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Environmental fate & pathways

Hydrolysis

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Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Testing was conducted between 02 October 2009 and 04 February 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

(1) Source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74- anion. Only the pyrophosphate anion is capable of undergoing hydrolysis. It is therefore considered acceptable to assess the cation and anion separately.
Since Na+ and K+ are similar ions they are not expected to significantly influence the hydrolysis of the anion and thus data from a soluble sodium or potassium pyrophosphate is considered suitable for read-across.
(3) Sodium and potassium pyrophosphates are ionic in nature and therefore dissociate readily into cations and anions in water the toxicity of the both the cation and the anion must be addressed. Potassium and Sodium cations are essential micronutrients that are ubiquitous in the environment. As such, their uptake is tightly regulated and is therefore not considered to pose a risk for ecotoxicity. The pyrophosphate anion is unstable in aqueous solutions with the degree of instability varying according to pH. In distilled water pyrophosphates will hydrolyse slowly via abiotic mechanisms to inorganic phosphate. In natural waters a number of different processes can occur; abiotic hydrolysis, biotic degradation (as a result of the action of phosphatases which cleave pyrophosphate into orthophosphate subunits) and assimilation by organisms in the water all resulting in an ultimate breakdown product of orthophosphate. It is therefore deemed scientifically justified to avoid any further vertebrate testing and use the data from a study conducted on an orthophosphate (with either a potassium or sodium cation) for risk assessment purposes (appropriate assessment factors to be considered). Any further testing would not be scientifically justified as all substances would ultimately dissociate to their anionic and cationic forms in natural waters and these ions (Na+, K+ and PO43-(from P2O74-) are all ubiquitous and are not considered to pose a risk of ecotoxicity.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of GLP inspection: 15 September 2009 Date of Signature on GLP certificate: 26 November 2009
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
The buffer solutions were filtered through a 0.2 µm membrane filter to ensure they were sterile before commencement of the test. Also these solutions were subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen content.

Preparation of samples
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 3.0 x 10-2 g/l pyrophosphate anion in the four buffer solutions.
The test solutions were split into individual vessels for each data point.
The solutions were shielded from light whilst maintained at the test temperature.

Preliminary test/Tier 1
Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5°C for a period of at least 120 hours.

Tier 2
Results from the Preliminary test/Tier 1 showed it was necessary to undertake further testing at pH 4, with solutions being maintained at 50.0 ± 0.5°C, 60.0 ± 0.5°C and 70.0 ± 0.5°C.

Testing at pH 1.2
Results from the Preliminary test/Tier 1 at pH 4 showed it was necessary to undertake further testing at pH 1.2, with solutions being maintained at 37.0 ± 0.5°C.

Analysis of the sample solutions
The sample solutions were taken from the waterbath at various times and the pH of each solution recorded.

The concentration of pyrophosphate anion in the sample solutions was determined by ion chromatography (IC).

Samples
An aliquot of each sample solution was analysed without further treatment.

Sample blanks
pH 1.2 buffer solution.
pH 4 buffer solution.
pH 7 buffer solution.
pH 9 buffer solution.

Standards
Duplicate standard solutions of sodium pyrophosphate decahydrate (Sigma-Aldrich, purity: 101.9 %) were prepared in reverse osmosis water at a nominal concentration of 30 mg/l*.

Standard blank
Reverse osmosis water.
Buffers:
See attached buffer details.
Details on test conditions:
Refer to details on sampling and analytical methods.
Duration:
264.5 h
pH:
4
Initial conc. measured:
0.031 g/L
Duration:
216 h
pH:
4
Initial conc. measured:
0.031 g/L
Duration:
144 h
pH:
4
Initial conc. measured:
0.031 g/L
Duration:
78 h
pH:
4
Initial conc. measured:
0.031 g/L
Duration:
120 h
pH:
7
Initial conc. measured:
0.03 g/L
Duration:
120 h
pH:
9
Initial conc. measured:
0.03 g/L
Duration:
29.5 h
pH:
1.2
Initial conc. measured:
0.026 g/L
Number of replicates:
Refer to details on sampling and analytical methods.
Positive controls:
no
Negative controls:
no
Preliminary study:
Results
Please see attached results.

Discussion
The kinetics of the hydrolysis has been determined to be consistent with that of a pseudo-first order reaction, since the graphs of log10 concentration versus time were considered to be straight lines.
No significant peaks were observed at the approximate retention time of the test material on analysis of any matrix blank solutions.
Results for the preliminary test indicate that the rate of hydrolysis increases with a decrease in pH.
Test performance:
Validation
The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0 to 125 mg/l*. This was satisfactory with a correlation coefficient of 1.000 being obtained. This work was performed as part of Harlan Laboratories Project Number 2920/0050.
* as the pyrophosphate anion
Transformation products:
yes
No.:
#1
No.:
#2
Details on hydrolysis and appearance of transformation product(s):
Identification of Hydrolysis Products

Since pyrophosphates are generally prepared by heating their respective orthophosphates, the product of hydrolysis was expected to be orthophosphate. This expectation was confirmed since decreases in size of the pyrophosphate peak coincided with increases in size of the orthophosphate peak (at a retention time of approximately 2.3 minutes).

The mechanism of the pyrophosphate hydrolysis reaction will be as follows:

(P2O7)4- (+ H2O) ---------> 2 (PO4)3-

However, due to the pKa’s of orthophosphoric acid* at approximately 2.1, 7.2 and 11.9, the hydrolysis product at final solution pH’s of 1.2 and 4 will be orthophosphoric acid and monopotassium dihydrogen orthophosphate, respectively.

* from Albert and Serjeant, Ionisation Constants of Acids and Bases, A Laboratory Manual, 1962
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
282 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -0.999
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0.003 h-1
DT50:
268 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -0.998
pH:
4
Temp.:
60 °C
Hydrolysis rate constant:
0.01 h-1
DT50:
70.3 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -1.000
pH:
4
Temp.:
70 °C
Hydrolysis rate constant:
0.036 h-1
DT50:
19.2 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -1.000
pH:
7
Temp.:
25 °C
DT50:
> 1 yr
Type:
other: Test item is stable hydrolytically at pH 7
pH:
9
Temp.:
25 °C
DT50:
> 1 yr
Type:
other: Test item is stable hydrolytically at pH 9.
pH:
1.2
Temp.:
37 °C
Hydrolysis rate constant:
0.027 h-1
DT50:
26.1 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -0.997
Details on results:
See attached results.

See attached results.

Validity criteria fulfilled:
yes
Conclusions:
The estimated half-life at 25°C of the test material at pH 4, 7 and 9 is greater than 1 year.
This study is conducted according to an appropriate guideline and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint.

Executive summary:

Method

The determination was carried out using Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 .

Conclusion

The estimated rate constants and half-lives at 25°C of the test material are shown in the following table:

pH

Estimated rate constant (hr-1)

Estimated half-life

4

5.48 x 10-5

527 days

7

-

>1 year

9

-

>1 year

Under the physiologically relevant conditions of pH 1.2, 37 .0 ± 0.5°C, the half-life of the test material was determined to be 26.1 hours.

Endpoint:
hydrolysis
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

(1) Source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74- anion. Only the pyrophosphate anion is capable of undergoing hydrolysis. It is therefore considered acceptable to assess the cation and anion separately.
Since Na+ and K+ are similar ions they are not expected to significantly influence the hydrolysis of the anion and thus data from a soluble sodium or potassium pyrophosphate is considered suitable for read-across.
(3) Sodium and potassium pyrophosphates are ionic in nature and therefore dissociate readily into cations and anions in water the toxicity of the both the cation and the anion must be addressed. Potassium and Sodium cations are essential micronutrients that are ubiquitous in the environment. As such, their uptake is tightly regulated and is therefore not considered to pose a risk for ecotoxicity. The pyrophosphate anion is unstable in aqueous solutions with the degree of instability varying according to pH. In distilled water pyrophosphates will hydrolyse slowly via abiotic mechanisms to inorganic phosphate. In natural waters a number of different processes can occur; abiotic hydrolysis, biotic degradation (as a result of the action of phosphatases which cleave pyrophosphate into orthophosphate subunits) and assimilation by organisms in the water all resulting in an ultimate breakdown product of orthophosphate. It is therefore deemed scientifically justified to avoid any further vertebrate testing and use the data from a study conducted on an orthophosphate (with either a potassium or sodium cation) for risk assessment purposes (appropriate assessment factors to be considered). Any further testing would not be scientifically justified as all substances would ultimately dissociate to their anionic and cationic forms in natural waters and these ions (Na+, K+ and PO43-(from P2O74-) are all ubiquitous and are not considered to pose a risk of ecotoxicity.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Preliminary study:
Results
Please see attached results.

Discussion
The kinetics of the hydrolysis has been determined to be consistent with that of a pseudo-first order reaction, since the graphs of log10 concentration versus time were considered to be straight lines.
No significant peaks were observed at the approximate retention time of the test material on analysis of any matrix blank solutions.
Results for the preliminary test indicate that the rate of hydrolysis increases with a decrease in pH.
Test performance:
Validation
The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 0 to 125 mg/l*. This was satisfactory with a correlation coefficient of 1.000 being obtained. This work was performed as part of Harlan Laboratories Project Number 2920/0050.
* as the pyrophosphate anion
Transformation products:
yes
No.:
#1
No.:
#2
Details on hydrolysis and appearance of transformation product(s):
Identification of Hydrolysis Products

Since pyrophosphates are generally prepared by heating their respective orthophosphates, the product of hydrolysis was expected to be orthophosphate. This expectation was confirmed since decreases in size of the pyrophosphate peak coincided with increases in size of the orthophosphate peak (at a retention time of approximately 2.3 minutes).

The mechanism of the pyrophosphate hydrolysis reaction will be as follows:

(P2O7)4- (+ H2O) ---------> 2 (PO4)3-

However, due to the pKa’s of orthophosphoric acid* at approximately 2.1, 7.2 and 11.9, the hydrolysis product at final solution pH’s of 1.2 and 4 will be orthophosphoric acid and monopotassium dihydrogen orthophosphate, respectively.

* from Albert and Serjeant, Ionisation Constants of Acids and Bases, A Laboratory Manual, 1962
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
282 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -0.999
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0.003 h-1
DT50:
268 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -0.998
pH:
4
Temp.:
60 °C
Hydrolysis rate constant:
0.01 h-1
DT50:
70.3 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -1.000
pH:
4
Temp.:
70 °C
Hydrolysis rate constant:
0.036 h-1
DT50:
19.2 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -1.000
pH:
7
Temp.:
25 °C
DT50:
> 1 yr
Type:
other: Test item is stable hydrolytically at pH 7
pH:
9
Temp.:
25 °C
DT50:
> 1 yr
Type:
other: Test item is stable hydrolytically at pH 9.
pH:
1.2
Temp.:
37 °C
Hydrolysis rate constant:
0.027 h-1
DT50:
26.1 h
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: r = -0.997
Details on results:
See attached results.

See attached results.

Validity criteria fulfilled:
yes
Conclusions:
The estimated half-life at 25°C of the test material at pH 4, 7 and 9 is greater than 1 year.
This study is conducted according to an appropriate guideline and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint.

Executive summary:

Method

The determination was carried out using Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 .

Conclusion

The estimated rate constants and half-lives at 25°C of the test material are shown in the following table:

pH

Estimated rate constant (hr-1)

Estimated half-life

4

5.48 x 10-5

527 days

7

-

>1 year

9

-

>1 year

Under the physiologically relevant conditions of pH 1.2, 37 .0 ± 0.5°C, the half-life of the test material was determined to be 26.1 hours.

Description of key information

A number of studies exist to assess the hydrolysis of disodium dihydrogenpyrophosphate or analogous substances under both laboratory and natural conditions.
The key study for the endpoint ‘hydrolysis as a function of pH’ (O’Connor BJ, 2010 ) has been selected on the basis that the study is conducted to the recommended OECD guideline and under the conditions of GLP and therefore meets the regulatory requirements for this endpoint. However the data does not necessarily reflect a ‘real world’ situation as phosphates and essential cations such as Na+ are rapidly assimilated by microorganisms in soil and waters.
The key study reports the estimated half-life’s at 25°C of the test material were determined to be; 527 days at pH 4 and > 1 year at pH 7 and 9. Under the physiologically relevant conditions of pH 1.2, 37.0 ± 0.5°C, the half-life of the test material was determined to be 26.1 hours. The substance was shown to following the following mechanism of hydrolysis:
Pyrophosphate anion + water → 2 x orthophosphate anion
In reality and due to the pKa’s of orthophosphoric acid and the nature of the phosphate ion it is likely that in natural waters the hydrolysis product will be either orthophosphoric acid and monopotassium dihydrogen orthophosphate (which may also dissociate to phosphate ions and sodium ions).
Results for the preliminary test indicate that the rate of hydrolysis increases with a decrease in pH.
The additional supporting literature provides data to show that the rate of hydrolysis in natural waters is far greater than in distilled water. Pyrophosphates will not persist in natural waters. Biotic degradation and assimilation by algae and/or microorganisms will occur at a faster rate than hydrolysis in distilled water. The breakdown products of such reactions are the ubiquitous orthophosphate anion.

Key value for chemical safety assessment

Half-life for hydrolysis:
527 d
at the temperature of:
25 °C

Additional information

The hydrolytic half-life was determined for tetrapotassium pyrophosphate (EC No: 230 -785 -7). The ionic substance was assumed to undergo dissociation in aqueous solutions (resulting in potassium cations and pyrophosphate anions) therefore the cation was assumed to have a negligible influence on the rate of hydrolysis of the anion. This is expected to be replicated at environmentally relevant concentrations and on dissolution into complex environmental matrices. Although cation of the final matrix may retain some minor influence on the hydrolytic rate, such a relationship is considered beyond the scope of a standard test method and would not have been addressed or identified when testing in accordance with OECD method 111. Therefore, the rate of hydrolysis can be read across to the following substances:

- disodium dihydrogenpyrophosphate

- trisodium hydrogen diphosphate

- tetrasodium pyrophosphate

- calcium dihydrogenpyrophosphate

- dicalcium pyrophosphate

- tetrairon tris(pyrophosphate)

- copper (II) pyrophosphate

- magnesium pyrophosphate

- magnesium hydrogen pyrophosphate

 

No further testing is considered necessary.