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Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP; well documented study report following a screening study and method equivalent or similar to guideline with acceptable deviations according to the regulatory conclusion that the substance is hydrolytically stable at pH 5, 7 and unstable at pH 8.
Remarks:
The study would not fulfil the requirements of OECD TG 111 (2004) Tier 2 or Tier 3 requirements. The test was conducted at physiologically relevant temperature (40 °C) rather than the guideline preliminary test temperature 50 °C.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
Screening study examined: pH 2, 5, 7, 8.5 and 12 rather than guideline pH range 4, 7 and 9; duplicate tests were not performed; full analytical validation was not documented within the study; degradation products were not identified.
Qualifier:
equivalent or similar to
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
see above
Principles of method if other than guideline:
The test followed a method equivalent or similar to OECD TG 111 (hydrolysis as a function of pH) - as a screening study for the hydrolysis properties of the test substance. The screening study examined: pH 2, 5, 7, 8.5 and 12 using suitable buffers; at 40 °C for 28d by analytical monitoring through GC-FID analyses. Regulatory conclusion that the substance is hydrolytically stable at pH 5, 7 and unstable at pH 8.
GLP compliance:
no
Remarks:
In accordance with REACH Regulation (EC) 1907/2006: Annex XI: section 1.1.2 adequate and reliable (with restrictions) study information has been provided (not in accordance with GLP) but which can be considered equivalent to the relevant test method.
Radiolabelling:
no
Details on sampling:
- Sampling intervals for the parent/transformation products: on a regular basis throughout the test (typically at time = 0, 0.25, 1, 2, 4, 7, 15, 21 and 28 days
- Sampling method: Small aliquots of the test solution are extracted with an organic solvent (typically cyclohexane or ethyl acetate) containing a hydrocarbon standard (typically C12, C17 or C20). The extracts are analyzed by GC-FID and the results are plotted as (Area/Area Std) expressed in [%]. The measurement at time = 0 is set at 100% and the succeeding measurements are calculated relatively to the time = 0 measurement. Therefore the curves represent the percentage of product remaining in the test solution at the time of analysis.
- Other observation, if any (e.g.: precipitation, color change etc.): None reported.
Buffers:
- pH: test media are standard aqueous buffers at pH 2, pH 5, pH 7, pH 8.5 and pH 12 containing 1% of non ionic surfactant (Arkopal N 150).
- Type and final molarity of buffer: Molarity not reported.
• pH 2 (± 0.1) buffer : Reference Handbook of Chemistry and Physics buffer type A*
• pH 5 (± 0.1) buffer : Reference Handbook of Chemistry and Physics buffer type C*
• pH 7 (± 0.1) buffer : Reference Handbook of Chemistry and Physics buffer type D*
• pH 8.5 (± 0.1) buffer : Reference Handbook of Chemistry and Physics buffer type F*
• pH 12 (± 0.1) buffer : Reference Handbook of Chemistry and Physics buffer type I*
Details on test conditions:
TEST MEDIUM
- Volume used/treatment: Total volume not reported
- Kind and purity of water: Deionised water (no further details reported)
- Preparation of test medium: ; 200 – 300 ppm of raw material are dissolved in the pH buffer containing the surfactant (Arkopal N 150) and put into storage in an oven at 40°C.
- Renewal of test solution: None reported.
- Identity and concentration of co-solvent: non-ionic surfactant (Arkopal N 150) was used at 1% concentration
OTHER TEST CONDITIONS
- Adjustment of pH: None reported.
- Dissolved oxygen: Not reported.
Duration:
28 d
pH:
2
Temp.:
40 °C
Initial conc. measured:
>= 200 - <= 300 other: parts per million
Duration:
28 d
pH:
4
Temp.:
40 °C
Initial conc. measured:
>= 200 - <= 300 other: parts per million
Duration:
28 d
pH:
7
Temp.:
40 °C
Initial conc. measured:
>= 200 - <= 300 other: parts per million
Duration:
28 d
pH:
8.5
Temp.:
40 °C
Initial conc. measured:
>= 200 - <= 300 other: parts per million
Duration:
28 d
pH:
12
Temp.:
40 °C
Initial conc. measured:
>= 200 - <= 300 other: parts per million
Number of replicates:
None (with occasional re-injection if required).
Positive controls:
no
Negative controls:
no
Preliminary study:
1. pH 5, and 7, < 10% degradation after 5 days was observed. Similarly, after 28 days at pH 5 and pH 7, < 10% disappearance was observed. It can be concluded that under the conditions of the present test and at pH 5 and 7, the substance is hydrolytically stable (as defined in the OECD TG 111 for hydrolysis as a function of pH).
2. At pH 8.5 after 5 days about 10% degradation was observed. At 28 days, about 40% degradation of the parent substance was observed at 40°C. It can be concluded that at high pH 8.5, the test item is not hydrolytically stable.
3. At very low and very high pH (pH 2 and pH 12) the test item is very unstable with > 50% degradation in 5 days.
It can be concluded that under the conditions of the present test, the test substance is hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH – tier 1: less than 10% degradation at 5 days under acidic (pH 5) and neutral (pH 7) conditions. The substance is hydrolytically unstable: with greater than 10% degradation at 5 days under basic (pH 8.5) conditions.

The stability curve of the analysis is attached.
Test performance:
No unusual findings were reported in the study.
Transformation products:
not measured
pH:
2
Temp.:
40 °C
DT50:
< 2 d
Type:
not specified
Remarks on result:
other: at pH 2, ca. 90% disappearance of the substance was observed at 5 days
pH:
5
Temp.:
40 °C
Remarks on result:
other: at pH 5, < 10% disappearance of the substance was observed at 5 days and 28 days
pH:
7
Temp.:
40 °C
Remarks on result:
other: at pH 7, < 10% disappearance of the substance was observed at 5 days and 28 days
pH:
8.5
Temp.:
40 °C
Remarks on result:
other: at pH 8.5, 10% disappearance of the substance was observed at 5 days and 40% at 28 days
pH:
12
Temp.:
40 °C
Remarks on result:
other: At pH 12, ca. 85 % disappearance of the substance was observed at 5 days and > 95% observed at 28 days
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes, by use of appropriate buffers however pH was not continuously monitored throughout the study, sterility was not examined.
Validity criteria fulfilled:
yes
Remarks:
The study meets the validity criteria and reliable with limitations. This is limited as detailed in 'Rationale for reliability incl. deficiencies'. Guideline Tier 2 and 3 requirements are not met.
Conclusions:
Under the conditions of the study, the substance is hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH – tier 1: less than 10% degradation at 5 days and 28 days under acidic (pH 5) and neutral (pH 7) conditions. Under and basic (pH 8.5) conditions, the test item is unstable. The substance was very stable in very acidic and very basic conditions (pH 2 and pH 12) with greater than 90% degradation at 28 days.
Executive summary:

The hydrolytic stability of the test item was investigated using a method similar or equivalent to OECD TG 111 (hydrolysis as a function of pH) and EU Method A.7. The test media are standard aqueous buffers at pH 2, pH 5, pH 7, pH 8.5 and pH 12 containing 1% of non-ionic surfactant (Arkopal N 150). The tests are done in accelerated conditions at 40°C for approximately one month (28d). 200 – 300 ppm of test substance are dissolved in the pH buffer containing the surfactant and put into storage in an oven at 40°C. Commercial reference grades of buffer are utilised as listed in documented literature sources. Small aliquots of the test solution are extracted with an organic solvent (typically cyclohexane or ethyl acetate) containing a hydrocarbon standard (typically C12, C17 or C20) on a regular basis throughout the test (typically at time = 0, 0.25, 1, 2, 4, 7, 15, 21 and 28 days). The extracts are analysed by GC-FID. Under the analytical conditions employed the test item peak was eluted and the results were then plotted with time to show the degradation curves of the substance. For the test item at pH 5 and pH 7 < 10% degradation after 5 days was observed. Similarly, after 28 days at pH 5 and 7 < 10% degradation was observed. At pH 8.5 after 5 days about 10% degradation was observed. At 28 days, about 40% degradation of the parent substance was observed at 40°C. It can be concluded that at high pH 8.5, the test item is not hydrolytically stable. At pH 2 and 12 and 5 days, about 85 to 90% degradation of the parent substance was observed at 40°C. It can be concluded that under the conditions of the study at pH 5, and 7, the substance is hydrolytically stable. At pH 8.5 the degradation of the substance is greater, and the substance is unstable. At very low and very high pH, the substance is very unstable. It can be concluded that under the conditions of the present test the test item is hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH at mild acidic and neutral pH ranges. At mild basic pH ranges (pH 8.5) the test item is hydrolytically unstable.

Description of key information

Hydrolysis: stable at acidic and neutral pH ranges (pH 5 and 7), unstable at basic pH ranges (pH 8.5), eq. or similar to OECD TG 111 – Tier 1, non-GLP, 2012

Key value for chemical safety assessment

Additional information

Key Study : Eq. or similar to OECD 111 – Tier 1, non-GLP, 2012 : The hydrolytic stability of the test item was investigated using a method similar or equivalent to OECD TG 111 (hydrolysis as a function of pH) and EU Method A.7. The test media are standard aqueous buffers at pH 2, pH 5, pH 7, pH 8.5 and pH 12 containing 1% of non-ionic surfactant (Arkopal N 150). The tests are done in accelerated conditions at 40°C for approximately one month (28d). 200 – 300 ppm of test substance are dissolved in the pH buffer containing the surfactant and put into storage in an oven at 40°C. Commercial reference grades of buffer are utilised as listed in documented literature sources. Small aliquots of the test solution are extracted with an organic solvent (typically cyclohexane or ethyl acetate) containing a hydrocarbon standard (typically C12, C17 or C20) on a regular basis throughout the test (typically at time = 0, 0.25, 1, 2, 4, 7, 15, 21 and 28 days). The extracts are analysed by GC-FID. Under the analytical conditions employed the test item peak was eluted and the results were then plotted with time to show the degradation curves of the substance. For the test item at pH 5 and pH 7 < 10% degradation after 5 days was observed. Similarly, after 28 days at pH 5 and 7 < 10% degradation was observed. At pH 8.5 after 5 days about 10% degradation was observed. At 28 days, about 40% degradation of the parent substance was observed at 40°C. It can be concluded that at high pH 8.5, the test item is not hydrolytically stable. At pH 2 and 12 and 5 days, about 85 to 90% degradation of the parent substance was observed at 40°C. It can be concluded that under the conditions of the study at pH 5, and 7, the substance is hydrolytically stable. At pH 8.5 the degradation of the substance is greater, and the substance is unstable. At very low and very high pH, the substance is very unstable. It can be concluded that under the conditions of the present test the test item is hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH at mild acidic and neutral pH ranges. At mild basic pH ranges (pH 8.5) the test item is hydrolytically unstable.

 

References:

1. OECD TG 111 - hydrolysis as a function of pH, (2004)

2. ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7b: Endpoint Specific Guidance, R.7.9, v4.0, June 2017)