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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
From 25 August 2006 to 26 September 2006
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is considered as not reliable based on the following parameters: - No characterization of the test item - Determination of the partition coefficient with the HPLC method for a surface active agent without adjustment of the mobile phase pH's - Some compounds were eluted before the dead time of the column -The deviation between the values of log Pow derived from two measurements made under identical conditions and using the same set of reference substances is higher than 0.1 log units - No detailed information on the analytical method used (type of HPLC column, wavelenght of the detector...) - The study was not performed according to the last Guideline available at the time of the test
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
yes
Remarks:
The deviation between the values of log Pow derived from two measurements made under identical conditions and using the same set of reference substances is higher than 0.1 log units.
GLP compliance:
not specified
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Type:
log Pow
Partition coefficient:
1.38
Remarks on result:
other: weighted average value

The table above presented the HPLC retention times and log Pow data for reference compounds used in the study. Compounds were injected into the mobile phase of 50:50 methanol:water

Reference Compound

Detector

Mean Retention time (min)

Calculated log Pow

Thiourea

DAD

2.121

-

RI

2.679

-

2-butanone

DAD

3.109

0.35

RI

3.667

0.35

Aniline

DAD

3.846

0.82

RI

4.404

0.82

Benzonitrile

DAD

6.261

1.56

RI

6.820

1.56

p-cresol

DAD

7.405

1.76

RI

7.961

1.90

Methylbenzoate

DAD

13.190

2.38

RI

13.744

2.38

1-napthol

DAD

16.842

2.62

RI

17.392

2.62

The calibration graph of log(retention time) against published log Pow values for reference standards were presented in Attachment 1.

The test item appeared to fully dissolve in the mobile phase of 50:50 methanol: water used in this study.

The Diode Array Detector (DAD) showed a single peak forming before t0, implying a low Log Pow value.

The refractive Index Detector (RI) presented a large peak also before t0, implying a low Log Pow value for this sample. However, a second smaller peak was also on noted on the RI detector with a retention time of approximately 9.9 minutes. In the opinion of the Principle Investigator, this peak may well be an artefact form the production process of the test item. The weighted average of the two peaks was therefore 1.38 in this study. The data obtained with the sample were presented in the table above:

Detector

Peak number

Mean Retention time (min)

log Pow

% Area under peak

DAD

1

1.842

<0

-

RI

1

2.4596

<0

77.8

RI

2

9.953

2.03

22.2

Conclusions:
The weighted average value of Log Pow for the test item is 1.38.
Executive summary:

The study was assessed for the determination of the partition coefficient of the test item with HPLC method based on that outlined OECD guideline 117. A deviation from the guideline was observed during the study. Indeed, the deviation between the values of log Pow derived from two measurements made under identical conditions and using the same set of reference substances is higher than 0.1 log units. So the study didn't meet the quality criteria described in the OECD guideline 117. Under the conditions employed (HPLC conditions), one peak was detected using the Diode Array Detector. The Refractive Index Detector recorded two peaks with log Pow values of <0 and 2.03. The weighted average log Pow for this sample gave a figure of 1.38 (RI).

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 4 October 2012 to 25 January 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
2012-12-15
Type of method:
slow-stirring method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
2.1
Temp.:
25 °C
pH:
>= 7.6 - <= 7.85
Remarks on result:
other: log Pow of the C12 fraction (weighted average value)

Results:

Calibration curve for 1 -octanol phases analysis

Reference of calibration solution Peak area (area units) Conc (mg/L) Response factor Final Volume (ml) Dilution factor  Sample weight (mg) Conc back-calc Diff
A C= (w*P)/(V*Df) RF = A/C V Df w C'= (A-b)/a %
Lin 25% 1830264 19.31 9.48048E+04 100 4.0 20.11 18.49 -4.25%
Lin 25% 1845749 19.31 9.56069E+04 100 4.0 20.11 18.65 -3.37%
Lin 50% 3905839 39.71 9.83700E+04 100 1.0 10.34 40.46 1.89%
Lin 50% 3915468 39.71 9.86125E+04 100 1.0 10.34 40.56 2.14%
Lin 75% 5574447 57.14 9.75591E+04 100 1.0 14.88 58.12 1.72%
Lin 75% 5493480 57.14 9.61421E+04 100 1.0 14.88 57.26 0.21%
REF05 7463735 78.84 9.46752E+04 100 1.0 20.53 78.11 -0.91%
REF05 7502554 78.84 9.51676E+04 100 1.0 20.53 78.52 -0.39%
Lin 125% 9176261 96.38 9.52052E+04 100 1.0 25.10 96.24 -0.16%
Lin 125% 9169449 96.38 9.51346E+04 100 1.0 25.10 96.16 -0.23%
Lin 150% 10797715 112.59 9.59040E+04 100 1.0 29.32 113.40 0.72%
Lin 150% 10661311 112.59 9.46925E+04 100 1.0 29.32 111.95 -0.57%

Response function Peak Area = 94488.13*Concentration + 83143.53

The graph of the calibration curve is shown in Attachment 1.

Calibration curve for water phase analysis:

Reference of calibration solution Peak area (area units) Conc (mg/L) Response factor Final Volume (ml) Dilution factor  Sample weight (mg) Conc back-calc Diff
A C= (w*P)/(V*Df) RF = A/C V Df w C'= (A-b)/a %
REF 05 dil20 369203 3.94 9.36645E+04 100 20 20.53 3.90 -1.01%
REF 05 dil20 351222 3.94 8.91028E+04 100 20 20.53 3.69 -6.34%
REF 05 dil10 699817 7.88 8.87696E+04 100 10 20.53 7.74 -1.78%
REF 05 dil10 710573 7.88 9.01340E+04 100 10 20.53 7.86 -0.25%
REF 05 dil5 1413337 15.77 8.96387E+04 100 5 20.53 16.03 1.65%
REF 05 dil5 1437975 15.77 9.12013E+04 100 5 20.53 16.32 3.49%
REF 05 dil4 1720595 19.71 8.73009E+04 100 4 20.53 19.60 -0.56%
REF 05 dil4 1733152 19.71 8.79380E+04 100 4 20.53 19.75 0.20%
REF 05 dil2,5 2735643 31.53 8.67520E+04 100 2.5 20.53 31.40 -0.44%
REF 05 dil2,5 2734947 31.53 8.67299E+04 100 2.5 20.53 31.39 -0.48%

Response function Peak Area = 86061.61*Concentration + 33709.60

The graph of the calibration curve is shown in Attachment 1.

Main test results:

The three filtered aliquots of 50 mL obtained from the 1-octanol saturated phase were analyzed and the concentrations of the C12 fraction were found to be equal to 1.86 g/L (4.84 g/L of test item). This value is lower than the theoretical one and shows a weak dissolution of test item during the two hours of preparation.

The results for the C12 fraction concentration in the two phases at each time are given in the following table:

Vessel number and sampling time Concentration in the aqueous phase (mg/l) Concentration in the 1-octanol phase (mg/l) Pow ratio log Pow
12-091 Z1T=93H 12.70 1499 118.00 2.07
12-091 Z2T=93H 11.44 1524 133.20 2.12
12-091 Z3T=93H 12.14 1558 128.30 2.11
12-091 Z1T=117H 11.24 1497 133.20 2.12
12-091 Z2T=117H 11.94 1539 128.90 2.11
12-091 Z3T=117H 11.78 1582 134.30 2.13
12-091 Z1T=137H 11.54 1503 130.20 2.11
12-091 Z2T=137H 12.18 1601 131.40 2.12
12-091 Z3T=137H 13.38 1629 121.70 2.09
12-091 Z1T=144H 11.48 1511 131.60 2.12
12-091 Z2T=144H 12.78 1513 118.40 2.07
12-091 Z3T=144H 13.26 1569 118.30 2.07
12-091 Z1T=163H 12.02 1489 123.90 2.09
12-091 Z2T=163H 12.14 1552 127.80 2.11
12-091 Z3T=163H 12.34 1599 129.60 2.11

The pH of the saturated water phase at the start of the test was 7.88 at 21 °C.The measured pH of the aqueous phases were between 7.60 and 7.85 at 21 °C.

The average value of log Pow of the different vessel units is calculated as the average of the results of the individual experimental units weighed with their respective variances.The results are shown in the following table.

Vessel Z1 Mean value Z1 Standard deviation Z1 Vessel Z2 Mean value Z2 Standard deviation Z2 Vessel Z3 Mean value Z3 Standard deviation Z3
2,07 2,102 0,02 2,12 2,106 0,02 2,11 2,102 0,02
2,12 2,11 2,13
2,11 2,12 2,09
2,12 2,07 2,07
2,09 2,11 2,11

Mean / Vessel Average Standard deviation
Vessel Z1 2,102 2,103 0,02
Vessel Z2 2,106
Vessel Z3 2,102

Using the low stirring method, it was shown that the weighed average value of the 1-octanol/water partition coefficient log10 Pow of the C12 fraction present in test item is equal to 2.10 ± 0.02 at 25 ± .1°C.

Demonstration of attainment of equilibrium:

Achievement of chemical equilibrium is demonstrated by plotting for each vessel unit log Pow against time as shown in the figures shown in Attachment 2 where the slopes are very near to 0.

Conclusions:
Using the low stirring method, it was shown that the weighed average value of the 1-octanol/water partition coefficient log10 Pow of the C12 fraction present in test item is equal to 2.10 ± 0.02 at 25 ± 1°C.
Executive summary:

The n-octanol/water partition coefficient of the test item (= substance EC 939-455-3) was investigated in a GLP-compliant study performed in accordance with OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method). The mean n-octanol/water partition coefficient log10 Pow of the C12 fraction present in test item was 2.10 ± 0.02 at 25°C.

Description of key information

The n-octanol/water partition coefficient of the substance 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts (EC 939-455-3) was investigated in a GLP-compliant study (Meriaux, 2013) performed in accordance with OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method). The mean n-octanol/water partition coefficient log10 Pow of the C12 fraction present in the the substance was 2.10 ± 0.02 at 25°C.

The n-octanol/water partition coefficient of the substance had been previously investigated in a study (Hill, 2006) performed in accordance with OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method). The result of that study was not considered in the assesment as the HPLC method is not suitable for surface-active substance (the substance proved to be a surfactant) and the study suffered from various methodological deficiencies.

Key value for chemical safety assessment

Log Kow (Log Pow):
2.1
at the temperature of:
25 °C

Additional information

The n-octanol/water partition coefficient of the substance 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts (EC 939-455-3) was investigated in a GLP-compliant study (Meriaux, 2013) performed in accordance with standard methods, without deviations. The study is considered as reliable (Klimisch 1) and was selected as key study for the endpoint. The n-octanol/water partition coefficient of the substance was investigated in another study (Hill, 2006) which is considered as not reliable (Klimisch 3) and was disregarded for the endpoint.