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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2019-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Reason / purpose:
reference to other study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient - Shake Flask Method)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of method:
estimation method (solubility ratio)
Partition coefficient type:
octanol-water
Analytical method:
mass spectrometry
Key result
Type:
log Pow
Partition coefficient:
4.44
Temp.:
20 °C
pH:
7
Remarks on result:
other:
Remarks:
Based on the water solubility of 17.812 mg/L and octanol solubility of 500 g/L.
Type:
log Pow
Partition coefficient:
> 3.86
Temp.:
20 °C
pH:
7
Remarks on result:
other:
Remarks:
Based on the water solubility of < 0.1 g/L and octanol solubility of 731.3 g/L.
Details on results:
The test item was recovered completely from n-octanol solution using GC-MS measurement. A saturated solution in n-octanol could not be prepared.
The test item was not recovered from water solution and a analytical determination was technically not feasible.

Analytical results

Whether the sample was directly measured into aquatic media or spiked with organic solvent, the test substance immediately begun to move towards the surface of the water. That samples prepared in aqueous matrices were not homogeneous the phase separation. Thus, the entire sample volume was extracted with n-hexan but no improvement regarding the recovery was achieved. Thus, further trials according to the above mentioned protocol were performed.

 

The results were as follows:

 

Recovery of fortified samples

at 0.4 mg/L concentration level 32% (standard deviation 44%),

at 5 mg/L concentration level  63% (standard deviation 8%),

at 25 mg/L concentration level 65% (standard deviation 8%).

 

Recovery samples

Recovery samples from ultrapure water were prepared at 0.5 mg/L and 1.5 mg/L concentration levels. At 0.5 mg/L level the recovery was determined to be 57% (SD 76%) and at 1.5 mg/L the recovery was determined to be 28% (SD 34%).

Due to the high standard variation and the low recovery from aqueous media it was concluded that it was technically not possible to validate a suitable analytical method.

Solubility in n-octanol

Measured concentrations 

Ratio of solvents
(Test Item : n-Octanol)

Measured concentration, (g/L)

Mean concentration, (g/L)

Recovery,
(%)

Abs. Accuracy, (%)

1:9

89.4

83.9

106

6

81.3

80.9

1:1

475.5

422.4

108

8

397.6

394.1

9:1

718.0

731.3

102

2

774.1

701.9

Mean

-

-

105

-

 

Calculated partition coefficient (Pow) and log Pow (based on analytival results) 

Solubility in n-octanol, g/L

Solubility in water, g/L

Partition coefficient

Log Partition coefficient

Pow

Log Pow

> 731.3

< 0.1

> 7313.1

> 3.86

 

Refinement of the logPow calculation

It was not possible to determine the test item concentration in water. Thus, the water solubility was estimated by visual observation to be < 0.1 g/L. In order to achieve a more precise water solubility value, the water solubility was calculated using QSAR to be 17.812 mg/L. Please refer to the respective study record in IUCLID section 4.8 and 8. The test item is soluble in any ratio with octanol. Thus, a solubility of 500 g test item in 1 L solution was assumed as worst case. As per definition above this value it will be no longer a solubility of the test item in octanol but a solubility of octanol in the test item. Thus, 500 g/L was regarded as reliable worst case assumption

The log Pow was calculated using the following formula:  

Log (solubility octanol / solubility water).

 

The logPow was calculated as follows: log (500 / 0.017817) = 4.44.

Conclusions:
The partition coefficient was calculated to be logPow = 4.44 based on the individual solubilities of the test item in octanol and water.
Executive summary:

A study was conducted to determine the partition coefficient octanol / water according to EU method A.8. It was technically not possible to establish and validate a suitable method for the determination of the test item in water. Thus, it was not possible to perform the shake flask and slow stirring method according to OECD TG 107 or 123. The performance of the HPLC method according to OECD TG 117 was not possible as the substance cannot be detected using UV/VIS and the eluent is not compatible with LC/MS detection. Therefore, the logPow was estimated based on the individual solubilities of the test item in octanol and water. The water solubility was determined to be 17.812 mg/L (IUCLID section 4.8.). The test item was soluble in any ratio with octanol. Thus, a solubility of 500 g test item in 1 L solution was assumed. As per definition above this value it will be no longer a solubility of the test item in octanol but a solubility of octanol in the test item. Thus, 500 g/L was regarded as worst case assumption. The logPow of the test item was calculated to be 4.44 at 20 °C.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Qualifier:
according to
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals
Version / remarks:
May 2008
Deviations:
no
Principles of method if other than guideline:
Estimates the log octanol-water partition coefficient, log Kow, of chemicals using an atom/fragment contribution method.
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
SMILES: C(=CCCC(C=C)C)(C)C
Key result
Type:
log Pow
Partition coefficient:
4.88
Temp.:
25 °C
Remarks on result:
other: QSAR predicted value. The substance is within the applicability domain of the model.

KOWWIN Program (v1.68) Results:

===============================

 

Log Kow(version 1.68 estimate): 4.88

 

SMILES : C(=CCCC(C=C)C)(C)C

MOL FOR: C10 H18

MOL WT : 138.26

 

TYPE

 NUM

LOGKOW FRAGMENT DESCRIPTION

COEFF

VALUE

Frag

3

-CH3[aliphatic carbon]

 0.5473

1.6419

Frag

2

-CH2- [aliphatic carbon]

 0.4911

0.9822

Frag

1

-CH [aliphatic carbon]

 0.3614

0.3614

Frag

1

=CH2[olefinic carbon]

 0.5184

0.5184

Frag

3

=CH- or =C<[olefinc carbon]

 0.3836

1.1508

Const

 

Equation Constant

 

0.2290

Log Kow

 

 

 

 4.8837

 

Conclusions:
Using KOWWIN v1.68 the logPow of the test item was calculated to be 4.88 at 25 °C. The substance is within the applicability domain of the model.
Executive summary:

The logPow was calculated using KOWWIN v1.68 as part of EPISuite v4.11 from US Environmental Protection Agency.

Using KOWWIN v1.68 the log Kow of the test item was calculated to be 4.88 at 25 °C (EPI Suite, 2014).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Endpoint:
partition coefficient
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Justification for type of information:
In accordance with Annex XI section 2 of regulation (EC) No 1907/2006 the test was waived as testing is technically not possible. During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties. Please refer to the study record for more details about the analytical trials. Thus, the determination of the logPow using the shake flask method or the slow stirring method was not possible as the test item concentration in the water phase could not be determined. Furthermore, the substance cannot be detected using UV/VIS and the eluent is not compatible with LC/MS detection. Thus, the performance of the HPLC method was also technically not possible. Please refer to the study records in IUCLID section 4.7, 4.8 and section 8 for more details about the analytical trials.

Description of key information

The partition coefficient logPow was determined to be 4.44 at 20 °C and pH 7.1 based on the individual solubilities.

Key value for chemical safety assessment

Log Kow (Log Pow):
4.44
at the temperature of:
20 °C

Additional information

It was technically not possible to validate a suitable analytical method to determine the partition coefficient according to OECD TG 107/117. Thus, the available data were evaluated in a weight of evidence approach.

 

Testing technically not possible

In accordance with Annex XI section 2 of regulation (EC) No 1907/2006 the test was waived as testing is technically not possible. During the method validation study the test item could not be recovered from ultrapure water due to its behaviour and volatile properties. Please refer to the study record for more details about the analytical trials. Thus, the determination of the logPow using the shake flask method or the slow stirring method was not possible as the test item concentration in the water phase could not be determined. Furthermore, the substance cannot be detected using UV/VIS and the eluent is not compatible with LC/MS detection. Thus, the performance of the HPLC method was also technically not possible. Please refer to the study records in IUCLID section 4.7, 4.8 and section 8 for more details about the analytical trials.

 

Experimental results

A study was conducted to determine the partition coefficient octanol / water according to EU method A.8. It was technically not possible to establish and validate a suitable method for the determination of the test item in water. Thus, it was not possible to perform the shake flask and slow stirring method according to OECD TG 107 or 123. The performance of the HPLC method according to OECD TG 117 was not possible as the substance cannot be detected using UV/VIS and the eluent is not compatible with LC/MS detection. Therefore, the logPow was estimated based on the individual solubilities of the test item in octanol and water. The water solubility was determined to be 17.812 mg/L (IUCLID section 4.8). The test item was soluble in any ratio with octanol. Thus, a solubility of 500 g test item in 1 L solution was assumed. As per definition above this value it will be no longer a solubility of the test item in octanol but a solubility of octanol in the test item. Thus, 500 g/L was regarded as worst case assumption. The logPow of the test item was calculated to be 4.44 at 20 °C.

 

QSAR estimation

The logPow was calculated using KOWWIN v1.68 as part of EPISuite v4.11 from US Environmental Protection Agency.

Using KOWWIN v1.68 the log Kow of the test item was calculated to be 4.88 at 25 °C (EPI Suite, 2014). 

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose. 

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Conclusion

It was technically not possible to validate a suitable analytical method to determine the test item concentration in ultrapure water. Thus, the available data were evaluated in a weight of evidence approach. In a study was conducted to determine the solubility of the test item in octanol. The test item is miscible with octanol in any ratio. 500 g/L was chosen as key value for the calculation of the logPow. The water solubility was determined to be 17.817 mg/L. The logPow was calculated based on the individual solubilities in octanol and water to be 4.44. In addition the logPow was calculated using KOWWIN to be 4.88. The calculated and estimated logPow are in the same range and thus are regarded as reliable. The partition coefficient logPow of 4.44 was regarded as most reliable and chosen as key value for the chemical safety assessment.