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Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 April to 28 June 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to an internationally recognised method, and under GLP without deviation. Test substance ID is considered suitable.

Qualifier:

according to guideline

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Version / remarks:

23 March 2006

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.23 Partition Coefficient (1-Octanol/Water): Slow-Stirring Method

Version / remarks:

Commission Regulation (EU) No 260/2014, 24 January 2014

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

19 November, 2018

Type of method:

slow-stirring method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Storage conditions: Room temperature, in the dark, under an air atmosphere. On sub-sampling the test item from the original container received, amber glass containers were used.

Analytical method:

gas chromatography

Key result

Type:

log Pow

Partition coefficient:

4.77

Temp.:

25 °C

pH:

7.2

Details on results:

Weighted average log10 Pow: 4.77
Partition coefficient (Pow): 5.93 x 10^4
Variance weighted log10 Pow standard deviation: 2.29 x 10^-3

Table 4.7/1: Vessel 1, 2 & 3 – results

Sample Number	Equilibration Time (Hours)	Organic Phase Concentration (mg/L)	Aqueous Phase Concentration (mg/L)	Aqueous Phase pH	Log10 Pow
Vessel 1
1	49	2.01 x 10^4	0.334	7.1	4.78
2	72	2.01 x 10^4	0.341	7.2	4.77
3	96	2.03 x 10^4	0.334	7.2	4.78
4	164	2.02 x 10^4	0.343	7.2	4.77
5	170	2.02 x 10^4	0.344	7.2	4.77
6	187	2.09 x 10^4	0.342	7.2	4.78
7	193	2.01 x 10^4	0.349	7.1	4.76
8	211	2.00 x 10^4	0.343	7.2	4.77
9	217	2.00 x 10^4	0.363	7.1	4.74
Vessel 2
1	164	2.01 x 10^4	0.338	7.2	4.78
2	170	2.03 x 10^4	0.337	7.2	4.78
3	187	2.10 x 10^4	0.352	7.2	4.78
4	193	2.00 x 10^4	0.335	7.1	4.78
5	211	2.01 x 10^4	0.346	7.2	4.77
6	217	1.98 x 10^4	0.353	7.2	4.75
Vessel 3
1	164	2.04 x 10^4	0.340	7.2	4.78
2	170	2.06 x 10^4	0.335	7.2	4.79
3	187	2.07 x 10^4	0.339	7.2	4.79
4	193	2.02 x 10^4	0.340	7.1	4.77
5	211	2.02 x 10^4	0.345	7.2	4.77
6	217	2.02 x 10^4	0.345	7.2	4.77

 

For each of the three test vessels, the slope of the correlation was tested statistically to ensure it did not differ significantly from zero. This was performed using the t test and a probability value of P = 0.05.

Although this test was failed for Vessel 2, this was not considered to impact on the validity of the study result. This was since a statistically significant slope was detected in only one of the three vessels and more critically, this gradient was negligible; approximating to only 0.01 log units per day. In addition, the data set from Vessel 1 fully supported that partitioning equilibrium between the two phases was reached rapidly, with a log10 Pow value of 4.78 being obtained after only 49 hours stirring and the overall study result being a log10 Pow value of 4.77.

As equilibrium was concluded to have been demonstrated in all three vessels, the mean log10 partition coefficient value, the standard deviation and variance was calculated for each vessel, using the complete sampling dataset for all three vessels. This then also allowed the final variance weighted average and standard deviation to be calculated as the definitive result for the test. The results are summarized in the following table:

Table 4.7/2: Results

Vessel	1	2	3
Mean Log10 Pow	4.77	4.77	4.78
Standard Deviation	1.34 x 10^-2	1.11 x 10^-2	9.48 x 10^-3
Variance	1.80 x 10^-4	1.22 x 10^-4	9.00 x 10^-5

 

Weighted average log10 Pow: 4.77

Partition coefficient (Pow): 5.93 x 10⁴

Variance weighted log10 Pow standard deviation: 2.29 x 10^-3

Discussion

Vessel 1, sample number 1 to 3 inclusive, acted as a preliminary assessment of the partitioning equilibrium time. As consistent partition coefficient values were obtained for these samples removed over a three day period, the definitive test, Vessel 1, sample number 4 to 9 inclusive, and all samples from Vessel 2 and Vessel 3 was initiated. In the absence of any significant difference between the two sample sets for Vessel 1, all values have been used in the calculation of the definitive test result.

The solubility of the test item in n-octanol was confirmed to be greater than a nominal concentration of 30 g/L. Therefore, the nominal stock solution concentration of 20 g/L satisfied the guideline requirements of being below 70% saturation concentration in n-octanol and below 0.1 M.

In the absence of any relevant dissociating functional groups, no specific manipulation of the aqueous phase pH was required to ensure that the test item was present in an unionized form. Therefore the determination was performed at an approximately neutral pH.

In error, during the analysis of the diluted stock solution samples, an additional 2 minute hold period at 250 °C was incorporated into the gas chromatography instrument oven temperature program. This inconsistency was evaluated by the Study Director as not impacting on the validity or integrity of the analytical data, as the very minor change in the analytical method parameters occurred after the retention time of the test item, and therefore did not influence the analytical results in anyway.

Conclusions:

The substance has potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow>4).

Executive summary:

The partition coefficient of the test substance was determined under GLP according to OECD 123/EU A.23 guidelines, using a slow-stirring method.

Determinations were conducted in three vessels and concentrations were measured using a Gas chromatography validated method. The partition coefficient (Pow) of the test item has been determined at a test temperature of 25.0 ± 0.5 °C.

Three vessels were prepared, and six samples were taken in each phase after equilibration at 25°C, between 164 and 217 hours. The overall average was calculated weighted for the variance.

 

The weighted average log10 Pow has been determined to be 4.77 at 25.0°C (pH=7.2).

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

12-20 November, 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to an internationally recognised method, and under GLP. The result is borderline to the applicability range of the method. Therefore validation applies with restrictions.

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

11 March 2011

Type of method:

flask method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

- Physical state: white crystalline powder.
- Storage condition: Room temperature protected from direct sun light.

Analytical method:

gas chromatography

Type:

log Pow

Partition coefficient:

4.72

Temp.:

20 °C

ratio	ratio 1:10		ratio 1:20		ratio 2:10
replicate vessel	1	2	1	2	1	2
log Kow	4.74	4.74	4.71	4.70	4.74	4.70
mass balance	101.9%	103.5%	102.6%	103.2%	101.1%	99.0%

Mean log Pow and SD = 4.72 +/-0.02

The observed interval within the six log Pow values was [4.70 - 4.74] and the validity criteria was fulfilled (< +/-0.3 unit).

The pH of the water phase was not measured.

Conclusions:

The substance has potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).

Executive summary:

The partition coefficient of the test substance was determined under GLP according to EU A.8 guideline, flask method.

Determinations were conducted in duplicate for three solvents ratio, concentrations were measured using a GC-FID validated method. Individual results fulfilled the validity criteria for reproducibility, and mass balance was satisfactory, so the average value is retained.

The log Kow has been determined to be 4.72 at 20°C.

Description of key information

The data is relevant for classification in aquatic chronic toxicity hazard class, according to CLP criteria.

The substance has a high potential for bioaccumulation (log Kow > 4).

Key value for chemical safety assessment

Log Kow (Log Pow):

4.77

at the temperature of:

25 °C

Additional information

The Phytosafe 2012 study, conducted according to the A8, flask method and under GLP, was considered as reliable as it fulfilled the validity criteria. However, some restrictions were considered on accuracy, because the result was slightly out of the recommended applicability range for this method (>4).

Therefore, it was prefered to run a new study with the slow-stirring method

The Covance 2019, GLP, study is fully reliable and considered as the key study. The result (4.77) was found consistent with the supporting previous study (4.72).