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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:
2016-04-05 to 2016-08-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
extrapolation beyond the range of log Pow-values of reference compounds
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
adopted 2004
Deviations:
no
GLP compliance:
no
Other quality assurance:
ISO/IEC 17025 (General requirements for the competence of testing and calibration laboratories)
Remarks:
Merieux NutriSciences operates according to GLP Certification of Good Laboratory Practice
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
Lot No.: 50000067900
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
> 6
Temp.:
25 °C
pH:
ca. 7
Remarks on result:
other: substance is non-ionisable, thus pH is of low relevance
Details on results:
log Pow (arithmetic mean value, n=2): 10.8 (SD: 0.1)

The log Pow was determined in duplicate:
Result 1: log Pow 10.81
Result 2: 10.79

Details on measurements and evaluation:

Experimental results obtained with the reference substances (t0: 2.74 min, determined analyzing Uracil):

Referencesubstance

CAS

Purity Grade %

Conc. of ref. Solution (mg/ml)

tR(min)

K

logK

log Pow

Thymol

89-83-8

99.2

7.8

3.81

0.39

-0.411

3.3

Naphtalene

91-20-3

99.9

8.6

4.05

0.48

-0.320

3.6

Benzyl Benzoate

120-51-4

99.8

8.1

4.10

0.49

-0.306

4.0

Bibenzyl

103-29-7

99.2

8.0

4.68

0.71

-0.151

4.8

1-Dodecanol

112-53-8

98.1

7.5

5.32

0.94

-0.027

5.15

1-Tetradecanol

112-72-1

96.5

7.9

6.37

1.32

0.122

6.2

1-Tetradecanol was used instead of DDT (suggested by OECD 117), since the compounds have similar values of Log Pow.

For the quantification of capacity factor K, the following formula was used.

K= (tR-t0)/t0

Where:

tR: retention time of testing substance;

t0: dead-time (2.74 min) determined analyzing Uracil (CAS 66-22-8).

In order to correlate the measured capacity factor K of the test item (see below) with its Pow, a calibration graph using 6 points was done from the results for the 6 reference substances, plotting log Pow against log K (abscissa). The following regression function was determined:

y = 5.3247x + 5.4786; Coefficient of Determination (R^2) = 0.9814

y being log Pow, x being log K

Model used:                                   unweighted linear regression, (y=a+bx)

Slope:                                          5.3247

Intercept:                                   5.4786

Confidence interval of slope (α = 0.05):         4.31 – 6.34

Confidence interval of intercept (α = 0.05):       5.21 – 5.74

Test item analysis was performed in duplicate and results are reported in the following tables.

All reference compounds chosen have values of Pow below that of the test substance. As such, the regression function derived above was used to extrapolate log Kow values for the single peaks.

Area % of each Log Pow peak is reported, and for calculation of overall log Pow, log Pow-values for single chromatogrphic peaks are weighted according to peak area.

Results first run:

peak

TR first run
(min)

K

LogK

LogPow

Area %

LogPow
fraction

Weighted
average
Log P
ow

1

5.453

1.0

-0.005

5.45

0.61

0.03

10.81

2

14.336

4.2

0.626

8.81

0.61

0.05

3

15.352

4.6

0.663

9.01

0.54

0.05

4

19.435

6.1

0.784

9.66

3.92

0.38

5

26,262

8.6

0.933

10.45

1.42

0.15

6

31.591

10.5

1.022

10.92

92.89

10.14

Results second run:

peak

TR second run
(min)

K

LogK

LogPow

Area %

LogPow
fraction

Weighted
average
Log P
ow

1

5.461

1.0

-0.004

5.46

0.60

0.03

10.79

2

14.345

4.2

0.627

8.81

0.50

0.04

3

15.347

4.6

0.662

9.01

0.79

0.07

4

19.394

6.1

0.783

9.65

3.82

0.37

5

26.136

8.5

0.931

10.44

1.56

0.16

6

31.396

10.5

1.019

10.91

92.73

10.11

Repeatability: the values of log Pow measured are 10.81 and 10.79 and fall within a range of +/- 0.1 log units, in accordance with the acceptance criteria set by OECD TG 117/2004.

The average results of the test is Log Pow = 10.8 with a standard deviation of 0.1.

Conclusions:
log Pow (OECD 117) at 25°C: 10.8
Executive summary:

The n-octanol/water partition coefficient was determined according to OECD 117 (2004). Reverse phase HPLC method enables partition coefficients to be estimated in the Log Pow range between 0 and 6, but can be expanded to cover the Log Pow range between 6 and 10 in exceptional cases, with modification of the mobile phase. For this substance with a log Pow above 6 in fact, the mobile phase was adapted by increasing the volume fraction of organic phase (Methanol) with respect to the standard conditions.

Partition coefficient n-octanol water was determined from duplicate experiments:

log Pow (25°C): 10.8 (SD: 0.1).

The results of the single determinations are log Pow 10.81 and log Pow 10.79 and thus are within a range of +/- 0.1 log units, as demanded by OECD 117. The reference substances applied had log Pow values well below that of the test item, such that log Pow value for the test item had to be determined by extrapolation using the regression equation from the reference compound set.

Description of key information

log Pow (OECD 117) at 25°C: 10.8 

Key value for chemical safety assessment

Log Kow (Log Pow):
10.8
at the temperature of:
25 °C

Additional information

The n-octanol/water partition coefficient was determined according to OECD 117 (2004) from duplicate determinations:

log Pow (25°C): 10.8 (SD: 0.1).

The results of the single determinations are log Pow 10.81 and log Pow 10.79 and thus are within a range of +/- 0.1 log units, as demanded by OECD 117. The reference substances applied had log Pow values well below that of the test item, such that log Pow value for the test item had to be determined by extrapolation using the regression equation from the reference compound set.

The estimation of log Pow using QSAR (KOWWIN v.1.68) resulting in a value of 13.28 supports the high log Kow determined within the experimental key study.