Benzonitrile, 4-[(4-chloro-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.

Principles of method if other than guideline:

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

GLP compliance:

not specified

Type of method:

other: no data

Water solubility:

< 0.01 g/L

Temp.:

20 °C

pH:

6.1

Conclusions:

The water solubility of T002488 was determined to be <0.01 g/L and therefore considered slightly soluble.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 December 2015 - 25 April 2016

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

column elution method

Specific details on test material used for the study:

- Batch n°: I15FC2164
- Analytical purity: 102.2% (HPLC assay)
- Expiration date: 23 June 2017
- Storage condition: at room temperature

Key result

Water solubility:

0.839 mg/L

Conc. based on:

test mat. (dissolved fraction)

Temp.:

20 °C

pH:

>= 7.9 - <= 8

Details on results:

Preliminary test
The content of test item dissolved in the water sample was 0.929 mg/L.

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 of the blanks was < 0.2 NTU. According to this, no undissolved particles were detected in the blank eluates. The turbidity of the eluates with test item was slightly above 0.2 NTU (i.e. 0.265 and 0.302 NTU). As the specification was only slightly exceeded and the variation of the individual analyses was minimal it was considered not having any negative impact on the study.
A small response was observed at the retention time of the test item in one of the samples of the blank column. As the maximum contribution to the samples was 3%, it was considered not having any negative impact on the study.

The results for the samples taken at a flow rate of 12 and 24 mL/h are given in the table below.

Flow rate (mL/h)	Mean (n=10) (mg/L)	CV (%)	Mean (mg/L)	Maximum Difference (MD) (%)	pH
24	0.834	1.8	0.839	1.1	8.0
12	0.843	0.29			7.9

Conclusions:

The column elution method was applied for the determination of the water solubility of JNJ-4754724-AAA (T002488).
The water solubility of the test item at 20°C was 0.839 mg/L.
The pH of the aqueous samples was 7.9 – 8.0.

Description of key information

The water solubility of T002488 was determined in a GLP study performed according to the OECD Guideline 105, EU Method A.6 and EPA OPPTS 830.7840 (Klimisch 1, Reingruber, 2016) using the column elution method and was determined to be 0.839 mg/L at 20°C and pH 7.9 - 8.0.

Key value for chemical safety assessment

Water solubility:

0.839 mg/L

at the temperature of:

20 °C

Additional information

A supporting study (J&J PRD, 2002) with insufficient documentation, and therefore assigned as Klimisch 4 study, concluded that the water solubility of T002488 is < 0.01 g/L at 20°C, which is in line with the result of the key study by Reingruber (2016).