(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP conditions and in acc. with OECD guideline No 107.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

EC Number:

205-334-2

EC Name:

(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

Cas Number:

138-59-0

Molecular formula:

C7H10O5

IUPAC Name:

(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

Details on test material:

- Description : white powder
- Purity : 98,9 %
- Test substance storage : in refrigerator in the dark
- Stability under storage conditions : stable
- Expiry date : 3 March 2002

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

ca. -1.5

Temp.:

21 °C

pH:

ca. 1

Details on results:

-Rekker calculation method (Pow}
From the structural formula of Shikimic Acid, the log Pow was calculated to be -1.96.

The results of the Calculation method and the Flask-shaking method are not in agreement.
The Flask-shaking method is a more accurate method than the Calculation method.

Applicant's summary and conclusion

Conclusions:

The Pow for Shikimic Acid is 0.029 (log Pow= -1.5) at 21.0 ± 0.5°C and pH 1.

Executive summary:

The Rekker calculation method was performed for a preliminary estimation of the partition coefficient (n-octanol/water), Pow of Shikimic Acid. Based on the result of the Calculation method, it was decided to perform the Flask-shaking method at pH 1 (i.e. the pH at which the test substance is> 99% in its non-ionised form according to pKa calculations performed).

Calculation method : from the structural formula of Shikimic Acid,the log Pow was calculated to be -1.96.

From the structural formula of Shikimic Acid, the pKa values for acidic groups were calculated to be 3.1, 14.5, 16.6 and 18.3. According to the EEC and OECD guidelines, the partition coefficient (n-octanol/water) has to be determined at a pH at least one unit above the pKa for a basic group and at least one unit below the pKa for an acidic group. At pH 1, i.e the pH at which the Flask-shaking method was performed, > 99% of the test substance was in a non-ionised form. Flask-shaking method Double distilled water adjusted to pH 1 was used as the aqueous phase in the n-octanol/water test system.

The test was performed at 21.0 ± 0.5°C. Under the conditions of the test, the partition coefficient (n-octanol/water), Pow of Shikimic Acid was determined to be 0.029 (log Pow -1.5).

Conclusion:

The results of the Calculation method and the Flask-shaking method are not in agreement.Since the Flask-shaking method is a more accurate method than the Calculation method,the result of the Flask-shaking method is reported as the partition coefficient (n-octanol/water), Pow of Shikimic Acid. The Pow for Shikimic Acid is 0.029 (log Pow= -1.5) at 21.0 ±0.5°C and pH 1.

The determination of the partition coefficient (n-octanol/water) of Shikimic Acid was based on the following guidelines:

- OECD guidelines for testing of chemicals no.107: "Partition coefficient (n­octanol/water): Shake Flask Method", Adopted July 27, 1995.

- EEC directive 92/69 EEC, Part A, Methods for the determination of physico-chemical properties, A.8: "Partition coefficient", EEC Publication no. L383, December 1992.