(4'-methyl-3-fluoro[1,1'-biphenyl]-4-yl)-boronic acid

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 19, 2017 - March 28, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

GLP compliance:

no

Type of method:

column elution method

Key result

Water solubility:

3.9 mg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

6.5

Preliminary test:

In a stepwise procedure, increasing volumes of demineralized water were added at room temperature to a defined amount of the test item. After each addition of an amount of water the mixture was treated with ultrasound for 10 minutes and visually checked for any undissolved particles.

 

Table 1: Results of the preliminary test

Amount of test item /mg	Added volume of demineralized water / mL	Total volume of demineralized water / mL	Appearance of mixture
97.0	0.1	0.1	not dissolved
97.0	0.4	0.5	not dissolved
97.0	0.5	1.0	not dissolved
97.0	1.0	2.0	not dissolved

 

Three additional preliminary tests were carried out with specified amounts of the test item and 100 ml and 500 ml demineralized water, respectively. After each addition of an amount of water, the mixture was stirred for at least 24 hours, and visually checked for any undissolved particles.

 

Table 2: Results of the preliminary tests

Amount of test item /mg	Total volume of demineralized water / mL	Appearance of mixture
10.2	100	Not dissolved
13.1	500	Not dissolved
4.2	500	Not dissolved

 

The preliminary test showed that the water solubility of the test item is < 10 mg/L. According to the preliminary test the water solubility was determined by the column elution method in the main test.

 

Column elution method

94.0 mg of the test item were dissolved in 100 mL in acetone (15 min ultrasonic bath). For charging the columns in each case 25 mL of the test item solution was added to about 3 g of sea sand and the mixtures were shaken. The solvent was then removed under reduced pressure using a rotary evaporator (40 °C, approx. 10 mbar). The dry residues were placed into the columns of the test apparatus, which have afterwards been filled with water (test temperature: 23.2 °C; water pH at 23.2 °C: 6.1). After a swelling time of 2 h pumps were started to rinse the test item coated sand with demineralized water. At the end of the study it was confirmed that residual test item remained on the columns. The residual test item was eluted with 50 mL acetone.

As blank value demineralized water was tested. No signal was detected in the range of the retention time of the test item. The concentration of the test item was quantified by HPLC.

 

Column 1:

Rotation period of the fraction collector:          90 min per fraction

Duration of sampling:                           about 47 h (31 fractions)

 

Table column elution method, column 1 (approx. 12.5 mL/h)

Fraction no	V / mL	pH	Water solubility / mg/L
20	19.0	6.1	3.69
21	19.0	6.2	3.71
22	19.0	6.2	3.70
23	19.0	6.4	3.70
24	19.0	6.2	3.71

 

The water solubility was found to be 3.7 mg/L.

 

Column 2:

Rotation period of the fraction collector:          45 min per fraction

Duration of sampling:                           about 47 h (62 fractions)

 

Table column elution method, column 2 (approx. 25.0 mL/h)

Fraction no	V / mL	pH	Water solubility / µg/L
45	17.0	6.5	4.08
46	17.0	6.7	3.95
47	17.0	6.7	3.90
48	17.0	6.5	4.07
49	16.5	6.3	3.99

 

The water solubility was found to be 4.0 mg/L.

 

In both columns the concentration of five consecutive fractions was constant within ± 30 %. No increasing or decreasing tendency was observed.

 

Table Coating check:

	Amount of test item used for coating /mg	Measured concentration of  test item in eluate /mg/L	Amount of test item  eluated /mg
Column 12.5 mL/h	23.5	1.554 / 1.554	7.8
Column 25.0 mL/h	23.5	0.781 / 0.782	3.9

 

The coating check was successful. Enough test item remained on the columns. The water solubility cs of the test item was determined to be 3.9 mg/L (mean value of the columns).

 

Conclusions:

The water solubility cs of the test item at a temperature of 20°C was determined according to the column elution method. The water solubility of the test item was determined to be 3.9 mg/L.

Executive summary:

The water solubility of the test item at a temperature of 20°C was determined according to the column elution method (EU Method A.6, OECD 105). It was found to be 3.9 mg/L.

Description of key information

The water solubility cs of the test item at a temperature of 20°C was determined according to the column elution method was found to be cs = 3.9 mg/L.

Key value for chemical safety assessment

Water solubility:

3.9 mg/L

at the temperature of:

20 °C