3-(4,4-dimethylcyclohex-1-en-1-yl)propanal

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2011

Reliability:

4 (not assignable)

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 unstable 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.

Reason / purpose for cross-reference:

other:

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 analytically monitoring by GC-FID.

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

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-ionioc 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: ppm

Duration:

28 d

pH:

5

Temp.:

40 °C

Initial conc. measured:

>= 200 - <= 300 other: ppm

Duration:

28 d

pH:

7

Temp.:

40 °C

Initial conc. measured:

>= 200 - <= 300 other: ppm

Duration:

28 d

pH:

8.5

Temp.:

40 °C

Initial conc. measured:

>= 200 - <= 300 other: ppm

Duration:

28 d

pH:

12

Temp.:

40 °C

Initial conc. measured:

>= 200 - <= 300 other: ppm

Number of replicates:

None (with occasional re-injection if required).

Positive controls:

no

Negative controls:

no

Preliminary study:

1. pH 2, 5 and 7, ca. 10 to 15% degradation after 5 days was observed. Similarly, after 28 days at pH 2 , 5 and 7, ca. 30 to 35% disappearance was observed.
2. At pH 8.5, ca. 20% degradation after 5 days was observed. Similarly, after 28 days at pH 8.5, ca. 55% disappearance was observed.
3. At higher pH, the degradation of the substance is greater. At very basic pH (pH 12), the substance disappears to ca. 10% within 4 days and essentially completely disappears by day 7.

It can be concluded that under the conditions of the present test, the test substance is not hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH – tier 1: where greater than 10% degradation at 5 days under acidic (pH 5), neutral (pH 7) and basic (pH 8.5) conditions is suggested.

Test performance:

No unusual findings were reported in the study.

Transformation products:

not measured

pH:

5

Temp.:

40 °C

DT50:

> 28 d

pH:

7

Temp.:

40 °C

DT50:

> 28 d

pH:

8.5

Temp.:

40 °C

DT50:

ca. 20 d

Type:

(pseudo-)first order (= half-life)

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 unstable as defined in the OECD TG 111 for hydrolysis as a function of pH – tier 1: where greater than 10% degradation at 5 days under acidic (pH 5), neutral (pH 7) and basic (pH 8.5) conditions is suggested. At pH 2, 5 and 7, ca. 10 to 15% degradation after 5 days was observed. Similarly, after 28 days at pH 2 , 5 and 7, ca. 30 to 35% disappearance was observed. At higher pH, the degradation of the substance is greater. At pH 8.5, ca. 20% degradation after 5 days was observed. Similarly, after 28 days at pH 8.5, ca. 55% disappearance was observed. At very basic pH (pH 12), the substance disappears to ca. 10% within 4 days and essentially completely disappears by day 7.

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 was eluted and the results were then plotted with time to show the degradation curves of the substance. At pH 2, 5 and 7, ca. 10 to 15% degradation after 5 days was observed. Similarly, after 28 days at pH 2 , 5 and 7, ca. 30 to 35% disappearance was observed. At higher pH, the degradation of the substance is greater. At pH 8.5, ca. 20% degradation after 5 days was observed. Similarly, after 28 days at pH 8.5, ca. 55% disappearance was observed. At pH of 8.5, after about 20 days there is 50% degradation. The t1/2 appears to be ca. 20 days. At very basic pH (pH 12), the substance disappears to ca. 10% within 4 days and essentially completely disappears by day 7. Under the conditions of the study, the substance is hydrolytically unstable as defined in the OECD TG 111 for hydrolysis as a function of pH – tier 1: where greater than 10% degradation at 5 days under acidic (pH 5), neutral (pH 7) and basic (pH 8.5) conditions is suggested.

Description of key information

Hydrolysis: unstable at acidic, neutral and alkali pH ranges (pH 5, 7 to 8.5) : ca. 10 to 15% degradation at day 5 through 30 to 35% day 28 (t1/2 > 28 days), at pH of 8.5, after about 20 days there is 50% degradation (t1/2 appears to be ca. 20 days), at  40 °C, 1 atm, eq. or similar to OECD TG 111 – Tier 1, non-GLP, 2011

Additional information

Hydrolysis: eq. or similar to OECD TG 111 - preliminary screening study, 2011 : 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 was eluted and the results were then plotted with time to show the degradation curves of the substance. At pH 2, 5 and 7, ca. 10 to 15% degradation after 5 days was observed. Similarly, after 28 days at pH 2 , 5 and 7, ca. 30 to 35% disappearance was observed. At higher pH, the degradation of the substance is greater. At pH 8.5, ca. 20% degradation after 5 days was observed. Similarly, after 28 days at pH 8.5, ca. 55% disappearance was observed. At pH of 8.5, after about 20 days there is 50% degradation. The t1/2 appears to be ca. 20 days. At very basic pH (pH 12), the substance disappears to ca. 10% within 4 days and essentially completely disappears by day 7. Under the conditions of the study, the substance is hydrolytically unstable as defined in the OECD TG 111 for hydrolysis as a function of pH – tier 1: where greater than 10% degradation at 5 days under acidic (pH 5), neutral (pH 7) and basic (pH 8.5) conditions is suggested.