4-[4-(3,4-Difluorophenyl)-cyclohexyl]-cyclohexanone

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22.08. - 06.09.02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

column elution method

Key result

Water solubility:

1.9 mg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

> 5.9 - < 6.7

Details on results:

Result run1:
Evaluation of the fractions 9 to 16. The water solubility was found to be 1.78 mg/L.
 
Result run 2:
Evaluation of the fractions 21 to 26. The water solubility was found to be 1.97 mg/L

Individual Results

Preliminary Visual Estimation of the Water Solubility

Increasing water amounts were added stepwise to about 100 mg of the test substance.

 

Appearance of the test mixtures

Amount of the test item in mg	Total volume in mL	Appearance of mixture
101.35	0.1	undissolved
	0.5	undissolved
	1	undissolved
	2	undissolved
	10	undissolved
	100	undissolved

 

Increasing water amounts were added to about 10 mg of the test substance.

 

Appearance of the test mixtures

Amount of the test item in mg	Total volume in mL	Appearance of mixture
10.84	100	undissolved
10.03	500	undissolved
I 10.41	1000	undissolved|

The solution was stirred for 21 hours.

 

The preliminary visual experiments showed that the water solubility of the test substance is lower than 10 mg/L. Therefore the water solubility had to be determined by the column-elution method.

 

Column-Elution Method

Run 1:

Rotation period of the fraction accumulator: 90 min per fraction

Average fraction volume: between 10.2 mL/h and 10.5 mL/h

Flow rate: 45 min per fraction 15.5 mL

Duration of sampling: about 24 h (16 fractions)

 

Run 2:

Rotation period of the fraction accumulator: 45 min per fraction

Average fraction volume: 14.2 mL

Flow rate: between 17.3 mL/h and 21.3 mL/h

Duration of sampling: about 24 h (32 fractions)

 

Run 3 (blank):

Rotation period of the fraction accumulator:

Average fraction volume: between 18.0 mL/h and 21.1 mL/h

Flow rate: 14.7 mL

Duration of sampling: about 24 h (32 fractions)

 

Concentration and pH

Column-elution method: Run 1

Fraction No,	V	PH	Measurement	Water Solubility
	in mL		in mg/L	in mg/L
9	15.5	6.0	0.84	1.67
10	15.5	6.0	0.87	1.74
11	15.3	6.0	0.89	1.79
12	15.3	6.0	0.88	1.75
13	15.5	5.9	0.90	1.80
14	15.5	5.9	0.95	1.90
15	15.7	6.0	0.92	1.83
16	15.5	6.0	0.88	1.76

 

Column-elution method; Run 2

Fraction No.	V in mL	PH	Measurement in mg/L	Water Solubility in mg/L
21	14.0	6.7	0.98	1.96
22	13.5	6.6	1.00	2.01
23	13.0	6.6	1.01	2.03
24	13.5	6.4	1.00	2.00
25	13.0	6.4	0.93	1.87
26	13.0	6.4	0.97	1.93

 

Column-elution method: Run 3 (blank)

Fraction No.	V	PH	Measurement	Water Solubility I
	in mL		in mg/L	in mg/L
21	14.3	6.3	<0.2	<0.4
22	14.3	6.1	<0.2	<0.4
23	14.0	6.3	<0.2	<0.4
24	14.0	6.2	<0.2	<0.4
25	13.5	6.2	<0.2	<0.4
26	13.5	6.1	<0.2	<0.4

 

According to the guideline, the data of the fractions 1 to 5 were not taken into account for the following evaluation. The values for the water solubility were calculated from the fractions 9 to 16 for column 1, from fractions 21 to 26 for column 2 and 3. Fractions 6 to 8 for column 1 and fractions 7 to 20 and 27 to 32 for column 2 and column 3 were discarded.

 

 

Result run1:

Evaluation of the fractions 9 to 16. The water solubility was found to be 1.78 mg/L.

 

Result run 2:

Evaluation of the fractions 21 to 26. The water solubility was found to be 1.97 mg/L

Conclusions:

The water solubility of the test substance at a temperature of 20 °C was determined to be 1.9 mg/L.

Executive summary:

The water solubility was determined according to OECD 105 using the column elution method with HPLC analysis. In a preliminary test increasing water amounts were added stepwise to about 100 mg of the test substance. After undissolved increasing water amounts were added to about 10 mg of the test substance. The water solubility of the test substance was less than 10 mg/L and had to be determined using the column elution method. 0.08971 g of the test substance were dissolved in 25 mL acetonitrile. 10 mL of this solution were added to about 3 g of sea-shore sand and the mixture was shaken. The solvent was then removed under reduced pressure using a rotary evaporator. Two identical samples were prepared; one of them was exposed to a flow rate of 12.5 mL/h, the other one to 25 mL/h. After measurement of volume, pH and temperature, the selected fractions were directly subjected to HPLC analysis. The water solubility of the test substance at a temperature of 20°C and pH=6 was determined (average over both runs) to be 1.9 mg/L.

Description of key information

The water solubility of the test substance at a temperature of 20 °C was determined to be 1.9 mg/L (reference 4.8 -1).

Key value for chemical safety assessment

Water solubility:

1.9 mg/L

at the temperature of:

20 °C

Additional information

The water solubility was determined according to OECD 105 using the column elution method with HPLC analysis. In a preliminary test increasing water amounts were added stepwise to about 100 mg of the test substance. After undissolved increasing water amounts were added to about 10 mg of the test substance. The water solubility of the test substance was less than 10 mg/L and had to be determined using the column elution method. 0.08971 g of the test substance were dissolved in 25 mL acetonitrile. 10 mL of this solution were added to about 3 g of sea-shore sand and the mixture was shaken. The solvent was then removed under reduced pressure using a rotary evaporator. Two identical samples were prepared; one of them was exposed to a flow rate of 12.5 mL/h, the other one to 25 mL/h. After measurement of volume, pH and temperature, the selected fractions were directly subjected to HPLC analysis. The water solubility of the test substance at a temperature of 20°C and pH=6 was determined (average over both runs) to be 1.9 mg/L.