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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:
January 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 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
Partition coefficient type:
other: QSAR
Key result
Type:
log Pow
Partition coefficient:
4.1
Temp.:
25 °C
Remarks on result:
other: Constituent 1
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:
4.8
Temp.:
25 °C
Remarks on result:
other: Constituent 3
Key result
Type:
log Pow
Partition coefficient:
6.7
Temp.:
25 °C
Remarks on result:
other: Constituent 4
Key result
Type:
log Pow
Partition coefficient:
6.5
Temp.:
25 °C
Remarks on result:
other: Constituent 5
Key result
Type:
log Pow
Partition coefficient:
6.4
Temp.:
25 °C
Remarks on result:
other: Constituent 6
Key result
Type:
log Pow
Partition coefficient:
4.2
Temp.:
25 °C
Remarks on result:
other: Constituent 7
Key result
Type:
log Pow
Partition coefficient:
2.8
Temp.:
25 °C
Remarks on result:
other: Constituent 8
Key result
Type:
log Pow
Partition coefficient:
4.7
Temp.:
25 °C
Remarks on result:
other: Constituent 9
Key result
Type:
log Pow
Partition coefficient:
4.5
Temp.:
25 °C
Remarks on result:
other: Constituent 10
Key result
Type:
log Pow
Partition coefficient:
6.5
Temp.:
25 °C
Remarks on result:
other: Constituent 11
Key result
Type:
log Pow
Partition coefficient:
6.9
Temp.:
25 °C
Remarks on result:
other: Constituent 12
Key result
Type:
log Pow
Partition coefficient:
4.6
Temp.:
25 °C
Remarks on result:
other: Constituent 13
Key result
Type:
log Pow
Partition coefficient:
4.7
Temp.:
25 °C
Remarks on result:
other: Constituent 14
Key result
Type:
log Pow
Partition coefficient:
4.4
Temp.:
25 °C
Remarks on result:
other: Constituent 15
Key result
Type:
log Pow
Partition coefficient:
3
Temp.:
25 °C
Remarks on result:
other: Constituent 16
Key result
Type:
log Pow
Partition coefficient:
4
Temp.:
25 °C
Remarks on result:
other: Constituent 17
Key result
Type:
log Pow
Partition coefficient:
6.5
Temp.:
25 °C
Remarks on result:
other: Constituent 18
Key result
Type:
log Pow
Partition coefficient:
6.7
Temp.:
25 °C
Remarks on result:
other: Constituent 19
Key result
Type:
log Pow
Partition coefficient:
2.5
Temp.:
25 °C
Remarks on result:
other: Constituent 20

The partition coefficient of the test item was estimated using the recommended QSAR modeliSafeRat®, based on Regression based-Fragment Approach’(RFA) method. The constituents of the substance are within the applicability domain of the model (MW, descriptors).

log Kow = between 2.8 -6.9 for Carrot seeds oil rich in carotol.

log Kow = between 2.5 -6.9 for Carrot seeds oil rich in geraniol.

Partition coefficient of the major constituents of Carrot seeds oil depending on the quality, was reported below:

Constituents log Kow of constituents in carotol-rich Carrot Seeds oil at 25°C log Kow of constituents in geraniol-rich Carrot Seeds oil at 25°C
Constituent 1 4.1 4.1
Constituent 2 4.4 4.4
Constituent 3 4.8 4.8
Constituent 4 6.7 6.7
Constituent 5 6.5 6.5
Constituent 6 6.4 6.4
Constituent 7 4.2 4.2
Constituent 8 2.8 2.8
Constituent 9 4.7 4.7
Constituent 10 4.5 4.5
Constituent 11 6.5  -
Constituent 12 6.9 6.9
Constituent 13 4.6 4.6
Constituent 14 4.7 4.7
Constituent 15 4.4 4.4
Constituent 16  - 3.0
Constituent 17  - 4.0
Constituent 18 - 6.5
Constituent 19  - 6.7
Constituent 20  - 2.5
Conclusions:
The log KOW of the major constituents of the substance at ambient temperature (15 to 19 constituents corresponding to 79 - 85% of the composition depending on the quality) are ranging between 2.8 and 6.9 for the Carrot seeds oil (rich in carotol) and between 2.5 and 6.9 for the Carrot seeds oil (rich in geraniol).
Executive summary:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the noctanol/water partition coefficients of the consituents of two qualities of Carrot Seeds oil, 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 log KOW of the major constituents of the substance at ambient temperature (15 to 19 constituents corresponding to 79 - 85% of the composition depending on the quality) are ranging between 2.8 and 6.9 for the Carrot seeds oil (rich in carotol) and between 2.5 and 6.9 for the Carrot seeds oil (rich in geraniol).

Description of key information

The partition coefficient of the major constituents of the substance at ambient temperature(15 to 19 constituents corresponding to more than 79 - 85% of the composition depending on the quality) are ranging between 2.8 and 6.9 mg/L for the carotol-rich quality and between 2.5 and 6.9 mg/L for the geraniol-rich quality (estimated by QSAR).

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 15 to19 of them represent more than 85% of the carotol-rich mixture and more than 79% of the geraniol-rich mixture.

Partition coefficient of these constituents were estimated using a valid QSAR model iSafeRat®, based onRegression based-Fragment Approach’(RFA) method.

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

Finally, the log KOW of the constituents were reported below:

Constituents log Kow of constituents in carotol-rich Carrot Seeds oil at 25°C log Kow of constituents in geraniol-rich Carrot Seeds oil at 25°C
Constituent 1 4.1 4.1
Constituent 2 4.4 4.4
Constituent 3 4.8 4.8
Constituent 4 6.7 6.7
Constituent 5 6.5 6.5
Constituent 6 6.4 6.4
Constituent 7 4.2 4.2
Constituent 8 2.8 2.8
Constituent 9 4.7 4.7
Constituent 10 4.5 4.5
Constituent 11 6.5  -
Constituent 12 6.9 6.9
Constituent 13 4.6 4.6
Constituent 14 4.7 4.7
Constituent 15 4.4 4.4
Constituent 16  - 3.0
Constituent 17  - 4.0
Constituent 18 - 6.5
Constituent 19  - 6.7
Constituent 20  - 2.5

Considering that as 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), we considered the logKOW of the major constituents and no single key value was retained (nor calculated weighted logKOW nor worst-case)