Reaction mass of Reaction product of 1-chloro-3-{[1-chloro-3-(dodecyloxy)propan-2-yl]oxy}propan-2-ol with methyl diethanolamine and [3-(dodecyloxy)-2-hydroxypropyl]bis(2-hydroxyethyl)methylammonium chloride

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-03-19 to 2018-03-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-03-19 to 2018-03-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

yes

Remarks:

Gel formation was observed when large volumes of test material are dissolved in water. Therefore, it was not possible to weigh the fivefold saturation concentration of the test item in water in order to perform a main study as described in the guidelines.

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

2014

Deviations:

yes

Remarks:

Gel formation was observed when large volumes of test material are dissolved in water. Therefore, it was not possible to weigh the fivefold saturation concentration of the test item in water in order to perform a main study as described in the guidelines.

GLP compliance:

yes

Type of method:

flask method

Key result

Water solubility:

> 500 g/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

9.03

Details on results:

By means of visual assessment, the transition point from gel-like to dissolved solution was determined. The content of the first completely dissolved solution was determined by LC-MS-MS. The test item concentration in this solution was determined as 493.4 g/L at 20.0 °C.
The measured water solubility is no definitive value but only a limit solubility. The higher concentred solutions were not able to determine because of the high viscosity.
Therefore, water solubility of test item was estimated to lie at or above this value and therefore stated as > 500 g/L.

Observations main study at room temperature:

Flask	g test item	mL H2O	Appearance	Tyndall effect	Viscosity	pH
1	10.0012	5	turbid	not tested	high viscous	-
2	10.0016	10	turbid	not tested	high viscous	8.82
3	10.0006	20	clear liquid	yes	slightly viscous	9.03
4	10.0014	25	clear liquid	yes	not viscous	9.00
5	10.0010	30	clear liquid	yes	not viscous	8.99
6	10.0001	35	clear liquid	yes	not viscous	9.04
7	10.0011	40	clear liquid	yes	not viscous	9.02
8	10.0006	45	clear liquid	yes	not viscous	9.03
9	10.0011	50	clear liquid	yes	not viscous	8.89

Conclusions:

The water solubility of the test item was estimated to be > 500 g/L at 20.0 °C.

Executive summary:

In the current study the water solubility of the test item was determined by visual assessment and subsequent measurement using LC-MS/MS. Due to the surface tension properties of the test item, deviations to OECD 105, flask method were required.

The first main test was aborted because gel formation hampered the assessment of the water solubility. In a second main test, flasks with a loading rate of 200 to 2000 mg/L were shaken for 25h. The transition point from gel-like to dissolved solution was determined by visual assessment. The content of the first completely dissolved solution was determined by LC-MS/MS.

The measured water solubility is no definitive value but only a limit solubility. The higher concentred solutions were not able to determine because of the high viscosity. Therefore, water solubility of test item was estimated to lie at or above this value and therefore stated as > 500 g/L at 20.0 °C.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: OECD Guidelines for the Testing of Chemicals, Method No. 105: "Water Solubility"

Version / remarks:

adopted 27. Jul. 1995

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EU) No 260/2014 amending Regulation (EC) No 440/2008: Method A.6: "Water solubility"

Version / remarks:

adopted 24 January 2014

Deviations:

no

Principles of method if other than guideline:

Because the test item shows surface activity, the determination of the Partition Coefficient according OECD 107 and EU A 8 is not possible. Therefore, the determination of 1-octanol solubility was performed using a modified flask method based on OECD 105 and EU A.6 guidelines.Determination of the log Pow of the test item obtained from the individual solubility values in 1-octanol and water.

GLP compliance:

yes

Type of method:

flask method

Remarks:

modified based on OECD 105 and EU A.6 guidelines

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of Reaction product of 1-chloro-3-{[1-chloro-3-(dodecyloxy)propan-2-yl]oxy}propan-2-ol with methyl diethanolamine and [3-(dodecyloxy)-2-hydroxypropyl]bis(2-hydroxyethyl)methylammonium chloride

IUPAC Name:

Reaction mass of Reaction product of 1-chloro-3-{[1-chloro-3-(dodecyloxy)propan-2-yl]oxy}propan-2-ol with methyl diethanolamine and [3-(dodecyloxy)-2-hydroxypropyl]bis(2-hydroxyethyl)methylammonium chloride

Test material form:

other: solid, very viscous yellow paste

Study design

Analytical method:

liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< 0.14

Temp.:

20 °C

Remarks on result:

other: pH not determined

Details on results:

- First experiment:
The mean measured test item concentrationin n-octanol was 501.1 g/L.
Since the substance was completely dissolved after three days, no maximum solubility could be determined and a second experiment was carried out.
- Second experiment:
The mean measured test item concentration in n-octanol was 693.8 g/L. A standard deviation of 48.9 g/L was calculated, giving a relative standard deviation of 7.1 %.
- Calculated Log Pow:
The water solubility determined in study 16110901G910 was used. As the determination of water solubility of test item was problematic due to gel formation when large volumes of test item were mixed with water, only a visual assessment of the water solubility with subsequent LC-MS-MS measurement was performed. The lowest possible value for water solubility was used for calculation of the log Pow. The water solubility was found to be > 500 mg/L. The Pow value was calculated as < 1.39, the log Pow was stated as < 0.14.

Applicant's summary and conclusion

Conclusions:

The log Pow of test item, as calculated from the solubilities in water and n-octanol, is < 0.14.

Executive summary:

This study was performed in order to determine the partition coefficient of the test item by calculation from individual solubility values of the test item in 1-octanol and water. Because the test item shows surface activity, the determination of the partition coefficient according OECD 107 and EU A.8 is not possible. Therefore, the determination of 1-octanol solubility was performed using a modified flask method based on OECD 105 and EU A.6 guidelines.

The solubility of the test item in 1-octanol was determined by measurement of the test item concentrations using LC-MS-MS. Solubility of the test item in water was determined in a separate study.

 

In the pre-test using 1-octanol, solubility in the range 100 – 200 g/L was estimated. In the first main experiment, the mean measured test item concentration in three flasks was 501.1 g/L. In thesecond experiment, the test item concentration in the solutions was determined as 693.8 ± 48.9 g/L at 20.0 ± 0.3 °C. This value was used for the calculation of the partition coefficient.

The water solubility value was determined to be > 500 g/L. The Pow value was calculated as < 1.39, and the resulting limit log Pow value is < 0.14.