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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04-06-2001 to 10-08-2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met with acceptable deviations.
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
yes
Remarks:
Calibration reference substances were injected singularly rather than simultaneously. Expert judgement indicates this is not a significant deviation in that the standards retention times should not be impacted.
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient)
Deviations:
yes
Remarks:
see above
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: February 2000; signature: April 2000
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Type:
log Pow
Partition coefficient:
6.6
Temp.:
40 °C
pH:
ca. 7
Remarks on result:
other: mean log Pow; (n=2)

HPLC method

The mean void time (t0) was determined to be 0.561 minutes.

The results of the HPLC method are given in the Table 3. The calibration curves of the log k’ of the reference substances as function of log Pow had a regression line represented by the equation:

Calibration: log Pow = A + B x log k’ = -0.573 + 0.298 + log Pow ; where n = 6 and r = 0.994.

 

Table 2. Calibration data

Standard

Retention Time (min)

Capacity Factor (k')

Log10 k'

Log10 Pow

Injection 1

Injection 2

Mean

Thiourea (dead time)

2.735

2.736

2.736

-

-

-

Benzene

6.003

6.003

6.003

1.19

7.72 x 10^-2

2.1

Toluene

7.992

7.992

7.992

1.92

0.284

2.7

Naphthalene

9.734

9.736

9.735

2.56

0.408

3.6

Phenanthrene

18.015

18.018

18.017

5.59

0.747

4.5

Triphenylamine

41.063

41.084

41.074

14.0

1.15

5.7

DDT

57.502

57.537

57.520

20.0

1.30

6.2

 

Table 3. Test item determination

Peak

Injection

Retention Time (min)

Capacity Factor (k')

Log10 k'

Log10 Pow

Mean
Log10 Pow

1

1

69.278

24.3

1.39

> 6.20

> 6.20

2

69.269

24.3

1.39

> 6.20

* two isomers generated the same Log Pow result (coeluted)

Conclusions:
The partition coefficient of the test item was determined to be log Pow = 6.60 at 40°C and ca. pH 7.0
Executive summary:

The n-octanol/water partition coefficient was determined using the HPLC method within EU Method A.8 in accordance with GLP. The test was performed within a mobile phase of 75% methanol : 25% HPLC water. Samples of the test item were analysed via HPLC on a C18 column with refractive index detector. Calibration was performed using six reference items with known log POW values (given by the guidelines). The dead time of the HPLC system was determined with thiourea. The dead time and the reference items were measured in duplicate. The test item was injected and measured in duplicate. The partition coefficient of the test item was determined to be log Pow > 6.20 at a mean temperature 40°C and approximately neutral pH. Applicant assessment indicates the extrapolated n-octanol/water by linear regression would be log Pow = 6.60. This would be deemed a scientifically acceptable extrapolation.

Description of key information

n-octanol/water: log Pow = 6.60 at 40 °C and pH 7, EU Method A.8 – HPLC method, 2001

Key value for chemical safety assessment

Log Kow (Log Pow):
6.6
at the temperature of:
40 °C

Additional information

Key study : EU Method A.8, 2001 : The n-octanol/water partition coefficient was determined using the HPLC method within EU Method A.8 in accordance with GLP. The test was performed within a mobile phase of 75% methanol : 25% HPLC water. Samples of the test item were analysed via HPLC on a C18 column with refractive index detector. Calibration was performed using six reference items with known log POW values (given by the guidelines). The dead time of the HPLC system was determined with thiourea. The dead time and the reference items were measured in duplicate. The test item was injected and measured in duplicate. The partition coefficient of the test item was determined to be log Pow > 6.20 at a mean temperature 40°C and approximately neutral pH. Applicant assessment indicates the extrapolated n-octanol/water by linear regression would be log Pow = 6.60. This would be deemed a scientifically acceptable extrapolation.

Supporting data: QSAR Predictions KOCWIN v2.00 model, 2019 :

Log Koc (main constituents): (1-ethoxyethoxy)cyclododecane : 4.39

Based on Log Kow regression from Log Kow = 6.60, extrapolated measured data (OECD TG 117, 2001).

 

Consideration of a measured log Koc (4.43) by the OECD TG 121 guideline method for the main constituents versus the model prediction log Koc (4.39) utilising the Log Kow 6.60 input parameter, indicates agreement with the QSAR prediction within ±0.1 logarithmic units. Which is within the accuracy (±0.5) and repeatability (±0.25) criteria stated by the OECD TG 121 guideline.

 

The weight of evidence indicates that the substance main constituents have log Pow = 6.60 using a combination of measured data and with consideration to agreeement within measured and QSAR predictions in related endpoints (adsorption coefficient).