Adenosine 5'-(trihydrogen diphosphate), monopotassium salt

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 - 23 December 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

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:

According to the guideline, this test should be conducted with the non-ionised form. However, in the environmentally relevant pH range of 5 to 9, the amount of non-ionised species is negligible.

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:

According to the guideline, this test should be conducted with the non-ionised form. However, in the environmentally relevant pH range of 5 to 9, the amount of non-ionised species is negligible.

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'-(trihydrogen diphosphate), monopotassium salt

EC Number:

274-533-4

EC Name:

Adenosine 5'-(trihydrogen diphosphate), monopotassium salt

Cas Number:

70285-70-0

Molecular formula:

C10H14KN5O10P2

IUPAC Name:

potassium;[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate

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:

Sum of impurities from ADP, K (each < 1 %)

IUPAC Name:

Sum of impurities from ADP, K (each < 1 %)

Test material form:

solid: particulate/powder

Details on test material:

Batch No.: 37779100
Storage Conditions: Refrigerator (approx. 2 °C to 8 °C)

Specific details on test material used for the study:

Lot No.: 37779100
Storage: 2–8 °C, protected from light

Study design

Analytical method:

liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< -2.13

Temp.:

22 °C

pH:

5

Remarks on result:

other: temperature: 22 to 23°C

Details on results:

CALCULATION METHOD
According to the guideline, this test should be conducted with the non-ionised form. However, in the environmentally relevant pH range of 5 to 9, the amount of non-ionised species is negligible (see Figure 1 for the theoretical distribution of the different test item species as a function of pH). Thus, any log POW determined in this range is most likely a log DOW. Therefore, an even lower value than
-4.83 (see section 5.3) is expected, which is out of the scope of the OECD 107 test (log Pow of -2 to 4) as well as the OECD 117 test (log Pow of 0 to 6) and the OECD 123 test (log Pow =4). Therefore, the focus of this study was to demonstrate, that the log Pow of the test item at an environ¬mentally relevant pH is indeed below -2. To guarantee defined pH conditions during the test, a 10 mM acetate buffer was used at pH 5.0, where the log DOW is expected to be highest in the environmentally relevant pH range of 5 to 9 (https://chemicalize.com/#/calculation).

FLASK METHOD
The log POW of Adenosine 5’-diphosphate monopotassium salt (dried) was determined according to the OECD guideline 107. The determined log POW values were in the range of <-2.14 to <-2.13 for all three volume ratios and all replicates. The recovery rates of the mass balance calculations for each replicate ranged from 100 to 102%.The determined log POW value of Adenosine 5’-diphosphate monopotassium salt (dried) (CAS no. 70285-70-0) at pH 5.0 and 22 to 23 °C is <-2.13. 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

 

Table: Concentrations in the two phases, mass-balance and log P_OW determinations

Replicate	Phase	Determined concentration [mg/l]	Mass balance: Total introduced [mg] *	Mass balance: Total determined [mg] **	Mass balance: Recovery rate [%] ***	Pow	log Pow	Mean Stdev
Ratio 1:2_A	1-Octanol	<30.0	271	277	102	<0.007	<-2.14	<-2.13
	Aqueous	4118
Ratio 1:2_B	1-Octanol	<30.0	271	276	102	<0.007	<-2.14
	Aqueous	4107
Ratio 1:4_A	1-Octanol	<30.0	324	327	101	<0.007	<-2.13
	Aqueous	4081
Ratio 1:4_B	1-Octanol	<30.0	324	328	101	<0.007	<-2.13
	Aqueous	4093
Ratio 1:8_A	1-Octanol	<30.0	361	364	101	<0.007	<-2.13
	Aqueous	4083
Ratio 1:8_B	1-Octanol	<30.0	361	360	100	<0.007	<-2.13
	Aqueous	4037

*     Test item concentration in the stock solution (4051 mg/l) times the solvent volume of the 1-octanol phase

**   Sum of determined concentration in aqueous phase times the solvent volume of aqueous phase (content in 1-octanol phase was not accounted for, as the determined concentration was below the LOQ of 30.0 mg/l)

*** Percentage of total determined / total introduced into the system

 

 

 

Applicant's summary and conclusion

Conclusions:

The shake flask method according to the OECD guideline 107 was applied for the determination of the log Pow of Adenosine 5’-diphosphate monopotassium salt (dried) (CAS no. 70285-70-0).
The determined log POW value of Adenosine 5’-diphosphate monopotassium salt (dried) at pH 5.0 and 22 to 23 °C is <-2.13.

Executive summary:

The log POW of the test item Adenosine 5’-diphosphate monopotassium salt (dried) (CAS no. 70285-70-0) was determined according to the OECD guideline 107.
Acetate buffer at pH 5.0, 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 in the range of <-2.14 to <-2.13 for all three volume ratios and all replicates. The recovery rates of the mass balance calculations for each replicate ranged from 100 to 102%.
The determined log POW value of Adenosine 5’-diphosphate monopotassium salt (dried) at pH 5.0 and 22 to 23 °C is <-2.13.
From a theoretical point of view, log POW only applies to the partitioning of the non-charged species between 1-octanol and the aqueous phase. Based on model calculations for the species distribution of Adenosine 5’-diphosphate as function of the pH, the species are always ionised in the environmentally relevant pH range of 5 to 9 so that the value determined in this study very likely corresponds to a log DOW.
The validity criterion was fulfilled.