Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-02-03 to 2017-05-23
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 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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
White to light yellow powder
Specific details on test material used for the study:
- Batch n°: A16FC1793
- Analytical purity: 100.2%
- Expiration date: 08 June 2018 (retest date)
- 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:
3.5
pH:
7
Remarks on result:
other: Column temperature was 35°C+-1°C.
Type:
log Pow
Partition coefficient:
3.3
pH:
11
Remarks on result:
other: Column temperature was 35°C+-1°C.
Details on results:
Calculation method
- The Pow of the test item was calculated to be 1.3 x 10^3 (log Pow 3.1) using the Rekker calculation method.
- No pKa values for acidic groups in the molecular structure of the test item in the logarithm range of 1 - 14 were calculated.
- The following pKa values for basic groups were calculated: pKa 8.9 for 1-SUBST.-PIPERAZINE; pKa 4.9 for RRRNH+

Main study
In the chromatogram of the test solution, one test item peak was observed.
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’ = 0.332 x log Pow – 0.801 (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 at pH7:

Substance   tr,1 (min)  tr,2 (min)  mean tr (n=2)  log Pow  Pow
 Formamide (t0) 0.574 0.577 0.576    
 Benzylalcohol 0.754 0.749   1.1  
 Nitrobenzene 0.930 0.926   1.9  
 Toluene 1.489 1.488   2.7  
 1,4-Dichlorobenzene 1.927 1.927   3.4  
 Biphenyl 2.596 2.596   4.0  
 Dibenzyl 4.330 4.337   4.8  
 Triphenylamine 7.950 7.978   5.7
 4,4’-DDT 11.456 11.486   6.5
 Test item  1.943  1.939  1.941 3.5  3.5E+3

Pow of the test item at pH11:

Substance   tr,1 (min)  tr,2 (min)  mean tr (n=2)  log Pow  Pow
 Formamide (t0) 0.544 0.548 0.546    
 Benzylalcohol 0.658 0.656   1.1  
 Nitrobenzene 0.782 0.779   1.9  
 Toluene 1.209 1.205   2.7  
 1,4-Dichlorobenzene 1.516 1.514   3.4  
 Biphenyl 1.933 1.927   4.0  
 Dibenzyl 2.934 2.921   4.8  
 Triphenylamine 4.888 4.862   5.7
 4,4’-DDT 6.980 6.945   6.5
 Test item 1.313  1.312  1.313 3.3  2.1E+3

Applicant's summary and conclusion

Conclusions:
The HPLC method was applied for the determination of the partition coefficient (Pow) of JNJ-118781-AAA (T000841).

The Pow of the test item was 3.5E+3 at pH7 and 2.1E+3 at pH11 which correspond to the log Pow values of 3.5 and 3.3 respectively.