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Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Aug 2020 - 31 Dec 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021
Report date:
2021

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EPA OPPTS 835.2120 (Hydrolysis of Parent and Degradates as a Function of pH at 25°C)
Version / remarks:
October 2008
Qualifier:
according to guideline
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Version / remarks:
March 04, 2016
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Version / remarks:
April 13, 2004
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
1-Chloro-6-Hydroxyhexane
IUPAC Name:
1-Chloro-6-Hydroxyhexane
Constituent 2
Chemical structure
Reference substance name:
6-chlorohexan-1-ol
EC Number:
217-925-2
EC Name:
6-chlorohexan-1-ol
Cas Number:
2009-83-8
Molecular formula:
C6H13ClO
IUPAC Name:
6-chlorohexan-1-ol
Test material form:
liquid: viscous
Specific details on test material used for the study:
Batch: 191217
Purity: 98.64%

Study design

Analytical monitoring:
yes
Remarks:
A gas chromatographic method with mass spectrometric detection (GC-MS) for the quantitative analysis of the test item in water was developed.
Buffers:
Acetate buffer pH 4, 0.1 M: Solution of 16.7% 0.1 M sodium acetate in water and 83.3% 0.01 M acetic acid in water. Buffer contained 0.0009% (w/v) sodium azide.
Phosphate buffer pH 7, 0.1 M: Solution of 0.1 M potassium di-hydrogenphosphate in water adjusted to pH 7 using 10N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.

Borate buffer pH 9, 0.1 M: Solution of 0.01 M boric acid in water and 0.1 M potassium chloride in water adjusted to pH 9 using 10N sodium hydroxide. Buffer contained 0.0009% (w/v) sodium azide.
Details on test conditions:
Preparation of Solutions
Stock and Spiking Solutions
Stock solutions of the test item were prepared in dichloromethane at concentrations of 1000
and 2000 mg/L. Spiking solutions of the test item were prepared in acetone at concentrations of 5000 mg/L.
Calibration Solutions
Six calibration solutions in the concentration range of 0.1 – 6 mg/L were prepared from two stock solutions. The end solution of the calibration solutions was dichloromethane.

Sample Injections
Calibration solutions were injected in duplicate. Test samples were analyzed by single
njection.

Calibration Curves
Calibration curves were constructed using six concentration levels. For each level, duplicate responses were used. Linear regression analysis was performed using the least squares method with a 1/concentration² weighting factor. The coefficient of correlation (r) was > 0.99 for each curve.

Results and discussion

Preliminary study:
At pH 4, pH 7 and pH 9, a degree of hydrolysis of ≥ 10% was observed after 5 days.
According to the guideline, the higher Tier test was required to determine the half-life time of the test item.
Small responses at the retention time of the test item were detected in a few chromatograms of the blank buffer solutions. It was considered to derive from the analytical system since similar responses were found in the analytical blanks. The maximum contribution to the samples was 0.010%. It was considered that it has no significant effect on the results of the test samples.
The mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.
Test performance:
The rate of hydrolysis of the test item as a function of pH was determined at pH values normally found in the environment (pH 4-9). The buffer solutions were filter-sterilised through a 0.2 μm FP 30/0.2 CA-S filter (Whatman,Dassel, Germany) and transferred into a sterile vessel. To exclude oxygen, nitrogen gas was purged through the solution for 5 minutes. The test item was spiked to the solutions at a target concentration of 50 mg/L using a spiking solution in acetone. For each sampling time, duplicate sterile vessels under vacuum were filled with 6 mL test solution and placed in the dark in a temperature controlled environment at 49.8°C +- 0.2°C.
The spiking volume was ≤ 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.
The concentration of the test item in the test samples was determined immediately after preparation (t=0) and after 2.4 hours and 5 days. The samples taken at t=2.4 hours and t=5 days were cooled to room temperature using running tap water. Analysis was performed on subsamples of 10 mL. The samples were extracted in a 5:1 (v:v)
ratio with dichloromethane. The shaking time was 30 seconds. The extracts were 100-fold
diluted with dichloromethane to obtain concentrations within the calibration range.
Blank buffer solutions containing a similar content of blank spiking solution were treated
similarly as the test samples and analyzed at t=0.
The pH of each of the test solutions (except for the blanks) was determined at each sampling
time. Test samples were prepared and treated similarly as during the preliminary test. The pH of each of the test solutions (except for the blanks) was determined at least at the beginning and at the end of the test. The study was performed at the following temperatures: 19.8°C +- 0.4°C; 39.9°C +-0.6°C; 49.9°C +- 0.1°C.
Transformation products:
not measured
Details on hydrolysis and appearance of transformation product(s):

Research to investigate the identity or nature and rates of formation and decline of hydrolysis products was not required since the studies were conducted according to the testing guidelines provided in Annex VIII (volume 10-100 tons/year).
Total recovery of test substance (in %)open allclose all
% Recovery:
ca. 96
pH:
4
Temp.:
20 °C
Duration:
> 0 - <= 745 h
% Recovery:
ca. 97
pH:
4
Temp.:
40 °C
Duration:
> 0 - <= 745 h
% Recovery:
ca. 99
pH:
4
Temp.:
50 °C
Duration:
> 0 - <= 745 h
% Recovery:
ca. 91
pH:
7
Temp.:
20 °C
Duration:
> 0 - <= 788 h
% Recovery:
ca. 91
pH:
7
Temp.:
40 °C
Duration:
> 0 - <= 788 h
% Recovery:
ca. 96
pH:
7
Temp.:
40 °C
Duration:
> 0 - <= 788 h
Dissipation DT50 of parent compoundopen allclose all
Key result
pH:
9
Temp.:
50 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
15 d
Key result
pH:
9
Temp.:
40 °C
Hydrolysis rate constant:
0.001 h-1
DT50:
44 d
Key result
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
0 h-1
DT50:
73 d
Key result
pH:
9
Temp.:
20 °C
Hydrolysis rate constant:
0 h-1
DT50:
73 d
Key result
pH:
7
Temp.:
50 °C
Hydrolysis rate constant:
0.002 h-1
DT50:
14 d
Key result
pH:
7
Temp.:
40 °C
Hydrolysis rate constant:
0.001 h-1
DT50:
43 d
Key result
pH:
7
Temp.:
25 °C
Hydrolysis rate constant:
0 h-1
DT50:
106 d
Key result
pH:
7
Temp.:
20 °C
Hydrolysis rate constant:
0 h-1
DT50:
147 d
Key result
pH:
4
Temp.:
50 °C
Hydrolysis rate constant:
0 h-1
DT50:
18 d
Key result
pH:
4
Temp.:
40 °C
Hydrolysis rate constant:
0 h-1
DT50:
59 d
Key result
pH:
4
Temp.:
25 °C
Hydrolysis rate constant:
0 h-1
DT50:
157 d
Key result
pH:
4
Temp.:
20 °C
Hydrolysis rate constant:
0 h-1
DT50:
224 d
Other kinetic parameters:
The rate constant (kobs) 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
Details on results:
MAIN STUDY TIER 2
pH 4
The analytical results of the main study at pH 4 are given in "Any other information on results incl.tables" Small responses at the retention time of the test item were detected in a few chromatograms of the blank buffer solutions. It was considered to derive from the analytical system since similar responses were found in the analytical blanks. The maximum contribution to the samples was 0.39%. It was considered that it has no significant effect on the results of the test samples. The mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item. The rate constant (kobs) 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


pH 7
The analytical results of the main study are given in "Any other information on results incl.tables".
Small responses at the retention time of the test item were detected in a few chromatograms of the blank buffer solutions. It was considered to derive from the analytical system since similar responses were found in the analytical blanks. The maximum contribution to the samples was 0.16%. It was considered that it has no significant effect on the results of the test samples.
The mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.
For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations were plotted against time. At all temperatures linear relationships were obtained. The half-life times of the test item were determined according to the model for pseudo-first order reactions. All logarithms of the relative concentrations were correlated with time using linear regression analysis. The rate constant (kobs) 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

pH 9

The analytical results of the main study are given in "Any other information on results incl.tables". Small responses at the retention time of the test item were detected in a few chromatograms of the blank buffer solutions. It was considered to derive from the analytical system since similar responses were found in the analytical blanks. The maximum contribution to the samples was 0.090%. It was considered that it has no significant effect on the results of the test samples.
The mean recoveries of the test item containing buffer solutions at t=0 fell within the criterion range of 90-110%. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.

For testing of pseudo-first order kinetics the mean logarithms of the relative concentrations between 10% and 90% were plotted against time. At all temperatures linear relationships were obtained. The half-life times of the test item were determined according to the model for pseudo-first order reactions. All logarithms of the relative concentrations were correlated with time using linear regression analysis. The rate constant (kobs) 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

Applicant's summary and conclusion