Benzonitrile, 4-[(1,6-dihydro-4-hydroxy-6-oxo-2-pyrimidinyl)amino]-

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Insufficient documentation for an assessment of reliability.

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

An excess of product is shaked with solvent during 24 hours at 20 deg C. After filtration the concentration in solution is determined with UV spectrometry.

GLP compliance:

not specified

Type of method:

other: no data

Water solubility:

< 10 mg/L

Temp.:

20 °C

pH:

6.9

Conclusions:

The water solubility of the test item was determined to be <10mg/L at 20°C and pH 6.9.
Interpretation of results: slightly soluble (0.1-100 mg/L).

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 July 2015 - 23 February 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

Deviations:

no

GLP compliance:

yes

Type of method:

column elution method

Specific details on test material used for the study:

- Batch n°: I15CB0987
- Analytical purity: 99.3%
- Expiration date: 17 May 2016
- Storage condition: at room temperature

Key result

Water solubility:

6 mg/L

Conc. based on:

test mat. (dissolved fraction)

Loading of aqueous phase:

52.2 other: mg

Incubation duration:

ca. 12 h

Temp.:

20 °C

pH:

ca. 6.8 - ca. 7.5

Remarks on result:

other: 2 h equilibration at flow rates 12ml/h and 24 ml/h

Details on results:

Preliminary test
The content of test item dissolved in the water sample was 2.63 mg/l. This value might have been overestimated as the centrifugation method was found to be insufficient to remove all undissolved test item. This was considered acceptable as the column elution method was going to be used in the main study.

Main test
The results for the samples taken at a flow rate of 12 and 24 mL/h are given in the table in the next section.
The coefficient of variation (CV) (n = 10) was ≤ 30% at both flow rates. It demonstrated that the system was equilibrated at all flow rates. The maximum difference (MD) on the mean values of the samples at both flow rates was also ≤ 30%. Based on this, the water solubility of the test item is given as the mean value of these measurements. The turbidity of the eluates was < 0.2 NTU. According to this, no undissolved particles were detected in the eluates.

The results for the samples taken at a flow rate of 12 mL/h and 24 mL/h are as follows:

Flow rate [mL/h]	Mean [mg/L]	pH
24	6.46	7.5
12	5.54	6.8

Conclusions:

The column elution method was applied for the determination of the water solubility of JNJ-4370561-AAA (T002326).
The water solubility of the test item at 20°C was 6.00 mg/L. The pH of the aqueous samples was 7.5 – 6.8.

Description of key information

The water solubility of T002326 was determined in a GLP study performed according to the OECD Guideline 105, EU Method A.6 and EPA OPPTS 830.7840 (K1, Reingruber, 2016) and was reported to be 6 mg/L at 20°C and pH 6.8-7.5.

Key value for chemical safety assessment

Water solubility:

6 mg/L

at the temperature of:

20 °C

Additional information

A study for which the reliability was not assignable (K4, J&J PRD) concluded that the water solubility of T002326 is <10 mg/L at 20°C and pH 6.9. This study is considered as supporting study and in agreement with the result of the key study.