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

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

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:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

27 July 1995

Deviations:

yes

Remarks:

visual observation

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

30 May 2008

Deviations:

yes

Remarks:

visual observation

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Type of method:

flask method

Key result

Water solubility:

ca. 52.6 - ca. 90 other: %w/w

Temp.:

20 °C

pH:

ca. 3 - ca. 3.88

Remarks on result:

other: Range of pH values measured during preliminary test. Range of pH values in definitive test: 3.09-3.15.

Details on results:

The standard methods were not applicable to this test item due to the high indeterminable saturation levels produced. It was therefore not possible to prepare samples at five times the saturation level as recommended in the guidelines. No analysis could be performed due to the high solubility producing unfilterable mixtures. Therefore the water solubility was determined based on visual inspection. Throughout testing the test item/water mixtures have been shown to be single phase homogenous solutions at concentrations below 52.6% w/w and above 90% w/w. The evidence of a single homogeneous solution above 90% w/w is evidence of either the test item absorbing water or water dissolved in the test item. It is therefore not possible to narrow the water solubility result further between this range.

Preliminary test results:

Sample ID	Observations	Concentration [% w/w]	pH
A	Solution was clear colorless with no signs of excess test item.	5.01	3.88
B	Solution was clear colorless with no signs of excess test item.	10.0	3.61
C	Solution was colorless, slightly cloudy, with no signs of excess test item.	25.0	3.27
D	Solution had two distinct layers, lower layer was a clear yellow liquid, upper layer was slightly hazy colorless solution. Partition 4 mm lower layer, 12 mm upper layer.	50.0	3.19
E	Unhomogeneous phase present at the topmost part of the solution (approximately 2 mm), hazy pale yellow solution at the bottom of the solution, approximately 18 mm.	75.0	3.00
F	Unhomogeneous phase present at the topmost part of the solution (approximately 2 mm), hazy pale yellow solution at the bottom of the solution, approximately 16 mm.	80.0	3.05
G	Clear pale yellow solution with no sign of excess test item.	90.0	3.52
H	Clear pale yellow solution with no sign of excess test item.	95.0	3.83

Preliminary test result: water solubility in the range 25 to 50% w/w at 20.0 ± 0.5 ºC. Note that from 75% w/w the test item shows varying signs of absorption of water, or the water is soluble in the test item.

Definitive test results:

The results of the definitive test for the water solubility are shown in the following table:

Sample ID	Observations	Concentration %w/w	pH
1	Clear yellow single-phase solution, no presence of excess test item	30.1	3.15
2	Clear yellow single-phase solution, no presence of excess test item	35.0	3.14
3	Clear yellow single-phase solution, no presence of excess test item	37.5	3.14
4	Clear yellow single-phase solution, no presence of excess test item	40.0	3.13
5	Clear yellow single-phase solution, no presence of excess test item	42.4	3.12
6	Clear yellow single-phase solution, no presence of excess test item	45.0	3.15
7	Clear yellow single-phase solution, no presence of excess test item	47.2	3.11
8	Clear yellow single-phase solution, no presence of excess test item	50.1	3.10
9	Clear yellow single-phase solution, no presence of excess test item	52.6	3.09

 

Temperature: 20.0 ± 0.5°C

Observation: "Clear yellow single phase solution, no presence of excess test item" for nine samples at various concentrations between 30.1 and 52.6 % w/w.

Conclusion:

The water solubility of the test item has been determined to be in the range of 52.6 to 90.0% w/w of solution at 20.0 ± 0.5°C.

Conclusions:

Water solubility in the range of 52.6 to 90.0 w/w% at 20.0 ± 0.5°C was determined for the substance by visual inspection and in compliance with GLP. The result is considered to be reliable.

Description of key information

Water solubility: ≥560 g/L at 20°C and pH 3.09 - 3.1 (applies to both Cyrene™ and Gem Diol forms)

Key value for chemical safety assessment

Water solubility:

560 g/L

at the temperature of:

20 °C

Additional information

Water solubility in the range 52.6 to 90.0 w/w% at 20.0 ± 0.5°C and pH 3.09 - 3.15 was determined for Cyrene™ using a flask method with visual observation. During the study, it was observed that the standard test guidelines, OECD 105/EU Method A.6 are not applicable to the test substance due to the high indeterminable saturation levels produced. It was not possible to prepare samples at five times the saturation level as recommended in the guidelines. No analysis could be performed due to the high solubility producing unfilterable mixtures. Therefore, the water solubility of Cyrene™ was determined based on visual inspection. The result is considered to be reliable.

 

A water solubility of ≥50 w/w% is equivalent to approximately ≥560 g/L (see calculation below).

 

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

In 50% w/w Cyrene™ and water there would be a mixture of Cyrene™ and Gem Diol forms present. Both species are predicted to be highly water soluble and the indicative value of 560 g/L is applied to both forms. Any remaining uncertainty in the value of water solubility is not considered to be important for the chemical safety assessment as the water solubility is very high.

Calculation of water solubility

The substance is soluble at 50% w/w and above.

Density of Cyrene™ 1.25 g/cm³.

Density of water is 1 g/cm³.

 

For x kg of solution, there are 0.5x kg of Cyrene™ and 0.5x kg of water.

Volume of Cyrene™ = 0.5x kg / 1.25 kg/L = 0.4x L

Vol of water = 0.5x kg / 1 kg/L = 0.5x L

Total volume of solution = 0.9x L

 

Concentration of Cyrene™ = 500x g / 0.9x L = 560 g Cyrene™ /L solution