3-Fluorphenylboric acid

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.10.2016 - 13.12.2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

no

Type of method:

flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

2

Temp.:

23 °C

pH:

7

Preliminary visual estimation of the n-octanol solubility

Defined amounts of the test item were stirred with increasing volumes of n-octanol at room temperature and visually checked for any undissolved parts.

Table 1: Results of the preliminary visual estimation of the n-octanol solubility

Amount of test item / mg	Added volume of n-octanol / mL	Total volume of n-octanol / mL	Stirring time / min	Appearance of mixture
104.2	10	10	0	directly dissolved
605.0	-	10	30	dissolved
1691	-	10	20	dissolved
2732	-	10	30	dissolved
8972	-	10	120	not dissolved

According to this preliminary test the solubility of the test item in n-octanol was between 273 mg/L and 894 mg/L.

Calculation of the partition coefficient logPow from the preliminary test

The partition coefficient Pow may be estimated from the saturation concentrations in n-octanol and water by the following equation:

Pow = cS (n-octanol) / cS (water)

c = saturation concentration in g/L

The estimated partition coefficient was calculated with the water solubility previously determined (cS = 27.1 g/L) and the solubility in n-octanol obtained in the preliminary test. It was calculated to be: logPow = 1.0 to 1.5.

Also the program KOWWIN (part of EPI Suite) was used for calculating the logPow of the test item. The calculated value was 1.89.

Therefore, according to the guidelines the partition coefficient n-octanol/water of the test item at room temperature was determined by the shake flask method.

Shake flask method

In order to meet the requirements of the guideline to perform the shake flask method with the non-ionized form of the test item (free base), the shake flask method was done in buffer solution at pH 7: KH2P04, c = 0.05 mol (adjusted with NaOH to pH = 7). A specified amount of the test item was dissolved in 100 mL n-octanol (saturated with buffer solution). 10 mL of this solution were added to six different flasks (experiment: 1A, 1B, 2A, 2B, 3A, 3B). Subsequently, different amounts of n-octanol (saturated with buffer solution) and 20 mL buffer solution (pH 7, saturated with n-octanol) were added to the flasks. All mixtures were shaken for several minutes at ambient temperature (23 °C). After separation of the phases each phase was centrifuged (30 minutes at 23 °C and 15000 rpm) and the pH values of the aqueous phases were measured. The concentrations of the test item in the different phases were determined by HPLC.

Table 2: Test conditions and results of the shake flask method

Experiment	1A	1B	2A	2B	3A	3B
Amount of test item / mg	129.2
Concentration of the stock solution / mol/L	0.009
Volume of added stock solution / mL	10	10	10	10	10	10
Volume of added n-octanol /mL	0	0	10	10	30	30
Volume of added buffer / mL	20	20	20	20	20	20
pH of the aqueous phase at 23 °C	7.0	7.1	7.0	7.1	7.0	7.1
Measured concentration in aqueous phase / mg/L	0.61 / 0.61	0.62 / 0 62	0.31 / 0.30	0.29 / 0.30	0.14 / 0.15	0.14 / 0.14
Mean concentration in aqueous phase / mg/L*	12.1	12.4	6.11	596	2.88	2.87
Measured concentration in n-octanol phase / mg/L	0.14 / 0.14	0.14 / 0.13	0.07 / 0.07	0.07 / 0.07	0.04 / 0.03	0.04 / 0.03
Mean concentration in* n-octanol phase / g/L	1.13	1.09	0.56	0.58	0.27	0.28

* For the mean concentration the sample preparation (dilution) was taken into account.

The following partition coefficients were calculated from the measured and unrounded concentration values.

Table 3: Partition coefficients of the shake flask method at pH 7

Experiment	Pow	logPow	Average logPow
1A	92.7433	1.97	1.96
1B	87.8618	1.94
2A	92.5558	1.97	1.98
2B	97.4955	1.99
3A	94.7724	1.98	1 98
3B	96.7936	1.99
Mean value (experiment 1A to 3B)			2.0
Standard deviation			< 0.1

The six determined logPow values were within a range of ± 0.3 units as requested by the guideline. The partition coefficient Pow of the test item was determined to be: log Pow = 2.0

Conclusions:

The logPow of the test substance was determined to be 2.0 at 23 °C and pH 7.

Executive summary:

A study was conducted in accordance with OECD TG 107 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance using the shake flask method. Preliminary tests were performed to determine the solubility of the test item in n-octanol. The solubility of the test item in n-octanol was between 273 mg/L and 894 mg/L. Based on this result and the water solubility of 27.1 g/L a logPow of 1.0 - 1.5 was calculated. Using EpiSuite the logPow was estimated to be 1.89. Based on this information the shake flash method was performed. In order to meet the requirements of the guideline to perform the shake flask method with the non-ionized form of the test item (free base), the shake flask method was done in buffer solution at pH 7: KH2P04, c = 0.05 mol (adjusted with NaOH to pH = 7). A specified amount of the test item was dissolved in 100 mL n-octanol (saturated with buffer solution). 10 mL of this solution were added to six different flasks (experiment: 1A, 1B, 2A, 2B, 3A, 3B). Subsequently, different amounts of n-octanol (saturated with buffer solution) and 20 mL buffer solution (pH 7, saturated with n-octanol) were added to the flasks. All mixtures were shaken for several minutes at ambient temperature (23 °C). After separation of the phases each phase was centrifuged (30 minutes at 23 °C and 15000 rpm) and the pH values of the aqueous phases were measured. The concentrations of the test item in the different phases were determined by HPLC. The partition coefficient logPow was determined to be 2.0.

Description of key information

The logPow of the test substance was determined to be 2.0 at 23 °C and pH 7.

Key value for chemical safety assessment

Log Kow (Log Pow):

2

at the temperature of:

23 °C

Additional information

A study was conducted in accordance with OECD TG 107 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance using the shake flask method. Preliminary tests were performed to determine the solubility of the test item in n-octanol. The solubility of the test item in n-octanol was between 273 mg/L and 894 mg/L. Based on this result and the water solubility of 27.1 g/L a logPow of 1.0 - 1.5 was calculated. Using EpiSuite the logPow was estimated to be 1.89. Based on this information the shake flash method was performed. In order to meet the requirements of the guideline to perform the shake flask method with the non-ionized form of the test item (free base), the shake flask method was done in buffer solution at pH 7: KH2P04, c = 0.05 mol (adjusted with NaOH to pH = 7). A specified amount of the test item was dissolved in 100 mL n-octanol (saturated with buffer solution). 10 mL of this solution were added to six different flasks (experiment: 1A, 1B, 2A, 2B, 3A, 3B). Subsequently, different amounts of n-octanol (saturated with buffer solution) and 20 mL buffer solution (pH 7, saturated with n-octanol) were added to the flasks. All mixtures were shaken for several minutes at ambient temperature (23 °C). After separation of the phases each phase was centrifuged (30 minutes at 23 °C and 15000 rpm) and the pH values of the aqueous phases were measured. The concentrations of the test item in the different phases were determined by HPLC. The partition coefficient logPow was determined to be 2.0 at 23 °C and pH 7 (reference 4.7-1).