diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06.05.2015 - 07.05.2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - HPLC Method)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, Energie, Landwirtschaft und Verbraucherschutz, Mainzer Straße 80, D65189 Wiesbaden

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

4

Temp.:

25 °C

pH:

4

Type:

log Pow

Partition coefficient:

4

Temp.:

25 °C

pH:

7

Type:

log Pow

Partition coefficient:

4

Temp.:

25 °C

pH:

9

Final Results

The partition coefficients (1-octanol/water) of Mefenpyr-diethyl (AE F107892), pure substance, were determined according to the European Commission Council Regulation (EC) No 440/2008, Annex, Part A, method A.8., OECD Guideline 117 and US EPA Product Properties Test Guideline OCSPP 830.7570 (HPLC-method). Nine neutral calibration substances were injected into an HPLC-system under the same analytical conditions as the test item (column temperature 25 °C). Calibration curves were created by using the measured retention times (log k’-values) and the known log P_OW-values of the calibration substances for linear regression. The measured log k’-values of the test item were within the calibrated log k’-range. From the resulted calibration curves and their equations the log P_OW values of the test item were interpolated for pH 4, pH 7 and pH 9.

The partition coefficients (1-octanol / water) of the test item were:

	pH 4		pH 7		pH 9
	RUN 1	RUN 2	RUN 1	RUN 2	RUN 1	RUN 2
log POW	4.04	4.05	4.04	4.05	4.04	4.04
log POW(mean)	4.0		4.0		4.0
POW	10000		10000		10000

The results show that the partition coefficient of AE F107892, pure substance, is not pH dependent.

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

17.12.1990 - 18.12.1990

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

GLP compliance:

yes

Remarks:

Pharma Research Quality Assurance (GLP)

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

Pow

Partition coefficient:

6 783

Temp.:

21 °C

pH:

6.3

Type:

log Pow

Partition coefficient:

3.83

Temp.:

21 °C

pH:

6.3

Details on results:

log Pow = 3.83
pH=6.3 (aqueous phase)
Phase ratio octanol/water: 4/40 (v/v)
Concentration range: 1.46E-06 mol/L - 1.33E-07 mol/L in aqueous phase

Experimental values:

Equil.	Starting conditions			Final conc.		material balance [%]	Kow	pH
	conc. (calculated) [ug/ml]	octanol Vol. [ml]	water Vol. [ml]	water [ug/ml]	octanol [ug/ml]
50	3579.6	4	40	0.541	3768.1	105.4	6965	6.32
100	3579.6	4	40	0.546	3665.3	102.5	6713	6.26
50	1789.8	4	40	0.273	1883.4	105.4	6899	6.33
100	1789.8	4	40	0.268	1504.3	<84.2>	<5613>	6.35
50	357.96	4	40	0.050	349.7	97.8	6994	6.35
100	357.96	4	40	0.054	339.5	95.0	6346	6.31
Mean S.D. C.V. %						101.2	6783	6.32
						4.7	268	0.33
						4.6	3.9	0.5

< > outliers

Validation of the analytical procedure:

For the determination of recovery rates 20 mL of bidistilled water were spiked at 3 concentration levels (0.1 mg/L, 0.25 mg/L, 2 mg/L) with 1 ml of a stock solution containing Hoe 107892 in acetonitrile. The resulting solutions were subjected to the analytical procedure as described in Details on methods. Experimentally found concentrations were compared with the theoretical values and the recovery rate was determined as 103.5% with a standard deviation of 2.3%. Individual values of recovery rates are listed in the table:

Hoe 107892, sample	Theory [mg/L]	1. inj. [mg/L]	2. inj. [mg/L]	3. inj. [mg/L]	4. inj. [mg/L]	Mean [mg/L]	Recovery [mg/L]
1.	1.9624	2.071	2.103			2.087	106.3
2.	1.9624	2.014	2.016			2.015	102.7
1.	0.2453	0.260	0.245			0.253	102.9
2.	0.2453	0.261	0.262	0.261	0.249	0.258	105.2
1.	0.0981	0.125	0.126			<0.126>	<127.9>
2.	0.0981	0.097	0.100			0.099	100.4
Mean S.D. C.V. [%]							103.5
							2.3
							2.2

< > outliers

The HPLC method had been determined earlier as linear up to a concentration of the sample solution of 40mg/100mL. The limit of detection was determined as 3x the noise level of blank solutions. A value of the limit of detection = approx. 18 mg/L for the octanol phase and approx. 0.015 mg/L for the aqueous phase, sufficiently lower than the lowest concentration in the experiment (approx. 0.05 mg/L for the aqueous phase).

Reference 3

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

03.09.2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Qualifier:

no guideline followed

Principles of method if other than guideline:

ACD/Labs logD and logP software

GLP compliance:

no

Type of method:

other: calculation with a dedicated modeling software

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.24

pH:

> 4 - < 10

Details on results:

3.24 +/- 0.65

As expected, because of no ionisable parts in the molecule, the values obtained did not depend on pH.

Reference 4

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Remarks:

estimated by calculation

Adequacy of study:

supporting study

Study period:

8.02.2005 - 9.02.2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

Principles of method if other than guideline:

Calculation on the basis of previously measured solubility values in 1-octanol and in water.

Type of method:

other: calculation

Partition coefficient type:

octanol-water

Type:

Pow

Partition coefficient:

5 550

Temp.:

20 °C

pH:

6.2

Type:

log Pow

Partition coefficient:

3.7

Temp.:

20 °C

pH:

6.2

Details on results:

Saturation concentration in 1-octanol: 111000 mg/L
Saturation concentration in water: 20 mg/L
Pow = 111000/20 = 5500, log Pow = 3.7
pH for the water phase.

Study confirms the previously obtained experimental value of logPow = 3.83 (M-127650 -01 -1 -01, 1990)

Description of key information

4.0 at 25 °C and pH = 4, 7 and 9 (OECD 117, HPLC method)

Key value for chemical safety assessment

Log Kow (Log Pow):

4

at the temperature of:

25 °C

Additional information

Determination at 21° C and pH=6.3 Kow: 6783

log Kow (= log P): 3.83

The partition coefficient was determined at pH 6.3 only because the substance has neither acidic nor basic function groups and thus dissociation, if any, is negligible. The Log Pow has been calculated for a range of pH values. Log P = 3.24 ± 0.65 for pH 4 to 10. Additionally, the Log Pow has been calculated from the solubilities in resp. water and n-octanol, due to the value obtained for the surface tension: Log Pow = 3.7.