1,1'-{(phenylmethanediyl)bis[(3-substituted benzene-4,1-diyl)diazene-2,1-diyl{1-[3-(dimethylamino)propyl]-2-hydroxy-4-methyl-6-oxo-1,6-dihydropyridine-5,3-diyl}]}dipyridinium chloride lactate salts

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 21 - March 09, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study compliant with TG guideline and conducted under GLP in recognized contract research organization.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

Principles of method if other than guideline:

Since the test substance is a salt mixture, the flask-shaking method, HPLC method and calculation method are not applicable. Based on this, it was decided to use the estimation method for the determination of the Pow. The solubility of the test substance in n-octanol and in water was determined. The quotient of the n-octanol solubility and the water solubility is an estimation of the Pow.

GLP compliance:

yes (incl. QA statement)

Type of method:

other: estimation method

Partition coefficient type:

octanol-water

Test material

Reference

Name:

Unnamed

Type:

Constituent

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Partition coefficient 1

Type:

Pow

Partition coefficient:

0.009

Temp.:

20 °C

Partition coefficient 2

Type:

log Pow

Partition coefficient:

-2.04

Temp.:

20 °C

Details on results:

Increasing concentrations of dissolved test substance in octanol were observed in the 24, 48 and 72 hour test samples (see Table 1). In order to determine the maximum solubility, the stirring period was extended to 96, 120, 144 and 168 hours (see Table 2).
The maximum difference (MD) of the mean concentrations determined in the 96, 120, 144 and 168 hour test samples was> 15%. The 144 hour and 168 hour measurements were significantly higher than the 96 and 120 hour measurements, respectively. A plateau, i.e. maximum solubility, has been reached after 120 hours. Since the measured octanol concentrations after 144 and 168 hours of stirring were significantly higher than the concentrations measured at earlier sampling points, the samples were visually interpreted after overnight standing: the 120 hour samples was still a clear solution whereas the 144 hour and 168 hour samples had turned turbid, indicating precipitation of test substance. An explanation for this finding cannot be given. The results of the 144 hour and 168 hour samples were considered not reliable and therefore not used in any further calculations.
According to the guidelines, the octanol solubility of the test substance is given as the mean value of the mean analysed concentrations.
No test substance was detected in the pre-treated samples from the blank octanol mixture.

Any other information on results incl. tables

Table 1 Main study - n-octanol solubility of the test substance

Stirring time	Analysed concentration
	Individual	Mean¹	MD
[hours]	[g/l]	[g/l]	[%]
24	4.49	5.70	49.6
48	5.51
72	7.46

¹ Mean of the concentrations obtained at all stirring times.

 

Table 2 Main study - n-octanol solubility of the test substance

after extended stirring

Stirring time	Analysed concentration
	Individual	Mean¹	MD
[hours]	[g/l]	[g/l]	[%]
96	9.03	9.07	0.9
120	9.11
144	21.0
168	20.6

¹ Mean of the concentrations obtained at96 and 120 hours.

Applicant's summary and conclusion

Conclusions:

For classification purposes:: logPow <3