Adenosine 5'-(tetrahydrogen triphosphate), disodium salt

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 - 24 November 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

The final concentrations in the water phase were determined to be 0.011 to 0.012 M instead of 0.01 M. However, the deviation is minor and the validity criterion (the log Pow values determined have to be in a range of +- 0.3 units) was fulfilled.

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:

The final concentrations in the water phase were determined to be 0.011 to 0.012 M instead of 0.01 M. However, the deviation is minor and the validity criterion (the log Pow values determined have to be in a range of +- 0.3 units) was fulfilled.

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:

Adenosine 5'-(tetrahydrogen triphosphate), disodium salt

EC Number:

213-579-1

EC Name:

Adenosine 5'-(tetrahydrogen triphosphate), disodium salt

Cas Number:

987-65-5

Molecular formula:

C10H14N5O13P3.2Na

IUPAC Name:

disodium hydrogen [({[5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl phosphonato)oxy]phosphonate

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

impurity 2

Reference substance name:

Unknown impurities.

Molecular formula:

Not available as unknown impurities.

IUPAC Name:

Unknown impurities.

Test material form:

solid: crystalline

Details on test material:

Storage conditions: 2-8°C
Batch No: 11678500

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< -2.66

Temp.:

24 °C

pH:

7

Remarks on result:

other: The determined log POW values ranged from <-2.71 to <-2.63 for all three volume ratios and all replicates. Std. deviation from six determinations: ±0.03.

Details on results:

Calculation method
The log Pow of the test item was calculated to be -3.61 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 three- and fourfold negatively charged species dominate. Therefore, an even lower log Pow than -3.61 is expected.

Flask method
The determined log Pow values ranged from -2.71 to -2.63 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 101%. 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	<15.0	7697	<0.0019		<-2.71	7.0
1:4	<15.0	7468	<0.0020		<-2.70	7.0
1:9	<15.0	6698	<0.0022		<-2.65	7.0
1:9	<15.0	6833	<0.0022		<-2.66	7.0
1:19	<15.0	6370	<0.0024		<-2.63	7.0
1:19	<15.0	6389	<0.0023		<-2.63	7.0
Mean					<-2.66

Further remarks

The result obtained is, as expected, out of the scope of the OECD 107 test, as the intended log Pow range of this method is -2 to 4. Most likely, the real log Pow of the test item is much lower than -2.66. This is demonstrated by the predicted log Pow value of -3.61 for the uncharged molecule (EPI Suite™ v4.10, KOWWIN v1.68). Furthermore, the test item molecule is three- and fourfold negatively charged at pH 7.0, therefore, the expected log Pow at pH 7.0 is even lower than -3.61.

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 ATP, Di-Na (CAS 987-65-5). The determined log Pow value of ATP, Di-Na at pH 7.0 is <-2.66 with a standard deviation of ± 0.03.

Executive summary:

The log Pow of ATP, Di-Na (CAS 987-65-5) 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 <-2.63 to <-2.71 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 101%.

The determined log Pow value of ATP, Di-Na at pH 7.0 is <-2.66 with a standard deviation of ± 0.03. The validity criterion was fulfilled.