3-tert-butyladipic acid

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-05-22 to 2017-05-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

July 27, 1995

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

March 19, 2014

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

Version / remarks:

March 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Changzhou Sunlight Pharmaceutical Co., Ltd., China; 20160505 / 116727
- Expiration date of the lot/batch: May 2017
- Purity test date: 30.01.2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: stable

Key result

Water solubility:

4.89 g/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

3.6

Remarks on result:

completely miscible

Details on results:

The calibration solutions were prepared in 1 – 100 μg/mL range. The calibration samples were analysed by HPLC-UV method with three replicate injections from each.

Table 1: Regression data

Analytical occasion	Constant	X Coefficient	R. Squared
26 May 2017	295	5261	1.000

Table 2: Results of the determination of water solubility of the test substance

Sampling time	Measured concentration of test substance (g/L )		Measured pH
	Test vessels	Mean
After 24 h	5.339	5.02	3.59
	4.878		3.59
	4.843		3.58
After 48 h	4.845	4.83	3.60
	4.885		3.60
	4.761		3.59
After 72 h	4.652	4.81	3.63
	4.806		3.62
	4.981		3.61

The test substance concentrations were calculated with the help of the calibration equation given in Table 1.

Measured concentrations of the test substance are summarised in Table 2. The repeatability of the determination was < 15 % and thus within the range required by the guidelines.

Conclusions:

A water solubility of 4.89 ± 0.285 g/L at 20 °C was determined for the test substance.

Executive summary:

The water solubility of the test substance was determined with the shake flask method according to OECD guideline 105 and EU method A.6 (TOXICOOP, 2017).

A preliminary test for solubility was carried out as a range finding test for the decision whether the column elution method or the flask method has to be used for the performance of the main test. The solubility of the test item was higher than 10 mg/L, therefore the shake-flask method was used for the main test.

About 2.5 g test item was weighed into stoppered Erlenmeyer flasks (nine parallels) according to the estimated solubility based on the Preliminary Test. After the addition of 100 mL ultra-pure water, the flasks were agitated at 30 °C. After one day, three of the vessels were removed and re-equilibrated at 20 °C for 24 hours. The content of the vessel was then centrifuged at 20 °C and the concentration in the clear aqueous phase was determined by HPLC. The other flasks were treated similarly after initial equilibration at 30 °C for two and three days, respectively. The samples were diluted before the analysis (two parallel dilutions). The pH of each sample was recorded.

The saturated samples were centrifuged at 20 °C, at 13000 rpm (5 min) and the concentration in the clear aqueous phase was determined by HPLC. The samples were diluted 200-fold with ultrapure water before HPLC measuring.

The test substance was measured in the final solution using the previously validated reverse phase HPLC method with UV detection. The water solubility of the test substance was determined to be 4.89 ± 0.285 g/L (95% confidence interval) at 20 °C ± 0.5 °C using the shake-flask method for the performance of the main test.

Description of key information

A water solubility of 4.89 ± 0.285 g/L at 20 °C was determined for the test substance.

Key value for chemical safety assessment

Water solubility:

4.89 g/L

at the temperature of:

20 °C

Additional information

The water solubility of the test substance was determined with the shake flask method according to OECD guideline 105 and EU method A.6 (TOXICOOP, 2017).

A preliminary test for solubility was carried out as a range finding test for the decision whether the column elution method or the flask method has to be used for the performance of the main test. The solubility of the test item was higher than 10 mg/L, therefore the shake-flask method was used for the main test.

About 2.5 g test item was weighed into stoppered Erlenmeyer flasks (nine parallels) according to the estimated solubility based on the Preliminary Test. After the addition of 100 mL ultra-pure water, the flasks were agitated at 30 °C. After one day, three of the vessels were removed and re-equilibrated at 20 °C for 24 hours. The content of the vessel was then centrifuged at 20 °C and the concentration in the clear aqueous phase was determined by HPLC. The other flasks were treated similarly after initial equilibration at 30 °C for two and three days, respectively. The samples were diluted before the analysis (two parallel dilutions). The pH of each sample was recorded.

The saturated samples were centrifuged at 20 °C, at 13000 rpm (5 min) and the concentration in the clear aqueous phase was determined by HPLC. The samples were diluted 200-fold with ultrapure water before HPLC measuring.

The test substance was measured in the final solution using the previously validated reverse phase HPLC method with UV detection. The water solubility of the test substance was determined to be 4.89 ± 0.285 g/L (95% confidence interval) at 20 °C ± 0.5 °C using the shake-flask method for the performance of the main test.