Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03.05.2018 - 24.09.2018
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Slow-stir modification, analytical method: UV/VIS absorption at 572 nm

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Version / remarks:
Slow-stir modification of the shake flask method
Deviations:
no
Principles of method if other than guideline:
The test is based on the partition of the test substance into two nearly immiscible phases (water and octanol) at 25 °C and subsequent determination of the
concentration of the test substance in both phases. The slow-stir modification of the equilibration step was applied. Essential requirements of the established
OECD method were taken into account as far as applicable. The partition coefficient determined by this method is calculated from the ratio of concentrations
of the test substance in either phase.
GLP compliance:
not specified
Other quality assurance:
other: Laboratory accredited by DAkkS
Type of method:
slow-stirring method
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent

Study design

Analytical method:
photometric method

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
> 2
Temp.:
25 °C
Remarks on result:
other: Start in Octanol.
Remarks:
When starting in water: log Pow=0,2
Details on results:
Comparing the two starting conditions, start in octanol and start in water, it is clearly shown that test results are different.
log Pow (start in octanol): >2
log Pow (start in water): 0,2

Any other information on results incl. tables

 

 Flask 1

Start in octanol

Flask2

Start in octanol 

 Flask 3

Start in octanol

Flask 4

Start in water 

Flask 5

Start in water  

Start 6

Start in water 

 Partition coefficient

log Pow

 >1,5 >1,0   >1,4  0,33  0,12

 -0,08

 
 

Applicant's summary and conclusion

Conclusions:
Comparing the two starting conditions (start in octanol and start in water) it is clearly shown that test results are different.
„start in octanol“, the entire sample weight remains in the octanol phase. Obviously a diffusion mechanism into the water phase doesn’t exist, most probably
because the coexisting neutral compounds (acid and amine) don’t tend to move into the octanol-water interface where the mandatory proton transfer might take place. Therefore the experimental partition coefficient depends on the chosen sample weight and the octanol volume only. Log Pow can be calculated to be > 2.

In contrast, the diffusion of the test substance from the aqueous phase into octanol is easy because the surface-active properties lead to an accumulation
of the ionic compound in the octanol-water interface. The poor recovery rates when startin in water indicate that more than half of the sample amount is
concentrated in the interface. The calculated mean values for these flasks are 1,4 (Pow) and 0,2 (log Pow), respectively.

An important consequence of these conclusions is that molecules which have diffused from the aqueous phase into octanol won’t find their way back.
That means that none of the two starting conditions leads to a dynamic equilibrium which is essential for an experimental determination of partition coefficients.

Therefore the partition coefficients found in this test should be regarded as an estimate, not as a key figure of the test substance.