2-chlorophenyl cyclopentyl ketone

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 June 2017 - 14 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

2-chlorophenyl cyclopentyl ketone

EC Number:

229-802-0

EC Name:

2-chlorophenyl cyclopentyl ketone

Cas Number:

6740-85-8

Molecular formula:

C12H13ClO

IUPAC Name:

2-chlorophenyl cyclopentyl ketone

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study reports): JNJ-54582034-AAA (T003642)
- Physical state: liquid
- Appearance: yellow liquid

Specific details on test material used for the study:

- Batch n°: I16KB4361
- Analytical purity: 98.4% (HPLC assay)
- Test item storage: In refrigerator (2-8°C), container flushed with argon
- Stable under storage conditions until: 19 Sep 2017 (retest date)

Results and discussion

Water solubility

Key result

Water solubility:

0.02 g/L

Conc. based on:

test mat. (dissolved fraction)

Loading of aqueous phase:

0.18 g/L

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 6.4 - <= 7.1

Details on results:

Preliminary test
The content of test item dissolved in the water sample was 0.0265 g/L (centrifuged twice). This value might have been slightly overestimated. Checking the centrifugation procedure a difference of 16% was observed.

Main study
The results for the samples taken at 24, 48 and 72 hours, for the first sampling, where samples were centrifuged twice, the second sampling, where samples were centrifuged three times. For each sampling, the centrifugation procedure was checked centrifuging one more time.
A small response on the retention time of the test item was detected in the pretreated samples from the blank water mixture. As the maximum contribution to the samples was <1%, the integrity of the study was not impacted.
Centrifuging the water solubility samples three times rather than twice, a significant decrease in test item concentration was observed (first sampling). Hence, new samples were taken and an extra centrifugation step was added to sample pretreatment (second sampling). Checking the centrifugation procedure, again a significant difference was observed. Obviously centrifugation did not lead to a stable test item concentration. Based on visual evaluation no undissolved test item was present already after the first centrifugation. The fact that the test item concentration kept decreasing with each centrifugation step might have been taken place due to adsorption of the test item to the walls of the centrifugation vessel or to volatilization of the test item during centrifugation. As the test item is a liquid, it is not possible to remove undissolved test item by filtration. The obtained results were, therefore, considered what was technically feasible. The water solubility of the test item is considered as 0.02 ± 0.01 g/L. This range covers all experimentally observed results of analysis and also a back-calculated water solubility without applying centrifugation.

Any other information on results incl. tables

The results for the first sampling taken at 24, 48 and 72 hours are given in the table underneath.

Stirring time (hours)	Analysed concentration (g/L)	pH
24	0.0209	6.9
48	0.0228	6.9
72	0.0198	6.7
72*	0.0147	6.6

* This sample was centrifuged 3 times to check the centrifugation method. The concentration decreased with 30% compared to the other samples which were centrifuged 2 times.

The results for the second sampling taken at 24, 48 and 72 hours are given in the table underneath.

Stirring time (hours)	Analysed concentration (g/L)	pH
24	0.0121	6.4
48	0.0118	7.1
72	0.0123	6.9
72*	0.0105	6.7

* This sample was centrifuged 3 times to check the centrifugation method. The concentration decreased with 30% compared to the other samples which were centrifuged 2 times

Applicant's summary and conclusion

Conclusions:

The flask method was applied for the determination of the water solubility of JNJ-54582034-AAA (T003642).
The water solubility of the test item at 20°C was 0.02 ± 0.01 g/L.
The pH of the aqueous samples was 6.4 – 7.1.