Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 September - 17 December 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of method:
flask method
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as stated in study reports): JNJ-4508530-AAA (T002707)
- Physical state: solid (powder)
- Appearance: white, beige powder
Specific details on test material used for the study:
Batch n°: I15BB0573
Analytical purity: > 97.0%
Expiration date: 08 February 2017
Storage condition: at room temperature

Study design

Analytical method:
high-performance liquid chromatography
photometric method

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
-2.2
Temp.:
20 °C
pH:
7.1
Type:
log Pow
Partition coefficient:
0.4
Temp.:
20 °C
pH:
11
Details on results:
Calculation of Pow
The Pow of the test item was calculated to be 1.45E-1 (log Pow -0.84) using the Rekker calculation method.

Calculation of the pKa
The pKa values in the logarithm range of 1 - 14 for acidic and basic groups in the molecular structure of the test item were calculated using the Perrin calculation method. Only a basic group was identified (ARNH(C=NH)NH2), for which a pKa of 9.52 was calculated. Therefore, it was decided to perform the test both at pH 7 (potentially partly dissociated basic group) and pH 11 (assumed to be unionised).

Preliminary test
The content of test item dissolved in the n-octanol sample was 2.49 g/L.

Main study
The analysed concentration of the stock solution was 0.489 g/L for the determination at pH 7 and 0.482 g/L for the determination at pH 11. Based on this, the nominal quantity of the test item in the test samples was 0.977 mg and 0.964 mg, respectively. The recoveries were determined according to these values. The log Pow values were within the criterion range of ± 0.3 log units units except one of the 2:1 ratio samples at pH 7. This was considered acceptable in view of the low Pow and log Pow (and the associated low concentrations in the octanol phase) of the test item when determined at pH 7. Based on this, the Pow and log Pow of the test item is given as the mean value of all measurements. Small responses were detected in the pretreated samples from the blank mixtures. It was probably due to carry over, since similar signals were observed in the analytical blanks.
Detailed results at pH 7 are given in the table in the field 'Any other information on results incl. tables'.

Any other information on results incl. tables

 Ratio n-octanol:water (v:v)   Analysed concentration
 n-octanol (g/L)  water (g/L)
 Pow Pow (mean)  log Pow     pH     
 1:1  0.000863  0.172  5.0 E-3  4.6 E-3  -2.3  7.1
 1:1  0.000684  0.166  4.1 E-3    -2.4  7.1
 1:2  0.000868  0.124  7.0 E-3  8.7 E-3  -2.2 7.1
 1:2  0.00127  0.122  1.0 E-2    -2.0  7.1
 2:1  0.000685  0.245  2.8 E-3  4.0 E-3  -2.6  7.1
 2:1  0.00130  0.253  5.1 E-3    -2.3  7.1
 Mean      5.7 E-3    -2.2  
 Standard deviation      2.7 E-3      

Recovery was between 101 and 106%.

Applicant's summary and conclusion

Conclusions:
The shake flask method at pH 7 and pH 11 was applied for the determination of the partition coefficient (Pow) of JNJ-4508530-AAA (T002707).

The Pow value of the test item at pH 7 and 20°C was 5.7E-3, corresponding to a log Pow value of -2.2.
The Pow value of the test item at pH 11 and 20°C was 2.5, corresponding to a log Pow value of 0.4.