Diethyl ethoxymethylenemalonate

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 July 2017 - 27 November 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:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EU Method A.24 (Partition Coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) Method)

Version / remarks:

March 1, 2016

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl ethoxymethylenemalonate

EC Number:

201-725-7

EC Name:

Diethyl ethoxymethylenemalonate

Cas Number:

87-13-8

Molecular formula:

C10H16O5

IUPAC Name:

diethyl ethoxymethylenemalonate

Test material form:

liquid

Specific details on test material used for the study:

- Batch n°: JC170405
- Analytical purity: 99.5%
- Expiration date: 12 April 2018
- Storage condition: at room temperature

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Key result

Type:

log Pow

Partition coefficient:

1.5

pH:

7

Remarks on result:

other: Test item - peak 1 (Area: 99%)

Remarks:

Column temperature was 35°C ± 1°C

Partition coefficient 2

Key result

Type:

log Pow

Partition coefficient:

2.1

pH:

7

Remarks on result:

other: Test item - peak 2 (Area 1.4%)

Remarks:

Column temperature was 35°C ± 1°C

Details on results:

Calculation of the Pow
The Pow of the test item was calculated to be 1.02 x 10^2 (log Pow 2.01) using the Rekker calculation method.

Calculation of the pKa
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, one major peak and one small test item peak were observed. A small response at the retention time of the test item was detected in the chromatogram of the blank sample. It was considered as contamination with no significant effect on the results of the test samples.
The equation of the regression line was: log k’ = 0.330 × log Pow – 0.837 (r = 0.994, 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 test item

Substance	tr,1 [min]	tr,2 [min]	mean tr (n=2)	log Pow	Pow	Area (%)
Formamide (t0)	0.607	0.607	0.607
Benzyl alcohol	0.775	0.776		1.1
Nitrobenzene	0.947	0.948		1.9
Toluene	1.484	1.486		2.7
1,4-Dichlorobenzene	1.906	1.908		3.4
Biphenyl	2.536	2.539		4.0
Dibenzyl	4.161	4.166		4.8
Triphenylamine	7.556	7.553		5.7
4,4'-DDT	10.879	10.860		6.5
Test item - peak 1	0.871	0.876	0.874	1.5	2.8E1	99
Test item - peak 2	1.048	1.051	1.050	2.1	1.3E2	1.4

Applicant's summary and conclusion

Conclusions:

The HPLC method was applied for the determination of the partition coefficient (Pow) of JNJ-39005525-AAA (EMME).
The Pow value of the test item at neutral pH was 2.8E1. This corresponds to a log Pow value of 1.5 (major peak; area 99%).
The Pow value of the test item at neutral pH was 1.3E2. This corresponds to a log Pow value of 2.1 (small peak; area 1.4%).