1H-Pyrazolo[3,4-c]pyridine-3-carboxylic acid, 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-, ethyl ester

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 15 February 2012 and 03 March 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Version / remarks:

- using the shake-flask method, designed to be compatible with Method A8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 107 of the OECD Guidelines for Testing of Chemicals, 27 July 1995.

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

using the shake-flask method, designed to be compatible with Method A8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 107 of the OECD Guidelines for Testing of Chemicals, 27 July 1995.

Deviations:

no

GLP compliance:

yes

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

172

Temp.:

22.8 °C

Remarks on result:

other: The partition coefficient of the test item has been determined to be 172 at 22.8 ± 1.0 °C, log10 Pow 2.23.

Details on results:

Due to the tabular nature of this information & to retain the integrity & coherence of the original Harlan Laboratories Ltd. Study report please see section “Any other information on results incl. tables”

Results

Preliminary assessment

The log₁₀P_owwas calculated to be:    3.64. The full KOWWIN calculation is presented in Appendix 3 - Attachment 2.

Please see Attachment 3 for the Typical Chromatography.

The mean peak are asobtained for the standard, stock and sample solutions are shown in the following two tables:

 

Table 3.12 – Organic Phase

 

Solution	Mean PeakArea
Standard 41.0 mg/L	5.9154 x 10^6
Standard 40.8 mg/L	5.7112 x 10^6
Sample 1	5.4480 x 10^6
Sample 2	5.4327 x 10^6
Sample 3	5.3603 x 10^6
Sample 4	5.4458 x 10^6
Sample 5	5.3423 x 10^6
Sample 6	5.4337 x 10^6
Stock solution A	5.6138 x 10^6
Stock solution B	5.5347 x 10^6

 

Table 3.13– Aqueous Phase

 

Solution	Mean PeakArea
Standard 5.10 mg/L	7.1811 x 10^5
Standard 5.09 mg/L	7.2396 x 10^5
Sample 1	1.6659 x 10^5
Sample 2	1.8634 x 10^5
Sample 3	1.8534 x 10^5
Sample 4	1.8529 x 10^5
Sample 5	1.3520 x 10^5
Sample 6	1.1427 x 10^5

 

 

The analysed concentration (mg/L) and weights (mg) for the respective phases are shown in the following table:

 

Table 3.14

 

Sample Number	Organic Phase		Aqueous Phase			% Recovery
	Analysed Concentration (mg/L)	Weight (mg)†	Analysed Concentration (mg/L)	Weight (mg)†	pH
1	383	28.7	2.35	0.176	6.8	98.3
2	382	28.7	2.63	0.197	7.3	98.1
3	377	13.9	2.62	0.194	7.3	97.5
4	383	17.2	2.62	0.236	7.2	99.0
5	376	10.5	1.91	0.214	7.1	97.8
6	382	8.41	1.61	0.142	7.3	99.1

 

pH of n-octanol saturated water:       6.9
Temperature:                                     22.8 ± 1.0 °C

 

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

 

Table 3.15

 

Sample Number	Organic/Aqueous Volume Ratio	Partition Coefficient	Log10Pow	Mean Partition Coefficient
1	1:1	163	2.21	154
2		145	2.16
3	1:2	144	2.16	145
4		146	2.17
5	1:4	197	2.29	217
6		237	2.37

 

Mean P_ow : 172                      log₁₀P_ow: 2.23                       P_owstandard deviation : 37.6

† From analysis of the respective phase

 

   

Validation

Organic phases: The linearity of the detector response with respect to concentration was assessed over the concentration range of 0 to 102 mg/L. This was satisfactory with a correlation coefficient (r²) of 1.000 being obtained.

 

Aqueous phases: The linearity of the detector response with respect to concentration was assessed over the concentration range of 0 to 22 mg/L. This was satisfactory with a correlation coefficient (r²) of 1.000 being obtained.

 

Conclusions:

The partition coefficient of the test item has been determined to be 172 at 22.8 ± 1.0 °C, log10 Pow 2.23.

Executive summary:

The determination was carried out using the shake-flask method, designed to be compatible with Method A8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 107 of the OECD Guidelines for Testing of Chemicals, 27 July 1995.

A preliminary assessment of the partition coefficient was calculated based on fragment constant methodology using KOWWIN v1.67a (Sept 2008) © 2000 U.S. Environmental Protection Agency based on information on the test item provided by the Sponsor.

 

The calculation method is based on the theoretical fragmentation of the molecule into substructures for which reliable log P_owincrements are known. The log P_owis obtained by summing the fragment values and the correction terms for intramolecular interactions.

To conclude the partition coefficient of the test item has been determined to be 172 at 22.8±1.0°C,
log₁₀P_ow2.23.

Description of key information

The partition coefficient of the test item has been determined to be 172 at 22.8 ± 1.0 °C, the log10 Pow is 2.23.

Key value for chemical safety assessment

Log Kow (Log Pow):

2.23

at the temperature of:

22.8 °C