Trans-2-{4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3,5-difluorophenyl}-5-(trans-4-propylcyclohexyl)-1,3-dioxane

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16.09.2011 - 09.11.2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

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:

< 0.1 mg/L

Conc. based on:

test mat. (dissolved fraction)

Temp.:

20 °C

pH:

6.2

Preliminary Visual Estimation of the Water Solubility

Different amounts of the test item and water were stirred at room temperature until the mixture appeared dissolved or the water solubility could be estimated to be below 10 mg/L.

Table 1: Appearance of the test mixtures

Amount of the test item in mg	Total volume in mL	Appearance of mixture
8.6	100	Undissolved*
8.1	500	Undissolved*
2.0	500	Undissolved*

* After adding the indicated amount of water, the solution was stirred at room temperature for about 1 day.

The solubility of the test item in water was below 4.0 mg/L. Therefore, the water solubility had to be determined by the "column elution method".

Column elution method

lndividual Conditions

Column 1:

Rotation period of the fraction accumulator: 90 min per fraction

Average fraction volume: 18.8 mL

Flow rate: between 12.3 mL/h and 12.7 mL/h

Duration of sampling: about 47 h (31 fractions)

Column 2:

Rotation period of the fraction accumulator: 45 min per fraction

Average fraction volume: 17.9 mL

Flow rate: between 23.3 mL/h and 24.7 mL/h

Duration of sampling: about 47 h (62 fractions)

Column 3 (blank):

Rotation period of the fraction accumulator: 45 min per fraction

Average fraction volume: 17.5 mL

Flow rate: between 22.0 mL/h and 24.7 mL/h

Duration of sampling: about 90 h (56 fractions)

Table 2: Results for Column 1

Fraction no.	V in mL	pH	Water solubility in µg/L
23	12.3	6.2	< 18.4*
24	12.3	62	< 18.4*
25	12.3	6.3	< 18.4*
26	12.3	6.3	< 18.4*
27	12.3	6.3	< 18.4*

* < indicates below the detection limit

According to the guideline the run can be stopped if the concentrations of five fractions do not differ more than ± 30 % without any raising or descending tendency.

Table 3: Results for Column 2

Fraction no.	V in mL	pH	Water solubility in µg/L
54	17.5	6.2	< 18.4*
55	17.5	6.1	< 18.4*
56	17.5	6.2	< 18.4*
57	17.5	6.3	< 18.4*
58	17.5	6.2	< 18.4*

* < indicates below the detection limit

According to the guideline the run can be stopped if the concentrations of five fractions do not differ more than ± 30 % without any raising or descending tendency.

Table 4: Results for Column 3 (blank)

Fraction no.	V in mL	pH	Water solubility in µg/L
25	18.0	6.4	< 18.4*
26	18.0	6.4	< 18.4*
27	18.0	6.4	< 18.4*
28	18.0	6.2	< 18.4*
29	18.0	6.4	< 18.4*

* < indicates below the detection limit

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 fractions 23 to 27 for column 1, from the fractions 54 to 58 for column 2, from the fractions 25 to 29 for column 3. All other fractions were discarded.

Result column 1:

Evaluation of the fractions 23 to 27: The water solubility was found to be below the detection limit of 0.018 mg/L.

Result column 2:

Evaluation of the fractions 54 to 58: The water solubility was found to be below the detection limit of 0.018 mg/L.

Result column 3:

Evaluation of the fractions 25 to 29: The blank concentration was found to be below the detection limit of 0.018 mg/L.

Standards for recheck

The recovery of the 'recheck samples' was between 81.1 % and 95.4 % indicating a sufficient accuracy of the analytical method.

Coating check

Table 6: Coating Check

	Amount used for coating in mg	Measured concentration in mg/L	Amount eluted per column in mg
Column 1	23.8	0.055 / 0.057	13.9
Column 2	23.8	0.055 / 0.054	13.6

The coating check was successful.

Conclusions:

The water solubility of the test substance was determined to be < 0.1 mg/L (<0.018 mg/L) at 20 °C.

Executive summary:

The water solubility of the test item was determined according to OECD 105 and Regulation (EC) No. 440/2008 method A.6 using the column elution method with HPLC analysis. 95.2 mg of the test item were dissolved in 100 mL acetone. 25 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 (35 °C, 40 mbar). The dry residues were placed into the columns of the test apparatus, which have afterwards been filled with water (test temperature: 20 °C; water pH at 22.4 °C: 5.7). After a swelling time of 2 h pumps were started to rinse the substance coated sand with demineralised 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. Two identical samples were prepared, one of them was exposed to a flow rate of 12.5 mL/h (column 1), the other one to 25.0 mL/h (column 2). Another experiment was performed according to this procedure (flow rate 25.0 mL/h) but without test item ("blank" = column 3). The aqueous fractions were diluted 0.5 mL to 1 mL with methanol and measured by means of HPLC. The water solubility of the test item was determined to be <0.1 mg/L (<0.018 µg/L) at 20 °C (pH = 6.1 – 6.4).

Description of key information

The water solubility of the test substance was determined to be < 0.1 mg/L (<0.018 mg/L) at 20 °C.

Additional information

The water solubility of the test item was determined according to OECD 105 and Regulation (EC) No. 440/2008 method A.6 using the column elution method with HPLC analysis. 95.2 mg of the test item were dissolved in 100 mL acetone. 25 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 (35 °C, 40 mbar). The dry residues were placed into the columns of the test apparatus, which have afterwards been filled with water (test temperature: 20 °C; water pH at 22.4 °C: 5.7). After a swelling time of 2 h pumps were started to rinse the substance coated sand with demineralised 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. Two identical samples were prepared, one of them was exposed to a flow rate of 12.5 mL/h (column 1), the other one to 25.0 mL/h (column 2). Another experiment was performed according to this procedure (flow rate 25.0 mL/h) but without test item ("blank" = column 3). The aqueous fractions were diluted 0.5 mL to 1 mL with methanol and measured by means of HPLC. The water solubility of the test item was determined to be <0.1 mg/L (<0.018 µg/L) at 20 °C (pH = 6.1 – 6.4) (reference 4.8-1).