Disodium 1-amino-4-[[3-[(5-chloro-2,6-difluoro-4-pyrimidinyl)amino]-2-methyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 08, 2018 - March 13, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD 105 Flask Method

Version / remarks:

The shake flask method and the HPLC method were not applicable due to the low log POW.

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU Method A.6. Flask Method

Version / remarks:

The shake flask method and the HPLC method were not applicable due to the low log POW.

Deviations:

no

GLP compliance:

no

Type of method:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

-4.2

Temp.:

20 °C

Remarks on result:

other: pH not determined

Details on results:

Individual Results

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 parts.
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 / h Appearance of mixture
6.9 100 100 ~ 19 not dissolved
50 150 6 not dissolved
According to this preliminary test the solubility of the test item in n-octanol was below 46 mg/L (without correction for the purity).

Calculation of the partition coefficient log POW from the preliminary test
The estimated partition coefficient was calculated with the water solubility data determined in project PS20170234.04 (cS = 126 g/L) and the data obtained in the preliminary visual estimation of the n-octanol solubility. It was calculated to be: log POW < -3.4.
The shake flask method and the HPLC method were not applicable due to the low log POW.
Due to the calculations the partition coefficient was estimated based on the ratio of the solubilities in water and octanol. The octanol solubility was determined using the flask method.

Determination of the solubility in n-octanol: Flask method
The individual saturation solubility of the test item in n-octanol was performed within this study. After that, the partition coefficient was estimated based on the ratio of the test item solubility in n-octanol and water.
The flask method was performed as described in above. After equilibration (further stirring for about 3 d at 20 °C) the suspensions were taken and prepared for the analytical determination. The data for the evaluation are given in the following Table. The n-octanol solubility was calculated from the measured and unrounded concentration values and not from the rounded values given in the following Table.

Table : n-Octanol solubility experiments of the test item
Experiment 24 h experiment 48 h experiment 72 h experiment blank experiment (72 h)
Amount of test item / mg 11.7 11.3 13.4 --
Amount of octanol / mL 20 20 20 20
Stirring time at 30 °C / h 24 48 72 72
Dilution factor 40 40 40 40
Measured concentration / mg/L 0.206 / 0.206 0.164 / 0.166 0.209 / 0.210 -- / --
Mean concentration / mg/L 0.206 0.165 0.210 --
n-Octanol solubility / mg/L 8.24 6.60 8.39 --
The n-octanol solubility of the test item at 20 °C was determined to be 7.7 mg/L (± 1.0 mg/L) without correction of the purity.
The chromatograms of samples of the experiments showed beside the test item peak at a retention time of about 1.4 min an additional peak at 1.1 min. As this additional peak was also present in the blank experiment it is assumed that the additional peak mainly results from the buffer used as mobile phase in the HPLC analysis.

Calculation of the partition coefficient log POW from the individual solubilities
In the project PS20170234.04 the water solubility of the test item at 20 °C was determined to be 126 g/L (± 10 g/L) without correction of the purity. Within this project the n-octanol solubility of the test item at 20 °C was determined to be 7.7 mg/L (± 1.0 mg/L) without correction of the purity.
The partition coefficient POW of the test item was determined to be:
log POW = -4.2

Executive summary:

The partition coefficient (n-octanol/water) of the test item was estimated based on the ratio of the individual solubilities of the test item in water and n-octanol. The solubilities were determined according to the flask method. The shake flask method and the HPLC method were not applicable due to the low log P_OW.

It was found to be(without correction of the purity):

 

log P_OW = - 4.2

Description of key information

The partition coefficient (n-octanol/water) of the test item was estimated based on the ratio of the individual solubilities of the test item in water and n-octanol. The solubilities were determined according to the flask method. The shake flask method and the HPLC method were not applicable due to the low log P_OW.

Key value for chemical safety assessment

Log Kow (Log Pow):

-4.2

at the temperature of:

20 °C