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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 Aug 2018 to 19 Mar 2019
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:
2004
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
2008
Deviations:
no
Principles of method if other than guideline:
NA (study was performed according to guidelines).
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Batch number: TG 3774
Purity: 97% (by HPLC)
C: 62.84%, N: 4.33%, H: 8.59%
Physical state/Appearance: Off-white powder
Expiry date: 1 July 2020
Storage: Room temperature, under nitrogen, in the dark
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
Duplicate samples taken from test solutions at 0, 24 and 120 hours for test item concentration analysis and pH measurement.
Buffers:
The test system consisted of buffer solutions at pH 4, 7 and 9 (see ‘Any other information on materials and methods incl. tables’ for specification). Buffer solutions were passed through a 0.2 μm membrane filter to sterilise and then subjected to ultrasonication and degassing with nitrogen to minimise dissolved oxygen.
Details on test conditions:
Preparation of test solutions:
Stock solutions of test item were prepared at a nominal concentration of 50 mg/L in the three buffer solutions, with a 1% methanol co-solvent used to aid solubility. Stock solutions were split into individual glass vessels and sealed with minimal headspace. These test solutions were shielded from light and maintained at 50.0 ± 0.5°C.

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

Tier 3:
Identification of hydrolysis products was performed using the pH 9 sample solution after 120 hours incubation using HPLC-MS.
Duration:
5 d
pH:
4
Temp.:
50 °C
Initial conc. measured:
50 mg/L
Remarks:
Nominal concentration
Duration:
5 d
pH:
7
Temp.:
50 °C
Initial conc. measured:
50 mg/L
Remarks:
Nominal concentration
Duration:
5 d
pH:
9
Temp.:
50 °C
Initial conc. measured:
50 mg/L
Remarks:
Nominal concentration
Number of replicates:
Duplicate sample solutions
Positive controls:
no
Negative controls:
no
Statistical methods:
Degree of hydrolysis (decrease in test item concentration) as a percentage of initial concentration was calculated via the following equation:
Percentage of initial = Ct / C0 x 100

Where: Ct = concentration of test solution at time t (g/L)
C0 = concentration of test solution at time 0 (g/L)

Analytical concentration data were plotted as log10 Ct versus t (time). The plots, which gave a straight line, indicated pseudo first order kinetics. The reaction rate constant (k) was calculated from the slope of the best fit line from regression analysis using the following equation:
k = -slope x ln10

Where: k = rate constant (hr-1)

Half-life was calculated using the following equation:
t1/2 = ln2 / k

Where: t1/2 = half-life (hr)
Preliminary study:
The estimated half-life and rate constant values (in parentheses) of the test item at 50°C were 399 hours (1.74E-3 h-1) and 117 hours (5.93E-3 h-1) at pH 7 and 9, respectively. The test item was hydrolytically stable at pH 4, showing <10% hydrolysis after 5 days at 50°C (equivalent to a half-life >1 year at 25°C).
Test performance:
The linearity of the detector response with respect to test item concentration was assessed over the nominal concentration range of 5 to 100 mg/L for pH 4, 7 and 9, with results showing a satisfactory correlation coefficient (r) of 1.000 being obtained for each, thus validating the analytical method.

No significant peaks were observed at the approximate retention time of the test item on analysis of any matrix blank solutions.
Transformation products:
not measured
Details on hydrolysis and appearance of transformation product(s):
Tier 3 analysis of pH 9 hydrolysed test solution using HPLC-MS identified the molecular mass of the degradation products at a retention time of ca. 16.3 minutes. Due to a larger number of ions occurring as the mobile phase gradient progressed and poor ionisation potential of the functional groups, it was not possible to conclusively identify the masses of degradation products that occurred at retention times of ca. 18.8 minutes and 19.7 minutes. However, based on information gained on the degradation products at ca. 16.3 minutes, the hydrolysis mechanism was derived (see ‘illustration’ section).

The hydrolysis product in the mechanism is considered to undergo the reaction a second time with the other amino acid branch to form degradation products responsible for the peaks at ca. 18.8 minutes. Test item components with only one amino acid branch would therefore only undergo the hydrolysis reaction once, forming the peak ca. 19.7 minutes.
pH:
4
Temp.:
50 °C
Remarks on result:
hydrolytically stable based on preliminary test
pH:
7
Temp.:
50 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
399 h
Type:
(pseudo-)first order (= half-life)
pH:
9
Temp.:
50 °C
Hydrolysis rate constant:
0.006 h-1
DT50:
117 h
Type:
(pseudo-)first order (= half-life)
Other kinetic parameters:
Not applicable
Details on results:
The test was initially performed twice using flow injection analysis (FIA) with mass spectrometry detection and a mobile phase of methanol:water (50:50 v/v). Test samples were prepared at ca. 20 mg/L and incubated at 50°C in plastic vessels with the anticipation that the test item, which contained amine functional groups, might adsorb to the surface of a glass vessel. The time points were diluted by a factor of four using methanol and analysed against duplicate standards at ca. 5 mg/L in methanol:relevant buffer (75:25 v/v). The results for pH 7 and 9 were based on seven sets of duplicate time points (up to 648 and 337 hours respectively), while pH 4 was based on three sets of duplicate time points (0, 24 and 120 hours).

As the test item was not expected to hydrolyse, the test was repeated at pH 7 and 9 in glass vessels. After sampling for analysis, these glass vessels were emptied and washed with 25 mL of methanol and the methanolic wash then analysed along with the test samples. The methanolic washes showed no quantifiable level of the test item, therefore demonstrating that the test item had not absorbed to the glass vessel surfaces. The hydrolytic results from this determination mirrored those of the first determination in which results were based on just two duplicate time points (0 and 120 hours).

A HPLC-UV method was subsequently developed which had better injection repeatability and removed concern that the FIA method was not quantifiably consistent. The test was then repeated using the HPLC-UV method at a higher nominal test concentration (50 mg/L) to account for loss in method sensitivity.

The rate of hydrolysis was shown to increase with pH. The kinetics of the study were shown to be consistent with a pseudo-first order reaction.

Results from the two determinations using FIA-MS analysis were considered to be consistent with results generated using HPLC-UV analysis.
Results with reference substance:
Not applicable

 Test item concentration at pH 4, 50ºC

Time (Hours)

Concentration (mg/L)

% of Mean Initial Concentration

A

B

A

B

0

51.3

51.2

-

-

24

50.5

51.0

98.5

99.5

120

49.5

51.1

96.5

99.6

 

Test item concentration at pH 7, 50ºC

Time (Hours)

Concentration (mg/L)

% of Mean Initial Concentration

A

B

A

B

0

51.3

51.7

-

-

24

49.6

49.3

96.4

95.7

120

41.7

41.9

81.0

81.5

 

Test item concentration at pH 9, 50ºC

Time (Hours)

Concentration (mg/L)

% of Mean Initial Concentration

A

B

A

B

0

50.8

50.9

-

-

24

45.6

45.8

89.7

90.0

120

25.1

25.5

49.3

50.1

 

Estimated hydrolysis rate constant and half-life of test item at 50°C

pH

Estimated Rate Constant at 50°C (hr-1)

Estimated Half-Life at 50°C

4

n/a

>1 year

7

1.74E-3

399 hours

9

5.93E-3

117 hours

n/a = Not applicable (<10% hydrolysis occurred after 5 days)

Estimated hydrolysis rate constant and half-life of test item at 50°C using FIA-MS analysis, based on results from testing in plastic vessels (1stdetermination) and glass vessels (2nddetermination)

pH

Estimated Rate Constant at 50°C (hr-1)

Estimated Half-Life at 50°C

1stdetermination

2nddetermination

1stdetermination

2nddetermination

4

n/a

n/a

>1 year

n/a

7

1.49 x 10-3

2.20 x 10-3

464 hours

315 hours

9

5.74 x 10-3

6.57 x 10-3

121 hours

106 hours

n/a = Not applicable (<10% hydrolysis occurred after 5 days)

Validity criteria fulfilled:
yes
Conclusions:
The estimated half-life and rate constant (in parentheses) of the test item at 50°C were 399 hours (1.74E-3 h-1) and 117 hours (5.93E-3 h-1) at pH 7 and 9, respectively. The test item was hydrolytically stable at pH 4, showing <10% hydrolysis after 5 days at 50°C (equivalent to a half-life >1 year at 25°C).
Executive summary:

The hydrolytic stability of the test item, Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate, was assessed at a GLP accredited laboratory according to the OECD Guideline 111, “Hydrolysis as a function of pH”.

 

Test systems consisted of buffer solutions at pH 4, 7 and 9 treated with test item at nominal concentrations of 50 mg/L. Test solutions were incubated in the dark at 50.0 ± 0.5°C for a period of 120 hours. Duplicate samples were taken for test item concentration analysis (via HPLC-UV) from test solutions at 0, 24 and 120 hour periods.

 

The estimated half-life and rate constant (in parentheses) of the test item at 50°C were 399 hours (1.74E-3 h-1) and 117 hours (5.93E-3 h-1) at pH 7 and 9, respectively. The test item was hydrolytically stable at pH 4, showing <10% hydrolysis after 5 days at 50°C (equivalent to a half-life >1 year at 25°C).

Description of key information

The hydrolytic stability of the test item, Reaction mass of disodium N,N'-[(2-hydroxy-5-nonylphen-1,3-ylene)bis(methylene)]bis[N-methylaminoacetate] and sodium N-[(2-hydroxy-5-nonylphenyl)methyl]-N-methylaminoacetate, was assessed at a GLP accredited laboratory according to the OECD Guideline 111, “Hydrolysis as a function of pH” (Fox, 2019).

 

Test systems consisted of buffer solutions at pH 4, 7 and 9 treated with test item at nominal concentrations of 50 mg/L. Test solutions were incubated in the dark at 50.0 ± 0.5°C for a period of 120 hours. Duplicate samples were taken for test item concentration analysis (via HPLC-UV) from test solutions at 0, 24 and 120 hour periods.

 

The estimated half-life and rate constant (in parentheses) of the test item at 50°C were 399 hours (1.74E-3 h-1) and 117 hours (5.93E-3 h-1) at pH 7 and 9, respectively. The test item was hydrolytically stable at pH 4, showing <10% hydrolysis after 5 days at 50°C (equivalent to a half-life >1 year at 25°C).

Key value for chemical safety assessment

Half-life for hydrolysis:
399 h
at the temperature of:
50 °C

Additional information