(1RS,4Z,8E,12RS)-13-oxabicyclo[10.1.0]trideca-4,8-diene

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is readily biodegradable

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VIII, column 2 section 9.2.2.1 the study does not need to be conducted if the substance is readily biodegradable. The substance rapidly degrades biotically. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, July 2017 and Chapter R.7b: Endpoint Specific Guidance, R.7.9, June 2017) the study does not need to be conducted.

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

05-08-2019 to 07-01-2021

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 in specific pH ranges.

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

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

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.

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.

Specific details on test material used for the study:

- Physical state: Liquid
- Storage condition of test material: In refrigerator (2-8°C) protected from light container flushed with nitrogen
- Other: colourless liquid

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:

At pH 5, 7, 8.5 and 12, < 10% degradation after 5 days was observed. Similarly, after 28 days at pH 5, 7, 8.5 and 12, < 10% disappearance was observed. At pH 2, ca. 75% disappearance was observed at 5 days. Similarly, after 28 days at pH 2, ca.100% disappearance was observed. It can be concluded that under the conditions of the present test and at pH 5, 7, 8.5 and 12, the substance is hydrolytically stable (as defined in the OECD TG 111 for hydrolysis as a function of pH). At very low pH (highly acidic) the substance is hydrolytically unstable with ca. 50% at 48 to 72 hours and ca. 100% degradation from day 15.

Test performance:

No unusual findings were reported in the study.

Transformation products:

not measured

pH:

2

Temp.:

40 °C

Remarks on result:

other: at pH 2, the substance is hydrolytically unstable with ca. 50% at 48 to 72 hours and ca. 100% degradation from day 15.

Key result

pH:

5

Temp.:

40 °C

Remarks on result:

other: at pH 5, < 5% disappearance of the substance was observed at 5 days and 28 days

Key result

pH:

7

Temp.:

40 °C

Remarks on result:

other: at pH 7, < 5% disappearance of the substance was observed at 5 days and 28 days

Key result

pH:

8.5

Temp.:

40 °C

Remarks on result:

other: at pH 8.5, < 5% disappearance of the substance was observed at 5 days and 28 days

pH:

12

Temp.:

40 °C

Remarks on result:

other: At pH 12, < 5% disappearance of the substance was observed at 5 days and 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 under acidic (pH 5), neutral (pH 7) and basic (pH 8.5) conditions was observed at 5 days and 40°C. Less than 10% degradation was also seen up to 28 days at 40°C. Separately, at very low pH [pH 2 (highly acidic)] the substance is hydrolytically unstable with ca. 50% at 48 to 72 hours and ca. 100% degradation from day 15 at 40°C. At very high pH [[pH 12 (highly basic)] the substance is hydrolytically stable with less than 10% degradation at 5 to 28 days and 40°C. Conclusion: At pH 5, 7, 8.5, < 10% degradation of the parent substance was observed at 5 days and 28 days and 40°C. The substance is hydrolytically stable.

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 item 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 < 10% degradation after 5 days was observed at pH 5, 7, 8.5 and 12. Similarly, after 28 days at pH 5, 7, 8.5 and 12, < 10% disappearance was observed. At very low pH [pH 2 (highly acidic)] the substance is hydrolytically unstable with ca. 50% at 48 to 72 hours and ca. 100% degradation from day 15 at 40°C. At very high pH [[pH 12 (highly basic)] the substance is hydrolytically stable with less than 10% degradation at 5 to 28 days and 40°C. At very acidic pH (pH 2) the substance is hydrolytically unstable. At very basic pH (pH 12) the substance is hydrolytically stable. It can be concluded that under the conditions of the present test and at pH 5, 7, 8.5, the substance is hydrolytically stable at acidic, neutral and basic pH ranges (as defined in the OECD TG 111 for hydrolysis as a function of pH).

Description of key information

Hydrolysis: stable at acidic, neutral and alkali pH ranges (pH 5, 7 to 8.5) and ca. 0% degradation at day 5 through day 28, eq. or similar to OECD TG 111 – Tier 1, non-GLP, 2021

 

Note: substance is ‘readily biodegradable’, further testing is scientifically not necessary.

Supporting information: substance will rapidly (bio)degrade and mineralise with a DT50 of 10.5 to 10.8 days respectively for biotic and abiotic degradation systems at 0.5 μg/L and 12°C. This corresponds to a degradation rate of >0.043 day-1 or a degradation half-life, t½ < [ln 2/0.043] = 16 days, under environmentally realistic conditions

Key Data:

1. Biodegradation: rapidly (bio)degradable due to DT50 < 16 days for biotic mineralisation in simulated environmentally relevant conditions observed (at 0.5 μg/L and 12 °C). Simple First Order (SFO) model rate constants (k) were : 0.06624 and 0.06434 d^-1 for biotic mineralisation with equivalent DT50 = 10.5 and 10.8 days, respectively for both biotic and abiotic systems at 0.5 μg/L and 12 °C. Slightly slower degradation of parent occurred in the biotic group at the higher treatment level of 2.5 μg/L with DT50 21.1 and 5.14 days respectively for biotic and abiotic systems at 2.5 μg/L and 20°C, OECD TG 309, 2020

2. Ready Biodegradation (screening): not readily biodegradable ; mean biodegradation 0 % by BOD and GC (28 -days); transformation products were detected by GC, OECD TG 301F, 2020

 

Reference: Biodegradation - section.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

In accordance with REACH Regulation (EC) No. 1907/2006 Annex VIII, column 2 section 9.2.2.1 the study does not need to be conducted if the substance is readily biodegradable. The substance rapidly degrades biotically. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, July 2017 and Chapter R.7b: Endpoint Specific Guidance, R.7.9, June 2017) the study does not need to be conducted.

 

Supporting information on hydrolysis:

Eq. or similar to OECD 111 – Tier 1, non-GLP, 2021 : 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 item 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 < 10% degradation after 5 days was observed at pH 5, 7, 8.5 and 12. Similarly, after 28 days at pH 5, 7, 8.5 and 12, < 10% disappearance was observed. At very low pH [pH 2 (highly acidic)] the substance is hydrolytically unstable with ca. 50% at 48 to 72 hours and ca. 100% degradation from day 15 at 40°C. At very high pH [[pH 12 (highly basic)] the substance is hydrolytically stable with less than 10% degradation at 5 to 28 days and 40°C. At very acidic pH (pH 2) the substance is hydrolytically unstable. At very basic pH (pH 12) the substance is hydrolytically stable. It can be concluded that under the conditions of the present test and at pH 5, 7, 8.5, the substance is hydrolytically stable at acidic, neutral and basic pH ranges (as defined in the OECD TG 111 for hydrolysis as a function of pH).

 

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)