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

Dissociation constant

Administrative data

Endpoint:

dissociation constant

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 112 (Dissociation Constants in Water)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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: particulate/powder

Remarks:

migrated information: powder

Results and discussion

Dissociating properties:

not determined

Dissociation constant

No.:

#1

pKa:

7.36

Temp.:

22 °C

Remarks on result:

other: Deviation +- 0.05

Any other information on results incl. tables

Acid and base titrations were both conducted because, although the structure of the test substance includes base titratable groups such as alcohols, it was clear, based on other experiments as reported herein that the material hydrolyses rapidly in water giving unknown end products. The acid titration results showed that there are no acid titratable groups present. The sodium hydroxide titration indicated the presence of a weakly acidic group with a pKa of 7.36. The individual measurements, titration curves and details of the calculations are included in Appendix 5. The results are summarized in Table 27. The precision of the final calculated value falls within.the expected precision of the method.

Table 27 - Summary of Dissociation Constant Data for the Test Substance:

Method: Potentiometric titration

Test Temperature: 22 °C

Preliminary estimate of pKa from initial titration: 7.5 based on single calculated value using 0.0189 N sodium hydroxide

Standard deviation: ±0.05 (n=14)

Expected precision: ±0.06 (See Albert & Serjeant, pg 32)

Applicant's summary and conclusion

Conclusions:

Based on our measurements and observations we concluded that the test substance in water contained a single weakly acidic group with a pKa of 7.36 ± 0.05 at 22.0°C.

Executive summary:

Based on our measurements and observations we concluded that the test substance in water contained a single weakly acidic group with a pKa of7.36 ± 0.05 at 22.0°C. A pKa of this magnitude rules out the presence of a carboxylic acid group in the breakdown products present in water. Such a strongly acidic group would be expected to display a pKa in the range of 4. This suggested that the hydrolysis in water does not involve hydrolysis at the ester group but rather opening of the oxathiolane ring. Such a ring opening would be predicted to give rise to an enolizeable keto group. Such a group would be expected to display a pKa in the range of 7 or 8. The enolizeable keto groups in, for example, acetoacetone, display a pKa of 8.2, while diacetyl acetone, displays a pKa of 7 .4. The keto groups themselves are not acidic (Albert and Serjeant, 1962).