(2S)-6-fluoro-2-(oxiran-2-yl)chromane

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 March - 16 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EU method A.24 (Partition coefficient - HPLC method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Test material

Test material information

1

Reference substance name:

(2S)-6-fluoro-2-(oxiran-2-yl)chromane

EC Number:

930-889-9

Cas Number:

1219915-05-5

Molecular formula:

C11H11FO2

IUPAC Name:

(2S)-6-fluoro-2-(oxiran-2-yl)chromane

Test material form:

liquid

Details on test material:

Physical state: liquid
Appearence: light brown liquid

Specific details on test material used for the study:

- Batch n°: I16FB3013
- Analytical purity: 87.5%
- Expiration date: 07 June 2018
- Storage condition: at room temperature

Study design

Analytical method:

high-performance liquid chromatography

photometric method

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

>= 2.2 - <= 2.5

pH:

7

Remarks on result:

other: These log Pow values are determined based on the 2 major component peaks: log Pow 2.2 (34 area%) and 2.5 (54 area%). The minor peaks agreed with a log Pow value of 3.0 (3.2 area%), 3.2 (8.5 area%) and 5.2 (1.0 area%).

Remarks:

Column temperature: 35°C +/-1°C

Details on results:

Calculation method
The Pow of the test item was calculated to be 4.5 E2 (log Pow 2.7) using the Rekker calculation method.
No pKa values for acidic and basic groups in the molecular structure of the test item in the logarithm range of 1 - 14 were calculated.

Main study
In the chromatogram of the test solution, two major peaks and several small test item peaks were observed. Only peaks with an area of more than 1% are taken into account.
The results of the HPLC method show the calibration curve of the log k’ of the reference substances as function of log Pow.
The equation of the regression line was: log k’ = 0.335 * log Pow – 0.812 (r = 0.995, n = 16). Detailed results are given in the table in the field 'Any other information on results incl. tables'.

Any other information on results incl. tables

Pow of the reference substances and test item

Substance	tr,1 (min)	tr,2 (min)	mean tr (n=2)	log Pow	Pow
Formamide (t0)	0.630	0.628	0.629
Benzylalcohol	0.819	0.816		1.1
Nitrobenzene	1.014	1.010		1.9
Toluene	1.623	1.620		2.7
1,4-Dichlorobenzene	2.113	2.107		3.4
Biphenyl	2.850	2.847		4.0
Dibenzyl	4.772	4.770		4.8
Triphenylamine	8.829	8.829		5.7
4,4’-DDT	12.844	12.838		6.5
Test item - peak 1 (major component)	1.155	1.151	1.153	2.2	1.5E2
Test item - peak 2 (major component)	1.279	1.275	1.277	2.5	2.9E2
Test item - peak 3 (minor component)	1.597	1.591	1.594	3.0	9.4E2
Test item - peak 4 (minor component)	1.815	1.806	1.811	3.2	1.7E3
Test item - peak 5 (minor component)	5.843	5.829	5.836	5.2	1.4E4

Applicant's summary and conclusion

Conclusions:

The HPLC method at pH 7 was applied for the determination of the partition coefficient (Pow) of JNJ-42819543-AAA (T001596).
The Pow values of the major components of the test item were 1.5 x 10² (34 area%) and 2.9 x 10² (54 area%). These correspond to a log Pow value of 2.2 and 2.5, respectively.