Registration Dossier

Administrative data

Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26-27 May 2015
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
Deviations:
yes
Remarks:
A distinct saturation limit, as to be determined according to EU A.6, could not be identified for the main constituent of the test substance. Analytical method for quantification: Quantitative 1H-NMR using an internal standard
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
Deviations:
yes
Remarks:
A distinct saturation limit, as to be determined according to EU A.6, could not be identified for the main constituent of the test substance. Analytical method for quantification: Quantitative 1H-NMR using an internal standard
Principles of method if other than guideline:
Deviations: Due to extremely hydrophilic and hygroscopic nature of the test material, the experimental procedure could not be performed in full compliance to the guidelines. A distinct saturation limit, as to be determined according to EU A.6, could not be identified for the main constituent of the test substance.
Analytical method for quantification: Quantitative 1H-NMR using an internal standard
GLP compliance:
no
Type of method:
flask method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): reaction mass of tetra (potassium and sodium) (2R, 3R)-2-hydroxy-3-(phosphonatooxy) succinate and tetra (potassium and sodium) (2S,3S)-2-hydroxy-3-(phosphonatooxy) succinate
- Lot/batch No.: 010-2065

Results and discussion

Water solubility
Water solubility:
> 10 g/L
Temp.:
25 °C
pH:
9 - 9.2
Remarks on result:
other: The substance and its main constituents are considered to be very soluble. The total substance dissolves in water up to at least 40% w/w (at 25 °C). The main constituents are soluble in water in amounts of at least 67% w/w at this temperature.

Any other information on results incl. tables

Test substance solubility:

Generally, the test item solubility was excellent and up to 40% w/w optically clear solutions were obtained. For concentrations of 50% and higher, small amounts of insoluble material remained at the bottom of the glass after equilibration for 24h at 25 °C.

Solubility of the main constituent:

The turbidity occuring at concentration exceeding 40% w/w was assumed to be attributed to small amounts of the impurities described (especially potassium sodium tartrate). The solubility limit of the main constituent was expected to exceed 40% w/w significantly. Therefore a highly concentrated specimen was additionally investigated, which showed the presence of insoluble impurities concerning the content of the main constituent in the dissolved fraction. Even in contact with small amounts of water, the test material was sufficiently hydrated to change its aggregate state from solid to liquid. For concentrations of 80% w/w and more of the test material, a highly viscous, syrupy to tacky oil, is formed. Hence, the 3 highest sample solutions prepared (60, 70, 80 % w/w) have been investigated using NMR. Insoluble material residues were removed by centrifugation at 13000 rpm for 40 minutes. Approx. 150 mg of the clear upper layer were analyzed by a quantitative 1H-NMR technique using the internal standard sodium acetate as approx. 1% w/w stock solution in deuterium oxide.

The 80% w/w solution was of very high viscosity (> 3000 mPa s). Higher concentrations of substance were difficult for investigation due to high viscosity and related solid-liquid phase separation problems.

Substance concentration 010-2065 (approx. 84% w/w of main constituents)

60%

70%

80%

Concentration of main constituents (%w/w) theor.

50.70%

59.15%

67.60%

Concentration of main constituents found (%w/w)

50.45%

59.63%

68.03%

Main constituents found/main constituents theor. (%)

99.5%

100.8%

100.6%

As it can be derived from the table above, the match of theoretical and actual concentrations is excellent. Deviations are in the range of an experimental accuracy (ca. 1%). The study was performed without adjustement of pH. The main constituent is considered to be present in a fully deprotonated state at this value.

The main constituent is exclusively present in a dissolved state. It does not contribute to the formation of insoluble parts. It is not possible to determine an upper solubility limit for concentrations significantly higher than 68% w/w of the main constituents what corresponds to 80% w/w of the test substance. It can be concluded that the test material in its entirety shows very good water solubility.

The substance itself and its main constituents are considered to be very soluble in water. The total substance dissolves clearly in water up to at least 40% w/w (at 25 °C). The main constituents of the substance are soluble in water in amounts of at least 67% w/w at this temperature.

Applicant's summary and conclusion