(R)-2-(2,4-Difluorphenyl)-1,1-difluor-3-(tetrazol-1-yl)-1-{5-[4-(2,2,2-trifluorethoxy)-phenyl]-2-pyridyl}-2-propanol-(R,R)-tartrate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020-03-17 to 2020-06-04

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)

Qualifier:

according to guideline

Guideline:

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

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:

1.9

Temp.:

22 °C

Remarks on result:

other: pH of aqueous phase at 22 °C: 4.0 - 4.2 in six conducted experiments

Preliminary visual estimation of the n-octanol solubility:

A defined amount of the test item was stirred with increasing volumes of n-octanol at room temperature and visually checked for any undissolved particles. According to this preliminary test the solubility of the test item in n-octanol was between 0.2 g/L and 0.6 g/L (without correction for the purity).

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
3.0	5	5	55	not dissolved
	10	15	75	dissolved

The estimated partition coefficient was calculated with the water solubility (c = 0.75 g/L) and the data obtained in during the estimation of the n-octanol solubility. It was calculated to be: -0.6 < log Pow < -0.1. Therefore, according to OECD test guideline 107, the partition coefficient n-octanol/water of the test item at room temperature was determined by the shake flask method.

Shake flask method:

As the test item was not soluble in n-octanol (saturated with buffer solution) the shake flask method was performed with demineralized water (saturated with n-octanol) and n-octanol (saturated with demineralized water).

A specified amount of the test item was dissolved in 100 mL n-octanol (saturated with demineralized water). 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 demineralized water) and 20 mL demineralized water (saturated with n-octanol) were added to the flasks as described in Table 2. All mixtures were shaken for several minutes at ambient temperature (22 °C). After separation of the phases each phase was centrifuged (30 minutes at 22 °C and 15000 rpm) and the pH values of the aqueous phases were measured. For analytical measurements the samples were prepared and subsequently 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	14.7
Concentration of the stock solution / mmol/L	0.24
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 water / mL	20	20	20	20	20	20
pH of the aqueous phase at 22 °C	4.2	4.0	4.1	4.2	4.1	4.2
Measured concentration in aqueous phase / mg/L	0.20 / 0.18	0.25 / 0.25	0.09 / 0.09	0.09 / 0.08	0.07 / 0.07	0.07 / 0.07
Mean concentration in aqueous phase / mg/L^1)	1.89	2.49	0.89	0.85	0.26	0.27
Measured concentration in n-octanol phase / mg/L	2.73 / 2.78	2.73 / 2.76	1.42 / 1.42	1.45 / 1.44	0.71 / 0.71	0.73 / 0.73
Mean concentration in^1) n-octanol phase / mg/L	110.1	109.7	56.9	57.8	28.5	29.4

1) For the mean concentration the sample dilution is taken into account

The following partition coefficients are calculated from the measured and unrounded concentration values (Table 3).

Table 3: Partition coefficients of the shake flask method

Experiment	Pow	log Pow	Average log Pow
1A	58.24	1.77	1.71
1B	44.11	1.64
2A	63.68	1.80	1.82
2B	67.70	1.83
3A	108.4	2.04	2.04
3B	108.1	2.03
Mean value (experiment 1A to 3B)			1.85
Standard deviation			0.16

The six determined log Pow values are within a range of ± 0.3 units as requested by the OECD test guideline 107.

Conclusions:

The log Pow of the test item was determined to be 1.9 at 22 °C.

Executive summary:

The partition coefficient (n-octanol/water) of the test item was determined according to OECD guideline 107 by applying the shake flask method. The log Pow of the test item was determined to be 1.9 at 22 °C.

Description of key information

The partition coefficient (n-octanol/water) of the test item was determined according to OECD guideline 107 by applying the shake flask method. The log Pow of the test item was determined to be 1.9 at 22 °C.

Key value for chemical safety assessment

Log Kow (Log Pow):

1.9

at the temperature of:

22 °C