Disodium hydrogen citrate

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2017-07-13 to 2017-07-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

522.98 g/L

Conc. based on:

test mat.

Incubation duration:

94 h

Temp.:

20 °C

pH:

>= 4.57 - <= 4.6

Measurements during Equilibration

The data which was acquired during equilibration time (flask 1A-C, days 1 – 4) is presented in the following table:

Table 3: Equilibration phase

Time [h] (flask)	Temperature [°C]	pH*	Dilution factor	Peak area [mAU*min]	Measured values [g/L]	QC recovery [%]	Difference to previous sample [%]
23 1A	20.0	4	1000	4.9378	489.43	100.5**	-
				5.0515		99.8**
47 (1B)	19.9	4	1000	5.2439	523.50	99.1**	+7.0
				5.2486		98.4**
71 (1C)	20.1	4	1000	5.2695	533.11	97.7**	+1.8
				5.2588		97.0**
94 (1C)	20.0	4	2000	2.8899	517.21	none***	-3.0
				2.8684		none***

* pH during equilibration phase was tested using indicator paper

** Evaluated using calibration 1

*** Evaluated using calibration 2

As no more rising tendency was observed between samplings at 71 h and 94 h, the plateau was considered reached and sampling of flasks 2-6 was performed.

Measurements at Plateau

Table 4: Measurements at the plateau

Flask	Temperature [°C]	pH*	Dilution factor	Peak area [mAU-min]	Measured values [g/L]	QC recovery [%]
Blank	19.7	7.89		0.0138	< LOQ	103.2**
				0.0118		103.2**
2	19.6	4.60	2000	3.0850	536.29	103.2**
				3.0761		103.2**
3	19.6	4.57	2000	3.0921	540.30	103.2**
				3.1152		103.2**
4	19.5	4.60	2000	3.0577	533.67	103.2**
				3.0732		103.2**
5	19.5	4.60	2000	2.8000	495.30	103.2**
				2.8888		103.2**
6	19.6	4.59	2000	2.9276	509.36	103.2**
				2.9231		103.2**

* pH at the plateau was tested using a calibrated pH meter

** Evaluated using calibration 2

The measurements of flasks 2-6 were used for the calculation of the mean.

Table 5: Measurements used for calculation of solubility

Flask	Concentration [g/L]	Total Mean [g/L]	Total Standard Deviation [g/L] (Relative standard deviation [%])
2	536.29	522.98	19.64 (3.8)
3	540.30
4	533.67
5	495.30
6	509.36

Conclusions:

The water solubility of the test item was determined to be 522.98 ± 19.64 g/L. The result is also applicable for the water free form of the test item.

Executive summary:

A study was conducted according to OECD TG 105 and Regulation (EC) No. 260/2014 method A.6 in order to determine the water solubility of the test item by using shake flask method. The analytical determination was done by using HPLC method (reference 4.8-1). Equilibration time can be considered as approximately 4 days (94 h), as the measured values after 71 h and 94 h did not give significantly different values. All replicates showed good correspondence. Standard deviation of the five flasks which were used for the calculation of water solubility at the plateau was 19.64 g/L, corresponding to a relative standard deviation of 3.8 %. The pH value was 4.57 – 4.60 in all five flasks, the test temperature was in the acceptable range with 19.5 – 19.6 °C over the test duration (measured in the liquid at sampling time points). The water solubility of the test item was determined to be 522.98± 19.64 g/L. The result is also applicable for the water free form of the test item.

Description of key information

The water solubility of the test item was determined to be 522.98 ± 19.64 g/L.

Key value for chemical safety assessment

Water solubility:

522.98 g/L

at the temperature of:

20 °C

Additional information

A study was conducted according to OECD TG 105 and Regulation (EC) No. 260/2014 method A.6 in order to determine the water solubility of the test item by using shake flask method. The analytical determination was done by using HPLC method (reference 4.8-1). Equilibration time can be considered as approximately 4 days (94 h), as the measured values after 71 h and 94 h did not give significantly different values. All replicates showed good correspondence. Standard deviation of the five flasks which were used for the calculation of water solubility at the plateau was 19.64 g/L, corresponding to a relative standard deviation of 3.8 %. The pH value was 4.57 – 4.60 in all five flasks, the test temperature was in the acceptable range with 19.5 – 19.6 °C over the test duration (measured in the liquid at sampling time points). The water solubility of the test item was determined to be 522.98 ± 19.64 g/L.