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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 Apr - 21 Jun 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Version / remarks:
27 July 1995
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient)
Version / remarks:
30 May 2008
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom
Type of method:
flask method
Partition coefficient type:
octanol-water
Analytical method:
gas chromatography
Key result
Type:
Pow
Partition coefficient:
0.031
Temp.:
22 °C
pH:
ca. 5.18 - ca. 5.24
Key result
Type:
log Pow
Partition coefficient:
-1.52
Temp.:
22 °C
pH:
ca. 5.18 - ca. 5.24

Preliminary estimate:

The preliminary estimation of partition coefficient was a log Kow value of -0.28 (KOWWIN v1.68)

Definitive test:

The determination of partition coefficient was performed using the shake-flask method. This was due to the expected partition coefficient obtained in the preliminary assessment.

The mean peak areas obtained for the standard, stock and sample solutions are shown in the following two tables:

Organic phase:

Solution

Mean peak area

Standard 25.3 mg/L

1.2326E+06

Standard 25.6 mg/L

1.2854E+06

Organic phase matrix blank

< LOD

Sample 1

7.0305E+05

Sample 2

6.3135E+05

Sample 3

7.8620E+05

Sample 4

7.8007E+05

Sample 5

6.9707E+05

Sample 6

7.9389E+05

Aqueous phase:

Solution

Mean peak area

Standard 501 mg/L

2.6059E+07

Standard 523 mg/L

2.7407E+07

Aqueous phase matrix blank

< LOD

Sample 1

1.0110E+07

Sample 2

9.9981E+06

Sample 3

1.0213E+07

Sample 4

1.0485E+07

Sample 5

9.7851E+06

Sample 6

9.9685E+06

Stock solution A

1.0560E+07

Stock solution B

1.0492E+07

The total weights and analyzed concentration of the respective phases are shown in the following table:

Sample no.

Total weight [mg]*

Organic phase

Aqueous phase

% Recovery

Analyzed concentration [mg/L]

Weight [mg]**

Analyzed concentration [mg/L]

Weight [mg]**

pH

1

85.6

28.4

2.41

967

82.2

5.24

98.9

2

85.6

25.5

2.17

957

81.3

5.23

97.5

3

115

31.8

1.81

977

111

5.18

98.6

4

115

31.5

1.80

1003

114

5.19

101.2

5

57.4

28.2

3.21

936

53.4

5.21

98.6

6

62.4

32.1

3.98

954

59.1

5.22

101.1

* from analysis of the stock solution; ** from analysis of the respective phase

pH of n-octanol saturated water: 6.16

pH of stock solution: 5.57

Temperature: 22.0 ± 0.5°C

The partition coefficient determined for each sample is shown in the following table:

Sample no.

Organic/Aqueous volume ratio

Partition coefficient

Log Pow

Mean partition coefficient

1

1:1

2.94E-02

-1.53

2.80E-02

2

2.67E-02

-1.57

3

1:2

3.25E-02

-1.49

3.20E-02

4

3.14E-02

-1.50

5

2:1

3.01E-02

-1.52

3.19E-02

6

3.36E-02

-1.47

Pow standard deviation: 2.48E-03

The typical chromatograms are attached.

Validation:

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 125.1 to 2002 mg/L for aqueous samples. This was satisfactory with a correlation coefficient of 1.00 being obtained. The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 10.23 to 102.3 mg/L for organic samples. This was satisfactory with a correlation coefficient of 0.999 being obtained.

Conclusions:
A log Kow value of -1.52 at 22.0 ± 1.0°C and pH 5.18 to 5.24 was determined for the substance using a relevant test method and in compliance with GLP. The result is considered to be reliable.

Description of key information

log Kow: -1.52 at 22.0 ± 1.0°C and pH 5.18 to 5.24 (OECD 107)

Key value for chemical safety assessment

Log Kow (Log Pow):
-1.52
at the temperature of:
22 °C

Additional information

A log Kow value of -1.52 at 22.0 ± 1.0°C and pH 5.18 to 5.24 was determined for Cyrene™ using a flask method in accordance with Cyrene™ Test Guideline 107 and in compliance with GLP. The result is considered to be reliable.

 

In contact with water, the ketone group in the anhydrous Cyrene™ ((1S,5R)-6,8 -dioxabicyclo[3.2.1]octan-4-one) hydrates to form the hydrated Gem Diol form. The hydration is fully reversible and a dynamic equilibrium is established (see Physical and chemical properties endpoint summary for further details).

 

At the concentrations used in the log Kow study, the hydrated Gem Diol form would have been the major species present. Therefore, the measured value is representative of the Gem Diol form. At concentrations relevant for the environment and in vivo, the Gem Diol form also predominates. Therefore, the measured value may be used for both the environment and human health chemical safety assessment. It is not possible or useful to measure a log Kow for Cyrene™ itself.

 

The measured value is supported by a calculated value for the Gem Diol form of -1.0. This result was obtained using the algorithm from the WSKOWWIN v.1.43 program (part of Epi Suite v.4.11) with the measured water solubility of 560 g/L and molecular weight of 146.14 g/mol as inputs. KOWWIN v1.69 gives a prediction of 0.6 for the Gem Diol form; however, this is not considered reliable because multiple, poorly supported correction factors are applied. Any remaining uncertainty in the value of log Kow is not considered to be important for the chemical safety assessment as the log Kow is very low.

Calculation of log Kow

Equation from WSKOWWIN: log S (mol/L)  =  0.796 - 0.854 log Kow - 0.00728 MW +ΣCorrections

No correction factors are applicable to Gem Diol

MW = 146.14 g/mol

WS = 560 g/L 

Solubility, S = 3.83 mol/L

Log S (mol/L) = 0.583

Log Kow = [log S (mol/L) + 0.00728 MW -0.796] / -0.854 = -1.0