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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 April 2018 to 31 May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with international guidelines and in accordance with GLP. All relevant validity ctieria were met.
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
GLP compliance:
yes (incl. QA statement)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
Samples were taken at test start (0 h) and at a minimum of 8 spaced points, normally between 10 and 90 % of transformation, if possible. All test item containing samples were derivatized immediately (less than 5 min after sampling) via LC-DAD.
Derivitsation Solution: A solution of the derivatization reagent 2,4-Dinitrophenylhydrazine with a concentration of approximately 10 g/L was prepared in acetonitrile containing 10% of a hydrochloric acid solution (HCl, 1 M).
Derivitisation Procedure: 1 mL of the samples (including calibration, blank and fortified samples) was mixed with 100 µL derivation solution, kept at room temperature for at least 3 h for derivatization. Afterwards the samples were analyzed. The dilution factor of the derivatization process is negligible, because standards and samples were derivatized equally.
Buffers:
- pH: 4
- 0.18 g of sodium hydroxide and 5.7555 g of mono potassium citrate were dissolved in 500 mL purified water

- pH: 7
- 3.854 g of ammonium acetate were dissolved in 500 mL purified water.

- pH 9
- 0.426 g sodium hydroxide, 1.8638 g potassium chloride and 1.5458 g boric acid were dissolved in 500 mL purified water.
Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: HPLC vials, volume: 4 mL (nominal)
- Sterilisation method: filtration through 0.2 µm via sterile vacuum filtration, As transformation occurs the sterility of the test solutions was checked by colony forming units (CFU)-determination with Water Plate Count Agar. The CFU was determined from additional samples after incubation at 36 ± 1 °C for 48 hours and at 22 ± 1 °C for 72 hours.
- Lighting: Photolytic effects were avoided by using opaque water baths.
- Measures taken to avoid photolytic effects: The study was conducted protected from direct sunlight.
- Measures to exclude oxygen: Purging with helium for 2 hours prior to test initiation
- Details on test procedure for unstable compounds: N/A
- Details of traps for volatile, if any: N/A
- If no traps were used, is the test system closed
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No
TEST MEDIUM
- Volume used/treatment: Water
- Kind and purity of water: Purified water
- Preparation of test medium: 10 mg of the test item was dissolved in 10 mL acetonitrile (stock solution of 1 g/L) and diluted to a spiking solution with a concentration of 4.5 mg/L in acetonitrile. 4.23 mL of buffer solutions were spiked with 0.47 mL of the spiking solution to a test item concentration of 450 µg/L in the test containers. After the vials were sealed they were transferred into the thermostat. The time between test item application and transfer to thermostat as well as analysis of the start values did not exceed 30 min for all test conditions.
- Renewal of test solution: No
- Identity and concentration of co-solvent: Acetonitrile used for stock solution as described above (10 %, w/w)
OTHER TEST CONDITIONS
- Adjustment of pH: Yes, use of pH 4, 7 and 9 buffers as described in buffer section.
- Dissolved oxygen: Oxygen purged with helium
Duration:
718 h
pH:
4
Temp.:
20 °C
Initial conc. measured:
472 µg/L
Duration:
718 h
pH:
4
Temp.:
30 °C
Initial conc. measured:
472 µg/L
Duration:
718 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
472 µg/L
Duration:
717 h
pH:
7
Temp.:
20 °C
Initial conc. measured:
495 µg/L
Duration:
717 h
pH:
7
Temp.:
30 °C
Initial conc. measured:
495 µg/L
Duration:
717 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
495 µg/L
Duration:
716 h
pH:
9
Temp.:
20 °C
Initial conc. measured:
499 µg/L
Duration:
716 h
pH:
9
Temp.:
30 °C
Initial conc. measured:
499 µg/L
Duration:
716 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
499 µg/L
Number of replicates:
Duplicates per pH and sampling date, single injections
Positive controls:
no
Negative controls:
yes
Statistical methods:
The concentration of the test item was determined as a function of time. The ln concentrations were plotted against time (ln c vs. t) and the slope of the resulting regression graph gives the rate constant kobs [1/unit of time]:
kobs = -slope
The half-life (T1/2) [unit of time] of the reaction is given by:
T1/2 = 0.693/kobs

Mass balance could not be calculated on molar basis by converting the concentrations of the test item and the transformation product due to the results of the transformation product analysis.
Transformation products:
yes
No.:
#1
Details on hydrolysis and appearance of transformation product(s):
- Formation and decline of each transformation product during test:
2-Methyldecanoic acid was identified as transformation product at all test conditions. Almost all values were lower than the calibration range. Only a few desultory samples were within the calibration range and just one sample was higher than the LOQ.
% Recovery:
72.2
pH:
4
Temp.:
20 °C
Duration:
718 h
% Recovery:
49.8
pH:
4
Temp.:
30 °C
Duration:
718 h
% Recovery:
40.5
pH:
4
Temp.:
50 °C
Duration:
718 h
% Recovery:
67.7
pH:
7
Temp.:
20 °C
Duration:
717 h
% Recovery:
63.4
pH:
7
Temp.:
30 °C
Duration:
717 h
% Recovery:
48.7
pH:
7
Temp.:
50 °C
Duration:
717 h
% Recovery:
61.9
pH:
9
Temp.:
20 °C
Duration:
716 h
% Recovery:
47.7
pH:
9
Temp.:
30 °C
Duration:
716 h
% Recovery:
37
pH:
9
Temp.:
50 °C
Duration:
716 h
Key result
pH:
4
Temp.:
20 °C
Hydrolysis rate constant:
0 s-1
DT50:
1 351 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
4
Temp.:
30 °C
Hydrolysis rate constant:
0 s-1
DT50:
945 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0 s-1
DT50:
674 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
7
Temp.:
20 °C
Hydrolysis rate constant:
0 s-1
DT50:
1 307 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
7
Temp.:
30 °C
Hydrolysis rate constant:
0 s-1
DT50:
1 258 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
7
Temp.:
50 °C
Hydrolysis rate constant:
0 s-1
DT50:
785 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
9
Temp.:
20 °C
Hydrolysis rate constant:
0 s-1
DT50:
1 076 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
9
Temp.:
30 °C
Hydrolysis rate constant:
0 s-1
DT50:
825 h
Type:
(pseudo-)first order (= half-life)
Key result
pH:
9
Temp.:
50 °C
Hydrolysis rate constant:
0 s-1
DT50:
550 h
Type:
(pseudo-)first order (= half-life)
Other kinetic parameters:
For all test conditions the ln concentration vs. time plots have regression graphs with slopes significantly non zero. First order reaction kinetics was applied for data computation, as it represents the best fit reaction model.

Table 1. Reaction Rate Constants and Half Lives at pH 4, 20, 30 and 50 °C

   20 °C  30 °C  50 °C
 Slope of Regression Graph  -5.3E-04  -7.33E-04  -1.03E-03
 Correlation Factor (r2)  0.737  0.747  0.901
 Reaction Rate Constant (kobs [1/s]  1.42E-07  2.04E-07  2.86E-07
 Half-life (h)  1351  945  674
 Confidence Interval of Half-Life (h)  1019 - 2151  731 - 1435  583 - 813
 Half-life (d)  56.3 39.4   28.1
 Confidence Interval of Half-Life (d)  42.5 - 89.6  30.5 - 59.8  24.3 - 33.9

Table 2. Reaction Rate Constants and Half Lives at pH 7, 20, 30 and 50 °C

 20 °C  30 °C  50 °C
 Slope of Regression Graph  -5.3E-04  -5.51E-04  -8.82E-04
 Correlation Factor (r2)  0.857  0.727  0.861
 Reaction Rate Constant (kobs [1/s]  1.47E-07  1.53E-07  2.45E-07
 Half-life (h)  1307  1258  785
 Confidence Interval of Half-Life (h)  1068 - 1727  948 - 2013  657 - 1002
 Half-life (d)  54.5 52.4  32.7
 Confidence Interval of Half-Life (d)  44.5 to 72.0  39.5 - 83.9  27.4 - 41.8

Table 3. Reaction Rate Constants and Half Lives at pH 9, 20, 30 and 50 °C

 20 °C  30 °C  50 °C
 Slope of Regression Graph  -6.44E-04  -8.40E-04  -1.26E-03
 Correlation Factor (r2)  0.912  0.905  0.954
 Reaction Rate Constant (kobs [1/s]  1.79E-07  2.33E-07  3.50E-07
 Half-life (h)  1076  825  550
 Confidence Interval of Half-Life (h)  922 - 1313  712 - 997  500 - 613
 Half-life (d)  44.8 34.4  22.9
 Confidence Interval of Half-Life (d)  38.4 - 54.7  29.7 - 41.5  20.8 - 25.5

Table 4. Formation of Transformation Product

 pH Value  Temperature  Transformation Time (h)  Concentration (µg/L)
 4  30  718  79.8
 4  50  333  40.6
 4  50 718  45.6
 9  20  331  47.6
 9  20  499  43.1
 9  20  716  50.0
 9  30  716  59.3
Validity criteria fulfilled:
yes
Conclusions:
The test item showed a slow transformation rate (t1/2 > 30 d) for all test conditions.

The ambiguous temperature dependency of the reaction rate constants indicate, that the observed reaction could not be supposed as a classical hydrolysis. As the test item is an aldehyde, it could be assumed that oxygen diffusion into the test system led to an oxidation reaction and the observed reaction kinetics is a function of the diffusion rate.

In addition an unplanned malfunction event of the 30 °C thermostat (as shown in Figure 10) gave additional insight no identifiable disturbances within the ln concentration vs. time plots were observed, confirming the above mentioned hypothesis.

2-Methyldecanoic acid was detected as minor transformation product at all test conditions, but could not be quantified as almost all concentrations are lower than the calibration range.
Executive summary:

Hydrolysis as a function of pH was determined according to OECD Guideline No. 111 and Council Regulation (EC) No. 440/2008, Method C.7 for the test item 2-Methyldecan-1-al (batch number: 461/16) from 2018-04-27 to 2018-05-31 at Noack Laboratorien, Sarstedt, Germany.

Analyses of the test item 2-Methyldecan-1-al were performed after derivatization via LC DAD on a reversed phase analytical column using the test item as external standard. Analyses of the transformation product 2-Methyldecanoic acid were performed via UPLC MS on a reversed phase analytical column using an external standard. The analytical methods were validated with satisfactory results with regard to linearity, accuracy, precision and specificity.

The definitive test was conducted with a test item concentration of 450 µg/L in buffer solution of pH 4, 7 and 9 at temperatures of 20, 30 and 50 °C. Samples were taken at test start (0 h) and at 11 spaced points until test end. Pure test systems (buffer solutions) were analyzed at test start and test end and there was no analytical interference with the test item.

Reaction rate constants and half-lives were calculated at pH 4, 7 and 9 from the analyzed samples based on a first order reaction kinetics model. The test item showed a slow transformation rate (t1/2 > 30 d) for all test conditions.

The ambiguous temperature dependency of the reaction rate constants indicate, that the observed reaction could not be supposed as a classical hydrolysis. As the test item is an aldehyde, it could be assumed that oxygen diffusion into the test system led to an oxidation reaction and the observed reaction kinetics are a function of the diffusion rate.  

2-Methyldecanoic acid was detected as minor transformation product at all test conditions, but could not be quantified as almost all concentrations are lower than the calibration range.

Description of key information

Half-Life = >30 d (pH 4, 7 and 9; 20, 30 and 50 °C); OECD 111; Lange, 2018

Key value for chemical safety assessment

Half-life for hydrolysis:
54.5 d
at the temperature of:
20 °C

Additional information

In a single key study, hydrolysis as a function of pH was determined according to OECD Guideline No. 111 and Council Regulation (EC) No. 440/2008, Method C.7 for the test item 2-Methyldecan-1-al (batch number: 461/16) from 2018-04-27 to 2018-05-31 at Noack Laboratorien, Sarstedt, Germany. Analyses of the test item 2-Methyldecan-1-al were performed after derivatization via LC DAD on a reversed phase analytical column using the test item as external standard. Analyses of the transformation product 2-Methyldecanoic acid were performed via UPLC MS on a reversed phase analytical column using an external standard. The analytical methods were validated with satisfactory results with regard to linearity, accuracy, precision and specificity. The definitive test was conducted with a test item concentration of 450 µg/L in buffer solution of pH 4, 7 and 9 at temperatures of 20, 30 and 50 °C. Samples were taken at test start (0 h) and at 11 spaced points until test end. Pure test systems (buffer solutions) were analyzed at test start and test end and there was no analytical interference with the test item. Reaction rate constants and half-lives were calculated at pH 4, 7 and 9 from the analyzed samples based on a first order reaction kinetics model. The test item showed a slow transformation rate (t1/2 > 30 d) for all test conditions. The ambiguous temperature dependency of the reaction rate constants indicate, that the observed reaction could not be supposed as a classical hydrolysis. As the test item is an aldehyde, it could be assumed that oxygen diffusion into the test system led to an oxidation reaction and the observed reaction kinetics are a function of the diffusion rate.  2-Methyldecanoic acid was detected as minor transformation product at all test conditions, but could not be quantified as almost all concentrations are lower than the calibration range.

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