Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 March - 11 October 2016
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 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of method:
HPLC method
Remarks:
and the Rekker calculation method (preliminary estimation)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study reports): JNJ-117676-AAA (T000263)
- Physical state: solid (powder)
- Appearance: White, slight beige amorphous, crystalline, micropowder
Specific details on test material used for the study:
- Batch n°: I15BB0491
- Analytical purity: 99.8% (base titration)
- Expiration date: 04 February 2021
- Storage condition: at room temperature

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
1.8
pH:
7
Remarks on result:
other: T not determined
Key result
Type:
log Pow
Partition coefficient:
2.1
pH:
11
Remarks on result:
other: T not determined
Details on results:
Calculation method
Calculation of log Pow
The Pow of the test item was calculated to be 1.1 E+1 (logPow 1.0) using the Rekker calculation method.

Calculation of pKa values
A pKa value of 9.7 was calculated for 1 basic group in the molecule.
Based on the pKa value, it was decided to perform the test both at pH 7.0 (ionised form) and pH 11.0 (unionised form).

Main study at pH 7
The equation of the regression line was: log k' = 0.363 log Pow - 0.885 (r=0.993, n=12).

Main study at pH 11
The equation of the regression line was: log k’ = 0.387 log Pow – 1.101 (r=0.98, n=12).

Any other information on results incl. tables

Results - pH 7:

 Substance  tr,1 (min)  tr,2 (min) Mean tr (min)  logPow
 Formamide (t0 )  0.579 0.575  0.577  
 Benzylalcohol  0.754  0.755    1.1
 Nitrobenzene  0.923  0.919    1.9
Toluene  1.476  1.471    2.7
1,4-Dichlorobenzene  1.909  1.902    3.4
Biphenyl  2.570  2.561   4.0 
 1,2,4-Trichlorobenzene  2.958  2.947    4.2
 Test item  0.916  0.915  0.916  1.8

Results - pH 11:

 Substance  tr,1 (min)  tr,2 (min) Mean tr (min)  logPow
 Formamide (t0 )  0.567 0.567  0.567  
 Benzylalcohol  0.675  0.673    1.1
 Nitrobenzene  0.801  0.800    1.9
Toluene  1.233  1.232    2.7
1,4-Dichlorobenzene  1.549  1.549    3.4
 Biphenyl  1.975  1.975    4.0
 1,2,4-Trichlorobenzene  2.340  2.340    4.2
 Test item  0.856  0.858  0.857  2.1

Applicant's summary and conclusion

Conclusions:
The HPLC method was applied for the determination of the partition coefficient (Pow) of JNJ-117676-AAA (T000263).
The Pow value of the test item was 6.3E+1 at pH 7 (ionised form) and 1.2E+2 at pH 11 (unionised form).
This corresponds to a log Pow value of 1.8 at pH 7 and a log Pow value of 2.1 at pH 11.