimations):

Constituents: logKow at 25°C
Constituent 1 : 4.7
Constituent 2 : 6.6
Constituent 3 : 4.7
Constituent 4: 1.26
Constituent 5: 3.7
Constituent 6 : 4.0

Executive summary:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the noctanol/water partition coefficients of the consituents of the test item, a Natural Complex Substance. This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) 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, "Partition Coeficient (n-octanol/water): Shake Flask Method" and No. 123 "Partition Coeficient (n-octanol/water): Slow Stirring Method”.

The constituents are within the applicability domain (MW, descriptors).

Finally the logKOW of 6 major constituents of the substance (covering more than 94% of the composition) were determined to be between 1.26 and 6.6 at 25°C.

Description of key information

The partition coefficients of the constituents of the substance (6 components of the substance covering more than 94% of the composition) were estimated in the range between 1.26 and 6.6 at 25°C (valid QSAR estimations).

Additional information

No study was conducted on the oil itself.

The test item is a natural complex substance (NCS). It is a mixture of several constituents, but 6 of them represent more than 94% of that mixture.

The partition coefficients of the major constituents of the test item were estimated using the QSAR modeliSafeRat®, based on a core-centred substitution method (C2SM) method. The constituents of the substance were within the applicability domain (MW, descriptors).

The log KOW of constituents were predicted as follows:

Constituents: logKow at 25°C

Constituent 1       : 4.7

Constituent 2       : 6.6

Constituent 3       : 4.7

Constituent 4: 1.26

Constituent 5: 3.7

Constituent 6       : 4.0

As the substance is an UVCB with constituents of different log KOW, the global logKOW of the test item will depend on the composition and the loading rate (with varying ratio of constituents in the dissolved phase). Therefore we considered the logKOW of the 6 major constituents of the substance and no single key value was retained (nor calculated weighted logKOW nor worst-case).