Amides, C12-18(even-numbered) and C18(unsatd.), N-hydroxyethyl

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-2022

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:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

1 210 mg/L

Conc. based on:

test mat. (dissolved fraction)

Loading of aqueous phase:

10 g/L

Incubation duration:

24 - <= 72 h

Temp.:

20 °C

pH:

7

Water solubility:

159 mg/L

Conc. based on:

test mat. (dissolved fraction)

Loading of aqueous phase:

1 g/L

Incubation duration:

24 - <= 72 h

Temp.:

20 °C

pH:

7

Details on results:

For the loading rate of about 1 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 10.7 mg/L ± 0.9 mg/L (mean ± standard deviation). For the loading rate of about 10 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 32.6 mg/L ± 0.7 mg/L (mean ± standard deviation).The chromatographic profile of the water solubility sample was significantly different from the chromatogram of a standard solution. The peaks of four early eluting compounds on the reversed phase column were present in higher amounts in the sample as compared to the standard solution obtained by complete dissolution of the test substance in organic solvent. These four early eluting compounds had a higher polarity and thus a higher water solubility than later eluting compounds.

Conclusions:

Under the study conditions, at the loading rate of about 1 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 10.7 mg/L ± 0.9 mg/L (mean ± standard deviation). For the loading rate of about 10 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 32.6 mg/L ± 0.7 mg/L (mean ± standard deviation).The chromatographic profile of the water solubility sample was significantly different from the chromatogram of a standard solution. The peaks of four early eluting compounds on the reversed phase column were present in higher amounts in the sample as compared to the standard solution obtained by complete dissolution of the test substance in organic solvent. These four early eluting compounds had a higher polarity and thus a higher water solubility than later eluting compounds

Executive summary:

A study was conducted to determine the water solubility of amides, C12-18 and C18-unsatd., N-hydroxyethyl in water according to OECD Guideline 105 (shake-flask method). Vessels containing water and the test substance were shaken for approximately 24 hours, 48 hours, and 72 hours, respectively, at 30°C. Afterwards, the samples were equilibrated for another 24 hours at 20 °C. Then, the samples were filtered and diluted, and the concentrations in the clear solutions were determined by HPLC with UV-detection. The test substance gave a chromatographic profile consisting of several peaks. Therefore, the test was carried out at two different loading rates. For results evaluation, the sum of peak areas of all test substance related peaks was used.Since the test substance is a "substance of unknown or variable composition (UVCB)", the generaldefinition for water solubility ( = saturation mass concentration of the test substance in water at a given temperature) is not applicable, and the usually accepted meaning of "water solubility" in such cases is the composition of the aqueous solution formed at equilibrium under a defined set of conditions, with the loading rate as the main factor to consider.Saturation of water was achieved after 24 hours of shaking. There was no tendency of increasing values with incubation time determined, therefore the values of all incubation days were used for the calculation of the overall mean. For the loading rate of about 1 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 10.7 mg/L ± 0.9 mg/L (mean ± standard deviation). For the loading rate of about 10 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 32.6 mg/L ± 0.7 mg/L (mean ± standard deviation).The chromatographic profile of the water solubility sample was significantly different from the chromatogram of a standard solution. The peaks of four early eluting compounds on the reversed phase column were present in higher amounts in the sample as compared to the standard solution obtained by complete dissolution of the test substance in organic solvent. These four early eluting compounds had a higher polarity and thus a higher water solubility than later eluting compounds (Schöneck, 2022).

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From Aug. 30, 2010 to Sept. 08, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

yes

Remarks:

The relative standard deviation of six replicates exceeds the limit (≤15%), but the TOC analysis was considered as acceptable (see 'Any other information on results incl. tables' for further details)

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Type of method:

flask method

Water solubility:

36 mg/L

Temp.:

20 °C

pH:

7.9 - 8.4

Details on results:

- Water solubility of the test substance calculated via total organic carbon (TOC) at 20˚C is 36 mg/L.
- pH value of the sample solution was 7.9, 8.1, and 8.4 after 24, 48 and 72 h of incubation respectively.

Table 1: Water solubility study results

The concentrations of the different test solutions were calculated automatically using the equation of the calibration curve and considering the dilution factors of the test solutions. The results are listed in the following table (all results given in mg/L):

Incubation time (hours)	Water solubility (TOC mg/L)	Total Average (TOC mg/L)
24	35	36
48	42
72	30

* standard deviation: 6.0 mg/L; relative standard deviation: 17.0%

- The relative standard deviation of six replicates exceeds the limit (≤15%) according to the test procedure. However, as the test substance was identified as a heterogenous mixture (with wide range of polarities) as per the GCMS chromatogram, a more accurate determination was not considered possible. Hence, the TOC analysis was considered as the appropriate technique to quantify the analyte in aqueous solution, and the relative standard deviation of 17% was considered to be acceptable.

Conclusions:

Under the test conditions, the water solubility of 'amides, C12-18(even-numbered) and C18(unsatd.), N-(hydroxyethyl)' was determined to be 36 mg/L at 20 °C (i.e., slightly soluble).

Executive summary:

A study was performed to determine the water solubility of ‘amides, C12-18 (even-numbered) and C18 -unsatd., N-(hydroxyethyl)’ according to the EU Method A.6.

A preliminary experiment performed with the test substance showed high water solubility of above 10E-2 g/L. Hence, the water solubility was determined by the "shake flask method".

0.1773 g of the test substance (0.1561 g, 0.1197 g) was transferred to 100 mL of water and stirred in a heated water bath for 24 hours (48 hours, 72 hours) at 30˚C. After incubation, the sample suspension was cooled to 20˚C and stirred for 24 hours. The supernatant was then filtered using a syringe filter. After centrifugation (for 20 minutes, 4500 rpm) the clear supernatant was analyzed via TOC (Total organic carbon) method.

Under the test conditions, the water solubility of the test substance was determined to be 36 mg/L at 20 °C (i.e., slightly soluble).

Description of key information

The water solubility was determined according to OECD Guideline 105 (Schöneck, 2022).

The water solubility was also determined according to EU Method A.6 (Frischmann, 2010).

Key value for chemical safety assessment

Water solubility:

32.6 mg/L

at the temperature of:

20 °C

Additional information

In the OECD Guideline 105 study, for the loading rate of about 1 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 10.7 mg/L ± 0.9 mg/L (mean ± standard deviation). For the loading rate of about 10 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 32.6 mg/L ± 0.7 mg/L (mean ± standard deviation). Since the test substance is a UVCB, the general definition for water solubility ( = saturation mass concentration of the test substance in water at a given temperature) is not applicable, and the usually accepted meaning of “water solubility” in such cases is the composition of the aqueous solution formed at equilibrium under a defined set of conditions, with the loading rate as the main factor to consider. The chromatographic profile of the water solubility sample was significantly different from the chromatogram of a standard solution. The peaks of four early eluting compounds on the reversed phase column were present in higher amounts in the sample as compared to the standard solution obtained by complete dissolution of the test substance in organic solvent. These four early eluting compounds had a higher polarity and thus a higher water solubility than later eluting compounds.

According to EU Method A.6, the water solubility of the test substance was determined to be 36 mg/L at 20°C.

The value of 32.6 mg/L at 20°C at the loading rate of 10 g/L from the OECD Guideline 105 study was retained for risk assessment purposes.