Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 Jul - 16 Aug 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient - Shake Flask Method)
Version / remarks:
adopted in 2008
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Version / remarks:
adopted in 1995
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Department of Health, London, UK
Type of method:
flask method
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Storage conditions: room temperature in the dark

Study design

Analytical method:
high-performance liquid chromatography

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
< -3.05
Temp.:
22 °C
pH:
ca. 6.9

Any other information on results incl. tables

Preliminary estimate

Approximate solubility in n-octanol: <110 mg/L

Approximate solubility in water: >4.0E05 g/L

Approximate Pow: <2.8E-04

Log10Pow: <-3.6

 

Definitive test

The mean peak areas obtained for the standard, stock and sample solutions are shown in the following two tables.

Table 3: Organic phase

Solution

Mean peak area

Standard 10.0 mg/L

4.6953E06

Standard 10.0 mg/L

4.5948E06

Organic phase matrix blank

None detected

Sample 1

4.0808E05

Sample 2

<4.0808E05

Sample 3

<4.0808E05

Sample 4

<4.0808E05

Sample 5

<4.0808E05

Sample 6

<4.0808E05

 

Table 4: Aqueous phase

Solution

Mean peak area

Standard 507 mg/L

1.1638E08

Standard 504 mg/L

1.1575E08

Aqueous phase matrix blank

None detected

Sample 1

1.1423E08

Sample 2

1.1459E08

Sample 3

1.1440E08

Sample 4

1.1368E08

Sample 5

1.1444E08

Sample 6

1.1474E08

Stock solution A

1.1325E08

Stock solution B

1.1308E08

 

The total weights [mg] and analyzed concentration [mg/L] of the respective phases are shown in the following table.

Table 5

Sample number

Total weight

[mg]1)

Organic phase

Aqueous phase

% recovery

Analyzed concentration [mg/L]2)

Weight [mg]3)

Analyzed concentration [mg/L]

Weight [mg]3)

pH

1

78.84

1.763

7.05E-02

1.989E03

79.56

6.9

101

2

78.84

<1.763

<7.05E-02

1.995E03

79.80

6.9

~101

3

106.4

<1.763

<7.05E-02

1.992E03

107.6

7.0

~101

4

106.4

<1.763

<7.05E-02

1.980E03

106.9

7.0

~101

5

53.22

<1.763

<7.05E-02

1.993E03

53.81

7.0

~101

6

53.22

<1.763

<7.05E-02

1.998E03

53.95

7.0

~101

 

pH of n-octanol saturated water: 6.3

pH of stock solution: 7.1

Temperature: 22.0 ± 0.5°C

1)From analysis of the stock solution

2)See discussion section

3)From analysis of the respective phase

The partition coefficient determined for each sample is shown in the following table.

Table 6

Sample number

Organic/aqueous volume ratio

Partition coefficient

Log10Pow

Partition Coefficient

1

1:1

8.86E-04

-3.05

<8.85E-04

2

<8.84E-04

<-3.05

3

1:2

<8.85E-04

<-3.05

<8.88E-04

4

<8.90E-04

<-3.05

5

2:1

<8.85E-04

<-3.05

<8.84E-04

6

<8.82E-04

<-3.05

 

Mean Pow : <8.85E-04

log10Pow : <-3.05

Pow standard deviation : 2.78E-06

 

 

Validation

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 250 to 750 mg/L (aqueous) and 5 to 15 mg/L (organic). The results were satisfactory with a correlation coefficient (r) of 1.000 (aqueous) and 0.9985 (organic) being obtained.

 

Discussion

Due to the low concentration within the organic samples a limit of detection was applied to organic samples 2 to 6 based on organic sample 1 which had the highest concentration determined. Therefore, the overall result was a less than value.

The stock solution was prepared in n-octanol saturated water in place of water saturated n-octanol. This was due to low solubility of the test item in the organic phase. This issue has been considered to have had a negligible impact on the overall result and has been considered to be more appropriate to obtain a more realistic partition coefficient value.

 

Conclusion

The partition coefficient of the test item has been determined to be less than 8.85E-04 at 22.0 ± 0.5 °C, log10Pow less than -3.05.

Applicant's summary and conclusion