Triethyl phosphonoacetate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

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:

Study conducted in compliance with international and OECD standard guidelines under GLP conditions. The study report was well documented with all mandatory information included.

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2011-08-31

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 1.00g/l in the three buffer solutions.
The concentrations of each solution did not exceed the lesser of 0.01 mol/l or hafl the water solubility or the test item.
The test solutions were split into individual vessels for each data point.
The solutions were shielded from light whilst maintained at the test temperature.

Buffers:

- pH:4;7;9
- Type and final molarity of buffer:
pH4: 0.05 mmol.dm3
pH7: 0.05 mmol.dm3
pH9: 0.01 mmol.dm3
- Composition of buffer:
pH4: Potassium hydrogen phtalate :0.05 mmol.dm3
pH7: Disodium hydrogen orthophosphate (anhydrous) :0.03 mmol.dm3
Potassium dihydrogen orthophosphate (anhydrous) :0.02 mmol.dm3
Sodium chloride: 0.02 mmol.dm3
pH9: Disodium tetraborate 0.01 mmol.dm3
Sodium chloride: 0.02 mmol.dm3

Duration:

120 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

> 1.32 - < 1.33 g/L

Duration:

264.6 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

> 1.04 - < 1.05 g/L

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

1.03 g/L

Duration:

215 h

pH:

7

Temp.:

60 °C

Initial conc. measured:

> 0.997 - < 1.01 g/L

Duration:

96 h

pH:

7

Temp.:

70 °C

Initial conc. measured:

> 0.997 - < 1.01 g/L

Duration:

5 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

> 0.993 - < 0.994 g/L

Duration:

5 h

pH:

9

Temp.:

60 °C

Initial conc. measured:

> 0.987 - < 0.991 g/L

Duration:

4 h

pH:

9

Temp.:

70 °C

Initial conc. measured:

> 0.987 - < 0.991 g/L

Number of replicates:

2 replicates for each pH were taken from the waterbath at various time and the pH of each solution recorded. The concentration of each sample solution was determined by HPLC.

Positive controls:

not specified

Negative controls:

not specified

Preliminary study:

For pH 4, less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C.

Testing at pH 7 confirmed hydrolysis, as greater than 10% hydrolysis was observed prior to 120 hours incubation at 50°C. However, pH 7 preliminary test sampling continued beyond 120 hours in order to generate the necessary hydrolysis data. The extent of hydrolysis detected indicated that further testing conducted at 60.0 and 70°C, was also required to estimate the rate constant and half-life at 25°C.

The test at pH 9 indicated hydrolysis as greater that 10% after 120 hours of incubation at 50°C. The extent of hydrolysis after 24 hours indicated that further testing ,conducted at 50.0, 60.0 and 70.0°C, was required to estimate the rate constant and half-life at 25°C

Transformation products:

yes

No.:

#1

No.:

#2

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

pH:

7

Temp.:

25 °C

DT50:

106 d

pH:

9

Temp.:

25 °C

DT50:

33.7 d

Other kinetic parameters:

The kinetics of the study have been determined to be consistent with a pseudo-frist order reaction as the graphs of log concentration of the test item versus time are straight lines.

Preliminary test results at 50°C:

The test item concentration (pH 4) at the given time points are shown in the following tables:

Time point (hours)	Sample replicate	Mean peak area	Concentration (g/l)	% of mean initial concentration
Initial	Standard	1.168*10^7	1.14
	Standard	1.143*10^7	1.15
	A	1.350*10^7	1.33	100
	B	1.339*10^7	1.32	99.6
24.0	Standard	1.117*10^7	1.12
	Standard	1.040*10^7	1.04
	A	1.282*10^7	1.31	98.4
	B	1.229*10^7	1.25	94.3
96.0	Standard	1.005*10^7	1.01
	Standard	1.021*10^7	1.02
	A	1.278*10^7	1.28	96.6
	B	1.278*10^7	1.28	96.6
120.0	Standard	1.070*10^7	1.09
	Standard	1.119*10^7	1.09
	A	1.312*10^7	1.31	98.4
	B	1.303*10^7	1.30	97.7

Less than 10% hydrolysis after 5 days at 50°C, equivalent to a half-life greater than 1 year at 25°C

The test item concentration (pH 7) at the given time points are shown in the following tables:

Time point (hours)	Sample replicate	Mean peak area	Concentration (g/l)	Log concentration (g/l)	% of mean initial concentration
Initial	Standard	1.048*10^7	1.05
	Standard	1.079*10^7	1.04
	A	1.072*10^7	1.05	2.187*10^-2	101
	B	1.060*10^7	1.04	1.697*10^-2	99.4
24.0	Standard	9.833*10^6	1.00
	Standard	1.195*10^7	1.19
	A	9.508*10^6	0.957	-1.903*10^-2	91.5
	B	9.141*10^6	0.920	-3.612*10^-2	88.0
96.0	Standard	1.018*10^7	1.02
	Standard	1.029*10^7	1.02
	A	7.499*10^6	0.746	-0.127	71.4
	B	7.427*10^6	0.739	-0.131	70.7
120.0	Standard	1.050*10^7	1.02
	Standard	1.032*10^7	1.01
	A	6.942*10^6	0.678	-0.169	64.8
	B	7.005*10^6	0.684	-0.165	65.4
190.5	Standard	1.146*10^7	1.13
	Standard	1.117*10^7	1.09
	A	5.504*10^6	0.540	-0.268	51.6
	B	5.475*10^6	0.537	-0.270	51.3
264.6	Standard	1.087*10^7	1.05
	Standard	1.068*10^7	1.05
	A	4.001*10^6	0.390	-0.490	37.3
	B	4.441*10^6	0.432	-0.364	41.4

Testing a pH 7 confirmed hydrolysis as greater than 10%, hydrolysis was observed prior to 120 hours incubation at 50°C. However, the preliminary test sampling continued beyond 120 hours in order to generate the necessary hydrolysis data. The extent of hydrolysis detected indicated that further testing, conducted at 60.0 and 70.0°C, was also required to estimate the rate constant and half-life at 25°C

The test item concentration (pH 9) at the given time points are shown in the following tables:

Time point (hours)	Sample replicate	Mean peak area	Concentration (g/l)	% of mean initial concentration
Initial	Standard	1.071*10^7	1.06
	Standard	1.060*10^7	1.06
	A	9.257*10^6	1.03	99.7
	B	9.312*10^6	1.03	100
24.0	Standard	1.102*10^7	1.11
	Standard	1.063*10^7	1.06
	A	1.720*10^5	0.0191	1.86
	B	1.460*10^5	0.0162	1.58
96.0	Standard	1.000*10^7	1.00
	Standard	1.053*10^7	1.06
	A	none detected
	B	none detected
120.0	Standard	1.049*10^7	1.01
	Standard	1.034*10^7	1.02
	A	none detected
	B	none detected

The extent of hydrolysis after 24 hours indicated that further testing conducted at 50.0, 60.0 and 70.0°C was required to estimate the rate constant and half-life at 25°C.

Results of test at pH 7:

at 50.0°C:

The results are presented in the second table of the previous section. Based on the graph of Log concentration (g/l) versus time, the following parameters were calculated

Slope = -1.510*10 ^-3

kobs= 3.48 *10^-3 hours^-1 = 9.66*10^-7 second^-1

t_1/2 = 199 hours = 8.3 days

at 60.0°C:

The results are given in the following table:

Time point (hours)	Sample replicate	Mean peak area	Concentration (g/l)	Log concentration (g/l)	% of mean initial concentration
Initial	Standard	1.012*10^7	1.00
	Standard	1.114*10^7	1.10
	A	1.009*10^7	0.997	-1.263*10^-3	99.6
	B	1.017*10^7	1.01	- 2.166*10^-3	100
24.0	Standard	1.158*10^7	1.14
	Standard	1.032*10^7	1.03
	A	8.122*10^6	0.806	-9.374*10^-2	80.5
	B	8.086*10^6	0.802	-9.564*10^-2	80.2
48.0	Standard	1.044*10^7	1.05
	Standard	1.287*10^7	1.21
	A	6.541*10^6	0.633	-0.199	63.2
	B	6.547*10^6	0.634	-0.198	63.2
72.0	Standard	1.024*10^7	1.01
	Standard	1.071*10^7	1.06
	A	5.228*10^6	0.517	-0.287	51.6
	B	5.217*10^6	0.516	-0.288	51.5
96.0	Standard	1.074*10^7	1.08
	Standard	1.085*10^7	1.10
	A	4.166*10^6	0.420	-0.377	42.0
	B	4.392*10^6	0.443	-0.354	44.2
166	Standard	1.163*10^7	1.17
	Standard	1.331*10^7	1.18
	A	2.297*10^6	0.216	-0.665	21.6
	B	2.301*10^6	0.217	-0.664	21.6
215	Standard	1.018*10^7	1.02
	Standard	1.120*10^7	1.11
	A	1.700*10^6	0.170	-0.771	16.9
512	Standard	1.018*10^7	1.02
	Standard	1.120*10^7	1.11
	A	1.649*10^6	0.164	-0.784	16.4

Based on the graph of Log concentration (g/l) versus time, the following parameters were calculated

Slope = -3.70*10^-3

kobs= 8.53 *10^-3hours^-1= 2.37*10^-7second^-1

t_1/2= 81.3 hours

at 70.0°C:

The results are given in the following table:

Time point (hours)	Sample replicate	Mean peak area	Concentration (g/l)	Log concentration (g/l)	% of mean initial concentration
Initial	Standard	1.012*10^7	1.00
	Standard	1.114*10^7	1.10
	A	1.009*10^7	0.997	-1.263*10^-3	99.6
	B	1.017*10^7	1.01	-2.166*10^-3	100
20.3	Standard	1.158*10^7	1.14
	Standard	1.032*10^7	1.03
	A	6.253*10^6	0.620	-0.207	62.0
	B	6.528*10^6	0.621	-0.207	62.0
27.0	Standard	1.158*10^7	1.14
	Standard	1.032*10^7	1.03
	A	5.403*10^6	0.536	-0.271	53.6
	B	5.432*10^6	0.539	-0.268	53.8
44.7	Standard	1.044*10^7	1.05
	Standard	1.287*10^7	1.21
	A	3.784*10^6	0.366	-0.436	36.6
	B	3.734*10^6	0.361	-0.442	36.1
50.6	Standard	1.044*10^7	1.05
	Standard	1.287*10^7	1.21
	A	3.345*10^6	0.324	-0.490	32.3
	B	3.352*10^6	0.324	-0.489	32.4
69.3	Standard	1.024*10^7	1.01
	Standard	1.071*10^7	1.06
	A	2.338*10^6	0.231	-0.636	23.1
	B	2.327*10^6	0.230	-0.638	23
75	Standard	1.024*10^7	1.01
	Standard	1.071*10^7	1.06
	A	2.062*10^6	0.204	-0.691	20.4
	B	2.012*10^6	0.199	-0.701	19.9
96	Standard	1.074*10^7	1.08
	Standard	1.085*10^7	1.10
	A	1.384*10^6	0.140	-0.855	13.9
	B	1.423*10^6	0.143	-0.843	14.3

Based on the graph of Log concentration (g/l) versus time, the following parameters were calculated

Slope = -8.85*10^-3

kobs= 2.04 *10^-2hours^-1= 5.66*10^-6second^-1

t_1/2= 34.0 hours

Results of test at pH 9:

The results are given in the following section (" overall remarks, attachments")

 

Validity criteria fulfilled:

yes

Conclusions:

Estimated half life at 25°C for pH 4 is more than 1 year.
Estimated half life at 25°C for pH 7 is 106 days.
Estimated half life at 25°C for pH 9 is 33.7 hours.
The hydrolysis of the test item is attributed to the base catalyzed cleavage of the ester functional group to give diethoxyphosphinyl acetic acid and ethanol.

Executive summary:

The determination was carried out according Method C7 Abiotic Degradation, Hydrolysis as Function of pH of Commission Regulation (EC) 440/2008 of 30 May 2008, Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004 and accoding to GLP. No deviation from the guideline was observed.

The test item was dissolved in an aqueous solution at a specific pH value and incubated in the dark at a controlled temperature. The concentration of the test item was them determined as a function of time, using HPLC analysis.

A decreasing of test item concentrations was observed, so the logarithms of the concentrations were plotted against time (log ct). The plots were a straight line, the reaction was considered to be (pseudo-) first order. The rate constant and the half-life time were then calculated using the slope. From data generated at differing temperatures for any single pH, an estimation of the rate constant and half-life at 25°C was be determined by the use of the Arrhenius relationship.

The hydrolysis observed was attributed to the base catalyzed cleavage of the ester functional group to give diethyoxyphosphinyl acetic acid and ethanol. Indeed, the rate of hydrolysis increases with a increase in pH, which was consistent with the proposed base catalyzed hydrolysis pathway for the ester functional groups.

The rate constant and estimated half-life at 25°C of the test item are shown in the following table :

pH	Rate constant (s^-1)	Estimated half-life at 25°C
4	Not applicable	> 1 year
7	7.57*10^-8	106 days
9	5.72*10^-6	33.7 hours

Description of key information

Experimental rate constant value at pH 4: not applicable
Experimental estimated half-life at 25°C at pH 4: > 1year
Experimental rate constant value at pH 7: 7.75 x 10-8
Experimental estimated half-life at 25°C at pH 7: 106 days
Experimental rate constant value at pH 9: 5.72 x 10 -6
Experimental estimated half-life at 25°C at pH 9: 33.7 hours

Key value for chemical safety assessment

Half-life for hydrolysis:

106 d

at the temperature of:

25 °C

Additional information

The determination was carried out according Method C7 Abiotic Degradation, Hydrolysis as Function oh pH of Commission Regulation (EC) 440/2008 of 30 May 2008, Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004 and according to GLP. No deviation from the guideline was observed.

The test item was dissolved in an aqueous solution at a specific pH value and incubated in the dark at a controlled temperature. The concentration of the test item was them determined as a function of time, using HPLC analysis.

The hydrolysis observed was attributed to the base catalyzed cleavage of the ester functional group to give diethyoxyphosphinyl acetic acid and ethanol. Indeed, the rate of hydrolysis increases with an increase in pH, which was consistent with the proposed base catalyzed hydrolysis pathway for the ester functional groups.