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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Since test substance is highly soluble in octanol and very poorly soluble in water, the protocol EU A.8 is not applicable to determine the partition coefficient as the test substance concentration in water was not accurately quantified in the water solubility study and the true concentration can only be considered as <2 mg/L.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
not applicable
Principles of method if other than guideline:
Phytosqualane is highly soluble in octanol and very weakly soluble in water. In this case, the partition coefficient is calculated using the guidelines EU A.8 is not applicable as the phytosqualane concentration in water will be under detection limit.
The partition coefficient is calculated by the ratio of solubilities of Phytosqualane in n-octanol and in water, determined with the flask method (OECD 105 and EU A.6).
GLP compliance:
no
Type of method:
shake-flask method to: flask method
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
ca. 5.49
Temp.:
20 °C
pH:
ca. 6.38

Results of the three samples left one, two and three days at 20°C are given in the following table

 

Sample

Solubility in n-octanol (g/L)

Average solubility in n-octanol (g/L)

Standard deviation in n-octanol g/L

pH

One day

645.35

641.44

4.03

6.37

 

637.29

 

641.69

Two days

644.16

639.13

4.71

6.38

 

638.41

 

634.82

Three days

574.04

574.76

1.25

6.38

 

574.04

 

576.21

 

The concentrations measured do not differ by more than 15% (5.32%), therefore, the test is considered as valid. The n-octanol solubility is calculated with the nine values obtained forthe three days of experiment. The standard deviation is calculated with the same values.

The n-octanol solubility of Phytosqualane at 20°C is 618.45 +/- 32.93 g/L

 

The result is Pow = 309 225 +/- 16 465

 

The decimal logarithm of n-octanol/water partition coefficient (Log Pow) is 5.49 +/- 0.04

  

Remark: Even with a concentration of 618 g/L, the mixture is always monophasic. This means that the Phytosqualane is more soluble in octanol than 618 g/L. The solubility of Phytosqualane in octanol is underestimated in this test. The two chemicals seem to be soluble for all compositions. The value of LogPowat 5.49can bedefinedas a minimum value.

 

A last test was performed: a solution of 10 000g/L of Phytosqualane in octanol was prepared (the double of the concentration in preliminary test). In this solution the Phytosqualane is completely dissolved in octanol. This test shows that the solubility of Phytosqualane in octanol can’t be really calculated.

Conclusions:
The n-octanol/water partition coefficient (Pow) of Phytosqualane is the ratio of the n-octanol solubility and the water solubility

The result is Pow = 309 225 +/- 16 465

The decimal logarithm of n-octanol/water partition coefficient (Log Pow) is 5.49 +/- 0.04 .This partition coefficient can be defined as a minimum value.
Executive summary:

Phytosqualane is highly soluble in octanol and very weakly soluble in water. In this case, the partition coefficient is calculated using the guidelines EU A.8 is not applicable as the phytosqualane concentration in water will be under detection limit.

The partition coefficient is calculated by the ratio of solubilities of Phytosqualane in n-octanol and in water, determined with the flask method (OECD 105 and EU A.6).

The n-octanol/water partition coefficient (Pow) of Phytosqualane is the ratio of the n-octanol solubility and the water solubility The result is Pow = 309 225 +/- 16 465 The decimal logarithm of n-octanol/water partition coefficient (Log Pow) is 5.49 +/- 0.04 .This partition coefficient can be defined as a minimum value.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
24/04/2017
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
Justification for type of information:
See enclosed study report, QRPF and QMRF documents.
Principles of method if other than guideline:
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: QSPR model adapted specifically to OECD test guidelines 107 and 123
Remarks:
The results below is the anticipated log KOW value further to a study following OECD Guidleine No. 107 or 123
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
QSAR prediction from chemical structure of 2,6,10,15,19,23-hexamethyltetracosane.
Key result
Type:
log Pow
Partition coefficient:
ca. 17
Temp.:
25 °C
Remarks on result:
other: pH not applicable
Remarks:
from structure, no pH dependency anticipated
Conclusions:
The results is the anticipated log KOW value further to a study following OECD Guidleine No. 107 or 123. The log KOW is calculated as follows: 17
Executive summary:

Introduction.

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the n-octanol/water partition coefficient of the test item 2,6,10,15,19,23-hexamethyltetracosane. 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).

 

Methods.

The purpose of thein silicostudy was to determine the log KOWof 2,6,10,15,19,23-hexamethyltetracosane. 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 KOWwhich may be positive or negative. The final log KOWis determined by simple addition of the fragments. The predicted log KOWvalues 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.

 

Results.

The results below is the anticipated log KOWvalue further to a study following OECD Guidleine No. 107 or 123. The log KOWis calculated as follows:17

Description of key information

Since test substance is highly soluble in octanol and very poorly soluble in water, the protocol EU A.8 is not applicable to determine the partition coefficient as the test substance concentration in water was not accurately quantified in the water solubility study and the true concentration can only be considered as <2 mg/L.

As the water solubility could not be accurately determined the partition coefficient was calculated by the ratio of solubilities of squalan in n-octanol and in water, determined with the flask method (OECD 105 and EU A.6). Moreover the authors have been measured a solubility in octanol of the substance test at 618 g/L but they concluded this value is an underestimation and the actual solubility in octanol cannot be really calculated.

There are 2 main limitations in this study which lead us to consider the result as unreliable:

- the log KOWis calculated as the ratio of concentrations at the “solubility limit”, respectively in water and in octanol, while the phases should not be saturated by the substance;

- the measured value of solubility both in water and in octanol should not be considered as reliable since there are obvious signs in the experimentation that the substance has not reached its solubility.

In conclusion, the result of this log KOWstudy should be considered as invalid and not reliable for REACH purposes: an experimental study is inappropriate for the accurate measurement of octanol water partition coefficient of such a large hydrophobic molecule. It is assessed as a "disregarded study". The determination by calculation (QSAR) is currently the most appropriate method available.

The results below is the anticipated log KOWvalue by QSAR further to a study following OECD Guidleine No. 107 or 123.The log KOWis calculated as follows:17

Key value for chemical safety assessment

Log Kow (Log Pow):
17
at the temperature of:
25 °C

Additional information