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Partition coefficient

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Reference
Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Justification for type of information:
Data is from peer reviewed journal
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Principles of method if other than guideline:
Determination of octanol water partition coefficient of the test substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid. The study was performed according to OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method).
GLP compliance:
not specified
Type of method:
flask method
Partition coefficient type:
octanol-water
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (IUPAC Name): 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid
- Common name: Nicotine sulphate
- Molecular formula: C20H30N4O4S
- Molecular weight: 422.54 g/mol
- Smiles notation: CN1CCCC1C2=CN=CC=C2.CN1CCCC1C2=CN=CC=C2.OS(=O)(=O)O
- InChI: 1S/2C10H14N2.H2O4S/c2*1-12-7-3-5-10(12)9-4-2-6-11-8-9;1-5(2,3)4/h2*2,4,6,8,10H,3,5,7H2,1H3;(H2,1,2,3,4)/t2*10-;/m00./s1
- Substance type: Organic
- Physical state: Solid
- Locations of the label (if radiolabelling): Radiolabeling was done at the carbon position. The test substance, radiolabeled (S)-(-)-[pyridine-2-14C]nicotine hemisulfate (S-14CNHS), was synthesized by ChemSyn Science Laboratories (Lenexa, KS, USA) as a primary ethanol solution (630 µCi/ml) and was stored at -20 ± 5°C under an inert atmosphere protected from light. The stability of the test substance under these storage conditions and
of a representative dosing solution was determined by analysis of the chemical and radiochemical purity using reverse-phase HPLC with variable-wavelength and radiochemical detectors, and radio-optical purity was determined using a chiral HPLC method with variable-wavelength and radiochemical detectors.
- Analytical purity: Chemical purity was determined using reverse-phase high-performance liquid chromatography (HPLC) with a variable-wavelength detector. Purity was evaluated periodically during the course of testing. Radiochemical and radio-optical purities of the labeled S-14CNHS were 99% or greater throughout all the studies.
- Other: (S)-(-)-nicotine hemisulfate (S-NHS) was obtained from DeNovo (Lexington, KY, USA). All studies were performed at the Environmental Fate and Effects Laboratory of Roy F. Weston (West Chester, PA, USA). The S-NHS was stored at 4 ± 2°C in a septum-sealed, amber bottle with pressurized nitrogen in the headspace. Before initiation of the studies, the stability of the test substance under storage conditions for a representative dosing solution was determined by analysis of chemical and optical purity. Optical purity was determined using a chiral HPLC method with a variable-wavelength detector. Purity was evaluated periodically during the course of testing. Chemical and optical purities of the unlabeled S-NHS were 99% or greater throughout all the studies.
Key result
Type:
log Pow
Partition coefficient:
0.16
Temp.:
24.5 °C
pH:
7
Remarks on result:
other: Other details not known
Conclusions:
The partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid was determined to be 0.16 at a temperature of 24.5°C and pH 7.0, respectively.
Executive summary:

The partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acidwas determined according to OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method). Radiolabeling was done at the carbon position.The test substance, radiolabeled (S)-(-)-[pyridine-2-14C]nicotine hemisulfate (S-14CNHS), was synthesized by ChemSyn Science Laboratories (Lenexa, KS, USA) as a primary ethanol solution (630µCi/ml) and was stored at-20±5°C under an inert atmosphere protected from light. Thestability of the test substance under these storage conditions and of a representative dosing solution was determined by analysis of the chemical and radiochemical purity using reverse-phase HPLC with variable-wavelength and radiochemical detectors, and radio-optical purity was determined using a chiral HPLC method with variable-wavelength and radiochemical detectors.Chemical purity was determined using reverse-phase high-performance liquid chromatography (HPLC) with a variable-wavelength detector.Purity was evaluated periodically during the course of testing. Radiochemical and radio-optical purities of the labeled S-14CNHS were 99% or greater throughout all the studies. The test substance was prepared in deionized water as a mixture of S-NHS and S-14CNHS at a nominal concentration of 1,000 mg/L and a specific activity of approximately 1,000,000 dpm/mg. This stock solution was added to two series of test vessels (30-ml Teflonfluorinated ethylene propylene, Oak Ridge–style centrifuge tubes) in a volume of either 0.2 or 2 ml.Each of three buffer solutions (pH 3, 7, and 9) was added to triplicate vessels in each series to create a total aqueous volume of 15 ml.Five milliliters of 1-octanol (HPLC grade; purity,>99%; Sigma-Aldrich) were then added, for a total volume of 20 ml. Each octanol–buffer combination had been previously equilibrated together and separated.The tubes were agitated on a Labquakerocking platform shaker (approx.50 reversals/min; Barnstead, Dubuque, IA, USA) for 1 hr at 24.5°C and then centrifuged (10,620gfor 20 min atapprox.25°C) to separate the two phases. Triplicate aliquots of the organic and aqueous phases in each tube were collected for determination of the test substance concentration by liquid scintillation counting. TheKOW was calculated as the ratio of the concentration of the test substance in octanol to that in the aqueous buffer.The partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid was determined to be 0.16 at a temperature of 24.5°C and pH 7.0, respectively. Based on this value, chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid can be considered to be hydrophilic in nature.

Description of key information

Based on the available data from peer reviewed journal,the partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid was determined according to OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method). Radiolabeling was done at the carbon position. The test substance, radiolabeled (S)-(-)-[pyridine-2-14C]nicotine hemisulfate (S-14CNHS), was synthesized by ChemSyn Science Laboratories (Lenexa, KS, USA) as a primary ethanol solution (630µCi/ml) and was stored at-20±5°C under an inert atmosphere protected from light. The stability of the test substance under these storage conditions and of a representative dosing solution was determined by analysis of the chemical and radiochemical purity using reverse-phase HPLC with variable-wavelength and radiochemical detectors, and radio-optical purity was determined using a chiral HPLC method with variable-wavelength and radiochemical detectors. Chemical purity was determined using reverse-phase high-performance liquid chromatography (HPLC) with a variable-wavelength detector. Purity was evaluated periodically during the course of testing. Radiochemical and radio-optical purities of the labeled S-14CNHS were 99% or greater throughout all the studies. The test substance was prepared in deionized water as a mixture of S-NHS and S-14CNHS at a nominal concentration of 1,000 mg/L and a specific activity of approximately 1,000,000 dpm/mg. This stock solution was added to two series of test vessels (30-ml Teflonfluorinated ethylene propylene, Oak Ridge–style centrifuge tubes) in a volume of either 0.2 or 2 ml. Each of three buffer solutions (pH 3, 7, and 9) was added to triplicate vessels in each series to create a total aqueous volume of 15 ml. Five milliliters of 1-octanol (HPLC grade; purity,>99%; Sigma-Aldrich) were then added, for a total volume of 20 ml. Each octanol–buffer combination had been previously equilibrated together and separated. The tubes were agitated on a Labquake rocking platform shaker (approx.50 reversals/min; Barnstead, Dubuque, IA, USA) for 1 hr at 24.5°C and then centrifuged (10,620gfor 20 min atapprox.25°C) to separate the two phases. Triplicate aliquots of the organic and aqueous phases in each tube were collected for determination of the test substance concentration by liquid scintillation counting. TheKOW was calculated as the ratio of the concentration of the test substance in octanol to that in the aqueous buffer. The partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid was determined to be 0.16 at a temperature of 24.5°C and pH 7.0, respectively. Based on this value, chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid can be considered to be hydrophilic in nature.

Key value for chemical safety assessment

Log Kow (Log Pow):
0.16
at the temperature of:
24.5 °C

Additional information

Based on the available data in a key study from peer reviewed journal, the partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid was determined according to OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method). Radiolabeling was done at the carbon position. The test substance, radiolabeled (S)-(-)-[pyridine-2-14C]nicotine hemisulfate (S-14CNHS), was synthesized by ChemSyn Science Laboratories (Lenexa, KS, USA) as a primary ethanol solution (630µCi/ml) and was stored at-20±5°C under an inert atmosphere protected from light. The stability of the test substance under these storage conditions and of a representative dosing solution was determined by analysis of the chemical and radiochemical purity using reverse-phase HPLC with variable-wavelength and radiochemical detectors, and radio-optical purity was determined using a chiral HPLC method with variable-wavelength and radiochemical detectors. Chemical purity was determined using reverse-phase high-performance liquid chromatography (HPLC) with a variable-wavelength detector. Purity was evaluated periodically during the course of testing. Radiochemical and radio-optical purities of the labeled S-14CNHS were 99% or greater throughout all the studies. The test substance was prepared in deionized water as a mixture of S-NHS and S-14CNHS at a nominal concentration of 1,000 mg/L and a specific activity of approximately 1,000,000 dpm/mg. This stock solution was added to two series of test vessels (30-ml Teflonfluorinated ethylene propylene, Oak Ridge–style centrifuge tubes) in a volume of either 0.2 or 2 ml. Each of three buffer solutions (pH 3, 7, and 9) was added to triplicate vessels in each series to create a total aqueous volume of 15 ml. Five milliliters of 1-octanol (HPLC grade; purity,>99%; Sigma-Aldrich) were then added, for a total volume of 20 ml. Each octanol–buffer combination had been previously equilibrated together and separated. The tubes were agitated on a Labquake rocking platform shaker (approx.50 reversals/min; Barnstead, Dubuque, IA, USA) for 1 hr at 24.5°C and then centrifuged (10,620gfor 20 min atapprox.25°C) to separate the two phases. Triplicate aliquots of the organic and aqueous phases in each tube were collected for determination of the test substance concentration by liquid scintillation counting. TheKOW was calculated as the ratio of the concentration of the test substance in octanol to that in the aqueous buffer. The partition coefficient (log Pow) value of the substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid was determined to be 0.16 at a temperature of 24.5°C and pH 7.0, respectively.

Additional supporting study from authoritative databases indicates that the octanol water partition coefficient (log Pow) value of the substance 3 -[(2S)-1 -methylpyrrolidin-2 -yl]pyridine; sulfuric acid was estimated to be 0.4.

Thus, based on the available information, the logPow valueof the test substance 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acidranges from 0.16 to 0.4, respectively. On the basis of this value, chemical 3 -[(2S)-1 -methylpyrrolidin-2 -yl]pyridine; sulfuric acid can be considered to be hydrophilicin nature.