Reaction mass of calcium 2,6-bis(3-carboxylatopropanamido)hexanoate and isomers of calcium amino-(3-carboxylatopropanamido)hexanoate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 May 2017 - 06 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

Pow

Partition coefficient:

0.001

Temp.:

20 °C

pH:

>= 6.58 - <= 7.01

Key result

Type:

log Pow

Partition coefficient:

-3.25

Temp.:

20 °C

pH:

>= 6.58 - <= 7.01

The results of the measurements performed with the different ratio systems are presented in the following table:

Table 1: Results of the determination of the test item concentrations

Ratio of solvents (n-octanol : water)	Measured concentration of Test Item (µg/mL)		pH	Measured concentration of Test Item (µg/mL)
	In Aqueous phase	Mean		In n-octanol phase	Mean
10:1	81.33 86.42	83.87	6.59	0.041#  0.041#	0.041
	103.28 85.71	94.50	6.58	0.041#  0.041#	0.041
	92.86 86.73	89.80	6.59	0.041#  0.041#	0.041
Mean	89.39		6.59	0.041
RSD %	6			0.0
Measured test item µg	406.72			1.87
Total measured quantity of test item	408.6 µg
Total quantity of test item	451.04 µg			Recovery: 90.6 %
20:1	277.61* 187.56	187.56	7.00	0.089 0.100	0.094
	191.60 186.94	189.27	7.01	0.082 0.093	0.087
	190.01 191.41	190.71	7.01	0.090 0.104	0.097
Mean	189.18		7.01	0.093
RSD %	0.8			5.4
Measured test item µg	454.04			4.42
Total measured quantity of test item	458.5 µg
Total quantity of test item	451.04 µg			Recovery: 101.6 %
5:1	39.06* 52.76	52.76	6.74	0.041#  0.041#	0.041
	53.20 53.28	53.24	6.75	0.041#  0.041#	0.041
	53.21 53.37	53.29	6.75	0.041#  0.041#	0.041
Mean	53.10		6.75	0.041
RSD %	0.5			0.0
Measured test item µg	443.35			1.72
Total measured quantity of test item	445.1 µg
Total quantity of test item	451.04 µg			Recovery: 98.7 %

 

# measured concentration was below the limit of quantification, therefore, the lowest value of the calibration concentration was used for calculations

* outlier, not used for calculation

 

The concentrations of the test item were calculated with the help of the calibration equation. The calculated Pow and log Pow are summarised in the following table:

Table 2: Partition coefficients measured for Test Item

Ratio of solvents (n-octanol : water)	Partition coefficient		Log Pow
	Pow	Mean	Log Pow	Mean
10:1	0.0005	0.0005	-3.31	-3.34
	0.0004		-3.36
	0.0005		-3.34
20:1	0.0005	0.0005	-3.30	-3.31
	0.0005		-3.34
	0.0005		-3.29
5:1	0.0008	0.0008	-3.11	-3.11
	0.0008		-3.11
	0.0008		-3.11
Mean all ± 95 % confidence interval	-	0.0006 ± 0.0001	-3.25 ± 0.083
RSD %	-	26	3

  

Conclusions:

In conclusion, the partition coefficient (Pow) of the test item in n-Octanol/Water was determined to be 0.0006 ± 0.0001 (95 % confidence interval) which corresponds to log Pow of -3.25 ± 0.083 (95 % confidence interval) using the shake flask method. The test substance is a multi-constituent substance, but due to technical reasons only the partition coefficient of one component could be determined. Only one clean peak was determined, therefore, only one log Pow value can be stated.

Executive summary:

A study was conducted in accordance with OECD TG 107, Regulation (EC) No 440/2008 method A.8 and OPPTS 830.7550 to determine the partition coefficient of the test item using the shake flask method. A stock solution of the test item was prepared in n-octanol presaturated with water. This sample was sonicated for 20 minutes. The saturated solution was centrifuged at 20 °C (5 min, 4000 rpm). A volume of 20 mL of the sample was shaken with 4 mL Acetonitrile : Water = 1 : 9 (v/v). The phases were separated by centrifugation (4000 rpm, 5 min, 20 °C) and the aqueous phase was diluted with Acetonitrile : Water = 1 : 9 (v/v) for HPLC analysis. Test vessels with octanol/water mixture in different ratios were shaken for 5 minutes by hand. Separation of the two phases was achieved by centrifugation at 20 °C (5 min, 4000 rpm). Then the two phases were analysed using HPLC. The partition coefficient Pow of the test item was determined to be 0.0006 and the log Pow was -3.25, respectively. The test substance is a multi-constituent substance, but due to technical reasons only the partition coefficient of one component could be determined. Only one clean peak was determined, therefore, only one log Pow value can be stated.

Description of key information

The partition coefficient (Pow) of the test item in n-Octanol/Water was determined to be 0.0006 ± 0.0001 (95 % confidence interval) which corresponds to log Pow of -3.25 ± 0.083 (95 % confidence interval) using the shake flask method. The test substance is a multi-constituent substance, but due to technical reasons only the partition coefficient of one component could be determined. Only one clean peak was determined, therefore, only one log Pow value can be stated.

Key value for chemical safety assessment

Log Kow (Log Pow):

-3.25

at the temperature of:

20 °C

Additional information

A study was conducted in accordance with OECD TG 107, Regulation (EC) No 440/2008 method A.8 and OPPTS 830.7550 to determine the partition coefficient of the test item using the shake flask method. A stock solution of the test item was prepared in n-octanol presaturated with water.This sample was sonicated for 20 minutes. The saturated solution was centrifuged at 20 °C (5 min, 4000 rpm).A volume of 20 mL of the sample was shaken with 4 mL Acetonitrile : Water = 1 : 9 (v/v). The phases were separated by centrifugation (4000 rpm, 5 min, 20 °C) and the aqueous phase was diluted with Acetonitrile : Water = 1 : 9 (v/v) for HPLC analysis.Test vessels with octanol/water mixture in different ratios were shaken for 5 minutes by hand. Separation of the two phases was achieved by centrifugation at 20 °C (5 min, 4000 rpm). Then the two phases were analysed using HPLC. The partition coefficient Pow of the test item was determined to be 0.0006 and the log Pow was -3.25, respectively.The test substance is a multi-constituent substance, but due to technical reasons only the partition coefficient of one component could be determined. Only one clean peak was determined, therefore, only one log Pow value can be stated.