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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviation from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.
Reason / purpose:
reference to same study
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
GLP compliance:
yes (incl. certificate)
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Type:
log Pow
Partition coefficient:
> 6.5
Temp.:
22 °C
pH:
7
Details on results:
Calculation of the partition coefficient (Pow):
For the structural formula of EA-3098, the Pow was calculated to be 7.6 X 10E12 (log Pow = 12.9) using the Rekker calculation method.

HPLC method:
Main test:
No test substance peaks were observed in the HPLC chromatograms of EA-3098. Under the same chromatographic conditions, the retention time of 2,4-DDT (log Pow 6.5) was 30.5 minutes. Hence it was concluded that the log Pow of EA-3098 is >6.5.

HPLC chromatograms of the EA-3098 solution, the test substance blank solution, the 2,4-DDT reference solution and the 2,4-DDT blank solution are shown in Figures 1 to 4 (see attached background material).

Additional test:
Because no test substance peaks were observed during the main test an additional test was performed to make sure that the test substance can be eluted from the column.
In the chromatograms of the 193 mg/I EA-3098 test solution, one large peak and six small test substance peaks were observed. This clearly illustrates that the test substance EA-3098 can be eluted from the HPLC column and that, therefore, the partition constant as determined during the main test is correct.

HPLC chromatograms of the EA-3098 test solution and the test substance blank solution are shown in Figures 5 to 6 (see attached background material).

Calculation of the dissociation constant (pKa)

From the structural formula of EA-3098, the following pKa values for acidic and basic groups in EA-3098 were calculated using the Perrin's calculation method.

 

Acidic groups:

RRCHOH: 16.3

RRCHOH: 16.9

 

Basic groups:

RCONHR: -0.12

RCONHR: 0.48

Based on these calculations, the aqueous phase used during the HPLC method was not buffered. At neutral pH >90% of the test substance is in a non-ionised form.

Conclusions:
The HPLC method gave the following results:
The Pow value for EA-3098 is >3.2 x 10E6 (log Pow >6.5) at 22.0°C and at neutral pH.
Executive summary:

The determination of the partition coefficient (n-octanol/water) of EA-3098 was based on the following guidelines:

OECD 117 "Partition coefficient (n-octanol/water) High Performance Liquid Chromatography (HPLC) method" and EEC method A.8 "Partition Coefficient" EEC Directive 92/69/EEC.

The Rekker calculation method was used for a preliminary estimation of the partition coefficient. Based on the results of this method, it was decided to perform the HPLC method for an accurate determination of the partitioc coefficient.

Rekker calculation method (Pow):

From the structural formula of EA-3098, the log Pow was calculated to be 12.9.

Perrin's calculation method (pKa):

From the structural formula of EA-3098, the pKa values for the basic groups were calculated to be 0.48 and -0.12 and the pKa values for the acidic groups were calculated to be 16.3 and 16.9.

Based on these calculations, the aqueous phase used during the HPLC method was not buffered. At neutral, > 90% of the test substance is in a non-ionised form.

HPLC method:

Main test:

In the chromatograms of the 213 mg/l EA-3098 test solution, no test substance peaks were observed. Hence, it was concluded that the log Pow of EA-3098 is > 6.5 (Pow> 3.2 x 106).

Additional test:

Because no test substance peaks were observed during the main test an additional test was performed to make sure that the test substance can be eluted from the column.

In the chromatograms of the 193 mg/I EA-3098 test solution, one large peak and six small test substance peaks were observed. This clearly illustrates that the test substance EA-3098 can be eluted from the HPLC column and that, therefore, the partition constant as determined during the main test is correct.

Conclusion:

The Pow value for EA-3098 is >3.2 x 106 (log Pow >6.5) at 22.0°C and at neutral pH.

Description of key information

The Pow  value for EA-3098 is >3.2 x 106 (log Pow >6.5) at 22.0°C and at neutral pH.

Key value for chemical safety assessment

Log Kow (Log Pow):
6.5
at the temperature of:
22 °C

Additional information

The determination of the partition coefficient (n-octanol/water) of EA-3098 was based on the following guidelines:

OECD 117 "Partition coefficient (n-octanol/water) High Performance Liquid Chromatography (HPLC) method" and EEC method A.8 "Partition Coefficient" EEC Directive 92/69/EEC.

The Rekker calculation method was used for a preliminary estimation of the partition coefficient. Based on the results of this method, it was decided to perform the HPLC methood for an accurate determination of the partitioc coefficient.

Rekker calculation method (Pow):

From the structural formula of EA-3098, the log Pow was calculated to be 12.9.

Perrin's calculation method (pKa):

From the structural formula of EA-3098, the pKa values for the basic groups were calculated to be -0.48 and 0.12 and the pKa values for the acidic groups were calculated to be 16.3 and 16.9.

Based on these calculations, the aqueous phase used during the HPLC method was not buffered. At neutral, > 90% of the test substance is in a non-ionised form.

HPLC method:

Main test:

In the chromatograms of the 213 mg/l EA-3098 test solution, no test substance peaks were observed. Hence, it was concluded that the log Pow of EA-3098 is > 6.5 (Pow> 3.2 x 106).

Additional test:

Because no test substance peaks were observed during the main test an additional test was performed to make sure that the test substance can be eluted from the column.

In the chromatograms of the 193 mg/I EA-3098 test solution, one large peak and six small test substance peaks were observed. This clearly illustrates that the test substance EA-3098 can be eluted from the HPLC column and that, therefore, the partition constant as determined during the main test is correct.

Conclusion:

The Pow value for EA-3098 is >3.2 x 106(log Pow >6.5) at 22.0°C and at neutral pH.