Nα-acetyl-DL-tryptophan

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

key study

Study period:

07 Oct - 23 oct 2015

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)

Version / remarks:

adopted in 2008

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

no

Type of method:

flask method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Storage conditions: ambient temperature (10 – 30 °C)

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

< -1.7

Temp.:

23 °C

pH:

ca. 7

Results
Table 1 - Preliminary visual estimation of n-octanol solubility

Added test item amount [g]	Total test item amount [g]	Added n-octanol volume [mL]	Total n-octanol volume [mL]	Stirring time [min]	Appearance of mixture
0.0063	0.0063	10	10	140	Not dissolved
--	0.0063	90	100	1015	Few small particles
0.0171	0.0234	--	100	430

 

Results showed that the n-octanol solubility of the test item is < 0.63 g/L (without correction for the purity).

 

Calculation of the Partition Coefficient log P_OW
Using the water solubility determined in the study report 20150266.04 (c_S> 0.88 g/L) and the preliminary results, it was found that log P_OW< -0.2

Due to the calculation results, the shake flask method was performed.
The calculated value from KOWWIN was 1.2.

 

Shake Flask Method
The test item is a zwitterionic substance, thus the method had to be carried out at pH 7 (or the isoelectric point). The given values of the concentrations in the aqueous and n-octanol phases are mean values of two measurements.

Table 2 – Results and test conditions of the shake flask method

Experiment	1A	1B	2A	2B	3A	3B
Test item amount [mg]	22.3
Stock solution concentration [mg/L]	223
Added stock solution volume [mL]	10
Added n-octanol volume [mL]	0	0	10	10	30	30
Added buffer volume [mL]	20
pH of aqueous phase at 23 °C	7.0
Aqueous phase measured concentration [mg/L]	2.23 2.22	2.22 2.21	2.23 2.23	2.24 2.24	2.20 2.20	2.21 2.20
Aqueous phase mean concentration [mg/L]*	111.1	110.8	111.3	111.8	110.2	110.3
n-octanol phase measured concentration [mg/L]	< 0.06 < 0.06
n-octanol phase mean concentration [mg/L]*	< 2.28

*for the mean concentration, the sample preparation (dilution) is taken into account

The following partition coefficients were calculated from the measured and unrounded concentration values and not from the rounded values given in Table 2 .

Table 3 – Partition coefficients of the shake flask method at pH 7

Experiment	POW	lop POW	Average log POW
1A	0.025	< -1.69	< -1.69
1B	0.0206
2A	0.0205		< -1.69
2B	0.0204
3A	0.0207	< -1.68	< -1.68
3B	0.0207	< -1.69
Mean value (1A to 3B)			< -1.7
Standard deviation			0.002

 

The six determined log POW values are within a range of ± 0.3 units as requested by the guideline.

Conclusion: The partition coefficient at pH 7 and 23 °C of the test item was found to be:

log P_OW< -1.7

Description of key information

log POW < -1.7 at pH 7 and 23 °C (OECD 107, Shake Flask Method)

Additional information

The partition coefficient (n-octanol/water) was firstly estimated based on the ratio of the individual solubilities of the test item in water and n-octanol. The exact partition coefficient was determined according to the flask method described in the european Commission Regulation (EC) No. 440/2008, A.8. and in the OECD Guideline 107.

Based on calculations for logD performed using the model SPARC v4.6, the partition coefficient (log Pow) is equal to the log D at pH 7.