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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
November 6th, 2017
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 v2.3

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.7

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:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
yes
Remarks:
QSAR model
Qualifier:
equivalent or similar to
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 fragment based approach in which the molecule is divided into large and small fragments and each fragment is related to a specific log KOW contribution 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
Partition coefficient type:
other: QSAR
Key result
Type:
log Pow
Partition coefficient:
2.74
Temp.:
25 °C
Remarks on result:
other: Constituent 1
Remarks:
literature data
Key result
Type:
log Pow
Partition coefficient:
4.4
Temp.:
25 °C
Remarks on result:
other: Constituent 2
Key result
Type:
log Pow
Partition coefficient:
2.5
Temp.:
25 °C
Remarks on result:
other: Constituent 3
Key result
Type:
log Pow
Partition coefficient:
4.8
Temp.:
25 °C
Remarks on result:
other: Constituent 4
Key result
Type:
log Pow
Partition coefficient:
4.4
Temp.:
25 °C
Remarks on result:
other: Constituent 5
Key result
Type:
log Pow
Partition coefficient:
2.5
Temp.:
25 °C
Remarks on result:
other: Constituent 6
Key result
Type:
log Pow
Partition coefficient:
4.7
Temp.:
25 °C
Remarks on result:
other: Constituent 7
Key result
Type:
log Pow
Partition coefficient:
4.5
Temp.:
25 °C
Remarks on result:
other: Constituent 8
Key result
Type:
log Pow
Partition coefficient:
6.6
Temp.:
25 °C
Remarks on result:
other: Constituent 9
Key result
Type:
log Pow
Partition coefficient:
4.6
Temp.:
25 °C
Remarks on result:
other: Constituent 10
Key result
Type:
log Pow
Partition coefficient:
4.6
Temp.:
25 °C
Remarks on result:
other: Constituent 11

The partition coefficient of the constituents of the substance was estimated using the recommended QSAR modeliSafeRat®, based on Regression based-Fragment Approach’(RFA) method. 10 / 11 constituents were within the applicability domain of the model (MW, descriptors). One constituent was out of the applicability domain of the model. For this one peer reviewed literature data were used.

Log Kow = range of constituents 2.5 -6.6.

Conclusions:
The logKOW of 11 constituents of the test item were determined as follows (based on valid QSAR estimations or peer reviewed literature data):

Constituents: logKow at 25°C
Constituent 1 : 2.74
Constituent 2 : 4.4
Constituent 3 : 2.5
Constituent 4: 4.8
Constituent 5: 4.4
Constituent 6 : 2.5
Constituent 7 : 4.7
Constituent 8 : 4.5
Constituent 9: 6.6
Constituent 10: 4.6
Constituent 11: 4.6
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”.

When QSAR is used, the constituents are within the applicability domain (MW, descriptors). For one constituent out of the applicability domain of the model, a peer reviewed literature data was used.

Finally the logKOW of 11 major constituents of the substance (covering more than 90% of the composition) were determined to be between 2.5 and 6.6 at 25°C.

Description of key information

The partition coefficients of the constituents of the substance (11 components of the substance covering more than 90% of the composition) were estimated in the range between 2.5 and 6.6 at 25°C (valid QSAR estimations or peer reviewed literature data).

Key value for chemical safety assessment

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 11 of them represent more than 90% of that mixture.

The partition coefficients of the major constituents of the test item were estimated using the QSAR modeliSafeRat®, based on Regression based-Fragment Approach’(RFA) method. The constituents of the substance were within the applicability domain (MW, descriptors), except one constituent. For this one, a peer reviewed literature data was used.

The log KOW of constituents were predicted as follows:

Constituents: logKow at 25°C

Constituent 1: 2.74

Constituent 2: 4.4

Constituent 3: 2.5

Constituent 4: 4.8

Constituent 5: 4.4

Constituent 6: 2.5

Constituent 7: 4.7

Constituent 8: 4.5

Constituent 9:  6.6

Constituent 10: 4.6

Constituent 11: 4.6

As the substance is a 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 11 major constituents of the substance and no single key value was retained (nor calculated weighted logKOW nor worst-case).