L-cystine dihydrochloride

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 2018-02-06 to 2019-03-25

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:

1 005.8 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

5 g/L

Incubation duration:

>= 24 - <= 72 h

Temp.:

19.5 °C

pH:

1.6

Preliminary test

Preliminary Study

Added volume (mL)	0.1	0.5	1	2	10
Approx. solubility (g/L)	>1000	1000 - 200	200 - 100	100 - 50	50 - 10
Dissolution	no	no	no	no	no

As undissolved particles were visible in the lowest concentration (10 mL H2O), the experiment was continued. 100.2 mg of the test item were mixed with 100 mL water and the mixture was shaken for 94 hours at room temperature. Undissolved particles could be detected in the flask.
Additionally, 10.0 mg of the test item were mixed with 1000 mL water and the mixture was shaken for 22 hours. After this time, no undissolved particles could be detected in the flask; therefore, solubility was estimated as < 1 g/L.

Main test

The measurements on day 3 (flasks 2 – 6) were included in the calculation of the solubility of the test item in water.

Measurements used for calculation of solubility

Flask	Temperature (°C)	pH*	Dilution factor	Peak area (mAU*min)	Measured values*** (mg/L)	Total mean (mg/L)	Total SD (mg/L) Relative SD (%)
Blank	20.0	7**	-	n.a. n.a.	-
2	19.5	1.58	20	16.4283 15.9375	1035.5	1005.8	20.8 2.1
3	19.5	1.64	20	15.3602 15.2777	980.5
4	19.5	1.63	20	15.6986 15.9192	1011.7
5	19.5	1.62	20	16.0523 15.4610	1008.4
6	19.5	1.63	20	15.5639 15.4631	992.9

*pH at the plateau was tested using a calibrated pH meter
** tested with pH paper
***evaluated using sensitivity correction 96.1 %
n.a. no signal was detected
SD = Standard Deviation

Mean at the plateau is 1005.8 ± 20.8 mg/L.

Conclusions:

The water solubility of the test item at 19.5 °C and pH = 1.6 was determined to be 1005.8 ± 20.8 mg/L.

Executive summary:

The water solubility was determined according to OECD 105 and Regulation (EC) No. 440/2008 method A.6 using the shake flask method with HPLC analysis. The solubility of the test item was estimated to be < 1 g/L in the solubility pre-test. According to the guideline, the flask method was used for the determination of the solubility of the test item in water. 5 g/L nominal concentration was chosen. Three flasks 1A - 1C with the same loading rate were used during equilibration. Seven vessels (flasks blank, 1C (for the sampling point 72 h) and 2 – 6) were set onto the shaking apparatus immediately. After 24 h, flask 1B (for the sampling point 48 h) and after 48 h, flask 1A (for the sampling point 24 h) were set on the shaker and all flasks were shaken for further 24 h at room temperature (20.0 ± 5 °C). Then, flasks 1A - 1C were taken from the shaker, samples were taken, membrane filtered and analysed. The samples were diluted before the analysis (two dilutions). The pH of each sample was recorded. The water solubility of the test substance was determined to be 1005.8 ± 20.8 mg/L (95 % confidence interval) at 19.5 °C (pH = 1.6).

Description of key information

The water solubility of the test item at 19.5 °C and pH = 1.6 was determined to be 1005.8 ± 20.8 mg/L.

Key value for chemical safety assessment

Water solubility:

1 005.8 mg/L

at the temperature of:

19.5 °C

Additional information

The water solubility was determined according to OECD 105 and Regulation (EC) No 440/2008 method A.6 using the shake flask method with HPLC analysis (reference 4.8-1). The solubility of the test item was estimated to be < 1 g/L in the solubility pre-test. According to the guideline, the flask method was used for the determination of the solubility of the test item in water. 5 g/L nominal concentration was chosen.
Three flasks 1A - 1C with the same loading rate were used during equilibration. Seven vessels (flasks blank, 1C (for the sampling point 72 h) and 2 – 6) were set onto the shaking apparatus immediately. After 24 h, flask 1B (for the sampling point 48 h) and after 48 h, flask 1A (for the sampling point 24 h) were set on the shaker and all flasks were shaken for further 24 h at room temperature (20.0 ± 5 °C). Then, flasks 1A - 1C were taken from the shaker, samples were taken, membrane filtered and analysed. The samples were diluted before the analysis (two dilutions). The pH of each sample was recorded. The water solubility of the test substance was determined to be 1005.8 ± 20.8 mg/L (95 % confidence interval) at 19.5 °C (pH = 1.6).