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Water solubility

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Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24-03-2014 to 18-04-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 830.7840 (Water Solubility)
Deviations:
no
GLP compliance:
yes
Type of method:
column elution method
Water solubility:
24.7 mg/L
Conc. based on:
test mat.
Temp.:
19.9 °C
pH:
>= 7.7 - <= 7.8
Remarks on result:
other: mean two flow rates ; at 24 mL/h and 12 mL/h with n=10 samples

Preliminary test:

Test item was stirred with double distilled water or ISO-medium at a nominal concentration of 0.25 g/L at 20.0 ± 0.4°C for 72 hours (3 days). After stirring, the aqueous phase was centrifuged, treated and analysed. In the preliminary test the solubility of the test item in water and ISO-medium was slightly > 10^-2 g/L. The relatively large concentration difference between two-fold and threefold centrifugation (i.e. 16% and 14% respectively in ISO-medium and water) indicated that undissolved test item was not properly removed by the centrifugation procedure.

 

A flask method test was attempted: test item was stirred with water or ISO-medium at a nominal concentration of 0.09 g/L at 19.8 ± 0.3ºC. The aqueous phases that were stirred for 72 hours (3 days) were centrifuged, treated and analysed. Based on peak area, the concentration of the test item in water and ISO-medium was < 10^-2 g/L and large differences between two-fold, three-fold and four-fold centrifugation steps were observed indicating that undissolved test item could not be properly removed. Therefore, it was considered appropriate to perform the column elution method instead of the flask method.

 

Definitive test – Column Elution Method:

- The results for the samples taken at a flow rate of 12 and 24 mL/h are given below for the determination of the water solubility.

- The coefficient of variation (CV) (n = 10) was ≤ 30% at both flow rates for both water and ISO-medium. It demonstrated that the systems were equilibrated at all flow rates.

- The maximum difference (MD) on the mean values of the samples at both flow rates and for both water and ISO-medium was also ≤ 30%. Based on this, the solubility of the test item in water or in ISO-medium is given as the mean value of these measurements.

- The turbidity of the eluates from the solubility in ISO-medium was < 0.2 NTU. According to this, no undissolved particles were detected in the eluates.

- The turbidity of the eluates from the determination of the solubility in water were slightly above 0.2 NTU for the test item containing columns, i.e. 0.322 NTU at the flow rate of 24 mL/h and 0.210 NTU at the flow rate of 12 mL/h. The higher turbidity values were not considered to be caused by undissolved test item since there was no dependence between the determined test item concentration and the flow rate/turbidity.

- No test item was detected in the samples from the blank column.

 

Table 1 : definitive test – solubility of the test item in water medium

Flow Rate

[mL/h]

Sample #

Test Item Concentration Analysed

pH

Individual [mg/L]

Mean [mg/L]

CV [%]

Mean both flow rates [mg/L]

CV [%]

24

1

22.8

 

 

 

 

 

 

2

24.5

 

 

 

 

 

 

3

24.6

 

 

 

 

 

 

4

24.5

 

 

 

 

 

 

5

24.5

 

 

 

 

 

 

6

25.0

 

 

 

 

 

 

7

23.6

 

 

 

 

 

 

8

23.9

 

 

 

 

 

 

9

25.4

 

 

 

 

 

 

10

22.7

24.1

3.6

 

 

7.8

 

 

 

 

 

 

 

 

12

1

26.5

 

 

 

 

 

 

2

21.1

 

 

 

 

 

 

3

22.3

 

 

 

 

 

 

4

26.4

 

 

 

 

 

 

5

26.4

 

 

 

 

 

 

6

25.7

 

 

 

 

 

 

7

25.6

 

 

 

 

 

 

8

25.8

 

 

 

 

 

 

9

26.0

 

 

 

 

 

 

10

26.4

25.2

7.6

 

 

7.7

 

 

 

 

 

 

 

 

 

 

 

 

 

24.7

4.4

7.75

 

 

 

 

 

 

 

 

Conclusions:
Interpretation of results: slightly soluble (0.1-100 mg/L)
The test item water solubility was determined to be 24.7 mg/L at pH 7.7 - 7.8 and 20.0 °C.
Executive summary:

The water solubility of the substance was determined according to OECD Method 105 and EU Method A.6 in accordance with GLP using the column elution method. In an additional endpoint: Adjusted ISO-medium, formulated using RO-water (tap-water purified by reverse osmosis) was used as a further medium for solubility determination. Absolute test item quantities of 96.4 mg and 77.7 mg were mixed with 5 g LiChroprep Si 60 25-40 μm column material for the determination of the solubility in water and in ISO-medium, respectively. The mixture was homogenised by shaking overnight at room temperature. The column: 150 mm × 4.6 mm i.d. was filled with the carrier material and 0.5 μm frits (details in the full study report) were used to enclose the column. Double distilled water or ISO-medium was pumped through the column until it was completely filled. The system was allowed to equilibrate for two hours. After equilibration: the column was eluted overnight with double distilled water or ISO-medium at a flow rate of 12 mL/hour. The following day the flow was increased to 24 mL/hour. The temperature of the column was: 19.9°C ± 0.3°C. Ten consecutive samples of 2 mL were taken at each flow rate for analysis. The experiment was also performed using a column filled with blank carrier material. The procedure was identical to the procedure used for the column loaded with test item. At each flow rate, two consecutive samples were taken for analyses. The pH was measured from the fractions that were collected for the determination of the flow rates. Test item concentration was quantified using GC-MS. The solubility of the test item in water at 20°C was 24.7 mg/L. The pH of the aqueous samples was 7.7 – 7.8. The solubility of the test item in ISO-medium at 20°C was 12.4 mg/L. The pH of the ISO Medium samples was 7.4.

Description of key information

Water Solubility: 24.7 mg/L at pH 7.7 to 7.8 and 20 °C, OECD TG 105 : column elution method, 2014

Key value for chemical safety assessment

Water solubility:
24.7 mg/L
at the temperature of:
20 °C

Additional information

Key study : OECD TG 105, 2014 : The water solubility of the substance was determined according to OECD Method 105 and EU Method A.6 in accordance with GLP using the column elution method. In an additional endpoint: Adjusted ISO-medium, formulated using RO-water (tap-water purified by reverse osmosis) was used as a further medium for solubility determination. Absolute test item quantities of 96.4 mg and 77.7 mg were mixed with 5 g LiChroprep Si 60 25-40 μm column material for the determination of the solubility in water and in ISO-medium, respectively. The mixture was homogenised by shaking overnight at room temperature. The column: 150 mm × 4.6 mm i.d. was filled with the carrier material and 0.5 μm frits (details in the full study report) were used to enclose the column. Double distilled water or ISO-medium was pumped through the column until it was completely filled. The system was allowed to equilibrate for two hours. After equilibration: the column was eluted overnight with double distilled water or ISO-medium at a flow rate of 12 mL/hour. The following day the flow was increased to 24 mL/hour. The temperature of the column was: 19.9°C ± 0.3°C. Ten consecutive samples of 2 mL were taken at each flow rate for analysis. The experiment was also performed using a column filled with blank carrier material. The procedure was identical to the procedure used for the column loaded with test item. At each flow rate, two consecutive samples were taken for analyses. The pH was measured from the fractions that were collected for the determination of the flow rates. Test item concentration was quantified using GC-MS. The coefficient of variation (CV) (n = 10) was ≤ 30% at both flow rates for both water and ISO-medium. It demonstrated that the systems were equilibrated at all flow rates. The maximum difference (MD) on the mean values of the samples at both flow rates and for both water and ISO-medium was also ≤ 30%. Based on this, the solubility of the test item in water or in ISO-medium is given as the mean value of these measurements. The solubility of the test item in water at 20°C was 24.7 mg/L. The pH of the aqueous samples was 7.7 – 7.8. The solubility of the test item in ISO-medium at 20°C was 12.4 mg/L. The pH of the ISO Medium samples was 7.4.

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