Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 November 2017

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:

other: Expert statement supported by experimental data

Adequacy of study:

key study

Study period:

19 June 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented expert statement supported by experimental data

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

not applicable

Remarks:

not applicable for expert statement

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

Regulation (EC) No 440/2008

Deviations:

not applicable

Remarks:

not applicable for expert statement

Principles of method if other than guideline:

A study according to OECD guideline 105 was initiated. However, based on the preliminary results, a determination of the water solubility of the test item according to TG OECD 105 is not possible, because its water solubility is too high for the approach given by the guideline. Therefore an expert statement was prepared.

Other quality assurance:

ISO/IEC 17025 (General requirements for the competence of testing and calibration laboratories)

Type of method:

flask method

Key result

Water solubility:

> 1 000 g/L

Conc. based on:

test mat.

Remarks on result:

completely miscible

Remarks:

Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts” (CAS no. 70983-43-6) is miscible with water in a test item weight to water volume ratio of at least 10:1 at room temperature.

Details on results:

Preliminary test
The preliminary test indicated a water solubility of >1.000 g/L, as 0.1 g were completely dissolved in 0.1 mL of ultra-pure water.

Main test
Based on the results of the preliminary test, a determination of the water solubility of the test item “Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts according to TG OECD 105 is not possible, because its water solubility is too high for this approach.

The preliminary test according to TG OECD 105 showed that the test item was very soluble in water, as ca. 0.1 g could be readily dissolved in 0.1 ml of ultra-pure water. Based on the testing scheme provided in the guideline and given in the table below, this corresponds to a water solubility of >1000 g/l.

Testing scheme to determine the approximate water solubility in the preliminary test:

mL of water for 0.1 g test item	0.1	0.5	1	2	10	100	>100
Approx. solubility in g/L	>1000	1000 to 200	200 to 100	100 to 50	50 to 10	10 to 1	<1

This result was further confirmed by an additional test, which illustrated that addition of 0.1, 0.5, 1 and 10 ml of ultra-pure water to about 1 g of test item resulted in a clear solution in all cases. This demonstrates that “Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts” (CAS no. 70983-43-6) is miscible with water in a test item weight to water volume ratio of at least 10:1.

Conclusions:

The substance “Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts” (CAS no. 70983-43-6) is miscible with water in a test item weight to water volume ratio of at least 10:1 at room temperature as demonstrated in a preliminary test according to OECD 105.

Executive summary:

It was the aim of this study to determine the water solubility of the test item “Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts“ (CAS no. 70983-43-6) according TG OECD 105.

The preliminary test according to the guideline showed that the test item was very soluble in water, as about 0.1 g could be readily dissolved in 0.1 ml of ultra-pure water corresponding to a water solubility of >1000 g/L.

This result was further confirmed by an additional test, which illustrated that addition of 0.1, 0.5, 1 and 10 mL of ultra-pure water to about 1 g of test item resulted in a clear solution in all cases. This demonstrates that the test item is miscible with water in a test item weight to water volume ratio of at least 10:1.

Based on these results, a determination of the water solubility of the test item according to TG OECD 105 is not possible, because its water solubility is too high for the approach given by the guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Version / remarks:

2004

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Version / remarks:

Regulation (EC) No 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts

EC Number:

275-085-2

EC Name:

Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts

Cas Number:

70983-43-6

Molecular formula:

see structural formula below, for n=4 C13H24N2O3 HO.Na

IUPAC Name:

Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts

Test material form:

liquid

Remarks:

oily liquid

Details on test material:

Batch No.: 54542L16
Storage at room temperature, protected from light.

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

ca. -1.08 - <= 2.05

Temp.:

25 °C

pH:

7

Remarks on result:

other: mean of two determinations. LogPow is given as a range as the test item is a complex mixture. "Ca." was inserted to pass the completeness, the real lower value is <= -1.08. Range <= -1.08 to 2.05.

Details on results:

The dead time was determined to be 1.57 min.

The test item Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts is a complex mixture. Therefore, the log POW is given as a range, which is based on the evaluation of the first and the last test item peak found in the corresponding chromatogram.
The log POW value for the first test item peak with the shortest retention time was extrapolated. As its retention time was slightly shorter than the one for Thiourea, which was used as dead time marker, an extrapolation based on the regression data obtained by the injection of reference items was not possible. Instead, its log POW can be given as less than or equal to the one of Thiourea corresponding to <= -1.08 (exper. database match; Govers H. et al., (1986); EPI Suite v4.11). The log POW value for the last test item peak with the highest retention time was determined to be 2.05 (95% confidence limits: 1.89–2.21) in the first as well as the second determination.
Consequently, the log POW range for the test item „Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts” (CAS no. 70983-43-6), calculated as the mean of both determinations, is <= -1.08 to 2.05 (95% confidence limits for upper value: 1.89–2.21) at pH 7.0.

Any other information on results incl. tables

Regression for the determination of the log POW value of Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts with the single injection run

Plot log POW vs log k:

Last test item peak:

coefficient of regression (r^2)	0.989
intercept (A)	1.348
slope (B)	1.70
log POW	2.05
95% confidence interval for log POW	1.89 - 2.21

Regression for the determination of the log POW value of Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts with the mixed injection run

Plot log POW vs log k:

Last test item peak:

coefficient of regression (r^2)	0.989
intercept	1.347
slope	1.70
log POW	2.05
95% confidence interval for log POW	1.89 - 2.21

Further remarks:

Generally, TG OECD 117 is not recommended for the log POW determination of surface active substances, which the test item is known to be. However, the OECD 117 is the most suitable test guideline for a complex mixture such as the test item, as its test design is independent of the varying solubilities of the test item components in 1-octanol and water.

In the light of a determined water solubility of >1000 g/L (see cross-ref to water solubility), the obtained log POW range of <= -1.08 to 2.05 seems realistic to slightly overestimated.

Applicant's summary and conclusion

Conclusions:

The HPLC method was applied for the determination of the log Pow. The log POW range for the test item „Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts” (CAS no. 70983-43-6), calculated as the mean of both determinations, at pH 7 is <= -1.08 to 2.05 (95% confidence limits for upper value: 1.89–2.21).

Executive summary:

The log POW of the test item Imidazolium compounds, 2-C4-8 -alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts (CAS no. 70983-43-6) was determined according to TG OECD 117. This determination is based upon a regression analysis of the log POW values of reference items against their respective retention times as determined by HPLC analysis. As the test item is a complex mixture, the log POW is given as a range, which is based on the evaluation of the first and the last test item peak found in the corresponding chromatogram.

The following reference items were used: Caffeine, 4-Acetylpyridine, Acetophenone, Nitrobenzene, Anisole and Toluene. The dead time of the HPLC system was determined with Thiourea.

This set of reference items yielded a calibration with log POW values ranging from -0.07 to 2.7 and retention times ranging from 1.77 min to 9.58 min. The dead time of the HPLC system was 1.57 min.

Two determinations of the log POW value of the test item were conducted using a phosphate buffered system at pH 7.0 by injecting a mixed solution of all reference items as well as the single test item solution twice.

The log POW value for the first test item peak with the shortest retention time was extrapolated. As its retention time was slightly shorter than the one for Thiourea, which was used as dead time marker, an extrapolation based on the regression data obtained by the injection of reference items was not possible. Instead, its log POW can be given as less than or equal to the one of Thiourea corresponding to <= -1.08 (exper. database match; Govers H. et al., (1986); EPI Suite v4.11).

The log POW value for the last test item peak with the latest retention time was determined to be 2.05 (95% confidence limits: 1.89–2.21) in the first as well as the second determination.

Consequently, the log POW range for the test item „Imidazolium compounds, 2-C4-8-alkyl-1-(2-carboxyethyl)-4,5-dihydro-3-(hydroxyethyl), hydroxides, sodium salts”, calculated as the mean of both determinations, is <= -1.08 to 2.05 (95% confidence limits for upper value: 1.89–2.21) at pH 7.0.