Registration Dossier

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

Constituent 1
Reference substance name:
OS Menthol Ester
IUPAC Name:
OS Menthol Ester
Constituent 2
Chemical structure
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).