4,5-bis(hydroxymethyl)-2-phenyl-1H-imidazole

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 20 September 2021 to 15 February 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

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

2014

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 18-20 August 2020, Date on certificate: 04 March 2021

Type of method:

flask method

Key result

Water solubility:

194 mg/L

Conc. based on:

test mat. (dissolved fraction)

Loading of aqueous phase:

2 120 mg/L

Temp.:

20 °C

pH:

5

Remarks on result:

other: Mean of 24, 48 and 72 h incubation duration results

Preliminary Test

A preliminary test was carried out as a range finding test prior to the main test. The concentration range obtained gave an indication on the necessary analytical method sensitivity.

Increasing volumes of water were added at room temperature to 21.4 mg of the test sample in a 100 mL flask. After each addition of an amount of water, the mixture was shaken for 10 minutes and was visually checked for any undissolved parts of the sample.

The approximate solubility deduced from the necessary volume of pure water in which complete dissolution of the sample occurred is given in the table below.

Volume of water added (mL)	Solubilisation?	Approximate solubility
1	NO	-
10	NO	-
100	NO	< 214 mg/L

The test item (21.4 mg) was not solubilized by a water volume of 100 mL after 24 hours, corresponding to a solubility of less than 214 mg/L. Nevertheless, powder was observed on the wall of the flask or at the surface of the water. Therefore, another preliminary was performed.

10 mL of water were added at room temperature to 11.8 mg of the test sample in a 10 mL flask. The mixture was alternatively shaken with a vortex mixer and introduced in an ultrasonic bath. The content of the flask was then centrifuged (2850 g at 20°C for 15 minutes) and the supernatant analysed. The concentration measured was 421 mg/L. This value approximates the test item water solubility.

This value is greater than 10 mg/L, therefore the shake flask method was chosen to determine the solubility of the test item in ultrapure water.

 

Main Test

After the centrifugation of the samples, solid particles of the test item were observed at the bottom and in the surface of the containers, meaning that the test item was introduced in excess.

The following table presents the loading rates applied and the concentrations obtained during the study for each vessel.

	Incubation time at 30°C	Introduced test item (mg)	Loading rate (mg/L)	Analysis 1 (mg/L)	Analysis 2 (mg/L)	Average concentration (mg/L)
Vessel 1	24 h	529.8	2120	183	188	186
Vessel 2	48 h	530.5	2120	192	188	190
Vessel 3	72 h	530.6	2120	205	208	207
Mean (mg/L)						194
Maximum difference						10.7%

The equilibrium was considered as reached because the concentrations measured in the three vessels did not differ by more than ±15% (maximum difference of 10.7% between the samples at 186 mg/L and 207 mg/L). The test item water solubility was then calculated as the mean of the three samples concentrations: 194 mg/L.

The pH values measured in all three vessels, at the beginning and at the end of the experiment were 5 in each case.

 

The study was considered as valid since:

- the equilibrium was reached for the three vessels;

- the pH variation did not exceed 2 pH units

Conclusions:

The solubility of the test item in water at 20 ± 0.5 °C based on three determinations with the
shake flask method was 194 mg/L.

Executive summary:

A study was performed to assess the water solubility of test item by the shake flask method in accordance with OECD Guideline 105 and EU Test Method A.6 in accordance with GLP.

Three determinations in ultrapure water were carried out. About 530 mg of the test item was mixed with 250 mL of water (loading rate 2120 mg/L corresponding to 5 times the approximate solubility measured in the preliminary tests). The solutions were stirred for incubation times of 24h, 48h and 72h at 30°C for vessels 1, 2 and 3 respectively. The test item concentrations were determined after an equilibration period of 24h at the test temperature of 20°C.

The solubility of the test item in water at 20 ± 0.5 °C based on the mean of three determinations with the shake flask method measured with a validated HPLC method was 194 mg/L.

Description of key information

194 mg/L; OECD 105 (flask method); Mata, L. (2022)

Key value for chemical safety assessment

Water solubility:

194 mg/L

at the temperature of:

20 °C

Additional information

pH of saturated solution: 5