1-methoxy-4-[3-methyl-4-(2-phenylethoxy)but-3-en-1-yl]benzene

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12-07-2021 to 16-07-2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study performed under GLP with minor deviations. All relevant validity criteria were considered to be met.

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

Determination of the water solubility of the test item employing the flask method with slow stirring approach.The decision of the slow stirring method was made due to the test item properties. The test guideline was consistent with OECD Guideline 105 (water solubility) modified according to Letinski et. al. (2002) and OECD TG 123 (2006).

Deviations:

yes

Remarks:

Minor deviation: repeatability (deviation ≥ 15%) could not be fulfilled (actual: 24%). Water solubility was < 10 mg/L for the usage of the shake flask method, therefore the column elution and slow stirring method criterion (deviation ≤ 30%) can be adapted

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: November 2019 ; signature: August 2020

Type of method:

flask method

Key result

Water solubility:

0.263 mg/L

Conc. based on:

test mat.

Incubation duration:

72 h

Temp.:

20 °C

pH:

6.64

Remarks on result:

other: mean water solubility (n=3 ; 24, 48 and 72 h timepoints)

Preliminary test

A non-GLP preliminary test was performed to verify the definitive test study design. For this purpose, 0.5 mL test item was applied on top of approximately 50 mL purified water (18.2 MOhm/cm) with slow stirring at approx. 20 °C (ambient temperature) in duplicate. The test vessels were outfitted with a long cannula pierced through the lid into the water for sampling. The test item sank in small droplets to the ground of the vessel, negating the usage of the slow stirring approach for the determination of the water solubility. The column elution method was no alternative, as the test item is a liquid. After stirring overnight, both replicates appeared to be a homogenous, turbid mixture. Two aliquots of approx. 1.4 mL were taken from each replicate and centrifuged for 10 min at 20000x g and 20 °C. 0.5 mL of the supernatant was pipetted into fresh clear glass vials and checked negative for Tyndall effects. Afterwards, 0.5 mL acetonitrile were added for dilution and stabilization (dilution factor of 2) and the samples were analysed. The solubility was determined to be approximately 0.3 mg/L (or 300 µg/L). On this basis the slow-stir method adaptation to the flask-method was verified.

 

Definitive test:

The solubility of the test item in purified water (Mili-Q Advantage A10) with resistance 18.2 MΩ/cm was determined employing the flask method slow stirring approach at 20 ± 0.5 °C. The water solubility was respectively at pH 6.64:

Table 1.0: Water Solubility Results

Incubation Time (hours)	Replicate	Test item concentration (mg/L) #1	Mean
24	1	0.338
	2	0.324	0.331 mg/L
48	1	0.301
	2	0.282	0.291 mg/L
72	1	0.203
	2	0.266	0.234 mg/L
Mean (48-72 h)			0.263 mg/L
Deviation % (48-72 h) #2			24%

Where:

#1: Mean value of two injections, dilution factor of 2 and exact weight of the standard taken into account

#2: Calculated

 

Comments;

(i) Repeatability criteria: within the study, it was considered the criterion of the repeatability (deviation ≥ 15%) could not be fulfilled (actual: 24%). As the water solubility was below the general threshold of 10 mg/L for the usage of the shake flask method, the criterion given for the column elution and slow stirring method (deviation ≤ 30%) can be adapted and thus validating the study results.

(ii) Temperatures were kept constant within ± 0.5 °C. The analytical method (HPLC-DAD, external standard) for the determination of the test item was validated and tested with satisfactory results in regard to linearity, accuracy, precision and specificity.

Conclusions:

Interpretation of results: slightly soluble (0.1-100 mg/L)
The test item water solubility was determined to be 0.263 mg/L (or 263 µg/L) at pH 6.64 and 20.0 ± 0.5 °C

Executive summary:

The water solubility of the test item was determined according to the slow stirring adapted flask method of OECD Method 105 and EU Method A.6 in accordance with GLP. The solubility of the test item in purified water with resistance 18.2 MΩ/cm (i.e. conductivity: ≤ 0.5 µS/cm) and/or ≤ 10 ppb TOC was determined employing the flask method with slow stirring adaptation (≤ 100 rpm) at 20 ± 0.5 °C with incubation at test temperature for at least 24 h before the first sampling. Duplicate test vessels for each subjected to incubation time for at least 72 h at 20 ± 0.5 °C until equilibration was reached. Test vessels which were 100 mL amber glass stirring vessels with glass stopper, jacketed for temperature control. The test volume of purified water (with resistance 18.2 MΩ/cm) was 50 mL. The test item was transferred directly weighed into the test vessels and then purified water (50 mL) was added via positive displacement pipette. The vessels were closed by use of glass stopper to minimise volatilization/losses from the test system. Photolytic effects were avoided by use of amber glass. The test mixture replicates were incubated at 20 ± 0.5 °C with constant stirring at approx. 100 rpm for 24, 48 and 72 h, respectively. The pre-incubation step was not performed, in order to avoid potential emulsion formation. Samples were taken after the respective incubation times: 24, 48 and 72 h, respectively. There was not a tendency to increasing values up to 72 h and equilibration was apparently reached. Within the study, it was considered the criterion of the repeatability (deviation ≥ 15%) could not be fulfilled (actual: 24%). As the water solubility was below the general threshold of 10 mg/L for the usage of the shake flask method, the criterion given for the column elution and slow stirring method (deviation ≤ 30%) can be adapted and thus validating the study results. The analytical method (HPLC-DAD, external standard) for the determination of the test item was validated and tested with satisfactory results in regard to linearity, accuracy, precision and specificity. The mean water solubility (in purified water) of the test item was determined to be 0.263 mg/L (or 263 µg/L) of solution at pH 6.64 and 20.0 ± 0.5 °C. Within the study, it was considered the criterion of the repeatability (deviation ≥ 15%) could not be fulfilled (actual: 24%). As the water solubility was below the general threshold of 10 mg/L for the usage of the shake flask method, the criterion given for the column elution and slow stirring method (deviation ≤ 30%) can be adapted and thus validating the study results.

Description of key information

Water Solubility (slow stir) = 0.263 mg/L (or 263 µg/L) at 20 ± 0.5 °C and pH 6.64, OECD TG 105, 2021

Key value for chemical safety assessment

Water solubility:

0.263 mg/L

at the temperature of:

20 °C

Additional information

Key study : OECD TG 105, 2021 : The water solubility of the test item was determined according to the slow stirring adapted flask method of OECD Method 105 and EU Method A.6 in accordance with GLP. The solubility of the test item in purified water with resistance 18.2 MΩ/cm (i.e. conductivity: ≤ 0.5 µS/cm) and/or ≤ 10 ppb TOC was determined employing the flask method with slow stirring adaptation (≤ 100 rpm) at 20 ± 0.5 °C with incubation at test temperature for at least 24 h before the first sampling. Duplicate test vessels for each subjected to incubation time for at least 72 h at 20 ± 0.5 °C until equilibration was reached. Test vessels which were 100 mL amber glass stirring vessels with glass stopper, jacketed for temperature control. The test volume of purified water (with resistance 18.2 MΩ/cm) was 50 mL. The test item was transferred directly weighed into the test vessels and then purified water (50 mL) was added via positive displacement pipette. The vessels were closed by use of glass stopper to minimise volatilization/losses from the test system. Photolytic effects were avoided by use of amber glass. The test mixture replicates were incubated at 20 ± 0.5 °C with constant stirring at approx. 100 rpm for 24, 48 and 72 h, respectively. The pre-incubation step was not performed, in order to avoid potential emulsion formation. Samples were taken after the respective incubation times: 24, 48 and 72 h, respectively. There was not a tendency to increasing values up to 72 h and equilibration was apparently reached. Within the study, it was considered the criterion of the repeatability (deviation ≥ 15%) could not be fulfilled (actual: 24%). As the water solubility was below the general threshold of 10 mg/L for the usage of the shake flask method, the criterion given for the column elution and slow stirring method (deviation ≤ 30%) can be adapted and thus validating the study results. The analytical method (HPLC-DAD, external standard) for the determination of the test item was validated and tested with satisfactory results in regard to linearity, accuracy, precision and specificity. The mean water solubility (in purified water) of the test item was determined to be 0.263 mg/L (or 263 µg/L) of solution at pH 6.64 and 20.0 ± 0.5 °C. Within the study, it was considered the criterion of the repeatability (deviation ≥ 15%) could not be fulfilled (actual: 24%). As the water solubility was below the general threshold of 10 mg/L for the usage of the shake flask method, the criterion given for the column elution and slow stirring method (deviation ≤ 30%) can be adapted and thus validating the study results.