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Water solubility

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Endpoint:
water solubility
Remarks:
Critical Micelle Concentration
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
07 December 2016 to 13 September 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with international guideline and in accordance with GLP. All relevant validity criteria were met.
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Determination of the critical micelle concentration (CMC) by measuring the surface tension via tensiometer depending on the test item concentration in aqueous solution.
- Short description of test conditions: For this purpose, different concentrations of the test item were prepared in double distilled water.
- Parameters analysed / observed: The corresponding surface tensions was determined according to the requirements of the guidelines OECD 115 / EC A.5 using the OECD harmonized ring method, which is based upon the standards ISO 304-1985, DIN 53914, ASTM-D-1590 and ASTM-D-1331.
GLP compliance:
yes (incl. QA statement)
Type of method:
other: Critical Micelle Concentration
Key result
Water solubility:
>= 50 - <= 150 mg/L
Conc. based on:
test mat.
Temp.:
20 °C
Remarks on result:
other: Critical Micelle Concentration
Details on results:
The determination of the critical micelle concentration (CMC) was conducted by measuring the surface tension of the test item at 20 ± 0.5 °C and at different concentrations. For the evaluation of the CMC, a graph ‘Test Concentration’ vs. ‘Surface Tension’ was created.
The critical micelle concentration is calculated from the point of intersection of the two lines y1 and y2.
A non-GLP preliminary screening test for the determination of the CMC was conducted under similar conditions as range finder for the definitive GLP test with finally following results:
The non-GLP measurements were also conducted by measuring the surface tension of the test item at 20 ± 0.5 °C and at different concentrations. These values have been merged with those from the definitive test for the determination of the critical micelle concentration.

Surface tension of the test item at different test item concentrations (preliminary test)

Concentration
[mg/L]

Surface Tension1)
[mN/m]

Time2)
[h]

Time3)
[min]

Temp.4)
[°C]

4.12

60.69

67.9

7.5

20.3 – 20.4

4.71

64.96

69.0

17.3

20.1 – 20.2

5.49

57.78

69.8

10.2

20.2 – 20.4

8.24

54.99

70.4

18.0

19.7 – 20.0

12.36

58.49

71.2

33.4

20.1 – 20.5

16.48

54.47

89.6

33.2

19.8 – 20.3

24.72

52.40

91.5

14.6

19.7 – 20.0

32.96

51.81

92.9

24.4

20.2 – 20.3

41.20

51.91

94.0

16.6

20.3

49.44

49.33

95.6

49.7

19.8 – 20.2

98.88

43.27

17.2

11.5

19.9

247.20

30.07

18.4

12.8

20.2 – 20.2

494.40

28.02

19.2

22.3

201 – 20.4

988.80

23.59

20.7

7.6

19.9 – 20.0

1) The density of each test solution was in the range of 0.991 to 1.029 g/mL

2) Time from preparation of the test solution (stored at room temperature) until start of the measurement

3) Time from start of the measurement till end of the surface tension measurement

4) Temperature of the test solution during the determination of the respective surface tension  

Surface tension of the test item at different test item concentrations (definitive test)

Concentration
[mg/L]

Surface Tension1)
[mN/m]

Time2)
[h]

Time3)
[min]

Temp.4)
[°C]

8.24

60.54

26.2

20.3

20.3

12.36

56.57

25.0

13.1

19.9

16.48

56.20

27.5

11.8

20.0 – 20.2

24.72

54.43

25.5

13.9

19.9

32.96

54.36

28.3

14.3

20.1 – 20.2

41.20

46.48

26.1

14.1

19.8 – 19.9

49.44

55.05

28.9

12.9

19.7 – 20.0

98.88

52.77

26.9

31.4

19.7 – 20.2

164.80

52.61

29.2

9.2

20.0 – 20.3

247.20

48.11

27.8

9.9

20.0 – 20.1

494.40

31.99

29.7

14.6

19.9 – 20.3

988.80

44.53

28.4

8.1

19.9 – 20.0

1) The density of each test solution was in the range of 0.998 to 1.011 g/mL

2) Time from preparation of the test solution (stored in an air-conditioned room at 20 °C) until start of the measurement

3) Time from start of the measurement till end of the surface tension measurement

4) Temperature of the test solution during the determination of the respective surface tension  

The surface tension of the reference item n-heptane was determined on 2016-03-04 as 20.07 ± 0.02 mN/m (20 °C) for the platinum iridium ring with internal no. 1 (type RI 21), and is within the acceptable range of 20.23 ± 0.22 mN/m.

The temperatures of the test solutions were 20  0.5 °C, within the validity criteria.

Conclusions:
the critical micelle concentration of the test item is in the concentration range between 50 and 150 mg/L, when merging both data-sets obtained from the non-GLP preliminary screening test and the definitive GLP test, respectively.
Executive summary:

The critical micelle concentration of the test item was investigated via the surface tension following OECD Guideline 115 for the Testing of Chemicals (1995) and Council Regulation (EC) No. 440/2008, Method A.5 from 2016-12-08 and 2016-12-13 at the test facility.

The determination of the critical micelle concentration (CMC) was conducted by measuring the surface tension of the test item at 20 °C via tensiometer at twelve different aqueous concentrations in the expected CMC-range of 1 to 1000 mg/L.

Moreover, a non-GLP preliminary screening test was conducted under similar conditions as range finder for the definitive GLP test, which is also stated here.

As a result, it can be concluded that the value for the test item is in the concentration range between 50 and 150 mg/L, when merging both data-sets obtained from the non-GLP preliminary screening test and the definitive GLP test, respectively.

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
14 Aug 2013 - 25 Apr 2014
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
This study was not conducted in a GLP facility, but was conducted according to international guidelines.
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:
no
Type of method:
flask method
Key result
Water solubility:
16 mg/L
Conc. based on:
test mat.
Loading of aqueous phase:
10 g/L
Incubation duration:
>= 1 - <= 3 d
Temp.:
20 °C
pH:
>= 3.56 - <= 3.76
Details on results:
In the Preliminary test, approximate water solubility of the substance was determined to be more than 10 mg/L. Therefore, the Flask method of OECD guideline 105 was chosen for the Definitive study. The chemical amount dissolved in water was determined by HPLC. The water solubility of the substance was determined to be 16 mg/L at 20 °C.

The mean peak areas relating to the standard and sample solutions are shown in Table 1. The concentration of test material in the sample solution is shown in Table 2.

Table 1 Mean peak areas

SOLUTION

MEAN PEAK AREA

Standard 10 mg/L

74,951

Standardv5 mg/L

38,261

Standard 2.5 mg/L

21,522

Standard 1 mg/L

10,103

Standard 0.5 mg/L

6,326

Sample 1 A

22,433

Sample 1 B

22,449

Sample 2 A

27,525

Sample 2 B

27,033

Sample 3 A

26,249

Sample 3 B

27,150

Table 2. Concentration of test material in sample solution

SAMPLE NUMBER

TIME SHAKEN AT 30°C (hours)

TIME EQUILIBRATED AT 20°C (hours)

CONCENTRATION (mg/L)

pH AFTER TEST

1A

24

24

14

3.56

1B

24

24

14

3.60

2A

48

24

17

3.57

2B

48

24

17

3.59

3A

72

24

16

3.72.

3B

72

24

17

3.76

Mean concentration: 16 mg/L at 20 °C

Range: 14 to 17 mg/L at 20 °C

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0.5 to 10 mg/L. This was satisfactory with a coefficient of 0.9997 being obtained.

Conclusions:
The water solubility of the substance was determined to be 16 mg/L at 20 °C.
Executive summary:

The water solubility of the test substance was determined according to EU Method A.6 and OECD 105.

In the Preliminary test, approximate water solubility of the substance was determined to be more than 10 mg/L. Therefore, the Flask method of OECD guideline 105 was chosen for the Definitive study. The chemical amount dissolved in water was determined by HPLC. The water solubility of the substance was determined to be 16 mg/L at 20 °C.

After addition of glass double-distilled water to the flasks, they were shaken with a speed of 250 rpm at 30°C for 1 day, 2 days and 3 days. After stopping agitation, flask was equilibrated for approximately 1 day at 20 ± 0.5°C with occasional shaking. The contents of the flasks was then transferred to centrifuge plastic tube (50 mL), and then centrifuged for 5 min at a speed of 3000 rpm. The upper transparent aqueous solution was carefully taken by a pipette and filtered by a syringe-filter (0.45μm). The concentration of test material in the sample solution was determined by high performance liquid chromatography (HPLC). Duplicate aliquots (A and B) were diluted with acetonitrile (sample dilution factor: 5).

The water solubility of the substance was determined to be 16 mg/L at 20 °C.

Description of key information

Water Solubility = 16 mg/L; OECD 105; Anon, 2014

Critical Micelle Concentration = 50 - 150 mg/L; Anon, 2017

Key value for chemical safety assessment

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

Additional information

In a weight-of-evidence, two studies were used in order to define this endpoint. The water solubility of the test substance was determined according to EU Method A.6 and OECD 105. In the Preliminary test, approximate water solubility of the substance was determined to be more than 10 mg/L. Therefore, the Flask method of OECD guideline 105 was chosen for the Definitive study. The chemical amount dissolved in water was determined by HPLC. The water solubility of the substance was determined to be 16 mg/L at 20 °C.  After addition of glass double-distilled water to the flasks, they were shaken with a speed of 250 rpm at 30°C for 1 day, 2 days and 3 days. After stopping agitation, flask was equilibrated for approximately 1 day at 20 ± 0.5°C with occasional shaking. The contents of the flasks was then transferred to centrifuge plastic tube (50 mL), and then centrifuged for 5 min at a speed of 3000 rpm. The upper transparent aqueous solution was carefully taken by a pipette and filtered by a syringe-filter (0.45μm). The concentration of test material in the sample solution was determined by high performance liquid chromatography (HPLC). Duplicate aliquots (A and B) were diluted with acetonitrile (sample dilution factor: 5).   The water solubility of the substance was determined to be 16 mg/L at 20 °C.

As the measured surface tension for this substance was < 60 mN/m (Section 4.10), a measurement of the critical micelle concentration was undertaken for the substance. The critical micelle concentration is used as a surrogate value for water solubility for surfactant substances.

The critical micelle concentration of the test item was investigated via the surface tension following OECD Guideline 115 for the Testing of Chemicals (1995) and Council Regulation (EC) No. 440/2008, Method A.5 from 2016-12-08 and 2016-12-13 at the test facility.  The determination of the critical micelle concentration (CMC) was conducted by measuring the surface tension of the test item at 20 °C via tensiometer at twelve different aqueous concentrations in the expected CMC-range of 1 to 1000 mg/L.

Moreover, a non-GLP preliminary screening test was conducted under similar conditions as range finder for the definitive GLP test, which is also stated here.  As a result, it can be concluded that the value for the test item is in the concentration range between 50 and 150 mg/L, when merging both data-sets obtained from the non-GLP preliminary screening test and the definitive GLP test, respectively.

There are two important considerations to make with the presented studies:

  1. As discussed in Section 6.1, the substance is highly unstable in water and is very quickly transformed into the primary metabolite 2 -methyldecanoic acid. Given that the DT50 of the registered substance (2 -methyldecanal) is expected to be < 4 hours, it is relevant to base the chemical safety assessment on the transformation product, as this will be the relevant entity for environmental exposure. This approach is consistent with OECD 23 - Guidance Document on Aquatic Toxicity Testing of Difficult Substances. The measured water solubility when using 2 -methyldecanal as the test item, is consistent with the known water solubility of 2 -methyldecanoic acid (20 mg/L).
  2. As the critical micelle concentration of the substance is up to an order of magnitude higher than the known water solubility or the relevant entity for safety assessment, this is attributed to the presence of a surfactant impurity or minor transformation product. As such, the registered substance is not considered a "true surfactant" and therefore it is concluded that standard methods for the determination of water solubility and partition coefficient are valid for this susbtance.

The relevant value to use for the chemical safety assessment of this substance is water solubility = 16 mg/L.