Reaction mass of sodium hydrogen N-(1-oxooctadecyl)-L-glutamate and sodium hydrogen N-(1-oxohexadecyl)-L-glutamate

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 April 2008 and 19 September 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with GLP and agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Signature: 15/10/2007; Date of Inspection: 21/08/2007

Type of method:

flask method

Water solubility:

3.49 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

5.01 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

4.26 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

10 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

6.02 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

20 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

7.28 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

30.2 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

7.74 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

31.4 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

11.6 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

50 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

20 g/L

Conc. based on:

other: Concentration of main constituent 1.

Loading of aqueous phase:

101 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

0.161 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

5.01 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Key result

Water solubility:

0.186 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

10 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

0.35 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

20 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

1.36 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

31.5 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

0.968 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

30.2 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

1.26 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

31.4 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Key result

Water solubility:

5.13 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

50 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Water solubility:

7.1 g/L

Conc. based on:

other: Concentration of main constituent 2.

Loading of aqueous phase:

101 g/L

Temp.:

20 °C

pH:

> 7.3 - < 7.5

Remarks on result:

not determinable

Remarks:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded.

Details on results:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded. The concentration of the two main components of the test material at the various loading rates is shown below:
Loading Rate (g/l) 5.01, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 3.49 concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.161
Loading Rate (g/l) 10.0, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 4.26, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.186
Loading Rate (g/l) 20.0, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 6.02, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.350
Loading Rate (g/l) 31.5, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 7.28, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 1.36
Loading Rate (g/l) 30.2, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 7.28, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.968
Loading Rate (g/l) 31.4, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 7.74, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 1.26
Loading Rate (g/l) 50.0, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 11.6, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 5.13
Loading Rate (g/l) 101, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 20.0, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 7.10.

Preliminary test

The preliminary estimate of water solubility is shown in the following table:

Sample Number	Loading Rate (g/l)	Concentration Main Constituent 1 Corrected for Recovery (g/l)	Concentration Main Constituent 2 Corrected for Recovery (g/l)	Solution pH
A	5.01	3.49	0.161	7.3
B	10.0	4.26	0.186	7.2
C	20.0	6.02	0.350	7.4

Concentration range:    3.49 to 6.02 g/l of Main Constituent 1
                                   0.161 to 0.350 g/l of Main Constituent 2

Definitive test

The mean peak areas relating to the standard and sample solutions are shown in the following table:

Solution	Mean Area Main Constituent 1	Mean Area Main Constituent 2
Standard 51.6 mg/l	262.245	405.191
Standard 54.2 mg/l	246.595	438.948
Sample 1A	311.620	42.789
Sample 1B	309.676	42.563
Sample 2A	311.354	30.642
Sample 2B	310.145	30.268
Sample 3A	338.791	39.832
Sample 3B	321.835	39.550
Standard 50.0 mg/l	283.199	510.038
Standard 50.1 mg/l	283.903	510.701
Sample 4A	292.891	103.441
Sample 4B	291.843	103.334
Sample 5A	252.309	71.880
Sample 5B	250.054	71.084

 

The concentration (g/l) of the two components in the sample solutions is shown in the following table:

Sample Number	Time Shaken at ~ 30ºC (hours)	Time Equilibrated at 20ºC (hours)	Concentration Main Constituent 1 (g/l)	Concentration Main Constituent 2 (g/l)	Solution pH
1A	24	117½	6.47	0.536	7.3
1B	24	117½	6.43	0.533
2A	48	117½	6.46	0.384	7.4
2B	48	117½	6.44	0.379
3A	72	117½	7.03	0.499	7.4
3B	72	117½	6.68	0.496
4A	24	24	10.3	2.03	7.5
4B	24	24	10.3	2.03
5A	24	24	17.8	2.82	7.5
5B	24	24	17.6	2.79

The mean concentrations (g/l) of the two components in the samples corrected for recovery are shown in the following table:

Sample Number	Loading Rate (g/l)	Mean Concentration Main Constituent 1 (g/l)	Mean Concentration Main Constituent 1 Corrected for Recovery (g/l)	Mean Concentration Main Constituent 2 (g/l)	Mean Concentration Main Constituent 2 Corrected for Recovery (g/l)
1	31.5	6.45	7.28	0.535	1.36
2	30.2	6.45	7.28	0.382	0.968
3	31.4	6.86	7.74	0.498	1.26
4	50.0	10.3	11.6	2.03	5.13
5	101	17.7	20.0	2.80	7.10

 

Validation

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0 to 250 mg/l. This was satisfactory with correlation coefficients of 0.998 and 1.00 being obtained for main constituent 1 and 2 components respectively.

Procedural recovery determinations were performed and are shown in the following table:

Component	Nominal Concentration (mg/l)	Recovery (%)	Mean Recovery (%)
Main Constituent 1	50	84.4 to 93.9	88.6
Main Constituent 2	50	36.7 to 41.6	39.5

Since the sample solution was colloidal, centrifugation and filtration were necessary to provide a clear solution for analysis. The low recovery of main constituent 2 component was thought to be due to loss on filtration. As the recovery analysis was demonstrated to be consistent, it was deemed to be acceptable to correct the water solubility data for recovery. Therefore, the sample analysis procedure was considered to be adequate for test.

Conclusions:

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded. The concentration of the two main components of the test material at the various loading rates is shown below:
Loading Rate (g/l) 5.01, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 3.49, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.161;
Loading Rate (g/l) 10.0, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 4.26, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.186;
Loading Rate (g/l) 20.0, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 6.02, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.350;
Loading Rate (g/l) 31.5, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 7.28, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 1.36;
Loading Rate (g/l) 30.2, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 7.28, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 0.968;
Loading Rate (g/l) 31.4, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 7.74, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 1.26;
Loading Rate (g/l) 50.0, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 11.6, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 5.13;
Loading Rate (g/l) 101, concentration of Main constituent 1(g/l at 20.0 ± 0.5 °C) 20.0, concentration of Main constituent 2 (g/l at 20.0 ± 0.5 °C) 7.10.

Executive summary:

The water solubility of the test material was based on the flask method, Method A6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The water solubility of the test material has been demonstrated to be related to the amount of test material loaded. The concentration of the two main components of the test material at the various loading rates is shown in the following table:

Loading Rate (g/l)	Concentration of Main constituent 1 (g/l at 20.0 ± 0.5ºC)	Concentration of Main constituent 2 (g/l at 20.0 ± 0.5ºC)
5.01	3.49	0.161
10.0	4.26	0.186
20.0	6.02	0.350
31.5	7.28	1.36
30.2	7.28	0.968
31.4	7.74	1.26
50.0	11.6	5.13
101	20.0	7.10

Description of key information

Soluble (solubility of the test material is dependent on loading rate); at a Loading Rate of 5.01 g/L, concentration of main constituent 1 = 3.49 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 0.161 g/L at 20.0 ± 0.5 °C; at a Loading Rate of 101 g/L, concentration of main constituent 1 = 20.0 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 7.10 g/L at 20.0 ± 0.5 °C, EU Method A.6, Butler & White (2008).

Key value for chemical safety assessment

Water solubility:

27.1 g/L

at the temperature of:

20 °C

Additional information

The water solubility of the test material was determined in the key study (Butler & White 2008), which was performed in accordance with EU Method A.6 using the flask method. The study was performed under GLP conditions. The data was assigned a reliability score of 1 in accordance with the principles for assessing data quality as defined in Klimisch et al. (1997).

 

The water solubility was found to be related to the loading rate of the test material. The concentrations of the two main constituents of the multi-constituent substance at various loading rates are reported below:

Loading Rate 5.01 g/L: concentration of main constituent 1 = 3.49 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 0.161 g/L at 20.0 ± 0.5 °C;

Loading Rate 10.0 g/L: concentration of main constituent 1 = 4.26 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 0.186 g/L at 20.0 ± 0.5 °C;

Loading Rate 20.0 g/L: concentration of main constituent 1 = 6.02 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 0.350 g/L at 20.0 ± 0.5 °C;

Loading Rate 31.5 g/L: concentration of main constituent 1 = 7.28 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 1.36 g/L at 20.0 ± 0.5 °C;

Loading Rate 30.2 g/L: concentration of main constituent 1 = 7.28 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 0.968 g/L at 20.0 ± 0.5 °C;

Loading Rate 31.4g/L: concentration of main constituent 1 = 7.74 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 1.26 g/L at 20.0 ± 0.5 °C;

Loading Rate 50.0 g/L: concentration of main constituent 1 = 11.6 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 5.13 g/L at 20.0 ± 0.5 °C;

Loading Rate 101 g/L: concentration of main constituent 1 = 20.0 g/L at 20.0 ± 0.5 °C and concentration of main constituent 2 = 7.10 g/L at 20.0 ± 0.5 °C.

An overall water solubility of 27.1 g/l (sum of two components [1: 20 g/L, 2: 7.1 g/L]) has been used as the key value for chemical safety assessment. This represents the maximum measured solubility at the loading rate of 101 g/L.