4'-bromo-3-chloropropiophenone

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.-27.04.2020

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - HPLC Method)

Version / remarks:

European Commission Regulation (EC) No. 440/2008

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:

3.2

Temp.:

25 °C

pH:

ca. 4.5

Sample preparation

For the determination of the test item concentration aliquots of the centrifuged aqueous and n-octanol phases were taken and diluted as described below before the HPLC analyses. Sample preparation (aqueous phases): Aliquots of the aqueous phases were diluted from 0.25 ml to 1 ml with acetonitrile. Sample preparation (n-octanol phases): Aliquots of the n-octanol phases were diluted from 0.1 ml to 10 ml and again 0.05 ml to 1 ml with acetonitrile / demineralized water 75:25% (v/v). All samples were injected as single solutions twice.

 

The concentrations were quantified by comparing integrated peak areas with a calibration (external standard method with the test item). The solutions were determined by HPLC. The integration and calculation of the concentration was automatically carried out using the HPLC System Agilent 1100 series. The standards were prepared by dissolving the test item in acetonitrile and diluting it with acetonitrile / demineralized water 75:25 % (v/v).

 

 

Validation of the analytical method

Linearity: The detector linearity was checked (calibration at 6 concentration levels by twofold injection).

Calibration. y=mx, x: Amount (μg/l), y: Area m: 0.547

Correlation coefficient r: 0.99985

Quantification limit for measurement: 4.90 μg/l (lowest calibration standard)

 

Under consideration of the sample preparation this quantification limit corresponds to a quantification limit of 19.6

μg/l test item in samples of the aqueous phase and 9.8 mg/l test item in samples of the octanol phase (without correction for the purity).

 

Recovery

Standard	Measured concentration / μg/l	% Recovery (mean values)
B3 (c=19.6 μg/l)	19.1/18.90	96.9
C1 (c=476 μg/l)	489/489	102.8
B1 (c=784 μg/l)	792/792	101.1

 

All recovery values are calculated from the measured and unrounded concentration values and not from the rounded values given in the Table. The recovery of the standards indicated a sufficient accuracy of the analytical method

 

Repeatability:

The repeatability was checked by measuring standard A1 six-fold. The resulting area was used to calculate the standard deviation and the variation coefficient. The accuracy of the analytical method was evaluated as sufficient as the variation coefficient of the areas was < 2%.

 

 

Individual results

Preliminary visual estimation of the n-octanol solubility increasing amounts of the test item were stirred with a defined volume 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 81.2 g/l and

92.9 g/l (without correction for the purity).

 

Calculation of the partition coefficient log POW

The partition coefficient POWmay be estimated from the saturation concentrations in n-octanol and

water by the following equation:

POW=CSn-octanol/CSwater

CS=saturation concentration in g/L

 

The estimated partition coefficient was calculated with the water solubility data determined (CS=36.0mg/l) and the data obtained according to the preliminary test. lt was calculated to be: log POWca. 3.4. Also the program KOWWIN (part of EPI Suite) was used for calculating the log POWof the test item. The calculated value was 3.31. 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

A specified amount (see Table) of the test item was dissolved in 100 ml n-octanol (saturated with demineralized water). 1 0 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 the table. 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 analytics the samples were prepared as described as before and subsequently the concentrations of the test item in the different phases were determined by HPLC.

 

Test conditions and results of the shake flask method

Experiment	1A	1B	2A	2B	3A	3B
Amount of test item	128.9	128.9	128.9	128.9	128.9	128.9
Concentration of the stock solution /mol/l	0.005	0.005	0.005	0.005	0.005	0.005
Volume of added stock solution /ml	10	10	10	10	10	10
Volume of added n-octanol /ml	0	0	10	10	30	30
pH of the aqueous phase at 23°C	4.4	4.4	4.5	4.5	4.6	4.6
Measured concentration in aqueous phase / mg/l	0.22/0.22	0.19/0.19	0.10/0.10	0.10/0.10	0.10/0.10	0.04/0.04
Mean concentration in aqueous phase / mg/l	0.9	0.78	0.41	0.41	0.39	0.18
Measured concentration in n-octanol phase / mg/l	0.65/0.65	0.64/0.64	0.32/0.32	0.33/0.33	0.16/0.16	0.16/0.16
Mean concentration in n-octanol phase / mg/l	1295	1289	646	656	322	325

 

The following partition coefficients are calculated from the measured and unrounded concentration values and not from the rounded values given in the table.

 

Experiment	POW	Log POW	Average Log POW
1A	1445	3.16	3.19
1B	1654	3.22	3.19
2A	1560	3.19	3.20
2B	1612	3.21	3.20
3A	833	2.92	3.09
3B	1829	3.26	3.09
Mean			3.2
Standard Dev			0.1

 

 

The six determined log POWvalues are within a range of ± 0.3 units as requested by the guideline. The partition coefficient POWof the test item was determined to be: log POW= 3.2

Conclusions:

The partition coefficient (n-octanol/water) of the test item was determined according to the shake flask method the partition coefficient was determined at room temperature (22°C). It was found to be: log POW = 3.2

Executive summary:

A study was conducted in accordance with OECD 107 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance using the shake flask method. The partition coefficient POW is defined as the ratio of the equilibrium concentrations of a dissolved test item in the two-phase system consisting of n-octanol and water. The partition coefficient POWis dimensionless and usually given in the form of its logarithm to base ten.The partition coefficient (n-octanol/water) of the test item was determined at room temperature (22°C) to be: log POW= 3.2

Description of key information

The partition coefficient (n-octanol/water) of the test item was determined according to the shake flask method the partition coefficient was determined at room temperature (22°C). It was found to be: log POW= 3.2

Key value for chemical safety assessment

Log Kow (Log Pow):

3.2

at the temperature of:

22 °C

Additional information

A study was conducted in accordance with OECD 107 and Regulation (EC) No 440/2008 method A.8 to determine the partition coefficient of the test substance using the shake flask method. The partition coefficient POWis defined as the ratio of the equilibrium concentrations of a dissolved test item in the two-phase system consisting of n-octanol and water. The partition coefficient POWis dimensionless and usually given in the form of its logarithm to base ten. The partition coefficient (n-octanol/water) of the test item was determined at room temperature (22°C) to be: log POW= 3.2