(±)-dihydro-3-hydroxy-4,4-dimethylfuran-2(3H)-one

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline compliant GLP compliant

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

as at 1995

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Version / remarks:

as at 1992

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:

(±)-dihydro-3-hydroxy-4,4-dimethylfuran-2(3H)-one

EC Number:

201-210-7

EC Name:

(±)-dihydro-3-hydroxy-4,4-dimethylfuran-2(3H)-one

Cas Number:

79-50-5

Molecular formula:

C6H10O3

IUPAC Name:

(±)-dihydro-3-hydroxy-4,4-dimethylfuran-2(3H)-one

Details on test material:

- Name of test material (as cited in study report): dl-Lactone
- Physical state: white crystalline mass
- Analytical purity: 100.0 %
- Purity test date: not reported
- Lot/batch No.: 805046
- Expiration date of the lot/batch: 01 May 2002
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: At room temperature in the dark

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Type:

Pow

Partition coefficient:

0.202

Temp.:

21 °C

pH:

>= 6.3 - <= 6.5

Partition coefficient 2

Key result

Type:

log Pow

Partition coefficient:

ca. -0.69

Temp.:

21 °C

pH:

>= 6.3 - <= 6.5

Details on results:

- results of the calculation method and the Flask-shaking method are in agreement
- results of the Flask-shaking method are reported as the partition coefficient (n-octanol/water) of RS-Pantolactone
- The partition coefficient (n-octanol/water) of RS-Pantolactone = 0.202 ± 0.017 (log Pow = -0.69) at 21.0 ± 0.5°C.

Any other information on results incl. tables

CALCULATION METHOD

calculated from the structural formula of RS-Pantolactone (using the Rekker calculation method)

log Pow = - 0.02 (Pow = 0.96)

- Table 1: Individual measurements.

Volume [ml]			Concentration after equilibrium (1)		Total amount after equilibrium
Stock Solution (2)	n-octanol	Water	n-octanol [g/L]	Water [g/L]	n-octanol [g/L]	Water [g/L]
2	6	4	114	523	0.686	3.14
2	6	4	113	506	0.678	3.04
2	4	6	104	511	0.416	4.09
2	4	6	103	519	0.411	4.15
2	8	2	132	696	1.06	2.78
2	8	2	125	701	1.00	2.80
	6	6	n.d. (3)	n.d. (3)

(1) Mean of duplicate analysis. The maximum deviation between the responses was < 10%.

(2) Analysed test substance concentration in the stock solution: 1962 mg/ml (i.e. 3.92 mg per 2 ml).

(3) No test substance peak was observed in the HPLC chromatograms.

- Table 2: Partition coefficients (n-octanol/water) (Pow and log Pow) of DL-LACTONE.

Volume ratio n-octanol:water	Pow	Log Pow	pH aqueous phase
1 : 1 (blank)	-	-
1 : 1	0.219	-0.66	6.3
1 : 1	0.223	-0.65	6.3
1 : 2	0.203	-0.69	6.5
1 : 2	0.198	-0.70	6.5
2 : 1	0.190	-0.72	6.4
2 : 1	0.179	-0.75	6.4

Applicant's summary and conclusion

Conclusions:

The results of the calculation method and the Flask-shaking method are in agreement. Since the Flask-shaking method is a more accurate method than the calculation method, the results of the Flask-shaking method are reported as the partition coefficient (n-octanol/water) of RS-Pantolactone
The partition coefficient (n-octanol/water) of the test item is 0.202 ± 0.017 (log Pow = -0.69) at 21.0 ± 0.5°C.

Executive summary:

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

OECD guidelines for testing of chemicals no.107: "Partition coefficient (n-octanol/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.

Calculation from the structural formula:

From the structural formula of RS-Pantolactone, the logarithm of the partition coefficient (noctanol/ water), log P ow , was calculated to be -0.02 using the Rekker calculation method. Therefore, the flask-shaking method was chosen for the determination of the partition coefficient (n-octanol/water) of RS-Pantolactone.

Flask-shaking method:

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. The pKa value of RS-Pantolactone was calculated to be 13.2 for an acidic group. The water phase used during the Flask-shaking method was therefore not buffered.

In the test, the volumes water and n-octanol were 1:1, 1:2 and 2:1 (volumetric ratios n-octanol:water). Solutions were shaken vigorously for 5 min and subsequently centrifuged at 3500 g for 5 min for phase separation. Phases were analysed by HPLC-MS.

The partition coefficient (n-octanol/water) of RS-Pantolactone is:

Pow = 0.202 ± 0.017 (log P ow = -0.69).

Test temperature: 21.0 ± 0.5°C.

Conclusion:

The partition coefficient (n-octanol/water) of RS-Pantolactone is 0.20 (log Pow = -0.69) at 21.0 ± 0.5°C.