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Physical & Chemical properties

Water solubility

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Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24.04.-08.05.2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
Deviations:
no
GLP compliance:
no
Type of method:
column elution method
Key result
Water solubility:
< 0.047 mg/L
Temp.:
20 °C
Remarks on result:
other: pH not relevant

Table 1: Recovery

All recovery values are calculated from the measured and unrounded concentration values and not from the rounded values given in Table 1. The recovery of the standards indicated a sufficient accuracy of the analytical method.

 Standard  Measured concentration /µg/L % Recovery (mean values
 E (c = 397.5 µg/L) 406.33/408.27 102.5
 G (c= 132.5 µg/L)

124.62/133.29

137.76/134.89

97.3

102.9

 H (c= 23.40 µg/L) 23.39/24.78 102.9
 I (c = 46.80 µg/L)  43.43/42.78  92.1
 J (c = 260 µg/L)  242.85/237.01  92.3

Table 2: Repeatability

The repeatability was checked by measuring standard F six-fold. The resulting area was used to calculate the standard deviation and the variation coefficient.

 Measurement No.  Area / mAU*s
 1 59.400
 2 59.887 
 3 59.580
 4 59.800
 5  59.594
 6 59.679
 Mean value  59.7
 Standard deviation  0.2
 Variation coefficient / % 0.3

The accuracy of the analytical method was evaluated as sufficient as the variation coefficient of the repeatability measurements was < 2.

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/I.

Table 3: Results of the preliminary test

 

Amount of test item / mg

 

Total volume of demineralized water / mL

 Appearance of mixture
10.7 100 not dissolved
11.3 500 not dissolved
3.5 500  not dissolved

The solubility of the test item in water was found to be below 7.0 mg/I (without correction of the purity). Therefore the column elution method was performed for the determination of the water solubility of the test item.

Table 4: Column elution method, column 1 (approximately 12.0 mL/h)

 Fraction No.  V/mL  pH  water solubility /µg/L
21 18.0 5.7 <47
22 17.5   5.7 <47
23 17.5 5.7 <47
24 17.5 5.7 <47
 25 17.5 5.7

<47

The water solubility was found to be below the quantification limit of 47 µg/L.

Table 5: Column elution method, column 2 (approximately 25 mL/h)

 Fraction No.

 V/mL

 pH

 water solubility /µg/L

48

18.0

5.6

<47

49

18.0

5.6

<47 

 50

18.0

5.7

<47  

51

18.0

5.7

<47 

52

18.0

5.6

<47 

The water solubility was found to be below the quantification limit of 47 µg/L.

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

Table 6: Column elution method, column 3 (blank)

 Fraction No.

 V/mL

 pH

 water solubility /µg/L

49

17.5

5.6

<47

50

17.5

5.6

<47 

 51

17.5

5.6

<47  

52

17.5

5.6

<47 

53

17.5

5.6

<47 

The blank concentration was found to be below the quantification limit of 47 µg/L.

Table 7: Coating check

 

 

Amount of test item used for coating /mg

 

Measured concentration

of test item in eluate /mg/L

Amount of test item eluted / mg

 

 Column 1

26.2    

0.246/0.245

24.6

 Column 2

0.232/0.231

23.2

The coating check was successful. There was enough residual test item remained an the columns after the performance of the column elution method.

Conclusions:
The water solubility of the test item at a temperature of 20°C was found to be below the quantification limit: < 47 µg/L.
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. 104.9 mg of the test item were dissolved in 100 ml acetone using ultrasonic bath for 10 min 25 ml of this solution was added to about 3 g of sea sand and the mixture was shaken. This procedure was performed for column 1 and column 2. The solvent was then removed under reduced pressure using a rotary evaporator (50 °C, 40 mbar). The dry residues were placed into the columns of the test apparatus, which were afterwards filled with water (test temperature: 20 °C; pH of water at 22.9 °C; 5.6). After a swelling time of 2 h the pump was started to rinse the substance coated sand with distilled water. Two identical columns were prepared, one of them was exposed to a flow rate of about 12.5 ml/h (column 1), the other one to about 25.0 ml/h (column 2). Another experiment was performed according to this procedure but without test item ("blank" = column 3). The concentration of test item was determined by means of HPLC. Therefore, the aqueous fractions were diluted from 0.5 ml to 1 ml with acetonitrile. The volumes of all fractions were measured. For the analysed fractions the pH values and the temperatures were measured, too. 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. The eluate was diluted from 0.1 ml to 20 ml with acetonitrile and again from 0.1 ml to 1 ml with acetonitrile and distilled water (50:50 % v/v). Subsequently the concentration was quantified by HPLC.

The concentration of the test item was quantified by HPLC. The pH of each sample was recorded. The water solubility of the test item at a temperature of 20°C was found to be below the quantification limit: < 47 µg/L.

Description of key information

The water solubility of the test item at a temperature of 20°C was found to be below the quantification limit: < 47 µg/L.

Key value for chemical safety assessment

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. 104.9 mg of the test item were dissolved in 100 ml acetone using ultrasonic bath for 10 min 25 ml of this solution was added to about 3 g of sea sand and the mixture was shaken. This procedure was performed for column 1 and column 2. The solvent was then removed under reduced pressure using a rotary evaporator (50 °C, 40 mbar). The dry residues were placed into the columns of the test apparatus, which were afterwards filled with water (test temperature: 20 °C; pH of water at 22.9 °C; 5.6). After a swelling time of 2 h the pump was started to rinse the substance coated sand with distilled water. Two identical columns were prepared, one of them was exposed to a flow rate of about 12.5 ml/h (column 1), the other one to about 25.0 ml/h (column 2). Another experiment was performed according to this procedure but without test item ("blank" = column 3). The concentration of test item was determined by means of HPLC. Therefore, the aqueous fractions were diluted from 0.5 ml to 1 ml with acetonitrile. The volumes of all fractions were measured. For the analysed fractions the pH values and the temperatures were measured, too. 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. The eluate was diluted from 0.1 ml to 20 ml with acetonitrile and again from 0.1 ml to 1 ml with acetonitrile and distilled water (50:50 % v/v). Subsequently the concentration was quantified by HPLC.

The concentration of the test item was quantified by HPLC. The pH of each sample was recorded. The water solubility of the test item at a temperature of 20°C was found to be below the quantification limit: < 47 µg/L.