Triethyl phosphate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The source substance dibutlyl phosphate contains similar chemical moieties compared to the target substance:
1. Both substances are phosphate esters
2. Short-chain alkyl groups are linked to the phosphate group.
Both substances have a sufficient high water solubility in the range of 17.2 g/L (DBP) and 500 g/L indicating that solubility is not a restricting property for a hydrolysis.
The mechanism of hydrolysis of phosphate esters is the primary attack of a hydroxyl anion at the central phosphorus. Therefore, side-chains (if not steric hindrance occur as in the present case) do not have a relevant impact on this attack

Reason / purpose for cross-reference:

read-across source

Preliminary study:

The analytical results show no decrease in initial concentration of > 10% at pH 4,7 and 9.

Transformation products:

no

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-09-25 till 2012-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

Buffer pH 4, Fa. Fluka, Citric acid/NaOH/NaCl, Art-Nr.: 33643
Buffer pH 7, Fa. Fluka, KH2PO4/Na2HPO4, Art-Nr.: 33646
Buffer pH 9, Fa. Fluka, Na2B4O7/HCl, Art-Nr.: 33648

Details on test conditions:

The hydrolysis behaviour of dibutyl hydrogen phosphate was investigated at 50 °C at pH 4, pH 7 and pH 9 over a period of five days according to OECD TG 111. The stability was monitored by HPLC analysis using MS-detection.
Dibutyl hydrogen phosphate was dissolved in buffer solutions of pH 4, 7 and 9 to a volume of 200 ml.
Aliquots of the stock solution were taken to obtain individual vials for every test point. Preparation was carried out under nitrogen as flushing gas, to avoid oxygen.
Start concentration for hydrolysis was about 0.3 g/L.
The vials were closed and incubated at 50 °C in a heat regulator under dark to avoid any photolytic effects.
The pH of the blank buffer solution was checked at the beginning of the test. Additionally the pH of the hydrolysis solution was measured at each test point. The temperature during the experiment was also checked at each test point.
The calibration was verified daily at the level of 117.6 mg/l by using a control calibration solution.
At each test point the hydrolysis solution was directly led to the chromatographic measurement.

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

289 mg/L

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

291 mg/L

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

287 mg/L

Preliminary study:

The study was performed over 5 days at 50°C at pH 4,7 and 9. As no degradation was observed, the study was finished and no further tests at other temperatures were performed.

Transformation products:

no

% Recovery:

101.9

pH:

4

Temp.:

50 °C

Duration:

5 d

% Recovery:

97.8

pH:

7

Temp.:

50 °C

Duration:

5 d

% Recovery:

96.2

pH:

9

Temp.:

50 °C

Duration:

5 d

pH:

4

Temp.:

50 °C

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

50 °C

Type:

not specified

Remarks on result:

hydrolytically stable based on preliminary test

The overall degradation of dibutyl hydrogen phosphate observed with the determination of the content of dibutyl hydrogen phosphate at 50 °C at pH 4, 7 and 9 after 5 days is less than 10 %. Dibutyl hydrogen phosphate is therefore considered to be stable at 50 °C at pH 4, 7 and 9 and no half-life time and hydrolysis rate were calculated. Because no degradation was observed, no sterility test was performed in this case. No further tests at other temperatures are required.

Validity criteria fulfilled:

yes

Remarks:

Results of the solutions for verification of the calibration show stability of the chromatographic system. Recoveries of the test item are in the range from 97.5 % to 104.4% indicating a satisfying repeatability of the method.

Conclusions:

The substance is stable at pH 4, 7 and 9 at 50°C.

Executive summary:

The stability towards hydrolysis was investigated at pH 4, 7 and 9 at 50°C according to OECD Guideline 111 (Hydrolysis as a Function of pH). After 5 days the recoveries of dibutyl hydrogen phosphate are in the range of 97.5 % to 104.4%. Therefore, dibutyl hydrogen phosphate is regarded as hydrolytically stable, and no half-life time and hydrolysis rate were calculated.

Reference 3

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The source substance TCPP contains similar chemical moieties compared to the target substance:
1. Both substances are phosphate esters
2. Short-chain alkyl groups are linked to the phosphate group.
Both substances have a sufficient high water solublitly in the range of 1.08 g/L (TCPP) and 500 g/L indicating that solubility is not a restricting property for a hydrolysis.
The mechanism of hydrolysis of phosphate esters is the primary attack of a hydroxyl anion at the central phosphorus. Therefore, side-chains (if not steric hindrance occur as in the present case) do not have a relevant impact on this attack

Reason / purpose for cross-reference:

read-across source

Preliminary study:

The analytical results show no decrease in initial concentration of > 10% at pH 4,7 and 9.

Transformation products:

no

pH:

4

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

pH:

7

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

pH:

9

Temp.:

50 °C

Remarks on result:

hydrolytically stable based on preliminary test

Reference 4

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EEC Directive 84/449/EEC (1984-09-19)

GLP compliance:

yes

Specific details on test material used for the study:

Product name: TCPP

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Preliminary experiment:
Samples were taken at the beginning of the test and regularly afterwards to be able to estimate whether the half-life was lower than 2.4 hours or to estimate if less than 10% of the test substance was hydrolysed after 5 days.
At each sampling time a sample was taken, weighted and stored in refrigerator until analysis.

Buffers:

Buffer solutions were prepared as follows:
pH 4.0 - 100 ml 0.5 M potassium hydrogen phthalate and 0.8 ml 0.5 M NaOH diluted to 1000 ml with deionized water
pH 7.0 - 100 ml 0.5 M potassium dihydrogen phosphate and 5.92 ml 5 M NaOH diluted to 1000 ml with deionized water
pH 9.0 - 100 ml of 0.5 M boric acid and 100 ml 0.5 M potassium chloride and 4.32 ml 5 M NaOH diluted to 1000 ml with deionized water.
pH of buffer solutions were measured at 50 °C using a pH meter and adjusted with 0.5 M HCI or 0.5 M NaOH.

Duration:

5 d

pH:

4

Temp.:

50 °C

Duration:

5 d

pH:

7

Temp.:

50 °C

Duration:

5 d

pH:

9

Temp.:

50 °C

Preliminary study:

The analytical results show no decrease in initial concentration of > 10% at pH 4,7 and 9.

Transformation products:

no

pH:

4

Temp.:

50 °C

DT50:

1 yr

Type:

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

Remarks on result:

other: buffered solution

pH:

7

Temp.:

50 °C

DT50:

1 yr

Type:

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

Remarks on result:

other: buffered solution

pH:

9

Temp.:

50 °C

DT50:

1 yr

Type:

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

Remarks on result:

other: buffered solution

Details on results:

In preliminary test hydrolysis was below 1% after 5 days at all 3 pH values. In agreement with the guideline the test was considered complete and no
further testing has been performed.

The first peak out of three as found in the GC chromatogram of tris(2 -chloro-1 -methylethyl) phosphate containing about 78 - 79% of the total area was used for interpretation of the hydrolysis rate. The decrease of the area of the first peak was less than 1% after five days at all three testsed pH values indicating no hydrolysis. The stability of the two other isomers was checked by interpretation of the ratio of the peak areas of the three tris(2 -chloro-1 -methylethyl) phosphate isomers for a sample from the beginning and from the end of the hydrolyses test. The equivalence of these ratios indicate that non of the isomers is susceptible to hydrolyses.

The pH changes during the tests were small and always less than 0.05 pH units.

The measured temperature range during the test was 49.9 - 50.1°C.

Conclusions:

The test substance is hydrolytically stable, with an estimated half life of more than 1 year at 25 degree C.

Executive summary:

In a GLP-compliant report, preliminary hydrolysis testing was undertaken at 50ºC for five days. A decrease in concentration of less than 1% was observed at pH 4, 7 and 9. Based on this result, it is concluded with no need for further testing in accordance with the OECD guideline, that TCPP is stable in water at pH 4, 7 and 9 at 25ºC, with a half-life greater than or equal to one year.

(Geurts and van Veenendaal, 2001)

Description of key information

The substance triethyl phosphate is stable to hydrolysis at pH4, 7 and 9..  

Additional information

As no study for the hydrolysis for triethylphosphate at pH 4, 7 and 9 is available, data from similar alkyl phosphate in a read-across approach were taken (1. dibutyl phosphate, 2. tris-chlorpropyl phosphate, 3. supporting evidence for stability is given by literature data for non-guideline studies for triethyl phosphate)

1. The stability towards hydrolysis of dibutyl phosphate was investigated at pH 4, 7 and 9 at 50°C according to OECD Guideline 111 (Hydrolysis as a Function of pH). After 5 days the recoveries of the substance were in the range of 97.5 % to 104.4%. The stability was monitored by HPLC analysis using MS-detection. Dibutyl phosphate is found to be hydrolytically stable at 50°C at all three pH-values. Therefore it can be assumed that the substance is also stable at environmental relevant conditions.

2. The result of the GLP-complient report (Geurts & van Veenendaal, 2001) according to OECD 111 shows that TCPP_Tris(2 -chloro-1 -methylethyl) phosphate is stable in water. No degradation was found at 50°C at pH 4, 7 and 9 during the test period of 5 days. It is discussed in the European Union Risk Assessment Report of tri(2 -chloro-1-methylethyl) phosphate that phosphate esters are known to hydrolyse although this is expected to be slow under environmentally relevant conditions.

3. Mabey & Mill (1978) reviewed the available published hydrolysis data for a number of chemicals including phosphoric acid esters. Neutral hydrolysis is reported to be the dominant process for this class of compounds (phosphoric acid esters) at pH7. For triethyl phosphate, a half-life of 5.5 years at 25°C is calculated, based on the rate of hydrolysis at neutral pH.  The second order alkaline hydrolysis rate constant is estimated to be 1.75 x 10 -5 M-1 sec-1 at 27 degrees Celsius (Wolfe, 1980).

The substance triethyl phosphate is stable to hydrolysis under normal environmental conditions.

Two studies from similar phosphate esters are used in a read-across approach. The read-across justification is attached to the IUCLID file in chapter 13.