3-(diethylamino)-7-oxo-7H-[1]benzopyrano[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 27, 2017 to November 24, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

GLP compliance:

no

Type of method:

column elution method

Key result

Water solubility:

< 0.024 mg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

> 6.8 - < 9.1

Preliminary test:

Three preliminary tests were carried out with specified amounts of the test item and 100 mL and 500 mL demineralized water, respectively. After each addition of an amount of water, the mixture was stirred for at least 24 hours, and visually checked for any undissolved particles.

Table: Results of the preliminary test

Amount of test item / mg	Total volume of demineralized water / mL	Appearance of mixture
10.5	100	not dissolved
11.7	500	not dissolved
4.1	500	not dissolved

The preliminary test showed that the water solubility of the test item is < 10 mg/L. According to the preliminary test the water solubility was determined by the column elution method in the main test.

Column elution method:

101.61 mg of the test item were dissolved in 100 mL dichloromethane. For charging the columns in each case 25 mL of the test item solution was added to about 3 g of sea sand and the mixtures were shaken. The solvent was then removed under reduced pressure using a rotary evaporator (40 °C, approx. 40 mbar). The dry residues were placed into the columns of the test apparatus, which have afterwards been filled with water (test temperature: 20 °C; water pH at 26 °C: 7.1). After a swelling time of 2 h pumps were started to rinse the test item coated sand with demineralized water. At the end of the study it was confirmed that residual test item remained on the columns. The residual test item was eluted with 50 mL dichloromethane.

As blank value the used demineralized water was tested. No signal was detected in the range of the retention time of the test item.

The concentration of the test item was quantified by HPLC.

Column 1:

Rotation period of the fraction collector:                 90 min per fraction

Duration of sampling:                                             about 53 h (35 fractions)

Table: Column elution method, column 1 (approximately 12.5 mL/h)

Fraction no.	V / mL	pH	water solubility /µg/L
27	18.0	9.1	< 24.4
28	18.0	8.9	< 24.4
29	18.0	8.2	< 24.4
30	18.0	8.3	< 24.4
31	18.0	8.3	< 24.4

The water solubility was found to be below the quantification limit of 24.4 µg/L.

Column 2:

Rotation period of the fraction collector:       45 min per fraction

Duration of sampling:                                    about45 h(60 fractions)

Table: Column elution method, column 2 (approximately 25.0 mL/h)

Fraction no.	V / mL	pH	water solubility /µg/L
49	19.0	6.7	< 24.4
50	19.0	6.9	< 24.4
51	19.0	6.9	< 24.4
52	19.0	6.9	< 24.4
53	19.0	6.8	< 24.4

The water solubility was found to be below the quantification limit of 24.4 µg/L.

In both columns the concentration of five consecutive fractions was constant within ± 30 %. No increasing or decreasing tendency was observed.

Coating check:

Table: Coating check

	Amount of test item used for coating / mg	Measured concentration of test item in eluate / mg/L	Amount of test item eluted / mg
Column 12.5 mL/h	25.4	1.908 / 1.905	9.53
Column 25.0 mL/h		1.844 / 1.841	9.21

The coating check was successful. Enough test item remained on the columns.

The water solubility c_Sof the test item was below the quantification limit of 24.4 µg/L (mean value of the columns).

Executive summary:

The water solubility cS of the test item at a temperature of 20 °C was determined according to the column elution method. It was found to be below the quantification limit:

cS < 0.024 mg/L

Description of key information

The water solubility cS of the test item at a temperature of 20 °C was determined according to the column elution method. It was found to be below the quantification limit:

cS < 0.024mg/L

Key value for chemical safety assessment

at the temperature of:

20 °C