6,8-Dioxabicyclo[3.2.1]octan-4-one, (1S,5R)-

Partition coefficient

Link to relevant study record(s)

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

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Version / remarks:

27 July 1995

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Version / remarks:

30 May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 K_ow 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 K_ow [Cyrene^TM/Gem Diol]: -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

In contact with water, the ketone group of Cyrene™ ((1S,5R)-6,8 -dioxabicyclo[3.2.1]octan-4-one) hydrates to form the Gem Diol form. The hydration is fully reversible and a dynamic equilibrium is established (see attached document in Section 13 for further details).

At the concentrations used in the log K_ow study, the Gem Diol form would have been the major species present. A log K_ow value of -1.52 at 22.0 ± 1.0°C and pH 5.18 to 5.24 was determined for Cyrene™/Gem Diol using a flask method in accordance with OECD Test Guideline 107 and in compliance with GLP. The result is considered to be reliable.

 

Therefore, the measured value is considered 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 K_ow for Cyrene™ itself but the measured value has been reported for completeness.

 

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 K_ow is not considered to be important for the chemical safety assessment as the log K_ow is very low.

Calculation of log Kow

Equation from WSKOWWIN: log S (mol/L) = 0.796 - 0.854 log K_ow - 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 K_ow = [log S (mol/L) + 0.00728 MW -0.796] / -0.854 = -1.0