5-fluoro-2-methoxypyrimidin-4(3H)-one

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 September 2005 to 11 October 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1995

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

Pow

Partition coefficient:

0.595

Temp.:

25 °C

pH:

4

Key result

Type:

log Pow

Partition coefficient:

-0.226

Temp.:

25 °C

pH:

4

Details on results:

The pH values of the aqueous phases at the end of the shaking were 4.0 ± 0.1 and solutions were colourless.
For each ratio value, the concentration of test material in each phase was in good agreement with the theoretical concentration of the stock solution. Thus, the test material was shown to have a Pow value of 0.595 and a log Pow value of -0.226 ± 0.026 at 25 ± 1 °C.

Table l: Estimation of Pow and log Pow of the test material

Assay	Ratio (buffer/n-octanol)	Aqueous phase
		Concentration (µg/mL)			V (mL)	pH			µg of test material
		Assay 1	Assay 2	Mean
1	1/2	263	243	253	25	4.01			6325
2	1/2	237	242	240	25	3.98			5988
3	1/1	328	317	323	50	4.01			16 125
4	1/1	310	332	321	50	4.00			16 050
5	2/1	389	390	390	50	3.99			19 475
6	2/1	406	409	408	50	3.96			20 375
Assay	Ratio (buffer/n-octanol)	n-Octanol phase
		Concentration (µg/mL)			V (mL)			µg of test material
		Assay 1	Assay 2	Mean
1	1/2	133	137	135	50			6750
2	1/2	138	138	138	50			6900
3	1/1	193	195	194	50			9700
4	1/1	195	196	196	50			9775
5	2/1	247	246	247	25			6163
6	2/1	253	249	251	25			6275
Assay	Ratio (buffer/n-octanol)	Total amount or test material (µg)					Pow	log Pow
		Experimental		Theoretical*	Bias (%)
1	1/2	13 075		12 600	4		0.534	-0.273
2	1/2	12 888		12 600	2		0.576	-0.239
3	1/1	25 825		25 200	2		0.602	-0.221
4	1/1	25 825		25 200	2		0.609	-0.215
5	2/1	25 638		25 200	2		0.633	-0.199
6	2/1	26 650		25 200	6		0.616	-0.210
Mean							0.595	-0.226
Standard deviation							0.035	0.026

*504 µg/mL of test material in the mother solution.

Bias: Deviation from theoretical value

Conclusions:

Under the conditions of the study, the partition coefficient (log Pow) was determined to be -0.226 ± 0.026 at 25 ± 1 °C.

Executive summary:

The partition coefficient of the test material was investigated in a study which was performed in accordance with the standardised guidelines OECD 107 and EU Method A.8 under GLP conditions using the shake-flask method.

The partition coefficient was estimated to be -0.71 the PCKOC Program (v 1.67). In addition, the pKa of the test material were estimated to be -0.01 (H2L+/HL) and 6.59 (HL/L-).

For the definitive estimation, three series of duplicate measurements were performed in different volumes of a stock solution (in buffer pH = 4.0 pre-saturated with n-octanol) which were shaken with different volumes of n-octanol (pre-saturated with buffer pH = 4.0). After centrifugation, both organic and aqueous phases were analysed by HPLC with UV detection. The partition coefficients were calculated, for each ratio tested, from the measured concentration of test material in the organic and aqueous phases.

Under the conditions of the study, the Pow was determined to be 0.595 and the log Pow was determined to be -0.226 ± 0.026 at 25 ± 1 °C.

Description of key information

Under the conditions of the study, the Pow was determined to be 0.595 and the log Pow was determined to be -0.226 ± 0.026 at 25 ± 1 °C.

Key value for chemical safety assessment

Log Kow (Log Pow):

-0.226

at the temperature of:

25 °C

Additional information

The partition coefficient of the test material was investigated in a study which was performed in accordance with the standardised guidelines OECD 107 and EU Method A.8 under GLP conditions using the shake-flask method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The partition coefficient was estimated to be -0.71 the PCKOC Program (v 1.67). In addition, the pKa of the test material were estimated to be -0.01 (H2L+/HL) and 6.59 (HL/L-).

For the definitive estimation, three series of duplicate measurements were performed in different volumes of a stock solution (in buffer pH = 4.0 pre-saturated with n-octanol) which were shaken with different volumes of n-octanol (pre-saturated with buffer pH = 4.0). After centrifugation, both organic and aqueous phases were analysed by HPLC with UV detection. The partition coefficients were calculated, for each ratio tested, from the measured concentration of test material in the organic and aqueous phases.

Under the conditions of the study, the Pow was determined to be 0.595 and the log Pow was determined to be -0.226 ± 0.026 at 25 ± 1 °C.