Amides, C8-18 (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:

May, 2020 to April, 2021

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

Water solubility:

0.181 g/L

Conc. based on:

test mat. (dissolved fraction)

Remarks:

not corrected for FAA constituent purity

Loading of aqueous phase:

1 g/L

Incubation duration:

24 - 72 h

Temp.:

20 °C

pH:

7

Water solubility:

0.159 g/L

Conc. based on:

test mat. (dissolved fraction)

Remarks:

Corrected for 88% FAA constituent purity

Loading of aqueous phase:

1 g/L

Incubation duration:

24 - 72 h

Temp.:

20 °C

pH:

7

Water solubility:

1.37 g/L

Conc. based on:

test mat. (dissolved fraction)

Remarks:

not corrected for FAA constituent purity

Loading of aqueous phase:

10 g/L

Incubation duration:

24 - 72 h

Temp.:

20 °C

pH:

7

Key result

Water solubility:

1.206 g/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

Conclusions:

Under the study conditions, the water solubiluity of the test substance was determined to be 0.181 g/L at a loading rate of 1 g/L and 1.37 g/L at a loading rate of 10 g/L. The purity of the tested sample was reanalysed in September 2022. The FAA constituent fraction was calculated to correspond to 94% w/w uncorrected, i.e., 88% w/w corrected for overall sample purity. Based on 88% w/w purity, the water solubility values can be calculated as 0.159 g/L at the loading rate of 1 g/L and 1.206 g/L at the loading rate of 10 g/L.

Executive summary:

A study was conducted to determine the water solubility of amides, C8-18 (even-numbered) and C18-unsatd., N,N-bis(hydroxyethyl) (C8 -18 and C18-unsatd. DEA) according to OECD Guideline 105, in compliance with GLP. The shake-flask method was used.

Vessels containing water and the test substance were shaken for approximately 24 hours, 48 hours, and 72 hours, respectively, at about 30°C. Afterwards, the samples were equilibrated for another 24 hours at 20°C. Then, the samples were filtrated and diluted, and the concentrations 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 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 1. The "water solubility" based on a visual assessment test was found to be < 200 mg/L. This assessment is likely caused by the presence of low-soluble components remaining undissolved at the given test substance concentration.

For the loading rate of about 1 g/L, the "water solubility" at 20°C using the shake-flask method was found to be 0.181 g/L ± 0.035 g/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 1.37 g/L ± 0.048 g/L (mean ± standard deviation). For the loading rate of about 100 g/L, no clear solutions were obtained after filtration. Therefore, the test at the second loading rate was repeated with a lower loading rate of about 1 g/L. The chromatographic profile of the water solubility sample is significantly different from the chromatogram of a standard solution. The peaks of three early eluting compounds on the reversed phase column are present in higher amounts in the sample as compared to the standard solution. These three early eluting compounds have a higher polarity and thus a higher water solubility than later eluting compounds. During LC/MS structural identification work, the identity of these three compounds could be confirmed to be N-(2-hydroxyethyl)hexanamide, N-(2-Hydroxyethyl)octanamide and N-(2-hydroxyethyl)decanamide. Calculations based on estimated water solubilities of these compounds indicated that the "water solubility" of the test substance is caused by the individual water solubilities of these compounds (Schreitmüller, 2021).

The purity of the tested sample was reanalysed in September 2022. The FAA constituent fraction was calculated to correspond to 94% w/w uncorrected, i.e., 88% w/w corrected for overall sample purity. Based on 88% w/w purity, the water solubility values can be calculated as 0.159 g/L at the loading rate of 1 g/L and 1.206 g/L at the loading rate of 10 g/L.

Reference 2

Endpoint:

water solubility

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

supporting study

Study period:

From October 2009 to March 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data estimated by WATERNT v 1.01 using EPISUITE v 4

Principles of method if other than guideline:

WATERNT v 1.01 program of EPISUITE v 4

GLP compliance:

yes (incl. QA statement)

Type of method:

other: estimated

Water solubility:

>= 7.5 - <= 15 mg/L

Temp.:

25 °C

Remarks on result:

other: Estimated by WATERNT v 1.01 using EPISUITE v 4

Details on results:

As it can be seen from Table 1 that for 15 mg of amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) in 1L of water the calculated C18 amide amount of 0.345 mg/L exceeded its solubility limit which equals 0.187 mg/L. The same situation appeared for the C18’ constituent: The calculated amount of 0.705 mg/L is greater than its water solubility limit of 0.411 mg/L. In case of increasing the amount of amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) to 31 mg/L also the water solubility of C16 amide is exceeded. However for amounts of amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) up to and including 7.50 mg/L all constituents of amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) remain below the predicted solubility limits in water. Overall, based on the comparisons made in Table 1 it can be concluded that using the WATERNT model the water solubility of amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) is calculated to be between 7.5 and 15 mg/L.

Table 1. Calculated amides, C18-18 and C18 unsaturated, N-(hydroxyethyl)

constituents water solubility and their content in amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) -water mixtures

 

Component	Component concentration (%)	Calculated water solubility at 25 ºC (mg/L)	Constituent concentration after addition of x mg of Amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) to 1 L of water (mg/L)
			Amides, C18-18 and C18 unsaturated, N-(hydroxyethyl) added (mg/L)
			3.75	7.50	15.0	31.0
Amides:
C8	8.2	25039	0.3075	0.615	1.23	2.542
C10	7.00	2427.7	0.263	0.525	1.05	2.170
C12	47.00	231.39	1.763	3.525	7.05	14.570
C14	18.70	21.761	0.692	1.403	2.805	5.797
C16	9.40	2.025	0.353	0.705	1.41	2.914
C18	2.30	0.187	0.086	0.173	0.345	0.713
C18’	4.70	0.411	0.176	0.353	0.705	1.457
C18’’	2.30	0.903	0.086	0.173	0.345	0.713
free amine	0.40	10^6	0.150	0.300	0.600	1.200

Conclusions:

The water solubility of amides, C18-18 and C18 unsatd., N-(hydroxyethyl) was found to be between 7.5 and 15 mg/L at 25 ºC as estimated by WATERNT v 1.01 using EPI Suite v 4.

Executive summary:

Amides, C18-18 and C18 unsatd., N-(hydroxyethyl) consists of multiple constituents rendering the task of a reliable analytical quantification of the test item dissolved in water difficult. The experimental methods (EEC A.6 water solubility preliminary test and dilution test) were conducted which were based on visual analysis. The water solubility of amides, C18-18 and C18 unsatd., N-(hydroxyethyl) was found to be < 0.100 and < 0.0037 g/L at 20 ºC in EEC A.6 preliminary test and the dilution test, respectively. Since the water solubility limits which have been experimentally determined cannot be considered to be sufficiently reliable because of the weakness of the applied observation method, the water solubility was estimated by WATERNT v 1.01 using EPI Suite v 4 at 25 ºC and considered as the best estimate.The water solubility of amides, C18-18 and C18 unsatd., N-(hydroxyethyl) was found to be between 7.5 and 15 mg/L at 25 ºC as estimated by WATERNT v 1.01 using EPI Suite v 4. Therefore, amides, C8-18 and C18 unsatd., N-(hydroxyethyl) can be considered as slightly soluble in water.

Description of key information

Water solubility was determined according to OECD Guideline 105 (shake flask method) (Schreitmüller, 2021).

Water solubility had also previously been estimated using the WATERNT v 1.01 program of EPISUITE v. 4.0.

Key value for chemical safety assessment

Water solubility:

1 206 mg/L

at the temperature of:

20 °C

Additional information

In the study conducted according to OECD Guideline 105 (shake flask method), for the loading rate of about 1 g/L, the "water solubility" at 20°C was found to be 0.181 g/L ± 0.035 g/L (mean ± standard deviation). For the loading rate of about 10 g/L, the "water solubility" at 20°C was 1.37 g/L ± 0.048 g/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 three early eluting compounds on the reversed phase column were present in higher amounts in the sample as compared to the standard solution. These three early eluting compounds had a higher polarity and thus a higher water solubility than later eluting compounds. During LC/MS structural identification work, the identity of these three compounds could be confirmed to be N-(2-hydroxyethyl)hexanamide, N-(2-Hydroxyethyl)octanamide and N-(2-hydroxyethyl)decanamide. Calculations based on estimated water solubilities of these compounds indicated that the "water solubility" of the test substance is caused by the individual water solubilities of these compounds (Schreitmüller, 2021).

The purity of the tested sample was reanalysed in September 2022. The FAA constituent fraction was calculated to correspond to 94% w/w uncorrected, i.e., 88% w/w corrected for overall sample purity. Based on 88% w/w purity, the water solubility values can be calculated as 0.159 g/L at the loading rate of 1 g/L and 1.206 g/L at the loading rate of 10 g/L.

For risk assessment purposes, the corrected water solubility at the high loading rate was selected (1.206 g/L).

In earlier evaluations, the range of water solubility estimated using WATERNT v 1.01 was 7.5-15 mg/L.