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Physical & Chemical properties

Water solubility

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Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-09-23 till 2015-01-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study without restrictions.
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
Version / remarks:
(1995)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
Version / remarks:
(2008)
Deviations:
no
Principles of method if other than guideline:
To determine the water solubility of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one, two different methods can be used:
− The column elution method for solubility < 1E-2 g/L.
− The flask method for solubility ≥ 1E-2 g/L.
In a preliminary test, the water solubility of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one was found to be < 1E-2 g/L. Therefore, the column elution method is chosen for the determination of the water solubility.
For the main test 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one is eluted with water from a micro-column which is charged with silica gel, previously coated with an excess of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one. At 20 °C nineteen fractions are collected at a flow rate of 12 mL/h (column 1) and ten fractions are collected at a flow rate of 24 mL/h (column 2). For each fraction 10 mL are collected. After dilution with acetonitrile the concentration of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one in the solutions is determined by HPLC-analysis.
GLP compliance:
yes (incl. certificate)
Type of method:
column elution method
Water solubility:
< 0 g/L
Conc. based on:
test mat.
Temp.:
20 °C
pH:
>= 6.3 - <= 6.8
Key result
Water solubility:
ca. 11 µg/L
Conc. based on:
test mat.
Temp.:
20 °C
pH:
>= 6.3 - <= 6.8
Remarks on result:
other: Value not reported as such but obtained after having scrutinized the raw data.
Details on results:
Mean value of both columns: < 0.00002 g/L
Result of the preliminary test: 0.0022 g/L
The pH was in the range of 6.3 - 6.8.

Solution of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one

Initial weight: 25.5 mg / 50 mL

Solvent: Tetrahydrofuran

Content of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one: 99.9 %

Loading of the support

Support material: Chromosorb W/AW (0.15-0.18 mm), Merck

Initial weight of the support material: 600 mg

Volume of the solution of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one: 10 mL

Test temperature: 20 °C ± 0.5 °C

The concentrations of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one in the fractions were determined by HPLC. Nineteen fractions were collected from column 1 and ten fractions from column 2. Ten data points are listed in the following table including the five fractions with constant concentrations, which were used for the determination of the water solubility (marked with *). For each fraction 10 mL were collected.

The following table shows the results as given by the study report.

       Column 1 (12 mL/h) Column 2 (24 ml L/h)       
Fraction no.   pH value  Concentration  Fraction no.  pH value  Concentration
    [β] = g/L      [β] = g/L
6.5  < 0.00002   1  6.4  0.000024
10 6.6 < 0.00002  2  6.3  < 0.00002
11  6.7   < 0.00002*  3  6.5   < 0.00002
12 6.5    < 0.00002*  4 6.6    < 0.00002
13  6.5   < 0.00002*   5 6.7   < 0.00002* 
14  6.7   < 0.00002*   6 6.7   < 0.00002*
15  6.6   < 0.00002*   7 6.5   < 0.00002* 
16 6.8  < 0.00002   8 6.5   < 0.00002* 
17  6.8   < 0.00002   9 6.6    < 0.00002*
18  6.7   < 0.00002   10 6.6    < 0.00002

An in-depth-evaluation of the raw data was performed in order to better characterise the water solubility. The results of this evaluation are shown in the following table.

       Column 1 (12 mL/h) Column 2 (24 ml L/h)       
Fraction no.   pH value  Concentration  Fraction no.  pH value  Concentration
    [β] = g/L      [β] = g/L
6.5  0.000016   1  6.4 0.000024
10 6.6 0.000015  2  6.3 0.000008
11  6.7   0.000016*  3  6.5 0.000008
12 6.5   0.000017*  4 6.6  0.000004
13  6.5   0.000017*   5 6.7  0.000007* 
14  6.7   0.000014*   6 6.7  0.000007*
15  6.6   0.000017*   7 6.5  0.000006* 
16 6.8 0.000014   8 6.5  0.000005* 
17  6.8  0.000015  9 6.6  0.000007*
18  6.7  0.000013  10 6.6  0.000009
mean of relevant results marked with an asterix 0.000016   0.000006

Although the lowest calibration was given as 10 µg/L, a clear signal could be seen down to 5 µg/L. Therefore the results of both column were used. A final mean value from both columns results in a water solubility of 11 µg/L.

Conclusions:
Interpretation of results (migrated information): insoluble (< 0.1 mg/L)
The water solubility of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one determined by the column elution method at 20 °C and was about 11 µg/L.
Executive summary:

The water solubility of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one is determined by the column elution method using the methods of OECD Guideline 105 “Water solubility“ (1995) and the EC Guideline A.6 “Water solubility” (2008). The mean value of the both columns was < 0.00002 g/L at 20 °C. An in-depth-evaluation using the original raw data yielded in a water solubility of about 11 µg/L.

Description of key information

The water solubility of 14H-benz[4,5]isoquino[2,1-a]perimidin-14-one determined by the column elution method at 20 °C and was 11 µg/L.

Key value for chemical safety assessment

Water solubility:
11 µg/L
at the temperature of:
20 °C

Additional information

The study reported a water solubility of < 0.00002 g/L. Scrutinizing the raw data indicated a value of about 11 µg/L.

A supporting study performed similar to OECD 105 yieled a result of about 8 µg/L at 22 -25°C.