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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:

Experimental dates : August and September 2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

As the test substance is a surfactant, the CMC was determined rather than the standard solubility.

Qualifier:

no guideline available

Principles of method if other than guideline:

The method used in this study to determine the Critical Micelle Concentration, is a drop tensiometer, method describe in the book “Surfactants and interfacial Phenomena”, from Milton J. Rosen and Joy T. Kunjappu (Wiley). The surface tension is determined by the software for various concentrations. The surfactant concentration after each measurement is automatically increased and the measurement procedure is repeated. Below the critical micelle concentration, the surface tension decreases when the concentration of surfactant increases. Once the CMC has been reached or exceeded, the surface tension remains constant. The critical micelle concentration is determined by the slope change of the surface tension curve. It is determined by the software using the curve derivative.

GLP compliance:

no

Type of method:

other: CMC by drop tensiometer

Water solubility:

0.036 g/L

Conc. based on:

other: CMC

Temp.:

21 °C

pH:

ca. 7

Surface tension of water before measurement = 71.7 mN/m

Critical Micelle Concentration = 0.036 g/L

Surface tension at CMC = 30.4 mN/m

Increasement of surface tension after 1g/ L corresponds to non solubility observed during preparation of solutions of concentration over 1g/ L. This behavior doesn’t impact the determination of the CMC of the sample.

Executive summary:

As the test substance is a surfactant, the CMC was determined rather than the standard solubility.

The drop tensiometer was used to measure the surface tension for different solution concentrations.

The CMC was deduced from the graph as 0.036 g/L (36 mg/L).

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

06 August 2008 - 20 August 2008

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

The test substance is a surfactant; the measured solubility exceeds the CMC.

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

Principles of method if other than guideline:

not relevant

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Specific details on test material used for the study:

Expiry date April 10, 2009

Water solubility:

33 g/L

Temp.:

20 °C

pH:

>= 5.8 - <= 6.5

sample No.	Shaking time at 30ºC	Concentration analyzed (mg/L)	Concentration calculated (g/L)	Water solubility calculated (rounded) (g/L)
1	72	816,92	32,68	33,28 SD=1,66
2		795,408	31,82
3	48	833,457	33,34
4		823,046	32,92
5	24	810,802	32,43
6		913,022	36,52

The saturation mass concentration is calculated from the bold values

Conclusions:

Very soluble.

Executive summary:

The purpose of this study was to evaluate the solubility of test item in water according to OECD 105 and EU A6 guidelines.

The water solubility of the substance at 20ºC was determined to be 33.3 g/L (standard deviation ±1.66g/L) using the flask shaking method.

Reference 3

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

29-JUL-09 to 09-APR-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

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

Principles of method if other than guideline:

not relevant

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Remarks on result:

not determinable

Details on results:

Please see section Remarks on results including tables and figures.

The saturation concentration of the substance at 30 °C was estimated by a simplified flask method in the preliminary test to be higher than 10^-2g/L. Therefore, the flask shaking test was performed.

 

After a shaking time of 24 hours, 48 hours and 72 hours, respectively, at 30 °C, the samples were equilibrated for another 24 hours at 20 °C. Afterwards, the samples were centrifuged, diluted and analyzed by LC-MS/MS.

 

The tests led to inconsistent values. During preparation of test item solutions the formation of emulsions was observed. The test item solutions were turbid or the solutions were separated into two phases.

 

Summaries of obtained results for the different pH values are given in Table 2, Table 4 and Table 6 (see below).

 

A typical chromatogram of a standard solution is given in Figure 1(see attachment).A typical chromatogram of a sample solution after 72 hours of incubation at pH 7.0 is shown in Figure 2(see attachment). A LC chromatogram of a blank solution is shown in Figure 3(see attachment). The calibration curve and data are shown in Figure 4 and in Table 7(see attachment). The r² fit was 0.9941 (optimum 1.0000). This reflects the linearity of the LC-MS/MS -system within the calibration range of 6.78 ng/mL to 203.4 ng/mL of the test item.

Table 1       Data of the Performance of the Solubility Test at pH 5.0

Sample Solution No.	P1-1	P2-1	P1-2	P2-2	P1-3	P2-3
Weighed sample of the test item [mg]	4.445	4.395	4.301	4.192	4.819	4.910
Added volume of buffer solution pH 5.0	10	10	10	10	10	10
Agitation time at 30 °C [hours]	72	72	48	48	24	24
pH value of test item solution at the end of the test	4.73	5.02	5.03	5.08	5.04	5.01
Dilution factor before quantification	1000	1000	1000	1000	1000	1000
Centrifugation [g]	32049	32049	32049	32049	32049	32049

 

 

Table 2       Results of the Water Solubility of the substance at pH 5.0

Sample No.	Shakingtime at30 °C	Concentration analyzed	Concentration calculated	Water solubility calculated (rounded)
		[µg/L]	[mg/L]	[mg/L]
P1-1	72	101.729	101.73
P2-1		110.236	110.24
P1-2	48	74.982	74.98	108.4
P2-2		132.886	132.89	SD =21.76
P1-3	24	99.514	99.51
P2-3		131.272	131.27

 

 

SD = standard deviation

Table 3       Data of the Performance of the Solubility Test at pH 7.0

Sample Solution No.	P3-1	P4-1	P3-2	P4-2	P4-3	P4-3
Weighed sample of the test item [mg]	7.035	6.322	5.762	8.270	6.415	7.378
Added volume of buffer solution pH 7.0	10	10	10	10	10	10
Agitation time at 30 °C [hours]	72	72	48	48	24	24
pH value of test item solution at the end of the test	6.65	7.03	7.02	7.03	6.99	7.03
Dilution factor before quantification	1000	1000	1000	1000	1000	1000
Centrifugation [g]	32049	32049	32049	32049	32049	32049

 

 

Table 4       Results of the Water Solubility of the substance at pH 7.0

Sample No.	Shakingtime at30 °C	Concentration analyzed	Concentration calculated	Water solubility calculated (rounded)
		[µg/L]	[mg/L]	[mg/L]
P3-1	72	320.882	320.88
P4-1		246.639	246.64
P3-2	48	233.734	233.73	320.2
P4-2		518.695	518.69	SD =104.80
P3-3	24	331.155	331.16
P4-3		270.150	270.15

 

 

SD = standard deviation

Table 5       Data of the Performance of the Solubility Test at pH 9.0

Sample Solution No.	P5-1	P6-1	P5-2	P6-2	P5-3	P6-3
Weighed sample of the test item [mg]	34.73	33.36	33.52	31.77	32.13	33.82
Added volume of buffer solution pH 9.0	10	10	10	10	10	10
Agitation time at 30 °C [hours]	72	72	48	48	24	24
pH value of test item solution at the end of the test	8.98	8.78	8.92	8.97	8.87	9.03
Dilution factor before quantification	1000	1000	1000	1000	1000	1000
Centrifugation [g]	32049	32049	32049	32049	32049	32049

 

 

Table 6       Results of the Water Solubility of the substance at pH 9.0

Sample No.	Shakingtime at30 °C	Concentration analyzed	Concentration calculated	Water solubility calculated (rounded)
		[µg/L]	[mg/L]	[mg/L]
P5-1	72	8.513	8.51
P6-1		706.067	706.07
P5-2	48	< 6.78	6.78	< 123.6
P6-2		< 6.78	6.78	SD =285.34
P5-3	24	< 6.78	6.78
P6-3		< 6.78	6.78

 

 

SD = standard deviation

 

Conclusions:

The tests led to inconsistent values. During preparation of test item solutions the formation of an emulsion were observed. This turbidity could be caused by formation of micelles of the test item
in aqueous solutions, hence a method based on the critical micelle concentration (CMC) method is advised, but beyond the scope of this study.

Executive summary:

The purpose of this study was to evaluate the solubility of test item in aqueous solutions at pH 5.0, 7.0 and 9.0, which is specified by the saturation mass concentration of the test item in aqueous solutions at a given temperature.

The determination of the water solubility of test item was performed according to the EEC Directive 92/69, A.6 “Water Solubility” (1992) and the OECD guideline No. 105,“Water Solubility” (1995) using the flask shaking method.

The tests led to inconsistent values. During preparation of test item solutions the formation of an emulsion were observed. This turbidity could be caused by formation of micelles of the test item in aqueous solutions, hence a method based on the critical micelle concentration (CMC) method is advised, but beyond the scope of this study.

Reference 4

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Experimental dates : August and September 2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

As the test substance is a surfactant, the CMC was determined rather than the standard solubility.

Qualifier:

no guideline available

Principles of method if other than guideline:

The method used in this study to determine the Critical Micelle Concentration, is a drop tensiometer, method describe in the book “Surfactants and interfacial Phenomena”, from Milton J. Rosen and Joy T. Kunjappu (Wiley). The surface tension is determined by the software for various concentrations. The surfactant concentration after each measurement is automatically increased and the measurement procedure is repeated. Below the critical micelle concentration, the surface tension decreases when the concentration of surfactant increases. Once the CMC has been reached or exceeded, the surface tension remains constant. The critical micelle concentration is determined by the slope change of the surface tension curve. It is determined by the software using the curve derivative.

GLP compliance:

no

Type of method:

other: CMC by drop tensiometer

Water solubility:

0.196 g/L

Conc. based on:

other: CMC

Temp.:

21 °C

Surface tension of water before measurement = 71.3 mN/m

Critical Micelle Concentration = 0.196 g/L

Surface tension at CMC = 41.5 mN/m

The small "depression" observed around the CMC (0,3 g/ L) can be associated to the presence of tensioactive impurities.

Executive summary:

As the test substance is a surfactant, the CMC was determined rather than the standard solubility.

The drop tensiometer was used to measure the surface tension for different solution concentrations.

The CMC was deduced from the graph as 0.196 g/L (196 mg/L).

Description of key information

High apparent solubility, with formation of emulsions.

Critical micelle concentration (CMC) = 36 mg/L (at 21°C)

Key value for chemical safety assessment

Water solubility:

36 mg/L

at the temperature of:

21 °C

Additional information

An experimental study (Harlan 2008) was performed according to OECD 105, flask method and under GLP conditions. Validity criteria were fulfilled, and the substance was found to be very soluble with 33.3 g/L.

However, in second study (Harlan 2010) using also the flask method, the tests led to inconsistent values. During preparation of test item solutions the formation of emulsions was observed. This turbidity could be caused by formation of micelles of the test item in aqueous solutions.

This is consistent with the low surface tension, presented under IU section 4.10.

Therefore the 2008 study was considered as not reliable.

The determination of the critical micelle concentration (CMC) was therefore considered as more relevant. In the Processium 2019 study, the result was found very low (36 mg/L). This is considered as the key value for purpose of CSA.

As a conclusion, the 2008 result suggests that stable emulsions can be formed.