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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 August 2016 to 04 October 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
EU Method A.23 Partition Coefficient (1-Octanol/Water): Slow-Stirring Method
Version / remarks:
European Community (EC), EC no. 260/2014, Part A: Methods for the Determination of Physico-Chemical Properties, Guideline A.23: “Partition Coefficient (1-Octanol/Water): Slow stirring method”, Official Journal of the European Union no. L81, March 19, 2014.
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)
Version / remarks:
Organization for Economic Co-operation and Development (OECD), OECD Guidelines for the Testing of Chemicals no. 123: "Partition Coefficient (1-Octanol/Water); Slow-Stirring Method", March 23, 2006.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of method:
slow-stirring method
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
No further details specified in the study report.
Analytical method:
other: Ultra performance liquid chromatographic method with tandem mass spectrometric detection (UPLC-MS/MS).
Key result
Type:
log Pow
Partition coefficient:
2.1
Temp.:
25 °C
pH:
7
Key result
Type:
Pow
Partition coefficient:
140
Temp.:
25 °C
pH:
7
Details on results:
Calculation of the Pow
The Pow of the test item was calculated to be 1.45e+6 (log Pow 6.16) using the Rekker calculation method.

Main study – slow-stirring method
The analysed concentration of the spiking solution was 2.21 g/L which corresponded to a recovery of 105%. Recoveries were determined according to this value.
The chromatograms of the samples from the blank test solutions showed no peak at the retention time of the test item. It demonstrated that the sample treatment was adequate for the test samples.
The mean recovery of the QC samples in water was 93%. It demonstrated that the analytical method was adequate for the determination of the test item concentration in the water samples.
Equilibrium was achieved as five time points interspersed by a minimum period of five hours yielded a slope that was not significantly different from zero at a p-level of 0.05.

 Main study – Powof the test item

vessel

Sampling point

Date and time of sampling

Analysed concentration

Pow

Log Pow

1-octanol

[g/L]

Water

[g/L]

Rec

[%]

Individual

Mean

1

1

2

3

4

5

24-Aug-2016 06:14

24-Aug-2016 11:35

25-Aug-2016 06:40

29-Aug-2016 08:08

29-Aug-2016 14:00

2.08

2.16

2.54

2.22

2.39

0.0146

0.0154

0.0174

0.0168

0.0177

99

103

121

106

114

1.4 x 102

1.4 x 102

1.5 x 102

1.3 x 102

1.3 x 102

2.2

2.1

2.2

2.1

2.1

2.1

2

1

2

3

4

5

24-Aug-2016 06:14

24-Aug-2016 11:35

25-Aug-2016 06:40

29-Aug-2016 08:08

29-Aug-2016 14:00

2.08

2.49

2.38

2.26

2.31

0.0113

0.0130

0.0154

0.0158

0.0157

99

119

113

108

110

1.8 x 102

1.9 x 102

1.5 x 102

1.4 x 102

1.5 x 102

2.3

2.3

2.2

2.2

2.2

2.2

3

1

2

3

4

5

24-Aug-2016 06:14

24-Aug-2016 11:35

25-Aug-2016 06:40

29-Aug-2016 08:08

29-Aug-2016 14:00

2.07

2.28

2.51

2.41

2.34

0.0131

0.0142

0.0208

0.0178

0.0185

99

109

120

115

112

1.6 x 102

1.6 x 102

1.2 x 102

1.4 x 102

1.3 x 102

2.2

2.2

2.1

2.1

2.1

2.1

Mean log Pow               2.1

Mean Pow                    1.4 x 102

Average sigma low Pow            0.0127

 

Calculations of mean and sigma Pow

 

Vessel 11

Vessel 21

Vessel 31

Average

P value slope

0.05

0.05

0.05

 

Log Pow, i / av

2.1

2.2

2.1

2.1

Variance

Weighting factor (wi)

Low Pow* weighting factor

0.000228

4378

9383

0.00264

379

838

0.00245

407

873

 

Log Pow, i – log Pow, av

wi * (log Pow, i – log Pow, av)2

wi * (n-1)

-0.00512

0.115

8756

0.0639

1.55

757

-0.00437

0.00780

815

 

var log Pow, av

sigma log Pow, av

 

 

 

0.000162

0.0127

1The calculations were performed with exclusion of sampling point 1 because equilibrium was not reached yet.

Conclusions:
The slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® AH25. Based on the results, the Pow value at neutral pH and 25°C was determined to be 1.4e+2. It corresponds with a log Pow value of 2.1.
Executive summary:

The purpose of the study was to determine the following physico-chemical properties for Lowinox® AH25:

-Partition coefficient

 

The study was performed in accordance with the following guidelines:

European Community (EC), EC no. 260/2014, Part A: Methods for the Determination of Physico-Chemical Properties, Guideline A.23: “Partition Coefficient (1-Octanol/Water): Slow stirring method”, Official Journal of the European Union no. L81, March 19, 2014.

Organization for Economic Co-operation and Development (OECD), OECD Guidelines for the Testing of Chemicals no. 123: "Partition Coefficient (1-Octanol/Water); Slow-Stirring Method", March 23, 2006.

 

The slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® AH25. Based on the results, the Pow value at neutral pH and 25 °C was determined to be 1.4 x 102. It corresponds with a log Pow value of 2.1.

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
22 June 2010-13 September 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and EC guidelines and according to GLP principles.
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
3.3
Temp.:
25 °C
pH:
ca. 7
Remarks on result:
other: Test Substance
Key result
Type:
log Pow
Partition coefficient:
3
Temp.:
25 °C
pH:
ca. 7
Remarks on result:
other: Impurity I
Key result
Type:
log Pow
Partition coefficient:
3.6
Temp.:
25 °C
pH:
ca. 7
Remarks on result:
other: Impurity II

In the chromatogram of the test solution, one large peak and two small test substance peaks were observed. The large peak was considered to derive from the test substance and the small peaks were most likely from impurities.

Conclusions:
The HPLC method was chosen for the determination of the partition coefficient of Lowinox® AH25.

The Pow and log Pow values of the test substance and impurities with a peak area of > 1% at neutral pH were:

Test substance: Pow = 2.0 x 10E3, log Pow = 3.3
Impurity I: Pow = 9.8 x 10E2, log Pow = 3.0
Impurity II: Pow = 4.2 x 10E3, log Pow = 3.6

The test was performed at neutral pH.
Executive summary:

The aim of the study was to determine the following physico-chemical properties for Lowinox® AH25: Partition coefficient in accordance with the following guidelines:

Organization for Economic Co-operation and Development (OECD), OECD Guidelines for the Testing of Chemicals no. 117: "Partition Coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) Method", April 13, 2004.

European Community (EC), EC no. 440/2008, Part A: Methods for the Determination of Physico-Chemical Properties, Guideline AS: "Partition Coefficient", Official Journal of the European Union no. L 142, May 31, 2008.

 

The calculation method was used for a preliminary estimation of the Pow of the test substance.

Calculation was performed using the Rekker calculation method (PrologP 6.0, module in Pallas 3.0, CompuDrug International, San Francisco, CA, USA). Based on the calculation it was decided to perform the HPLC method for an accurate determination of the Pow·

 

Conclusion

The HPLC method was chosen for the determination of the partition coefficient of Lowinox® AH25.

The Pow and log Pow value of the test substance and impurities with a peak area of > 1% was:

Test substance

Impurity I

Impurity II

Neutral pH

Pow

Log Pow

2.0 x 103

9.8 x 102

4.2 x 103

3.3

3.0

3.6

Description of key information

Slow-stirring method

Based on the results, the Pow value at neutral pH and 25 °C was determined to be 1.4 x 102. It corresponds with a log Pow value of 2.1.

Calculation method

The Pow and log Pow value of the test substance and impurities with a peak area of > 1% was:

Test substance

Impurity I

Impurity II

Neutral pH

Pow

Log Pow

2.0 x 103

9.8 x 102

4.2 x 103

3.3

3.0

3.6

Key value for chemical safety assessment

Log Kow (Log Pow):
2.1
at the temperature of:
25 °C

Additional information

Slow-stirring method

The slow-stirring method was applied for the determination of the partition coefficient (Pow) of Lowinox® AH25. Based on the results, the Pow value at neutral pH and 25 °C was determined to be 1.4 x 102. It corresponds with a log Pow value of 2.1.

Calulation method

The calculation method was used for a preliminary estimation of the Pow of the test substance.

Calculation was performed using the Rekker calculation method (PrologP 6.0, module in Pallas 3.0, CompuDrug International, San Francisco, CA, USA). Based on the calculation it was decided to perform the HPLC method for an accurate determination of the Pow·

 

Conclusion

The HPLC method was chosen for the determination of the partition coefficient of Lowinox® AH25.

The Pow and log Pow value of the test substance and impurities with a peak area of > 1% was:

Test substance

Impurity I

Impurity II

Neutral pH

Pow

Log Pow

2.0 x 103

9.8 x 102

4.2 x 103

3.3

3.0

3.6