Triethyl phosphonoacetate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 16 December 2011 to 3 September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to internationally recognised guidelines, and under GLP. No deviation affected the quality of the study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2011-08-31

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

1.23

Remarks on result:

other: estimated value obtained by a QSAR (KOWWIN)

Type:

Pow

Partition coefficient:

13.4

Temp.:

30 °C

Remarks on result:

other: value obtained by HPLC method

Type:

log Pow

Partition coefficient:

1.13

Temp.:

30 °C

Remarks on result:

other: value obtained by HPLC method

Preliminary estimate:

The log Pow was estimated to be 1.23 using KOWWIN. The full calculation is presented below:

Log Kow(version 1.68 estimate): 1.23

SMILES : O=P(OCC)(OCC)CC(=O)OCC

Chemical Name : Acetic acid, (diethoxyphosphinyl)-, ethyl ester

Molecular Formula: C8 H17 O5 P1

Molecular Weight : 224.20

TYPE	NUM	LOGKOW FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	3	-CH3   [aliphatic carbon]	0.5473	1.6419
Frag	4	-CH2-  [aliphatic carbon]	0.4911	1.9644
Frag	1	-C(=O)O [ester, aliphatic attach]	-0.9505	-0.9505
Frag	2	-O-P   [aliphatic attach]	-0.0162	-0.0324
Frag	1	O=P	-2.4239	-2.4239
Factor	1	-P(=O)-C-C(=O)-  correction	0.8000**	0.8000
Const		Equation Constant		0.2290
NOTE		An estimated coefficient (**) used
Log Kow  =  1.2285

Calibration results:

The retention times of the dead time and the retention times, capacity factor (k') and log Pow values for the reference standards are shown in the following tables :

Dead time	Retention time (min)		Mean retention time (min)
	Injection 1	Injection 2
Thiourea	1.559	1.559	1.559

 

Dead time	Retention time (min)		Mean retention time (min)	Capacity factor (k’)	Log k’	Log Kow
	Injection 1	Injection 2
2-butanone	2.061	2.061	2.061	0.322	-0.492	0.3
Aniline	2.315	2.313	2.314	0.484	-0.315	0.9
Benzyl alcohol	2.623	2.632	2.628	0.685	-0.164	1.1
Benzonitrile	3.067	3.065	3.066	0.967	-1.47*10^-2	1.6
Benzene	6.642	6.64	6.641	3.260	0.513	2.1
Toluene	12.001	11.983	11.992	6.692	0.826	2.7

The parameters A and B from equation B were determined by the calibration curve of these reference standards :A = -0.775 and B -0.575. The calibration curve is shown on the attached illustration.

Partition coefficient of sample:

The retention times, capacity factor (k') and log Pow value determined for the sample are shown in the following table :

Injection	Retention Time (min)	Capacity factor (k’)	Log k’	Log Pow
1	2.725	0.748	-0.126	1.13
2	2.723	0.747	-0.127	1.13

Mean log Pow: 1.13

Partition coefficient 13.4

Discussion:

Regulatory guidance documents raise caution for the use of the HPLC estimation method for the determination of partition coefficient for surface active substances, as possible secondary interactions may occur between the test item and the HPLC column stationary phase. The absence of any such secondary interactions for this non-ionic surface active substance was strengthened in this case by the consistency between the computer estimated value of partition coefficient and that determined experimentally. Additional validation data in support of the computer estimated value of partition coefficient is presented the following section (Overall, remarks, attachments). Estimation of the partition coefficient from the saturation solubility of the test item in the individual solvents of n-octanol and water was not considered valid for this test item.  The miscibility of the test item in at least one of the solvents prevented obtaining any meaningful saturation concentrations, such that the estimation calculation process could not be completed.

In absence of any dissociating functional groups, no specific manipulation of the mobile phase pH was required. Therefore the determination was performed at an approximately neutral pH.

Conclusions:

The partition coefficient of the test item has been determined to be 13.4 at 30°C, log Pow 1.13. Although the test item was identified as being surface active, no interference in the HPLC estimation method was evident for this non-ionic test item. The experimental value was in strong agreement with the KOWWIN predicted value of log Pow 1.23. Although the validation of computer estimated values is beyond the scope of the Principles of GLP, assessment with literature values of log Pow for chemically similar substances indicated an accuracy of within ± 0.5 log units.

Executive summary:

The determination was carried out using an HPLC estimation method, according to Method A8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008, Method 117 of the OECD Guidelines for testing of Chemicals, 13 April 2004 and GLP. No deviation from the guideline was observed during the test.

Although the test item was identified as being surface active, no interference in the HPLC estimation method was evident for this non-ionic test item. The partition coefficient (Pow) of the test item is determined from its elution time, in comparison with recommended reference items, using a reverse phase column. Chemicals injected onto such a column move along by partitioning between the mobile phase, which is partly aqueous, and the hydrocarbon stationary phase. Elution time will depend of the hydrocarbon/water partition coefficient.

A preliminary assessment of the partition coefficient was calculated using KOWWIN v1.68a (Sept 2012)©2000 U.S Environmental Protection Agency. In the definitive test,a calibration curve was constructed from the retention time data of the dead time and reference standard solutions. With the log k' of the test item and the equation of the calibration curve of reference standard solutions, log Pow of the test item was calculated.

The KOWWIN predicted value of log Pow is 1.23. The experimental value at 30°C obtained by HPLC method (log Pow 1.13) is very close to the predicted value.

Description of key information

Experimental value Log Pow for the test item at 30°C: 1.13
Calculated value for Log Pow for the test item (QSAR): 1.23

Key value for chemical safety assessment

Log Kow (Log Pow):

1.13

at the temperature of:

30 °C

Additional information

The determination was carried out using an HPLC estimation method, according to Method A8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008, Method 117 of the OECD Guidelines for testing of Chemicals, 13 April 2004 and according to GLP. No deviation from the guideline was observed.

In absence of any dissociating functional groups, no specific manipulation of the mobile phase pH was required. Therefore the determination was performed at an approximately neutral pH.

Regulatory guidance documents raise caution for the use of the HPLC estimation method for the determination of partition coefficient for surface-active substances, as possible secondary interactions may occur between the test item and the HPLC column stationary phase. The absence of any such secondary interactions for this non-ionic surface-active substance was strengthened in this case by the consistency between the computer-estimated value of the partition coefficient and that determined experimentally. Estimation of the partition coefficient from the saturation solubility of the test item in the individual solvents of n-octanol and water was not considered valid for this test item.  The miscibility of the test item in at least one of the solvents prevented obtaining any meaningful saturation concentrations, such that the estimation calculation process could not be completed.