3,9-dimethyl-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane 3,9-dioxide

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016/09/13-2017/09/21

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)

Version / remarks:

adopted April 13, 2004

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

pH 4,
pH 7,
pH 9,
pH 1.2

Preliminary study:

13.2 Incubation and sampling at pH 1.2 (37°C, preliminary test)

Test solution:
51.48 mg of the test item (0.201 mmol) were placed into a 20 mL graduated flask, 2 mL of deuterium oxide (D2O) were added for NMR lock and the flask was filled up to the 20 mL mark with buffer solution pH 1.2.
This solution was homogenized by shaking and degassed by bubbling with nitrogen.

Incubation and sampling (37 ± 0.5°C)

Sampling interval Time [days] Number of samples
t0 0 2
t1 1 1
t2 5 1

14.1 Preliminary hydrolysis test at pH 1.2 and 37°C

The test at pH 1.2 and 37 °C was intended as a preliminary test only with the intention to prove that the test item will degrade quickly at this physiological relevant low pH and temperature.

After 5 days incubation at 37°C the test item concentration was reduced from an initial 99.747% to 40.044% equivalent to a reduction to 40.1% of the initial concentration or 59.9% hydrolysis.

The evaluation scheme for the preliminary hydrolysis test set out in OECD guideline 111 is not applicable since it was intended for a test at 50°C.

The current results confirm a rapid hydrolysis of the test item at pH 1.2 and 37°C.

Tab. 20 Results of the preliminary hydrolysis test at pH 1.2 and 37°C
Sampling interval Time [d] pH (T [°C]) % area Aflammit PCO 962
t0 0 1.41 (37.0) 99.747
t1 1 1.39 (37.0) 82.987
t2 5 1.37 (36.9) 40.044

Transformation products:

not specified

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

[5-(hydroxymethyl)-2-methyl-2-oxo-1,3,2-dioxaphosphinan-5-yl]methyl hydrogen methylphosphonate
2,2-bis(hydroxymethyl)propane-1,3-diyl bis[hydrogen methylphosphonate]

% Recovery:

ca. 99.3

St. dev.:

0.68

Duration:

ca. 4 d

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.6 h-1

DT50:

1.16 h

Type:

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

pH:

9

Temp.:

37 °C

Hydrolysis rate constant:

2.836 h-1

DT50:

0.244 h

Type:

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

pH:

9

Temp.:

50 °C

Hydrolysis rate constant:

12.306 h-1

DT50:

0.056 h

Type:

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

Key result

pH:

9

Temp.:

20 °C

Hydrolysis rate constant:

0.313 h-1

DT50:

2.22 h

Type:

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

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.011 h-1

DT50:

62.5 h

Type:

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

pH:

7

Temp.:

37 °C

Hydrolysis rate constant:

0.038 h-1

DT50:

18.1 h

Type:

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

pH:

7

Temp.:

50 °C

Hydrolysis rate constant:

0.134 h-1

DT50:

5.19 h

Type:

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

Key result

pH:

7

Temp.:

20 °C

Hydrolysis rate constant:

0.006 h-1

DT50:

108 h

Type:

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

pH:

4

Temp.:

37 °C

Hydrolysis rate constant:

0.001 h-1

DT50:

961 h

Type:

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

pH:

4

Temp.:

50 °C

Hydrolysis rate constant:

0.002 h-1

DT50:

301 h

Type:

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

pH:

4

Temp.:

60 °C

Hydrolysis rate constant:

0.005 h-1

DT50:

133 h

Type:

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

Key result

pH:

4

Temp.:

20 °C

Hydrolysis rate constant:

0 h-1

DT50:

5 035 h

Type:

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

Tab.20  Results of the preliminary hydrolysis test at pH 1.2 and 37°C

Sampling interval	Time [d]	pH (T [°C])	% area test item
t0	0	1.41 (37.0)	99.747
t1	1	1.39 (37.0)	82.987
t2	5	1.37 (36.9)	40.044

Validity criteria fulfilled:

yes

Conclusions:

The test item hydrolyses fast under elevated temperatures and acidic, neutral and alkaline conditions. At 50 °C the hydrolytic half-lives are 0.06 hours at pH 9, 5.39 hours at pH 7 and 12.5 days at pH 4.
Extrapolation to 20°C results in rapid hydrolysis under alkaline and neutral conditions with half-lives of 2.2 hours at pH 9 and 4.0 days at pH 7. At pH 4 and 20 °C a half-life of 209.8 days was calculated.
Acidic conditions of pH 4 are apart from the normal pH range of natural surface waters and the tolerance range of most aquatic biocoenosis and are therefore not considered to be representative for natural surface waters.
In summary, it can be concluded that the test item undergoes fast hydrolysis with half-lives of not more than 4 days under relevant environmental conditions.

Executive summary:

In the present study the hydrolysis of the test item (3,9-Dimethyl-2,4,8,10-tetraoxa-3,9-diphospha-spiro(5.5)undecane 3,9-dioxide) was tested according to OECD guideline 111 as full test at pH 4, 7 and 9 at the following temperatures:

 

·       pH 4    37°C, 50°C, 60°C

·       pH 7    25°C, 37°C, 50°C

·       pH 9    25°C, 37°C, 50°C

In addition to this the degradation of the test item in a preliminary test at pH 1.2 at 37°C over a time period of 5 days was investigated.

 

The test was carried out on non-labelled material.

 

Analysis was carried out by³¹P-NMR as % of total phosphorus detected. This procedure is considered equivalent to detection of radioactivity as³¹P-NMR has a molar response for phosphorus analogue to “counts” of radioactivity for a specific isotope. Incubation and analysis was conducted in sealed NMR tubes = closed system.

Recovery of the phosphorus introduced into the hydrolysis test was exemplarily shown at pH 7 and 37°C to be 100%. The relative bias of the concentration of the test item at pH 4 and pH 7 was -1.42% and -3.28% at pH 9 due to influence of the measuring system.

This was considered fully acceptable with regard to a minimum recovery of 70% issued in OECD Method 111 for non-labelled material.

 

Precision of the method (n= 6) showed a relative standard deviation of ± 0.45 %.

Sterility of samples was achieved by addition of approx. 200 mg/L thymol.

 

The test item hydrolysed under all test conditions. The degree of hydrolysis after 5 days at 50°C was determined as follows:

·       pH 1.2             40.1% of C₀left = 59.9% hydrolysis

·       pH 4               75.9% of C₀left = 24.1% hydrolysis

·       pH 7               not applicable, more than 90% degradation after 18.6 hours

·       pH 9               not applicable, more than 90% degradation after 740 seconds

 

The full hydrolysis test at pH 4 and 7 was carried out for 30 days. At pH 9 very rapid hydrolysis was observed.

The concentrations of the test item C as % of the initial dose C₀in the course of time could be described by the function Y (x = time in hours):

 

·       pH 4, 37°C:     Y = 99.477824 * e^-0.000721x        coefficient of correlation R²= 0.999917

·       pH 4, 50°C:    Y = 99.58433 * e^-0.00230x           coefficient of correlation R²= 0.99978

·       pH 4, 60°C:    Y = 99.04532 * e^-0.00519x           coefficient of correlation R²= 0.99971

·       pH 7, 25°C     Y = 97.7500 * e^-0.0111x              coefficient of correlation R²= 0.9995

·       pH 7, 37°C     Y = 97.6933 * e^-0.0383x              coefficient of correlation R²= 0.9999

·       pH 7, 50°C     Y = 97.608 * e^-0.134x                 coefficient of correlation R²= 0.999

·       pH 9, 25°C     Y = 97.116 * e^-0.600x                 coefficient of correlation R²= 1.000

·       pH 9, 37°C     Y = 95.126 * e^-2.836x                 coefficient of correlation R²= 0.998

·       pH 9, 50°C     Y = 98.903 * e^-12.306x               coefficient of correlation R²= 0.995

 

The deduced semilogarithmic plot LnC₀/C against time for determination of the rate constant all were linear and thus hydrolysis followed first order reaction kinetics.

The plots afforded the following equations (x = time in hours [h],rate constant [1/h] highlighted in bold):

 

·       pH 4, 37°C:     Y =0.0007214x + 0.0002982               R²= 0.9999100

·       pH 4, 50°C:    Y =0.002301x – 0.000913                   R²= 0.999765

·       pH 4, 60°C:    Y =0.005193x + 0.009593                   R²= 0.999706

·       pH 7, 25°C     Y =0.01109x + 0.02276                      R²= 0.99947

·       pH 7, 37°C     Y =0.03832x + 0.00886                      R²= 0.99988

·       pH 7, 50°C     Y =0.1335x + 0.0242                          R²= 0.9990

·       pH 9, 25°C     Y =0.600x +0.029                               R²= 1.000

·       pH 9, 37°C     Y =2.836x +0.050                               R²= 0.998

·       pH 9, 50°C     Y =12.306x + 0.011                            R²= 0.995

 

From the rate constants of three temperatures at each pH Arrhenius plots were produced for pH 4, 7 and 9. The following equations were obtained:

 

pH 4    lnk = -8875.070 * 1/T [K] + 21.379                               R²= 1.000

pH 7    lnk = -9591.782 * 1/T [K] + 27.662                               R²= 1.000

pH 9    lnk = -11646 * 1/T [K] + 38.558                                  R²= 0.9997

 

Two hydrolysis / degradation products were detected and identified.

[5-(hydroxymethyl)-2-methyl-2-oxo-1,3,2-dioxaphosphinan-5-yl]methyl hydrogen methylphosphonate

2,2-bis(hydroxymethyl)propane-1,3-diyl bis[hydrogen methylphosphonate]

 

Description of key information

The test item hydrolyses fast under elevated temperatures and acidic, neutral and alkaline conditions. At 50 °C the hydrolytic half-lives are 0.06 hours at pH 9, 5.39 hours at pH 7 and 12.5 days at pH 4.

Extrapolation to 20°C results in rapid hydrolysis under alkaline and neutral conditions with half-lives of 2.2 hours at pH 9 and 4.0 days at pH 7. At pH 4 and 20 °C a half-life of 209.8 days was calculated.

Acidic conditions of pH 4 are apart from the normal pH range of natural surface waters and the tolerance range of most aquatic biocoenosis and are therefore not considered to be representative for natural surface waters.

In summary, it can be concluded that the test item undergoes fast hydrolysis with half-lives of not more than 4 days under relevant environmental conditions.

Key value for chemical safety assessment

Half-life for hydrolysis:

108 h

at the temperature of:

20 °C