Phosphocreatine, sodium salt

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 - 22 August 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:

13 - 16 June 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 the high water solubility of the test item, the present study was conducted according to a modified TG OECD 105 design. 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

Specific details on test material used for the study:

Test item is hygroscopic and was therefore kept refrigerated and under nitrogen.

Key result

Water solubility:

>= 524 g/L

Conc. based on:

test mat. (dissolved fraction)

Temp.:

22 °C

pH:

11

Details on results:

Preliminary test
The preliminary test indicated a water solubility of 200-1000 g/L.

Main test
The results are given in the table in the next section. The water solubility of Phosphocreatine, sodium salt was determined according to a modified TG OECD 105 design. 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 a 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
No. 1	11	527	525	526
No. 2	11	524	524	524
No. 3	11	519	526	523
			Overall Mean	524

The concentrations of the three vessels differed by 0.6% (validity criterion given by OECD is met).

Conclusions:

The water solubility of Phosphocreatine, sodium salt (CAS no. 922-32-7) was determined according to a modified TG OECD 105 design.
The water solubility of the test item at 22°C was >=524 g/L. The pH of the aqueous samples was 11.

Executive summary:

The water solubility of Phosphocreatine, sodium salt (CAS no. 922-32-7) 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 Phosphocreatine, sodium salt is >= 524 g/L at pH 11 and at 22 °C.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

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'

Test guideline 2

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 given in the guideline, as the amount of non-charged species in the environmentally relevant pH range of 5 to 9 is negligible. Instead, the twice negatively charged species dominate. Therefore, the test was conducted at a pH of ca. 7.0.

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Phosphocreatine, sodium salt

EC Number:

213-074-6

EC Name:

Phosphocreatine, sodium salt

Cas Number:

922-32-7

Molecular formula:

C4H8N3O5P.2Na

IUPAC Name:

sodium [carbamimidoyl(methyl)amino](phosphono)acetate

impurity 1

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

Details on test material:

Batch No: 1413900

Specific details on test material used for the study:

Storage: 2-8 °C and protected from light. Test item is hygroscopic and was therefore kept refrigerated and under nitrogen.

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< -1.17

Temp.:

22 °C

pH:

7

Remarks on result:

other: The determined log POW values ranged from <-1.18 to <-1.16 for all three volume ratios and all replicates. Std. deviation from six determinations: ±0.005.

Details on results:

Calculation method
The log Pow of the test item was calculated to be -4.22 using EPI Suite™ v4.11, 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 three- and fourfold negatively charged species dominate. Therefore, an even lower log Pow than -4.22 is expected.

Flask method
The determined log Pow values ranged from <-1.16 to <-1.18 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 101% to 104%. 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	<159	2369	<0.0671		<-1.17	7.0
1:4	<159	2393	<0.0665		<-1.18	7.0
1:9	<159	2355	<0.0675		<-1.17	7.0
1:9	<159	2317	<0.0686		<-1.16	7.0
1:19	<159	2345	<0.0678		<-1.17	7.0
1:19	<159	2368	<0.0671		<-1.17	7.0
Mean					<-1.17

Further remarks:

The result obtained in this study is, as expected, quite low. A more precise determination was pre-vented by the limit of quantification of 159 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 - 1.17. This is corroborated by a determined water solubility of >=524 g/L at pH 11 and at 22 °C (see cross-ref. to water solubility study).

Applicant's summary and conclusion

Conclusions:

The shake flask method according to TG OECD 107 was applied for the determination of the log Pow of Phosphocreatine, sodium salt (CAS no. 922-32-7). The determined log Pow value of Phosphocreatine, sodium salt at pH 7.0 is <-1.17 with a standard deviation of ± 0.005.

Executive summary:

The log Pow of the test item Phosphocreatine, sodium salt (CAS no. 922-32-7) 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 ranged from <-1.16 to <-1.18 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 101% to 104%.

The determined log Pow value of Phosphocreatine, sodium salt at pH 7.0 is <-1.17 with a standard deviation of ± 0.005.

The validity criterion was fulfilled.