Diphenyl methylphosphonate

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
No surrogate or analogue material was used.

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: various times
- Others: determination of duplicate sample solutions

Buffers:

Buffer solution (pH: 4)
- Composition of buffer and their concentrations: Citric acid (31 mM); Sodium chloride (22 mM); Sodium hydroxide (34 mM)

Buffer solution (pH: 7)
- Composition of buffer and their concentrations: Disodium hydrogen orthophosphate (anhydrous) (15 mM); Potassium dihydrogen orthophosphate (10 mM); Sodium chloride (10 mM)

Buffer solution (pH: 9)
- Composition of buffer and their concentrations: Disodium tetraborate (5 mM); Sodium chloride (10 mM)

These solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.

Estimation method (if used):

Not applicable.

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: glass flasks; water bath
- Lighting: solutions were shielded from light
- Methods to minimise dissolved oxygen content: ultrasonication and degassing with nitrogen
- no other details on test system are given

TEST MEDIUM
- Preparation of test medium: Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 100 mg/L in the three buffer solutions. The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility. The test solutions were split into individual vessels for each data point.
- Identity and concentration of co-solvent: 1 % co-solvent of methanol was used to aid solubility

Duration:

120 h

pH:

4

Initial conc. measured:

>= 0.099 - <= 0.1 g/L

Duration:

384 h

pH:

7

Initial conc. measured:

>= 0.1 - <= 0.1 g/L

Duration:

23.5 h

pH:

9

Initial conc. measured:

>= 0.096 - <= 0.096 g/L

Duration:

78 h

pH:

7

Initial conc. measured:

>= 0.097 - <= 0.098 g/L

Duration:

48 h

pH:

7

Initial conc. measured:

>= 0.094 - <= 0.094 g/L

Duration:

24 h

pH:

9

Initial conc. measured:

>= 0.093 - <= 0.094 g/L

Duration:

2.5 h

pH:

9

Initial conc. measured:

>= 0.09 - <= 0.09 g/L

Number of replicates:

Duplicate sample solutions (A and B) were diluted by a factor of 2 using methanol (pH 4) or acidified methanol (pH 7 and pH 9).

Positive controls:

no

Remarks:

no information given

Negative controls:

yes

Remarks:

Matrix blanks have been prepared. Acidified methanol: reverse osmosis water (50:50 v/v) and methanol: reverse osmosis water (50:50 v/v).

Statistical methods:

No statistical methods are given.

Preliminary study:

pH 4 at 50 +/- 0.5°C
Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

pH 7 at 50 +/- 0.5°C
The extent of hydrolysis after 384 hours indicated that a further test (Tier 2), conducted at 60 °C and 70 °C, was required to estimate the rate constant and half-life at 25 °C.

pH 9 at 50 +/- 0.5°C
The extent of hydrolysis after 6 hours indicated that a further test (Tier 2), conducted at 40 and 60 °C, was required to estimate the rate constant and half-life at 25 °C.

Test performance:

Results from the preliminary test/Tier 1 showed it was necessary to undertake further testing at pH 7 and 9.

Transformation products:

not measured

Details on hydrolysis and appearance of transformation product(s):

Generally, hydrolysis products should be identified/confirmed using an analytical method like LC-MS or GC-MS. However, in this case, the test item was known to be the di-phenyl ester of methylphosphonic acid. Consequently, it is considered that one intermediate hydrolysis product will be the mono-phenyl ester of methylphosphonic acid, whereas the ultimate hydrolysis products will be phenol and methylphosphonic acid.

pH:

4

Temp.:

50 °C

DT50:

> 1 yr

Type:

(pseudo-)first order (= half-life)

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

ca. 0 h-1

DT50:

ca. 149 d

Type:

other: Arrhenius relationship

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

ca. 0.021 h-1

DT50:

ca. 33 h

Type:

other: Arrhenius relationship

Other kinetic parameters:

No other kinetic parameters are given.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes

PATHWAYS OF HYDROLYSIS
- Figures of chemical structures attached: No

Preliminary test / Tier 1 - pH 4

The mean peak areas relating to the standard and sample solutions are shown in the following table:

Solution	Mean Peak Area
Standard 50.2 mg/L	1.169*E7
Standard 50.3 mg/L	1.164*E7
Initial Sample A, pH 4	1.161*E7
Initial Sample B, pH 4	1.152*E7
Standard 50.1 mg/L	1.146*E7
Standard 50.4 mg/L	1.148*E7
48 Hour Sample A, pH 4	1.154*E7
48 Hour Sample B, pH 4	1.155*E7
Standard 50.3 mg/L	1.170*E7
Standard 50.3 mg/L	1.170*E7
120 Hour Sample A, pH 4	1.170*E7
120 Hour Sample B, pH4	1.129*E7

The test item concentrations for pH 4 at 50.0 °C +/- 0.5°C at the given time points are shown in the following tables:

Time (Hours)	Concentration (g/L)		% hydrolysis
	A	B	A	B
0	0.100	9.93*E-2	-	-
48	0.101	0.101	-1.34	-1.41
120	0.101	9.70*E-2	-0.934	2.64

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

Tier 2 - pH 7 and pH 9

The mean peak areas relating to the standard and sample solutions are shown in the following table:

Solution	Mean Peak Area
Standard 50.2 mg/L	1.205*E7
Standard 50.1 mg/L	1.203*E7
Initial Sample A, pH 7, 60°C	1.169*E7
Initial Sample B, pH 7, 60°C	1.174*E7
Standard 50.2 mg/L	1.226*E7
Standard 50.4 mg/L	1.248*E7
24 Hour Sample A, pH 7, 60°C	7.475*E6
24 Hour Sample B, pH 7, 60°C	7.544*E6
30.5 Hour Sample A, pH 7, 60°C	6.628*E6
30.5 Hour Sample B, pH 7, 60°C	6.591*E6
Standard 50.5 mg/L	1.197*E7
Standard 50.2 mg/L	1.188*E7
48 Hour Sample A, pH 7, 60°C	4.621*E6
48 Hour Sample B, pH 7, 60°C	4.623*E6
54.5 Hour Sample A, pH 7, 60°C	4.186*E6
54.5 Hour Sample B, pH 7, 60°C	4.240*E6
Standard 50.2 mg/L	1.361*E7
Standard 50.4 mg/L	1.304*E7
72 Hour Sample A, pH 7, 60°C	3.038*E6
72 Hour Sample B, pH 7, 60°C	2.984*E6
78 Hour Sample A, pH 7, 60°C	2.684*E6
78 Hour Sample B, pH 7, 60°C	2.658*E6
Standard 50.2 mg/L	1.226*E7
Standard 50.4 mg/L	1.248*E7
Initial Sample A, pH 7, 70°C	1.152*E7
Initial Sample B, pH 7, 70°C	1.156*E7
2 Hour Sample A, pH 7, 70°C	1.034*E7
2 Hour Sample B, pH 7, 70°C	1.035*E7
Standard 50.2 mg/L	1.243*E7
Standard 50.4 mg/L	1.260*E7
4Hour Sample A, pH 7, 70°C	9.445*E6
4 Hour Sample B, pH 7, 70°C	9.379*E6
6 Hour Sample A, pH 7, 70°C	8.611*E6
6 Hour Sample B, pH 7, 70°C	8.637*E6
Standard 50.5 mg/L	1.197*E7
Standard 50.2 mg/L	1.188*E7
24Hour Sample A, pH 7, 70°C	3.356*E6
24 Hour Sample B, pH 7, 70°C	3.359*E6
30 Hour Sample A, pH 7, 70°C	2.541*E6
30 Hour Sample B, pH 7, 70°C	2.577*E6
Standard 50.2 mg/L	1.361*E7
Standard 50.4 mg/L	1.304*E7
48 Hour Sample A, pH 7, 70°C	1.004*E6
48 Hour Sample B, pH 7, 70°C	1.023*E6
Standard 50.3 mg/L	1.226*E7
Standard 50.2 mg/L	1.214*E7
Initial Sample A, pH 9, 40°C	1.128*E7
Initial Sample B, pH 9, 40°C	1.146*E7
1 Hour Sample A, pH 9, 40°C	9.898*E6
1 Hour Sample B, pH 9, 40°C	9.961*E6
2 Hour Sample A, pH 9, 40°C	9.070*E6
2 Hour Sample B, pH 9, 40°C	8.985*E6
3 Hour Sample A, pH 9, 40°C	8.187*E6
3 Hour Sample B, pH 9, 40°C	7.936*E6
4 Hour Sample A, pH 9, 40°C	7.299*E6
4 Hour Sample B, pH 9, 40°C	7.243*E6
6 Hour Sample A, pH 9, 40°C	5.825*E6
6 Hour Sample B, pH 9,40°C	5.857*E6
Standard 50.4 mg/L	1.179*E7
Standard 50.3 mg/L	1.194*E7
24 Hour Sample A, pH 9, 40°C	8.113*E5
24 Hour Sample B, pH 9, 40°C	7.987*E5
Standard 50.4 mg/L	1.265*E7
Standard 50.3 mg/L	1.263*E7
Initial Sample A, pH 9, 60°C	1.131*E7
Initial Sample B, pH 9, 60°C	1.131*E7
0.5 Hour Sample A, pH 9, 60°C	7.436*E6
0.5 Hour Sample B, pH 9, 60°C	7.511*E6
0.75 Hour Sample A, pH 9, 60°C	5.963*E6
0.75 Hour Sample B, pH 9, 60°C	6.080*E6
1 Hour Sample A, pH 9, 60°C	4.847*E6
1 Hour Sample B, pH 9, 60°C	4.779*E6
1.5 Hour Sample A, pH 9, 60°C	3.370*E6
1.5 Hour Sample B, pH 9, 60°C	3.343*E6
Standard 50.4 mg/L	1.264*E7
Standard 50.3 mg/L	1.264*E7
2 Hour Sample A, pH 9, 60°C	2.354*E6
2 Hour Sample B, pH 9, 60°C	2.314*E6
2.5 Hour Sample A, pH 9, 60°C	1.486*E6
2.5 Hour Sample B, pH 9, 60°C	1.496*E6

The test item concentrations for pH 7 at 60.0 °C +/- 0.5°C at the given time points are shown in the following tables:

Time (Hours)	Concentration (g/L)		Log10[concentration (g/L)]		% hydrolysis
	A	B	A	B	A	B
0	9.74*E-2	9.77*E-2	-1.01	-1.01	-	-
24	6.08*E-2	6.13*E-2	-1.22	-1.21	37.7	37.1
30.5	5.39*E-2	5.36*E-2	-1.27	-1.27	44.8	45.1
48	3.90*E-2	3.90*E-2	-1.41	-1.41	60.0	60.0
54.5	3.53*E-2	3.58*E-2	-1.45	-1.45	63.8	63.3
72	2.29*E-2	2.25*E-2	-1.64	-1.65	76.5	76.9
78	2.03*E-2	2.01*E-2	-1.69	-1.70	79.2	79.4

Result:

Slope = -8.73 * E-3

k(obs) = 2.01 * E-2 hour ^ -1 = 5.58 * E-6 second ^ -1

t(1/2) = 34.5 hours = 1.44 days

The test item concentrations for pH 7 at 70.0 °C +/- 0.5°C at the given time points are shown in the following tables:

Time (Hours)	Concentration (g/L)		Log10[concentration (g/L)]		% hydrolysis
	A	B	A	B	A	B
0	9.37*E-2	9.39*E-2	-1.03	-1.03	-	-
2	8.40*E-2	8.42*E-2	-1.08	-1.08	10.4	10.3
4	7.59*E-2	7.53*E-2	-1.12	-1.12	19.1	19.7
6	6.92*E-2	6.94*E-2	-1.16	-1.16	26.3	26.0
24	2.83*E-2	2.84*E-2	-1.55	-1.55	69.8	69.8
30	2.15*E-2	2.18*E-2	-1.67	-1.66	77.1	76.8
48	7.58*E-2	7.72*E-3	-2.12	-2.11	91.9	91.8

Result:

Slope = -2.23 * E-2

k(obs) = 5.13 * E-2 hour ^ -1 = 1.43 * E-5 second ^ -1

t(1/2) = 13.5 hours

The test item concentrations for pH 9 at 40.0 °C +/- 0.5°C at the given time points are shown in the following tables:

Time (Hours)	Concentration (g/L)		Log10[concentration (g/L)]		% hydrolysis
	A	B	A	B	A	B
0	9.29*E-2	9.44*E-2	-1.03	-1.03	-	-
1	8.15*E-2	8.21*E-2	-1.09	-1.09	12.9	12.4
2	7.47*E-2	7.40*E-2	-1.13	-1.13	20.2	21.0
3	6.74*E-2	6.54*E-2	-1.17	-1.19	28.0	30.2
4	6.01*E-2	5.97*E-2	-1.22	-1.22	35.8	36.3
6	4.80*E-2	4.82*E-2	-1.32	-1.32	48.8	48.5
24	6.89*E-3	6.78*E-3	-2.16	-2.17	92.6	92.8

Result:

Slope = -4.71 * E-2

k(obs) = 0.109 hour ^ -1 = 3.01 * E-5 second ^ -1

t(1/2) = 6.39 hours

The test item concentrations for pH 9 at 60.0 °C +/- 0.5°C at the given time points are shown in the following tables:

Time (Hours)	Concentration (g/L)		Log10[concentration (g/L)]		% hydrolysis
	A	B	A	B	A	B
0	9.00*E-2	9.01*E-2	-1.05	-1.05	-	-
0.5	5.92*E-2	5.98*E-2	-1.23	-1.22	34.3	33.6
0.75	4.75*E-2	4.84*E-2	-1.32	-1.32	47.3	46.2
1	3.86*E-2	3.81*E-2	-1.41	-1.42	57.1	57.7
1.5	2.68*E-2	2.66*E-2	-1.57	-1.58	70.2	70.4
2	1.87*E-2	1.84*E-2	-1.73	-1.74	79.2	79.5
2.5	1.18*E-2	1.19*E-2	-1.93	-1.92	86.9	86.8

Result:

Slope = -0.346

k(obs) = 0.798 hour ^ -1 = 2.22 * E-4 second ^ -1

t(1/2) = 0.869 hours

The Arrhenius plots were constructed using the data shown in the following tables:

pH 7 Arrhenius data

T(°C)	T(K)	1/(T(K))	k(obs) (h^-1)	Ln k(obs)
50	332.15	3.095*E-3	5.09*E-3	-5.280
60	333.15	3.002*E-3	2.01*E-2	-3.907
70	343.15	2.914*E-3	5.13*E-2	-2.970

From the graph of the above data, the rate constant and half-life at 25 °C have been estimated to be as follows:

k(obs) = 1.94 * E-4 hour ^ -1 = 5.38 * E-8 second ^ -1

t(1/2) = 3.58 * E3 hours = 149 days

pH 9 Arrhenius data

T(°C)	T(K)	1/(T(K))	k(obs) (h^-1)	Ln k(obs)
40	313.15	3.193*E-3	0.109	-2.221
50	332.15	3.095*E-3	0.334	-1.095
60	333.15	3.002*E-3	0.798	-0.226

From the graph of the above data, the rate constant and half-life at 25 °C have been estimated to be as follows:

k(obs) = 2.10 * E-2 hour ^ -1 = 5.84 * E-6 second ^ -1

t(1/2) = 33.0 hours = 1.38 days

Validity criteria fulfilled:

yes

Remarks:

Basic criteria of the guideline are met.

Conclusions:

The study is regarded as a valid guideline study with certificated GLP compliance. At pH 4 the test substance can be regarded as stable at an ambient temperature of 25 °C (half-life greater than 1 year). At pH 7 and 9 further testing (Tier 2) was necessary. The higher the pH value (thus the more alkaline the environment), the lower the half-lives for diphenyl methylphosphonate.

Executive summary:

In accordance with GLP compliance, an assessment of hydrolytic stability was carried out using a procedure designed to be compatible with Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004.

The test item is dissolved in an aqueous solution at a specific pH value and incubated in the dark and at a specific temperature, in a water bath thermostated at the specific temperature with a maximum deviation of ± 0.5 °C. The concentration of the test item is determined as a function of time, using a suitable analytical method. In the case of decreasing concentrations, the logarithms of the concentrations are plotted against time (log10 (ct)). If the plot is a straight line, the reaction is considered to be of (pseudo-) first order. The rate constant and the half-life time is 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 is determined by the use of the Arrhenius relationship.

At pH 4 the test substance can be regarded as stable at an ambient temperature of 25 °C (half-life greater than 1 year). At pH 7 the estimated half-life at 25°C amounts 149 days with a hydrolysis rate constant of 1.94 E-4 h ^ -1. At pH 9 the estimated half-life at 25°C amounts 33 hours with a hydrolysis rate constant of 2.10 E-2 h ^ -1. Thus, the higher the pH value (thus the more alkaline the environment), the lower the half-lives for diphenyl methylphosphonate.

Description of key information

Study report according to OECD Guideline 111 and EU Method C.7 considering the hydrolysis potential of diphenyl methylphosphonate. The half-lives will decrease with higher pH values.
Calculation with HYDROWIN v2.00 (EPIWIN software by US-EPA): detected hydrolysable substance class: Phosphorus ester. The half-lives will decrease with higher pH values. 

Key value for chemical safety assessment

Half-life for hydrolysis:

149 d

at the temperature of:

25 °C

Additional information

The hydrolysis potential of the test substance is described by one study report (key study) as well as by an estimation with the computer program named HYDROWIN v2.00 (supporting study). In the following, available results are reported:

In accordance with GLP compliance, an assessment of hydrolytic stability was carried out using a procedure designed to be compatible with EU Method C.7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004. The test item is dissolved in an aqueous solution at a specific pH value and incubated in the dark and at a specific temperature, in a water bath thermostated at the specific temperature with a maximum deviation of ± 0.5 °C. The concentration of the test item is determined as a function of time, using a suitable analytical method. In the case of decreasing concentrations, the logarithms of the concentrations are plotted against time (log10 (ct)). If the plot is a straight line, the reaction is considered to be of (pseudo-) first order. The rate constant and the half-life time are 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 is determined by the use of the Arrhenius relationship. At pH 4 the test substance can be regarded as stable at an ambient temperature of 25 °C (half-life greater than 1 year). At pH 7 the estimated half-life at 25 °C amounts 149 days with a hydrolysis rate constant of 1.94 E-4/h. At pH 9 the estimated half-life at 25 °C amounts 33 hours with a hydrolysis rate constant of 2.10 E-2/h. Thus, the higher the pH value (thus the more alkaline the environment), the lower the half-lives for diphenyl methylphosphonate. Besides, further information is given by the supporting study.

Considering the supporting study, the hydrolysis potential of the test substance was determined by the computer program HYDROWIN v2.00 (EPIWIN software) of US-EPA (Chemservice S.A., 2011). The program estimates the hydrolysis rate constants for specific organic classes and, furthermore, a chemical´s half-live under typical environmental conditions is also determined.Only hydrolysis properties of esters, carbamates, epoxides, halomethanes (containing 1-3 halogens), specific alkyl halides and phosphorous esters can be estimated, since these are specific organic classes, which are able to undergo hydrolysis. When present, various hydrolysable compound-types will be identified.The prediction for the test substance indicated that "phosphorous ester" was detected as hydrolysable substance class. The higher the pH value (thus the more alkaline the environment), the lower the half-lives for this type of chemicals. For example: the half-life at pH 4 will be around 378 years, at pH 8 it will be about 14 days and at pH 10 it is predicted as about 3.3 days.

In conclusion, both the key and the supporting study determine comparable results. The higher the pH value, the lower the half-lives of diphenyl methylphosphonate.