Registration Dossier

Environmental fate & pathways

Hydrolysis

Currently viewing:

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-12-13 - 2018-03-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
201702001
- Expiration date of the lot/batch:
February 05, 2020
- Purity:
99.73% according to CoA

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
At 20°C ± 5°C in the dark
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products:
Preliminary Test (tier 1):
Proposed sampling points: 0, 3, 24, 120 h.
The test item will be incubated at 50°C at three different pH values (pH 4.0, 7.0 and 9.0). If less than 10% hydrolysis will be observed after 5 days (corresponding to a half-life time of t½ (25°C) > 1 year = the test substance was considered to be hydrolytically stable) of incubation no additional testing is required otherwise the main test will be performed with the specific pH-value.

Hydrolysis of unstable substances (tier 2):
The higher tier test was performed at the pH-values at which the test substance was found unstable in the preliminary test. The buffered solutions of the test substance should be thermostated at the selected temperatures. For each pH-value 10 data points (0h, 6h, 12h, 24h, 1d, 2d, 3d, 4d, 5d, 7d, 14d) were sampled so that the test item degradation was expected to be within the range 10 % to 90 %.

- Sampling method: Duplicate incubation flasks will be taken at each sampling time point. The test item and relevant hydrolysis products were analysed by an appropriate HPLC method. Aqueous test solution samples were directly injected in to the HPLC.

- Sampling intervals/times for pH measurements:
The pH of each test solution will be determined at least once in course of the study (e.g. at test start).

- Sampling intervals/times for sterility check: A sterility confirmation test will be carried out at least once in course of the study. A commercially available dip slide kit (e.g. Hycon GK-T/HS, Heipha Dr. Müller GmbH, Eppelheim, Germany) will be used for a total count of microorganisms and to determine the total count of yeast and moulds.

- Sample storage conditions before analysis: At each sampling time point the samples will be measured directly or stored in a freezer until measurement.


- Other observation, if any (e.g.: precipitation, color change etc.): None
Buffers:
Sterile aqueous solutions buffered at pH 4, 7 and 9:
- pH 4: 0.05 M phthalate buffer (20 mL NaOH (0.1 M) was added to 250 mL potassium dihydrogenphosphate (0.1 M). The solution was filled up to 1000 mL with pure water.)
- pH 7: 0.05 M phosphate buffer (135 mL NaOH (0.1 M) was added to 250 mL potassium dihydrogenphosphate (0.1 M). The solution was filled up to 500 mL with pure water. 296 mL NaOH (0.1 M) was added to 500 mL potassium dihydrogenphosphate (0.1 M). The solution was filled up to 1000 mL with pure water.
- pH 9: 0.05 M boric acid buffer (107 mL NaOH (0.1 M) was added to 250 mL of a solution of boric acid (0.1 M) in potassium chloride (0.1 M). The solution was filled up to 500 mL with pure water.
213 mL NaOH (0.1 M) was added to 500 mL of a solution of boric acid (0.1 M) in potassium chloride (0.1 M). The solution was filled up to 1000 mL with pure water.)

Details on test conditions:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: glass flasks (hermetically closed)
- Sterilisation method: Degased buffer solutions and the used glassware were sterilised by using an autoclave (20 min at 121°C) or by heating (> 3 h at 180°C) prior to application.
- Lighting: n.a., incubation in the dark
- Measures taken to avoid photolytic effects: incubation in the dark
- Measures to exclude oxygen: To avoid oxidation the buffer solutions were purged with inert gas (nitrogen) prior to sterilisation.
- Details on test procedure for unstable compounds: n.a.
- If no traps were used, is the test system closed: yes
- Is there any indication of the test material adsorbing to the walls of the test apparatus? No

TEST MEDIUM
- Volume used/treatment
A blank sample (2 replkicates) for each pH was prepared which consisted of the buffer solution (without application of the test item).
* Preliminary test (Tier 1): 8 samples per pH level inclusive blanks
* Main test (Tier 2):
- pH 7: 20°C: 20 samples inclusive blanks; 40°C: 16 samples inclusive blanks; 50°C: 16 samples inclusive blanks
- pH 9: 20°C: 20 samples inclusive blanks; 40°C: 16 samples inclusive blanks; 50°C: 20 samples inclusive blanks

- Kind and purity of water: Deionised water
- Preparation of test medium: Deionised water and analytical grade chemicals were used; the buffers were sterilised
- Renewal of test solution: No
- Identity and concentration of co-solvent: None

OTHER TEST CONDITIONS
- Adjustment of pH: none; test media were buffered (pH 4 and 7) according to the guideline; pH was measured with a pH-meter with an accuracy of 0.01 units and pH was adjusted to the nominal pH value ± 0.02 units.
- Dissolved oxygen: No data
Number of replicates:
two
Positive controls:
no
Negative controls:
no
Statistical methods:
Kinetic analysis and calculation of DT50 and DT90 values were performed using Cake (Version 3.2)
Preliminary study:
Preliminary test (Tier 1): The test item was found to be hydrolytically stable at pH 4 (DT50 > 1 year at 25°C) and hydrolytically unstable at pH 7 and 9.
Transformation products:
not specified
Remarks:
Expected degradation products are gallic acid and propanol.
% Recovery:
34.1
pH:
7
Temp.:
20 °C
Duration:
17 d
% Recovery:
< 5
pH:
7
Temp.:
40 °C
Duration:
6 d
% Recovery:
< 5
pH:
7
Temp.:
50 °C
Duration:
6 d
% Recovery:
39.7
pH:
9
Temp.:
20 °C
Duration:
10 d
% Recovery:
< 5
pH:
9
Temp.:
40 °C
Duration:
6 d
% Recovery:
< 5
pH:
9
Temp.:
50 °C
Duration:
6 d
pH:
4
Temp.:
25 °C
Half-life:
> 1 yr
Type:
(pseudo-)first order (= DT50)
Key result
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0.005 h-1
Half-life:
141 h
Type:
(pseudo-)first order (= DT50)
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
0.004 h-1
Half-life:
80 h
Type:
(pseudo-)first order (= DT50)
pH:
7
Temp.:
20 °C
Hydrolysis rate constant:
0.002 h-1
Half-life:
319 h
Type:
(pseudo-)first order (= DT50)
pH:
7
Temp.:
40 °C
Hydrolysis rate constant:
0.051 h-1
Half-life:
13.6 h
Type:
(pseudo-)first order (= DT50)
pH:
7
Temp.:
50 °C
Hydrolysis rate constant:
0.125 h-1
Half-life:
5.6 h
Type:
(pseudo-)first order (= DT50)
pH:
9
Temp.:
20 °C
Hydrolysis rate constant:
0.004 h-1
Half-life:
176 h
Type:
(pseudo-)first order (= DT50)
pH:
9
Temp.:
40 °C
Hydrolysis rate constant:
0.082 h-1
Half-life:
8.4 h
Type:
(pseudo-)first order (= DT50)
pH:
9
Temp.:
50
Hydrolysis rate constant:
0.249 h-1
Half-life:
2.8 h
Type:
(pseudo-)first order (= DT50)
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: pH not monitored; sterility maintained due to design of test vessels, temperature maintained
- Anomalies or problems encountered (if yes): No data

MAJOR TRANSFORMATION PRODUCTS: Yes: is not yet specified
MINOR TRANSFORMATION PRODUCTS: Yes: is not yet specified.

Validity criteria fulfilled:
yes
Conclusions:
Propyl gallate is hydrolytically stable at pH 4 (DT50 > 1 year at 25°C) but hydrolytically unstable at pH 7 and 9:
- pH 7: k = 0.005 h-1 ; DT50 = 141 h (6 d);
- pH 9: k = 0.009 h-1; DT50 = 80 h (3 d)
Executive summary:

Hydrolysis of propyl gallate was studied in the dark in sterile aqueous buffered solutions at pH 4 (phthalate buffer), pH 7 (phosphate buffer) and pH 9 (boric acid buffer).  The experiment was conducted in accordance with the OECD 111 (2004), and in compliance with the GLP standards. Quantification of the test item was conducted using HPLC-UV/Vis. For characterisation (specificity) of the test item retention times of the analyte peak from standards and sample solutions were compared (co-chromatography).

Preliminary test:

Samples were incubated at three different pH-values and at 50 °C. The test was carried out for 5 days. During incubation the concentration of the test item remained stable at pH 4. In case of pH 7 and 9 recoveries were <LOQ (5% of the nominal applied concentration) after 5 days. Thus the test item can be stated as hydrolytically stable at pH 4 and hydrolytically unstable at pH 7 and 9. The main test (Tier 2) was performed at pH 7 and 9.

Main test – pH 7:

Samples were incubated at 20, 40 and 50°C. The test was carried out for 408, 24 and 8 hours, respectively. During incubation the concentration of the test item decreased. At the end of incubation recoveries (mean) were 34.1% of the nominal applied concentration at 20°C and <LOQ (5% of the nominal applied concentration) at 40 and 50°C.

Hydrolysis rate constants and corresponding DT50and DT90values for the test item were determined for each temperature:

·      20°C: k = 0.002 h-1; DT50= 319 h (13 d); DT90= 1060 h (44 d)

·      40°C: k = 0.051 h-1; DT50= 14 h; DT90= 45 h

·      50°C: k = 0.125 h-1; DT50= 6 h; DT90= 19 h

The hydrolysis rate constant and the corresponding DT50value was calculated for a temperature of 25°C based on the arrhenius parameters:

·      25°C: k = 0.005 h-1;DT50= 141 h (6 d)

Main test – pH 9:

Samples were incubated at 20, 40 and 50°C. The test was carried out for 240, 48 and 8 hours, respectively. During incubation the concentration of the test item decreased. At the end of incubation recoveries (mean) were 39.7% of the nominal applied concentration at 20°C and <LOQ (5% of the nominal applied concentration) at 40 and 50°C.

Hydrolysis rate constants and corresponding DT50and DT90values for the test item were determined for each temperature:

·      20°C: k = 0.004 h-1;DT50= 176 h (7 d); DT90= 586 h (24 d)

·      40°C: k = 0.082 h-1;DT50= 8 h; DT90= 28 h

·      50°C: k = 0.249 h-1;DT50= 3 h; DT90= 9 h

The hydrolysis rate constant and the corresponding DT50value was calculated for a temperature of 25°C based on the arrhenius parameters:

·      25°C: k = 0.009 h-1; DT50= 80 h (3 d)

This study is classified as acceptable and satisfies the guideline requirement for hydrolysis study.

 

Description of key information

The present study reported by Strack (2018) investigated the hydrolytic behaviour of propyl gallate in aqueous solutions buffered at pH 4, 7 and 9 according to OECD 111.

The test item was found to be hydrolytically stable at pH 4 (DT50> 1 year at 25°C) and hydrolytically unstable at pH 7 and 9.

The hydrolysis rate constant and the corresponding DT50 value was calculated for a temperature of 25°C based on the Arrhenius parameters:

pH 7: k = 0.005 h-1; DT50= 141 h (6 d) at 25°C;

pH 9: k = 0.009 h-1; DT50= 80 h (3 d) at 25°C

Key value for chemical safety assessment

Half-life for hydrolysis:
141 h
at the temperature of:
25 °C

Additional information