Registration Dossier

Administrative data

Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-04-06 to 2017-06-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
yes
Remarks:
See section: Any other information on materials and methods incl. tables
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)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Fluorobenzene
EC Number:
207-321-7
EC Name:
Fluorobenzene
Cas Number:
462-06-6
Molecular formula:
C6H5F
IUPAC Name:
fluorobenzene
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
* batch: M15FB2364
* test item number: 207617/A
- Expiration date of the lot/batch: 2017-08-12 (retest date)
- Purity: 100% (based on GC)
- Puriy test date: 2017-06-14 (certificate release date)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:At room temperature
- Stability under test conditions: Stable
Radiolabelling:
no

Study design

Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent/transformation products:
* Tier 1: at the beginning and after 5 days
* Tier 2: at the beginning and at several sampling point after t=0.

- Sampling method:
* Tier 1: Concentration of the test item in the test sample was determined immediately after preparation. The samples taken at t=5 days were cooled to room temperature using running tap water. The sample were diluted in a 7:3 (v:v) ratio with acetonitrile and analysed. If necessary, the samples were further diluted with 30/70 (v/v) acetonitrile/water to obtain concentrations within the calibration range.
* Tier 2: Hydrolysis samples were analysed immediately after sampling.
Buffers:
- pH: 4, 7 and 9
- Type and final molarity of buffer: Acetate buffer pH 4, 0.1 M; Phosphate buffer pH 7, 0.1 M; Borate buffer pH 9, 0.1 M
- Composition of buffer:
* Acetate buffer pH 4, 0.1 M: Solution of 16.7% 0.1 M sodium acetate in water and 83.3% 0.1 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-hydrogen-phosphate 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 0.1 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:
TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: sterile vessel
- Sterilisation method: each solution was filter-sterilised through a 0.2 µm FP 30/0.2 CA-S filter (Whatman, Dassel, Germany) and transferred into a sterile vessel.
- Lighting: in the dark
- Measures taken to avoid photolytic effects: vessels placed in the dark
- Measures to exclude oxygen: Nitrogen was passed through the buffer solutions for about 5 minutes.
- Temperature:
* Tier 1: 49.9°C +/- 0.1°C
* Tier 2:
pH 4: 19.9°C ± 0.1°C; 49.4°C ± 0.9°C; 59.7°C ± 0.4°C
pH 7: 19.9°C ± 0.1°C; 49.4°C ± 0.9°C; 59.7°C ± 0.4°C
pH 9: 19.9°C ± 0.1°C; 49.4°C ± 0.9°C; 60.0°C ± 0.1°C
- If no traps were used, is the test system closed/open: under vacuum
- Is there any indication of the test material adsorbing to the walls of the test apparatus? no

TEST MEDIUM
- Volume used/treatment: 6 mL
- Kind and purity of water: Tap water purified by a Milli-Q water purification system (Millipore, Bedford, MA, USA)
- Preparation of test medium: The spiking volume was 1% of the sample volume. Nominal concentrations were not corrected for the spiking volume.
- Renewal of test solution: not applicable
- Identity and concentration of co-solvent: not applicable

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Dissolved oxygen: no data
Duration of testopen allclose all
Duration:
307.05 h
pH:
4
Temp.:
20 °C
Initial conc. measured:
43.7 - 46.6 mg/L
Duration:
306.93 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
45.3 - 47.3 mg/L
Duration:
206.25 h
pH:
4
Temp.:
60 °C
Initial conc. measured:
38.9 - 40 mg/L
Duration:
306.68 h
pH:
7
Temp.:
20 °C
Initial conc. measured:
45.1 - 45.5 mg/L
Duration:
306.03 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
45.2 - 45.3 mg/L
Duration:
206.08 h
pH:
7
Temp.:
60 °C
Initial conc. measured:
35.5 - 36.5 mg/L
Duration:
305.77 h
pH:
9
Temp.:
20 °C
Initial conc. measured:
44.5 - 46.8 mg/L
Duration:
305.65 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
44 - 44.6 mg/L
Duration:
205.78 h
pH:
9
Temp.:
60 °C
Initial conc. measured:
38.9 - 41.9 mg/L
Number of replicates:
-Calibration solutions were injected in duplicate.
-Test samples were analyzed by single injection.
Positive controls:
no
Negative controls:
no
Statistical methods:
No data

Results and discussion

Preliminary study:
At pH 4, pH 7 and pH9, the test item concentration decreased ≥ 10% within 5 days. According to the guideline, the higher Tier test was required to determine the half-life time of the test item.

A small response was observed in the blank buffer solutions at pH 4. The estimated values were calculated using the mean response factor of the lowest calibration solution and were significantly lower than the analysed samples. It was, therefore, considered not to have impact on the study results.
The mean recoveries of the buffer solutions at t=0 fell within the criterion range of 70-110% for non-labelled chemicals. It demonstrated that the analytical method was adequate to support the hydrolysis study on the test item.

Transformation products:
no
Total recovery of test substance (in %)open allclose all
% Recovery:
100 - 108
pH:
4
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
99 - 106
pH:
7
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
98 - 109
pH:
9
Temp.:
50 °C
Duration:
5 d
Remarks on result:
hydrolytically stable based on preliminary test
% Recovery:
87 - 93
pH:
4
Temp.:
20 °C
Duration:
307.05 h
% Recovery:
91 - 95
pH:
4
Temp.:
50 °C
Duration:
306.93 h
% Recovery:
78 - 80
pH:
4
Temp.:
60 °C
Duration:
206.25 h
% Recovery:
90 - 91
pH:
7
Temp.:
20 °C
Duration:
306.68 h
% Recovery:
90 - 91
pH:
7
Temp.:
50 °C
Duration:
306.03 h
% Recovery:
71 - 73
pH:
7
Temp.:
60 °C
Duration:
206.08 h
% Recovery:
89 - 94
pH:
9
Temp.:
20 °C
Duration:
305.77 h
% Recovery:
88 - 89
pH:
9
Temp.:
50 °C
Duration:
305.65 h
% Recovery:
78 - 84
pH:
9
Temp.:
60 °C
Duration:
205.78 h
Dissipation DT50 of parent compoundopen allclose all
pH:
4
Temp.:
50 °C
Type:
(pseudo-)first order (= half-life)
Remarks on result:
not determinable
pH:
7
Temp.:
50 °C
Type:
(pseudo-)first order (= half-life)
Remarks on result:
not determinable
pH:
9
Temp.:
50 °C
Type:
(pseudo-)first order (= half-life)
Remarks on result:
not determinable
pH:
4
Temp.:
20 °C
Type:
other: not pseudo-first order
Remarks on result:
not determinable
pH:
7
Temp.:
20 °C
Type:
other: not pseudo-first order
Remarks on result:
not determinable
pH:
9
Temp.:
20 °C
Type:
other: not pseudo-first order
Remarks on result:
not determinable

Any other information on results incl. tables

The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of JNJ-7820254-AAA (Fluorobenzene) at pH values normally found in the environment (pH 4-9). Plotting the mean logarithms of the relative concentrations between 10% and 90% in Tier 2 against time, non-linear relationships were obtained for all pH’s. Accordingly, the decrease of test item concentration was not caused by a pseudo-first order reaction. At the beginning of the test, the test item concentration decreased faster than at later time points of the study.  Adsorption and higher-order reactions were ruled out as reasons for the observed test item decrease. The decline was considered to be due to volatilization of the test item. As volatilization obviously dominated the results of Tier 2 testing, it was technically not possible to determine the half life time of the test item.

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
The preliminary test (Tier 1) and main study (Tier 2) were performed for the determination of the rate of hydrolysis of JNJ-7820254-AAA (Fluorobenzene) at pH values normally found in the environment (pH 4-9). The decrease of the test item concentration was not caused by a pseudo-first order reaction. The decline was considered to be due to volatilization of the test item.
As the test item did not show pseudo-first order behaviour, Tier 2 testing was discontinued before six sampling times covered the hydrolysis range of 10% to 90%. It was technically not possible to determine the half life time of the test item due to the test item being volatile. The results of the test can be considered reliable without restriction.