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Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 Jan 2019 - 20 Feb 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient - Shake Flask Method)
Version / remarks:
2016
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Version / remarks:
1995
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes
Type of method:
flask method
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of (S)-2-[(R)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide and (S)-2-[(S)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide
Cas Number:
943986-70-7
Molecular formula:
C11H20N2O2
IUPAC Name:
Reaction mass of (S)-2-[(R)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide and (S)-2-[(S)-2-Oxo-4-propyl-1-pyrrolidinyl]butyramide
Test material form:
solid
Details on test material:
- Appearance: Off-white solid
- Storage condition of test material: At room temperature protected from light

Study design

Analytical method:
other: UPLC-UV

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
0.9
Temp.:
20 °C
pH:
>= 6.8 - <= 6.9
Remarks on result:
other: non-buffered test system
Key result
Type:
Pow
Partition coefficient:
7.7
Temp.:
20 °C
pH:
>= 6.8 - <= 6.9
Remarks on result:
other: non-buffered test system
Details on results:
Using the Rekker calculation method the Pow of the test item was calculated to be 4.9 (log Pow 0.69) .

Using the Perrin calculation method the pKa values in the logarithm range of 1 - 14 for acidic and basic groups in the molecular structure of the test item were calculated as follows: no acidic pKa, basic pKa = 1.5 (for RCONH2).

Any other information on results incl. tables

Shake flask method

Analyzed concentrations and Pow of the test item

Ratio
n-octanol : water [v:v]

Analyzed concentration

Pow

log Pow

pH

n-octanol
[g/L]

water
[g/L]

individual

mean

1:1

0.155

0.0201

7.7

7.8

0.9

6.9

 

0.155

0.0195

7.9

 

0.9

6.9

1:2

0.212

0.0272

7.8

7.7

0.9

6.9

 

0.208

0.0274

7.6

 

0.9

6.9

2:1

0.122

0.0164

7.4

7.4

0.9

6.8

 

0.122

0.0164

7.4

 

0.9

6.8

Mean

7.7

 

0.9

 

Standard deviation

1.9x10-1

 

 

 

The analyzed concentration of the stock solution was 0.591 g/L. Based on this result the nominal quantity of the test item in the test samples was 1.18 mg. The calculated recoveries according to this value ranged from 88 – 90%.

 

Recoveries

Ratio
n-octanol : water [v:v]

Used phase volume

Analyzed quantity

Recovery

[%]

stock

[mL]

n-octanol

[mL]

water
[mL]

n-octanol
[mg]

water
[mg]

total
[mg]

1:1

2

4

6

0.928

0.120

1.05

89

 

 

 

 

0.928

0.117

1.05

88

1:2

2

2

8

0.847

0.218

1.06

90

 

 

 

 

0.833

0.219

1.05

89

2:1

2

6

4

0.974

0.0655

1.04

88

 

 

 

 

0.979

0.0657

1.04

88

These recovery values are lower than expected, because the nominal concentration of the stock solution was 0.524 g/L. Based on the nominal stock solution concentration, the expected quantity of the test item in the test samples should be 1.05 mg.When using this value, calculated recoveries would range from 99 – 102%. Considering the good agreement between the expected nominal quantity and the total analyzed quantity of test item in test samples, the partition coefficient results obtained are considered to be accurate.

The log Pow values were within the criterion range of ± 0.3 log units. The Pow and log Pow of the test item is given as the mean value of all measurements.

No test item was detected in the pretreated samples from the blank mixture.

Applicant's summary and conclusion

Conclusions:
The n-octanol - water partition coefficient of the substance at 20°C was determined to be 7.7 (log Pow = 0.9) using the shake flask method (non-buffered test system).

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