6,6-dimethoxy-2,5,5-trimethylhex-2-ene

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04-June-2014 to 28-Jul-2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Qualifier:

according to guideline

Guideline:

EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)

Principles of method if other than guideline:

List of protocol deviations

1. For the analysis of pH 4 at 50°C on 25 March 2016 the mean recovery of the t=0 samples was 64% which is < 70%
Evaluation: Since the recovery is only slightly below the criteria and the results will be calculated relative to initiative the results are accepted.

2. The variation of the hydrolyses at 20°C was > 0.5°C for both pH 4 and pH 7, 19.6 ± 0.6°C and 19.0 ± 1.3°C, respectively.
Since the deviation for pH 4 was considered small (i.e. ± 0.6°C) and the results for pH 7 over the period studies (30 days) were considered stable.

The study integrity was not adversely affected by the deviations.

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Test item: 205601/B
Identification: Methyl Pamplemousse
Appearance: Colourless to pale yellow liquid
Batch: AS00239830
Purity/Composition: See Certificate of Analysis
Test item storage:age conditions until: 11 March 2017 (expiry date)

Analytical monitoring:

yes

Buffers:

Acetate buffer pH 4, 0.01 M: solution of 16.7% 0.01 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. The buffer contains 0.0009% (w/v) sodium azide.

Phosphate buffer pH 7, 0.01 M: solution of 0.01 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Borate buffer pH 9, 0.01 M: solution of 0.01 M boric acid in water and 0.01 M potassium chloride in water adjusted to pH 9 using 1 N sodium hydroxide. The buffer contains 0.0009% (w/v) sodium azide.

Details on test conditions:

The rate of hydrolysis of the test substance as a function of pH was determined at pH values normally found in the environment (pH 4-9).
All solutions containing the test substance were protected from light.

Preliminary study:

A degree of hydrolysis of ≥ 10% was observed at pH 4 and pH 7 after 5 days. According to the guideline, the higher Tier test was required to determine the half-life time of the test item.
A degree of hydrolysis of < 10% was observed at pH 9 after 5 days. It demonstrated that the half-life time of the test item at 25°C is > 1 year. According to the guideline, no further tests were required.
No test item was detected in the blank buffer solutions.
The mean recoveries of the of the test item containing buffer solutions at t=0 fell within the acceptable criterion range of 70-110% (i.e. 88%, 86% and 80%).

Transformation products:

not measured

% Recovery:

91

pH:

4

Temp.:

20 °C

% Recovery:

105

pH:

4

Temp.:

30 °C

% Recovery:

64

pH:

4

Temp.:

50 °C

% Recovery:

76

pH:

7

Temp.:

20 °C

% Recovery:

73

pH:

7

Temp.:

50 °C

% Recovery:

76

pH:

7

Temp.:

70 °C

pH:

4

Temp.:

20 °C

DT50:

7.9 h

pH:

4

Temp.:

25 °C

DT50:

4.1 h

pH:

4

Temp.:

30 °C

DT50:

2.1 h

pH:

4

Temp.:

50 °C

DT50:

0.22 h

pH:

7

Temp.:

25 °C

DT50:

137 d

pH:

7

Temp.:

50 °C

DT50:

6.3 d

pH:

7

Temp.:

70 °C

DT50:

18 h

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Validity criteria fulfilled:

yes

Executive summary:

The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of Methyl Pamplemousse at pH values normally found in the environment (pH 4-9).

The half-life times of the test substance were:

pH 4		pH 7		pH 9
Temperature [°C]	t1/2	Temperature [°C]	t1/2	Temperature [°C]	t1/2
20	7.9 hours	25	137 days
25	4.1 hours	50	6.3 days	25	> 1 year
30	2.1 hours	70	18 hours
50	0.22 hours

 

Description of key information

The test item was found to be hydrolytically unstable at pH 4 (t1/2 = 4.1 h at 25 °C) and, to a certain extent, at pH 7 (t1/2 = 137 h at 25°C) but hydrolytically stable at pH 9. The worst-case half-life of >1 year at pH 9 has been used as the key value for chemical safety assessment.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C

Additional information

The rate of hydrolysis of the test substance as a function of pH was determined at pH values normally found in the environment (pH 4-9). A preliminary test (tier 1) was carried out at 50 °C. A degree of hydrolysis of < 10% was observed at pH 9 after 5 days. It demonstrated that the half-life time of the test item at 25 °C is > 1 year and that the test substance is hydrolytically stable at this pH. According to the guidelines, no further tests were required at this pH. In contrast, the degree of hydrolysis observed in the preliminary tests at pH4 and pH 7 was ≥ 10% (99 and 35% respectively after 5 days). Therefore higher tier (tier 2) hydrolysis tests were performed at three temperatures (20, 30 and 50 °C for pH 4; 20, 50 and 70 °C for pH 7). The results of the 20 °C test at pH 9 were not used because the deviation of the method was larger than the degree of hydrolysis (less than 10% for most sampling times). The half-life times of the test substance were determined according to the model for pseudo-first order reactions. The rate constant and half-life time of the test item at each temperature was obtained and the Arrhenius equation was used to determine the rate constant and half-life time at 25°C. The latter was calculated to be 4.1 hours at pH 4 and 137 days at pH 7. Research to investigate the identity or nature and rates of formation and decline of hydrolysis products was not performed. However, based on the chemical structure of the test item, acid catalysed hydrolysis of the acetal function most likley occurs to give the corresponding aldehyde (2,2,5-trimethylhex-4-enal, estimated log Kow of 3 using Kowwin v1.68).

The revised ECHA guidance (Chapter R.7b, version 4.0, June 2017) states that “For the PBT/vPvB assessment purposes, the testing temperature of 12°C is required for tier 2 testing purposes”. The ECHA rationale is “that 12°C is at present considered by authorities as the mean temperature of European surface waters and is required by the ECHA Member State Committee to be used as the testing temperature for new simulation degradation tests”. The OECD 111 guideline (adopted 13 April 2004) on hydrolysis suggests a temperature range of 10-70°C (preferably with at least one temperature below 25 °C utilised) since this encompasses the reporting temperature of 25 °C and most of the temperatures accounted in the field. In the study performed on Methyl Pamplemousse (study period Jun-Jul 2016), the lowest temperature employed was 20 °C. ECHA proposes that “a rough hydrolysis temperature correction estimate may be done by using the following equation: t ½ (X°C) = t ½ e (0.08 (T - X).” Applying this approximation to the experimentally determined half-life results for Methyl Pamplemousse gives an estimated half-life of 5-15 hours (pH 4) and 73-132 days (pH 7) at 12 °C – see table below.

 

pH	Temperature [°C]	t½	t½ Corrected to 12 °C	Unit
4	20	7.9	15.0	hours
	30	2.1	8.9	hours
	50	0.22	4.6	hours
7	50	6.3	131.7	days
	70	0.7	72.5	days

 

There is currently no cut off for hydrolysis rate, which could alone be used as justification to conclude that a substance is not persistent and, according to ECHA guidance R11, the degradation half-lives obtained in a hydrolysis test cannot be compared to the persistency criteria of Annex XIII (degradation half-life in freshwater > 40 days (P), > 60 days (vP)). Furthermore, rapid hydrolysis needs to be shown at all environmentally relevant pH. Based on the data above, Methyl Pamplemousse undergoes rapid hydrolysis at pH 4 (T/12 = 4.1h at 25°C; = 5-15h corrected to 12°C) but is not rapidly hydrolysed at pH 7 or pH 9.