Ethyl 2-methylbutyrate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 October to 31 October 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

photometric method

Type:

log Pow

Partition coefficient:

2

Remarks on result:

other: mean

Test Results for Ethyl 2-methylbutyrate:

- Date: 10/10/2011 - 24/10/2011

- Operator: G. Jordan

- Preparation: Sample tested as received.

- SOP Reference: CTL SOP No. 407A

- Preparation: The test material was tested in the as received condition as per the EC440/2008 test protocol.

 

Preliminary Estimation: The solubility of the sample in water was estimated by incrementally adding known amount of water to 6.8 mg of the test material in a vial. After each addition of the known amount of water, the mixture was shaken vigorously for about 10 minutes and then visually checked for any un-dissolved parts of the sample. This process was repeated until complete dissolution of the sample occurred. Similarly, the solubility in octanol was also determined using 13.4 mg of the sample. The table below (Estimation of partition coefficient) shows details the amount of water and octanol in which complete dissolution was observed. The partition coefficient was estimated from the aqueous and octanol solubility as 2.12 Log units.

 

From the estimated result, the shake -flask method was selected for the analysis.

 

Estimation of partition coefficient:

 

Solvent   Mass of sample   Solvent volume   Predicted solubility   Log P    Analysis method

 Water                  6.8                        10                             0.68                2.12  Shake Flask Method

Octanol              13.4                      0.15                          89.33               2.12   Shake Flask Method

(Mass of sample (mg); Solvent volume (ml); Predicted solubility (g/L))

 

Estimated log Pow= 2.12

 

Saturation of Aqueous and Octanol Phase: About 0.172 g of the test material was used to saturate a mixture of octanol saturated with water and water saturated with octanol in the ratio 1:1, 1:2 and 2:1 in three 100 mL flasks. The flasks were duplicated and labelled according to the ratio of the solvents. All six flasks were then shaken at a temperature in an incubated shaker at 200 rpm. The flasks were shaken for a duration of about 5 minutes then allowed to equilibrate for 96 hours prior to concentration analysis.

 

Analysis of Aqueous and Octanol phases: A set of cells with path length 1 cm was selected for the UV-spectrophotometric analysis of the test material. The cells were scanned and found to be transparent over the whole range of spectrum of the UV spectrophotometer (190 nm to 1100 nm). The cells were thoroughly cleaned and rinsed several times with the blank solution.

 

Because of the low aqueous solubility of the sample (as observed in the estimation), octanol was used as the solvent for the calibration solutions. Octanol was also applied as the blank for the analysis. The instrument was set to scan the blank solution from 250 nm to 190 nm to obtain a baseline spectrum. The baseline spectrum did not record absorbance readings ≥ ± 0.02 units from nominal zero.

 

Apparatus, Method and Test Conditions:

Equipment used: UV Spectrophotometer

Detector: UV

Detection wave length (nm): 225

Water used: HPLC

pH of water: 5.67

Calibration Graph: Calibration solutions with concentrations of 0.215 g.L^-1 to 4.309 g.L^-1 of the test material were prepared with octanol. The solutions were analysed using the Shimadzu UV1650 PC spectrophotometer. The concentrations of the solutions with the respective absorbance are shown in the Table below (Calibration Data). An analytical wavelength of 225 nm was selected for the analysis. Graph 11.A in the attached report shows the calibration graph obtained with the solutions. The calibration was found to be leaner at the analytical wavelength with respect to the concentrations.

 

Calibration Data:

Concentration (g/L) Absorbance 1 (Au) Absorbance 2 (Au) Mean Absorbance        

          0.000                       0.02                        0.02                      0.02

          0.215                       0.12                        0.12                      0.12

          1.077                       0.54                        0.52                      0.53

          2.155                       1.00                        1.00                      1.00

          3.591                       1.64                        1.63                      1.64

          4.309                       1.94                        1.95                      1.95

 

m= 0.4493 c= 0.0285 r2= 0.9998

Analytical Determination of the Concentration of Aqueous and Octanol Phase: The concentration of the phase solutions were also analysed using the Shimadzu PC1650 PC spectrophotometer. Octanol saturated with water was used as the blank for the analysis of the octanol phase. Because the test material has high solubility in octanol, the octanol phase was diluted by a factor of 100 prior to the UV spectrophotometric analysis. The mean concentrations of the octanol phase were therefore multiplied by the dilution factor to obtain the actual concentration.

 

The aqueous phase was analysed using water saturated with octanol as the blank. Due to the low aqueous solubility of the test material no dilution factor was applied. The pH of the aqueous phase from each flask was determined using Hannah Temperature - pH apparatus. The performance of the apparatus was verified using reference solutions of pH 4.01, 7.00 and 10.01; and found to be working within acceptable criteria prior to the pH determination.

 

From the concentration of the phase solutions, the partition coefficient of the test material in each flask was determined as contained in Table 11.3 of the attached report. The concentrations of the octanol phase from the 1:2 octanol-water ratios were comparatively higher than the concentration of the other ratios. The partition coefficient was suspected to be dependant on the concentration of the octanol phase.

 

As a result, the partition coefficient was calculated from the mean concentrations of the 1:1 and 1:2 octanol-water ratios as 2.0 log units.

See the attached report for Analytical Determinations.

Conclusions:

Log pow has been determined to be 2

Description of key information

The partition coefficient has been determined to be 2 at 20°C

Key value for chemical safety assessment

Log Kow (Log Pow):

2

at the temperature of:

20 °C

Additional information

Mean partition coefficient result (Log Pow): 2.0