N-(2-hydroxyethyl)dodecanamide

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 August 2017 - TBC

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was conducted in accordance with international guidelines and in accordance with GLP. All guideline validity criteria were met.

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

Regulation (EC) 440/2008 of 30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

27 July 1995

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

0.011 g/L

Conc. based on:

test mat.

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 7 - <= 8.5

Remarks on result:

other: Mean Value

Evaluation of Data:

The response factors of the standard peak areas (unit peak area per mg/L) were calculated using Equation 1:

 

Equation 1:

RF_STD= R_STD/C_STD

 

where:

RF_STD   =         response factor of the standard solution

R_STD     =         peak area of the standard solution

C_STD     =         concentration of the standard solution (mg/L)

 

Each sample solution concentration (mg/L) was calculated using Equation 2:

 

 

Equation 2:

C = (R_SPL/RF_STD) x D

 

where:

C         =         sample solution concentration (mg/L)

R_SPL     =         mean peak area of the sample solution

RF_STD   =         mean response factor of the standard solutions (unit peak area per mg/L)

D         =         dilution factor (0.4)

 

 

Results – Preliminary Test:

The preliminary estimate of the water solubility at 20.0 ± 0.5 °C was 7.94 x 10^-3g/L. The solution had a pH of 7.1.

 

Results – Definitive Test:

The mean peak areas relating to the standard and sample solutions are shown in Table 3:

 

Table 3:          Definitive Test – Peak Areas

Solution	Mean peak area
Standard 25.0 mg/L	2.137 x 10^5
Standard 25.7 mg/L	2.2121 x 10^5
Sample 1A	2.3794 x 10^5
Sample 1B	2.4606 x 10^5
Sample 2A	2.3130 x 10^5
Sample 2 B	2.5419 x 10^5
Sample 3A	2.3161 x 10^5
Sample 3B	2.6286 x 10^5

 

 

The concentration (g/L) of test item in the sample solutions is shown in Table 4:

 

Table 4:          Test item concentrations

Sample number	Time shaken at ~ 30°C (hours)	Concentration (g/L)	Mean concentration (g/L)	Solution pH
1A	72	1.11 x 10^-2	1.13 x 10^-2	7.4
1B	72	1.15 x 10^-2
2A	48	1.08 x 10^-2	1.13 x 10^-2	8.5
2B	48	1.18 x 10^-2
3A	24	1.08 x 10^-2	1.13 x 10^-2	7.0
3B	24	1.23 x 10^-2

 

Mean concentration  :          1.14 x 10^-2g/L at 20.0 ± 0.5 °C

Standard Deviation    :          1.31 x 10^-4g/L

 

 

Validation:

Recovery of analysis of the sample procedure was assessed and proved adequate for the test. At a nominal concentration of 10 mg/L, a mean percentage recovery of 90.3 % was obtained (range 82.1 to 98.2 %). Concentrations have not been corrected for recovery of analysis.

 

 

Discussion:

On completion of the equilibration period, the samples were clear and colourless with excess test item present. The solutions were centrifuged and filtered leaving a clear supernatant with no Tyndall beam observed.

 

As the water solubility was determined during the preliminary test to be above 10^-2g/L, the flask shaking test was performed.

 

All individual water solubility results were within ± 15% of the mean, thus satisfying the criteria specified in the guidelines..

Conclusions:

The water solubility of the test item has been determined to be 1.14 x 10-2 g/L at 20.0 ± 0.5 °C.

Executive summary:

EU Method A.6. – The water solubility of the test item was determined using the shake flask method.  The procedures employed were designed to be compatible with Method A.6., water solubility, of Commission Regulation (EC) No 440/2008 of 30 May 2008.

Following a preliminary test aliquots of test item (0.2 g) were added to three separate flasks containing purified water (200 ml each).  Each vessel was shaken at elevated temperature (200 rpm at 30.0 ± 1.0 °C) for 24, 48 and 72 hours respectively.  After shaking, each vessel was subject to static equilibration (20.0 ± 0.5 °C) 24 hours with swirling after approximately 3½ hours.  The solutions were centrifuged at 13,000 rpm for 15 minutes, filtered through 0.2 µm filters and analysed.  The concentration of test item in the sample solutions was determined by gas chromatography with nitrogen phosphorus detection (GC-NPD).

On completion of the equilibration period, the samples were clear and colourless with excess test item present.  The solutions were centrifuged and filtered leaving a clear supernatant with no Tyndall beam observed.  All individual water solubility results were within ± 15 % of the mean, thus satisfying the criteria specified in the guidelines.

The water solubility of the test item has been determined to be 1.14 x 10-2 g/L at 20.0 ± 0.5 °C.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

17 August 2017 - TBC

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Study was conducted in a comparable manner to international guidelines and in accordance with GLP. The validity criteria of the comparable guideline were met.

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 115

Version / remarks:

July 1995

Deviations:

no

Remarks:

The OECD 115 methodology was repeated several times (with no obvious deviations) as part of a determination of the critical micelle concentration of the test item.

Principles of method if other than guideline:

Determination of the surface tension of a series of solutions whose concentrations bracket the critical micellization concentration. Plotting of the graph of surface tension as a function of the logarithm of the concentration : the c.m.c. corresponds to a singular point on this curve.

GLP compliance:

yes (incl. QA statement)

Type of method:

other: Critical Micelle Concentration

Remarks:

CMC was assessed as a surogate water solubility value as the test item is surface active.

Key result

Remarks on result:

not determinable

Remarks:

The critical micelle concentration of the test item was could not be determined as no plateau of the surface tension was achieved.

Evaluation of Data:

The surface tension is given in mN/m (SI sub-unit).

 

Prior to preparation of the test item sample, the purified water was checked to ensure that it was within the water tolerance range of 0.990 to 1.010.

 

In order to calculate the surface tension, the mean test item sample dispersion reading was calculated from those values obtained from the apparatus considered to be on a consistent data plateau.

 

 

Results:

The readings, times and temperatures for the sample solutions are shown Table 2:

 

Table 2:          Surface Tension Plateau Readings

Sample	Time (mins)	Temperature (°C)	Reading (mN/m)	Mean surface tension (mN/m)
1	1216	20.4	40.0	40.0
	1225	20.4	40.0
	1233	20.6	40.0
8	1241	20.6	70.5	70.5
	1250	20.8	70.5
	1258	20.8	70.5
6	1284	20.8	69.0	69.0
	1293	21.0	69.0
	1301	21.0	69.0
7	1310	21.0	63.0	63.0
	1318	21.0	63.0
	1327	21.2	63.0
5	1340	21.2	55.0	55.0
	1351	21.2	55.0
	1360	21.2	55.0
4	1409	21.2	49.5	49.5
	1417	21.2	49.5
	1426	21.2	49.5
3	1435	21.2	50.0	50.0
	1443	21.2	50.0
	1452	21.4	50.0
2	1461	21.4	47.5	47.5
	1469	21.4	47.5
	1477	21.4	47.4

 

 

The concentration (mg/L), log₁₀of the concentration, surface tension and pH are shown in Table 3:

 

Table 3:          Concentration, surface tension dependence

Sample	Concentration (mg/L)	Log10concentration	Mean surface tension (mN/m)	pH
1	19.6	1.29	40.0	6.3
2	9.79	0.991	47.5	6.2
3	6.52	0.814	50.0	6.0
4	4.89	0.690	49.5	5.6
5	3.91	0.593	55.0	5.8
7	1.96	0.292	63.0	5.9
6	0.78	-0.106	69.0	6.0
8	0.39	-0.407	70.5	5.9

 

A plot of log₁₀concentration (mg/L) versus surface tension (mN/m) did not demonstrate a plateau in surface tension. As a consequence, a critical micelle concentration could not be determined.

 

 

Discussion:

The torsion balance was checked for accuracy using 0.500 g certified weight.

 

Samples 9 to 12 were not determined since the surface tension of samples 6 and 8 had levelled at approximately 70 mN/m and ether was not necessary to determine the additional samples. 

 

The CMC is an important characteristic of a surfactant. Before reaching the CMC, the surface tension changes greatly with the concentration of the surfactant. After reaching the CMC, the surface tension remains relatively constant or changes with a lower slope. The CMC is determined by establishing inflection points for pre-determined surface tension of surfactants in solution. Plotting the inflection point against the surfactant concentration provides the CMC by showing stabilization of phases.

 

The CMC is the concentration of a surfactant at which aggregates become thermodynamically soluble in an aqueous solution. Below the CMC there is not a high enough density of the surfactant to precipitate. Above the CMC, the solubility of the surfactant within the aqueous solution has been exceeded. Thus, the water solubility of a surfactant may be expressed in terms of the CMC.  

 

The surface tension of GDD water was checked throughout testing and was considered to be within acceptable limits. Therefore, no correction to the surface tension measurement was required. 

Conclusions:

The critical micelle concentration of the test item was could not be determined as no plateau of the surface tension was achieved.

Executive summary:

OECD 115 – The critical micelle concentration of the test item was sought using the ring method.  The procedures employed were designed to be compatible with OECD Guideline For the Testing of Chemicals, Technical Guideline 115, Surface Tension of Aqueous Solutions, as adopted by the Council on 27th July 1995.

Surface tension data on this test item⁽¹⁾ indicated that the test item meets the criteria for surface activity.  To reflect this finding, the critical micelle concentration of the test item was first sought as a surrogate water solubility value.  Critical micelle concentration was sought using repeated application of the OECD 115 method (non-harmonised ring method).  A saturated solution of test item in water was prepared, from which serial dilutions of test item was prepared.  Steady state surface tension values for each solution were obtained.  A plot of log₁₀concentration (mg/L) versus surface tension (mN/m) was prepared.

This plot did not demonstrate a plateau in surface tension.  As a consequence, a critical micelle concentration could not be determined.

⁽¹⁾Butler, R.  (2018).  EU Method A.5. N-(2-hydroxyethyl) dodecanamide: Determination of General Physico-Chemical Properties (unpublished report).  Report No: VW71MC

Description of key information

Water Solubility: 1.14 x 10 ^-2 g/l at 20 ºC.; EU Method A.4.; R. Butler (2018)

Key value for chemical safety assessment

Water solubility:

0.011 g/L

at the temperature of:

20 °C

Additional information

EU Method A.6. – The water solubility of the test item was determined using the shake flask method.  The procedures employed were designed to be compatible with Method A.6., water solubility, of Commission Regulation (EC) No 440/2008 of 30 May 2008.

Surface tension data on this test item⁽¹⁾ indicated that the test item meets the criteria for surface activity.  To reflect this finding, the critical micelle concentration of the test item was first sought as a surrogate water solubility value.  Critical micelle concentration was sought using repeated application of the OECD 115 method (non-harmonised ring method).  A saturated solution of test item in water was prepared, from which serial dilutions of test item was prepared.  Steady state surface tension values for each solution were obtained.  A plot of log₁₀concentration (mg/L) versus surface tension (mN/m) was prepared.  This plot did not demonstrate a plateau in surface tension.  As a consequence, a critical micelle concentration could not be determined.

Due to the measured concentration of a saturated solution of test item in water achieved during the critical micelle concentration study the shake flask method was thought to be the most appropriate method to determine the water solubility of the test item (this was verified by means of a guideline preliminary test).  Further, it was believed that the shake flask method was the more scientifically robust method to monitor potential surface interactions of the test item in solution.

Following a preliminary test aliquots of test item (0.2 g) were added to three separate flasks containing purified water (200 ml each).  Each vessel was shaken at elevated temperature (200 rpm at 30.0 ± 1.0 °C) for 24, 48 and 72 hours respectively.  After shaking, each vessel was subject to static equilibration (20.0 ± 0.5 °C) 24 hours with swirling after approximately 3½ hours.  The solutions were centrifuged at 13,000 rpm for 15 minutes, filtered through 0.2 µm filters and analysed.  The concentration of test item in the sample solutions was determined by gas chromatography with nitrogen phosphorus detection (GC-NPD).

On completion of the equilibration period, the samples were clear and colourless with excess test item present.  The solutions were centrifuged and filtered leaving a clear supernatant with no Tyndall beam observed.  All individual water solubility results were within ± 15 % of the mean, thus satisfying the criteria specified in the guidelines.

The water solubility of the test item has been determined to be 1.14 x 10^-2 g/L at 20.0 ± 0.5 °C.

⁽¹⁾ Butler, R.  (2018).  EU Method A.5. N-(2-hydroxyethyl) dodecanamide: Determination of General Physico-Chemical Properties (unpublished report).