1,3-Oxathiolane-2-carboxylic acid, 5-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2R,5R)-

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17.08.2004 to 07.12.2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP- Study performed

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

OS Menthol Ester

IUPAC Name:

OS Menthol Ester

Constituent 2

Reference substance name:

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-hydroxy-1,3-oxathiolane-2-carboxylate

EC Number:

604-569-1

Cas Number:

147126-62-3

Molecular formula:

C14H24O4S

IUPAC Name:

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-hydroxy-1,3-oxathiolane-2-carboxylate

Test material form:

solid: compact

Results and discussion

Water solubility

Water solubility:

> 0.051 - < 0.057 g/L

Temp.:

20.1 °C

pH:

4

Details on results:

Preliminary Test ·
A preliminary test was conducted in order to approximate the ·amount of sample that would dissolve in water and the time required to reach saturation. A 0.1 g sample was weighed into a 10 mL glass-stoppered graduated cylinder. Waater was added in increasing amounts at room temperature. After each addition of water the sample was shaken for 10 minutes, and then visually inspected for any undissolved parts. The experiment was continued in a 100 mL graduated cylinder. Once the appropriate amount of substance that dissolves was determined the solubility test was
conducted.

Definitive Test
The flask method was used for determination of solubility. About 5 times the amount of test substance necessary to saturate the desired volume of water (as determined in the preliminary test) was weighed into 3 glass flasks fitted with stoppers. The appropriate volume of water was added and flasks were placed in a water bath at 20°C +I- 0.5°C with constant shaking until equilibrium was reached. A portion of-each flask was sampled, filtered, extracted and analyzed at 24 hour intervals until the concentration of the test substance in solution differed by less than 15%.

Analytical Measurements
At each time point a 100 mL sample was filtered and extracted in a separatory funnel with dichloromethane (DCM). The aqueous samples were extracted 3 times and the pooled DCM extracts transferred to a round bottom flask. The combined extracts were evaporated to approximately 5 mL and transferred to a 10 mL volumetric flask and diluted to the mark. Detection was based on the absorbance of the test substance at 254 nm, using a Gilson Model 111 B UV detector. The absorbance of the test substance was not noticeably affected by the nature of the solvent, but as a general rule, the calibrations solutions were prepared in the same solvents as the samples. The concentration of the test substance in the calibration standards ranged from approximately 0.01 mg/mL to 0.55
mg/mL. In addition to the test samples, each daily analytical test batch contained a calibration verification standard (pure chemical in solvent), an extraction blank and a matrix spike. The final results were corrected for blank and spike recovery.

Raw Results
The results of the preliminary test indicated a solubility of less than 1 gram/litre. Based on the preliminary experiment, three flasks were prepared containing about 0.1 grams the test substance per 100 ml of water for the definitive test. The flasks were stirred and incubated at 20°G until equilibrium was reached. Samples were taken at three time points: 20, 41.5 and 66.5 hours. Table 16 summarizes the analytical measurements from the experiment. Raw data can be found in Appendix 3.
The Day 2 and Day 3 data agreed within ± 15% and were therefore pooled to calculate the final water solubility.
Average after 20 Hrs, 41.5 hrs and 66.5 Hrs. are 0.040, 0.053 and 0.055 mg/mL with RSD of 5.69, 6.42 and 1.69.

The final result is 0.054 ± 0.003 g/L (Mean± Std.Dev.) at 20.1 °C ± 0.3°C and pH 4

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)
We concluded from our solubility experiment that the test substance had a water solubility of 0.054 g/L.

Executive summary:

The final result is 0.054 ± 0.003 g/L (Mean± Std.Dev.) at 20.1 °C ± 0.3°C and pH 4