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Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 - 25 April 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose for cross-reference:
reference to other study
Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 - 26 January 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 105 (Water Solubility)
Version / remarks:
1995
Deviations:
yes
Remarks:
see principles of method if other than guideline
Qualifier:
according to guideline
Guideline:
EU Method A.6 (Water Solubility)
Version / remarks:
Regulation (EC) No 440/2008
Deviations:
yes
Remarks:
see principles of method if other than guideline
Principles of method if other than guideline:
Due to very high water solubility of the test item, estimated in a preliminary test, a modified TG OECD 105 design was conducted. Instead of equilibrating large amounts of test item (about five times in excess) with water by stirring over several days and subsequently separating the test item from the saturated solution, water was added in a stepwise procedure to a defined amount of test item until complete dissolution occurred.
GLP compliance:
yes (incl. QA statement)
Type of method:
flask method
Key result
Water solubility:
>= 511 g/L
Conc. based on:
test mat. (dissolved fraction)
Temp.:
23 °C
pH:
7.5
Details on results:
The preliminary test indicated a water solubility of >=500 g/L, as 0.1 g were completely dissolved in 0.2 mL of ultra-pure water.

Main test
The results are given in the table in the next section. The water solubility was determined as the mean of the replicates analysed with HPLC. As this method does not ensure complete saturation of the solution, it is given as minimum value in mass per volume of solution. The test is satisfactory, if the concentrations of the three vessels do not differ by more than 15%.

HPLC determinations:

 Test vessel  pH  Analysed concentration A (g/L)   Analysed concentration B (g/L)  Mean (g/L)
 No. 1  7.5  501  516  509
 No. 2  7.5  520  516  518
 No. 3  7.5  503  507  505
       Overall Mean  511

The concentrations of the three vessels differed by 3% (validity criterion given by OECD is met).

Conclusions:
The water solubility of a-Ketoglutarate disodium salt (CAS no. 305-72-6) was determined according to a modified TG OECD 105 design.
The water solubility of the test item at 23°C was >=511 g/L. The pH of the aqueous samples was 7.5.
Executive summary:

The water solubility of a-Ketoglutarate disodium salt (CAS no. 305-72-6) was determined according to a modified TG OECD 105 design.

To this end, increasing volumes of water were added in a stepwise procedure, to approximately 1 g of the test item at 22 ± 2 °C until complete dissolution, which occurred after addition of 1.4 mL of water. The concentration of test item was subsequently determined by HPLC with UV detection. The determined water solubility of a-Ketoglutarate disodium salt is >=511 g/L at pH 7.5 and at 23 °C.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Version / remarks:
1995
Deviations:
yes
Remarks:
see "Principles of method if other than guideline"
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient - Shake Flask Method)
Version / remarks:
Regulation (EC) No 440/2008
Deviations:
yes
Remarks:
see "Principles of method if other than guideline"
Principles of method if other than guideline:
The test was not performed with the non-charged species, as the amount of non-charged species in the environmentally relevant pH range of 5 to 9 is negligible. The test was conducted at a pH of ca. 6.25, were the once and twice negatively charged species are present in equal parts.
GLP compliance:
yes (incl. QA statement)
Type of method:
flask method
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 2-oxoglutarate
EC Number:
206-167-8
EC Name:
Disodium 2-oxoglutarate
Cas Number:
305-72-6
Molecular formula:
C5H6O5.2Na
IUPAC Name:
disodium 2-oxopentanedioate
impurity 1
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Oxidane
Test material form:
solid: crystalline
Remarks:
Crystalline powder
Details on test material:
Batch No: 14152300
Storage: 15 – 25 °C

Study design

Analytical method:
high-performance liquid chromatography

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
< -1.07
Temp.:
23 °C
pH:
7
Remarks on result:
other: The determined log POW values were < -1.07 for all three volume ratios and all replicates. Std. deviation from six determinations: ± 0.001.
Details on results:
Calculation method
The log Pow of the test item was calculated to be -2.08 using EPI Suite™ v4.10, KOWWIN v1.68.
KOWWIN only calculates the log Pow of the uncharged molecule, but the test item is ionisable. However, in the environmentally relevant pH range of pH 5 to 9, the amount of non-charged species is negligible. Instead, the twice negatively charged species dominate. Therefore, an even lower log Pow than -2.08 is expected.

Flask method
The determined log Pow values were <-1.07 for all three volume ratios and all replicates. For each replicate, the mass balance calculation showed that the experiment was reliably conducted, as the recovery rates ranged from 98% to 99%.
The log Pow of the test item is given as the mean value of all measurements. Detailed results are given in the table in the field 'Any other information on results incl. tables'.

Any other information on results incl. tables

Ratio n-octanol:water (v:v)

  Analysed concentration

n-octanol (mg/L)

  Analysed concentration water (mg/L)      Pow   log Pow    pH 
 1:4   <150   1775   <0.0846   <-1.07    7.0
 1:4   <150   1767   <0.0850   <-1.07    7.0
 1:9   <150   1772   <0.0847   <-1.07    7.0
 1:9   <150   1777   <0.0845   <-1.07    7.0
 1:19   <150   1771   <0.0848   <-1.07

   7.0

1:19   <150   1771 <0.0848   <-1.07    7.0
 Mean        <-1.07  

Further remarks

The result obtained in this study is in line with the predicted log Pow value of -2.08 for the uncharged molecule (EPI Suite™ v4.11, KOWWIN v1.68). A more precise determination was prevented by the limit of quantification of 150 mg/L in the 1-octanol phase, which resulted from a low UV absorbance of the test item molecule and from a high dilution factor necessary to analyze the 1-octanol samples by reversed-phase HPLC. Given that the amount of non-charged species is negligible in the environmentally relevant pH range of 5 to 9, where the twice negatively charged species dominates, it is very likely that the log Pow value is significantly lower than -1.07 as well as the one given by EPI Suite™. This is corroborated by a determined water solubility of >=511 g/L at pH 7.5 and at 23 °C (see cross-ref. water solubility study), which is much higher than the predicted 100 g/L (EPI Suite™ v4.11, WSKOW v1.42).

Applicant's summary and conclusion

Conclusions:
The shake flask method according to TG OECD 107 at pH 7.0 was applied for the determination of the log Pow of a-Ketoglutarate disodium salt (CAS 305-72-6). The determined log Pow value of a-Ketoglutarate disodium salt at pH 7.0 is < -1.07 with a standard deviation of ± 0.001.
Executive summary:

The log Pow of the test item a-Ketoglutarate disodium salt (CAS no. 305-72-6) was determined according to TG OECD 107.

Aqueous phosphate buffer at pH 7.0, 1-octanol and the test item were equilibrated in test vessels by shaking, applying three different volume ratios of the two solvents. Subsequently, the test item concentrations were determined in both solvent phases.

The determined log Pow values were all < -1.07 for all three volume ratios and all replicates. For each replicate, the mass balance calculation showed that the experiment was reliably conducted, as the recovery rates ranged from 98% to 99%.

The determined log Pow value of a-Ketoglutarate disodium salt at pH 7.0 is < -1.07 with a standard deviation of +- 0.001.

The validity criterion was fulfilled.