Reaction mass of (3E)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one and 4-(dodecylsulfanyl)-4-(2,6,6-trimethylcyclohex-2-en-1-yl)butan-2-one

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

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. The study would not fulfil the requirements of OECD TG 111 (2004) Tier 2 or Tier 3 requirements; however due to the demonstrated stability of the test item OECD TG 111 - Tier 2 and 3 requirements are not needed. The test was conducted at physiologically relevant temperature (40 °C) rather than the guideline preliminary test temperature 50 °C. The utilised test temperature is within the suggested temperature range for testing under guideline and would be physiologically relevant. Higher tier kinetic testing does not appear scientifically necessary.

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 report consisted of two studies conducted during two different time periods on the test substance. Experiment 1 (February 2013) examined constituents 1, 2 and 3. Experiment 2 (May 2001) examined constituent 1. Both experiments were conducted using the same methodology and were documented by the applicant within a single report.
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 constituent 1, 2 and 3 degradation.

GLP compliance:

no

Remarks:

non-GLP; well documented study report. Regulatory conclusion that the substance is hydrolytically stable. OECD TG 111 (2004) Tier 2 or Tier 3 requirements are not required; due to the demonstrated stability of the test item.

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, 0.21, 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 N150)
- 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.

Number of replicates:

None.

Positive controls:

no

Negative controls:

no

Preliminary study:

Experiment 1: The test substance was extracted from the aqueous phase using ethyl acetate.
Constituents 2 and 3:
At pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation. At 28d there was ca. 10% degradation but was not significantly declining. At pH 2 the substance was degraded by 20% (day 4). Further declines were seen to around 50% degradation at day 28. At pH 12 the constituent 2 and 3 rapidly declined to 0% (or 100% degradation) within 4 days.
Constituent 1:
At pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation. At 28d there was ca. 10% degradation but was not significantly declining. At pH 2 the substance was degraded by 10% (day 4) and 20% at day 15. There was no further significant decline within the duration of the test. At pH 12 the constituent 1 rapidly declined to 0% (or 100% degradation) within 4 days.
Constituents 1, 2 and 3 were defined as hydrolytically stable in the OECD TG 111 for hydrolysis as a function of pH

Experiment 2: The test substance was extracted from the aqueous phase using cyclohexane.
Constituent 1:
At pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation At 15 days and 28 days there was ca. 7.5% and 10% degradation, respectively. At pH 2 the substance was degraded by ca. 2% (day 4) and 15% at day 15. There was no further significant decline within the duration of the test. At pH 12 the constituent 1 was 10%, 30% and 40% degradation at days, 4, 15 and 28 respectively.
Constituents 1 was defined as hydrolytically stable in the OECD TG 111 for hydrolysis as a function of pH

Test performance:

No unusual findings were reported in the study.

Transformation products:

not measured

pH:

5

Temp.:

40 °C

DT50:

> 28 d

Remarks on result:

other: Representative of all measured constituents

pH:

7

Temp.:

40 °C

DT50:

> 28 d

Remarks on result:

other: Representative of all measured constituents

pH:

8.5

Temp.:

40 °C

DT50:

> 28 d

Remarks on result:

other: Representative of all measured constituents

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. This is limited as detailed in 'Rationale for reliability incl. deficiencies'. The study is reliable as indicates that the substance is hydrolytically stable. Guideline Tier 2 and 3 requirements are not required.

Conclusions:

The test substance was found to be stable to hydrolysis in water.

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. Constituent 1, 2 and 3 was then plotted with time to show the degradation curves of the substance. For Constituent 1 at pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation. At 28d there was ca. 10% degradation but was not significantly declining. For Constituents 2 and 3 at pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation. At 28d there was ca. 10% degradation but was not significantly declining. It can be concluded that under the conditions of the study the test substance is hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH.

Reference 2

Endpoint:

hydrolysis

Data waiving:

other justification

Justification for data waiving:

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 the study does not need to be conducted if the substance appears ‘highly insoluble’ in water. Applicant assessment of the water solubility and partition coefficient of the multi-constituent substance indicates that specific constituents are highly insoluble in water (< 0.001 mg/L). One identified constituent is moderately soluble (ca. 100 mg/L). For specific constituents testing would not be further required. The applicant completed a series of preliminary test with acceptable deviations under OECD TG 111 - tier 1 and has demonstrated that at 40 °C all the identified constituents are hydrolytically stable. Further testing does not appear scientifically necessary since there is adequate information both on water solubility and hydrolysis behaviour for hazard and risk assessment purposes. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7b: Endpoint Specific Guidance, R.7.9.2.2, June 2017) further information is not needed. Further testing for hydrolysis is not justified.

Description of key information

Substance is hydrolytically stable at all relevant pH and 40 °C, 1 atm, eq. or similar to OECD TG 111, 2016

Additional information

Eq. of similar to OECD TG 111, 2016 - 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. Constituent 1, 2 and 3 was then plotted with time to show the degradation curves of the substance. For Constituent 1 at pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation. At 28d there was ca. 10% degradation but was not significantly declining. For Constituents 2 and 3 at pH 5, 7 and 8.5. After 4 and 7 days there is ca. 5% degradation. At 28d there was ca. 10% degradation but was not significantly declining. It can be concluded that under the conditions of the study the test substance is hydrolytically stable as defined in the OECD TG 111 for hydrolysis as a function of pH.

 

Applicant assessment of the data indicates: At mildly acidic, neutral and mildly alkali pH the substance does not undergo complete degradation (> 99%) in a period > 28 days. The substance’s constituents will undergo complete degradation at strong alkali conditions (t1/2 = ca. 24 hours). At strong acid conditions the substance can undergo complete degradation however, this is in a period > 28 days. The substance should be defined as hydrolytically stable in the OECD TG 111 for hydrolysis as a function of pH since the substance will not undergo > 10% degradation within a period of 5 days at 40 °C which was confirmed by no relevant identified t1/2 within a period of 30 days at relevant pH range (5, 7 and 8.5).

 

In accordance with REACH Regulation (EC) No. 1907/2006 Annex VIII, column 2 section 9.2.2 the study does not need to be conducted if the substance appears ‘highly insoluble’ in water. Applicant assessment of the water solubility and partition coefficient of the multi-constituent substance indicates that specific constituents are highly insoluble in water (< 0.001 mg/L). One identified constituent is moderately soluble (ca. 100 mg/L). For specific constituents testing would not be further required. The applicant completed a series of preliminary test with acceptable deviations under OECD TG 111 - tier 1 and has demonstrated that at 40 °C all the identified constituents are hydrolytically stable. Further testing does not appear scientifically necessary since there is adequate information both on water solubility and hydrolysis behaviour for hazard and risk assessment purposes. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7b: Endpoint Specific Guidance, R.7.9.2.2, June 2017) further information is not needed. Further testing for hydrolysis is not justified.