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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Similar method to guideline study. The number of concentrations tested and replicates exceed guideline requirements; uncertainty in the results has been quantified. Reproducibility of the logP for a given n-octanol/buffer ratio met guidelines (±0.3); maximum inter n-octanol/buffer ratio variation was 0.5. Limited information on experimental details, purity of the substance, measured pH of the solutions. Only the concentration in the aqueous phase was determined.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
yes
Remarks:
Only the aqueous phase was analysed
GLP compliance:
no
Type of method:
shake-flask method to: flask method
Partition coefficient type:
octanol-water
Analytical method:
photometric method
Type:
log Pow
Partition coefficient:
1.38
Temp.:
25 °C
pH:
ca. 7.4
Remarks on result:
other: ±0.19 (average of 4 different n-octanol/buffer experiments); nominal pH of the buffer
Details on results:
Average LogP (from 5 different concentrations) for each n-octanol/buffer ratio:
1:20 logP=1.15±0.02, 1:30 logP=1.35±0.02, 1:70 logP=1.65±0.07, 1:80 logP=1.38±0.04
Conclusions:
The study is considered to be not reliable due to limited reporting of some experimental details, in particular measured pH of the solutions, and only the concentration of the substance in the aqueous phase was determined.
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Similar method to guideline study. Very limited information on experimental details, purity of the substance, attainment of equilibrium, number of replicants, and results of different n-octanol/buffer ratios. Only the concentration in the aqueous phase was determined.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
yes
Remarks:
Only the concentration in the aqueous phase measured
GLP compliance:
no
Type of method:
shake-flask method to: flask method
Partition coefficient type:
octanol-water
Analytical method:
photometric method
Type:
log Pow
Partition coefficient:
1.25
Temp.:
25 °C
pH:
1
Details on results:
LogP was derived from the reported graphical results (Figure 1) by the Registrant.
Conclusions:
The study is not considered to be reliable because of very limited information on experimental details, purity of the substance, attainment of equilibrium, number of replicants, and results of different n-octanol/buffer ratios. Only the concentration in the aqueous phase was determined.
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Limited experimental information reported. No explicit demonstration that equilibrium was obtained. No information on replicates.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
yes
Remarks:
Only the aqueous phase analysed
GLP compliance:
no
Type of method:
shake-flask method to: flask method
Partition coefficient type:
octanol-water
Analytical method:
photometric method
Type:
log Pow
Partition coefficient:
1.25
Temp.:
25 °C
pH:
5.62
Conclusions:
Limited experimental details were reported.
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline method. The substance forms part of the training set of the logPow vs Retention time/acetonitrile percentage relation, and as such is correlated (to a small extent) with the literature value used.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Retention times of a substance on a reverse-phase HPLC column were measured as a function of acetonitrile/water ratio. The slope and intercept were derived from the linear relationship between log retention time and percentage acetonitrile. A further linear regression was made between literature LogPow and the experimental slope and intercept from 26 compounds.
GLP compliance:
no
Type of method:
HPLC method
Remarks:
Modified
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Type:
log Pow
Partition coefficient:
1.22
Temp.:
22 °C
pH:
> 4.6
Details on results:
LogPow calculated by the Registrant from the logPow vs retention time/acetonitrile percentage dependance regression (equation 7), and the substance specific parameters (Table 3).
The retention time/acetonitrile percentage correlation coefficient (linearity) for the substance was 0.984; slope=-0.0255; logk'0=0.871
Conclusions:
The method used was non-guideline, and in addition, the substance forms part of the training set of the logPow vs Retention time/acetonitrile percentage relation, and as such is correlated (to a small extent) with the literature value used.
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-standard method. Well documented.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Microemulsion containing 1.44-2.88wt% SDS, 6.49wt% 1-butanol, and 0.82wt% n-heptane in a phosphate buffer were used as a model for the n-octanol/water partition system (pH range 1.4-7.4). Migration Index was used instead of retension time and gave better correlation with logP.
GLP compliance:
no
Type of method:
other: microemulsion electrokinetic chromatography
Partition coefficient type:
octanol-water
Analytical method:
other: Capillary electrophoresis
Type:
log Pow
Partition coefficient:
1.37
Temp.:
25 °C
pH:
1.4
Conclusions:
Non-standard method. Well documented.
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Similar method to guideline study. Very limited information on experimental details, purity of the substance, attainment of equilibrium, number of replicants, pH or temperature. Only the concentration in one phase was determined. Only the final logP was reported.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Principles of method if other than guideline:
Method followed that of Fujita et al, J. Am. Chem. Soc., 1964, 86, 5175
GLP compliance:
no
Type of method:
shake-flask method to: flask method
Partition coefficient type:
octanol-water
Analytical method:
photometric method
Type:
log Pow
Partition coefficient:
1.26
Remarks on result:
other: ±0.01
Details on results:
Average of 2 determinations.

Description of key information

1.38±0.19, pH ca. 7.4, 25°C, shake flask, Medic-Saric 2004
1.25, pH=1, 25°C, shake flask, Plaizier-Vercammen 1987
1.25, pH=5.62, 25°C, shake flask, Umeyama 1971
1.22, pH>4.6, 22°C, RP-HPLC, Valko 1984
1.37, pH=1.4, 25°C, microemulsion electrokinetic chromatography, Ostergaard 2003
1.26±0.01, shake flask, Hansch 1967
1.31, 25°C, differential titration, Berner 1989

Key value for chemical safety assessment

Log Kow (Log Pow):
1.29
at the temperature of:
25 °C

Additional information

Several studies were available from the literature, and most were in very good agreement (better than the required agreement between replicates for the current OECD shaken-flask guideline of ±0.3 log units). One (Wiczling, 2006) was discarded as a clear outlier. While none were considered to be reliable as stand-alone studies, the main reason was due to a lack of reported experimental detail, or experimental deficiencies, rather than fundamental flaws in the experiments. As a result, the average and estimated standard deviation were calculated for all values for which the temperature and pH were reported: n=5, logPow=1.29±0.08. When the remaining two studies were included, there was no change: n=7, logPow=1.29±0.06. Because the substance is ionisable, the major factor which could influence the results is the pH of the determination. pKa1 for the substance is ca. 8.5, indicating the experiment should be conducted under acidic conditions. Including in the average only studies conducted under clearly acidic conditions gives n=4, logPow=1.27±0.07. Essentially, there is no difference between the above averages, so the overall average is taken as being reliable and suitable for risk assessment, classification and labelling purposes, based on the weight-of-evidence, and in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.2.