1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-(C8-18(even numbered) acyl) derivs., hydroxides, inner salts

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

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

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).

Reference 2

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

Guideline:

OECD Guideline 123 (Partition Coefficient (1-Octanol / Water), Slow-Stirring Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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.