Registration Dossier

Administrative data

Endpoint:
biodegradation in soil: simulation testing
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
see attached justification
Cross-referenceopen allclose all
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
biodegradation in water: ready biodegradability
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
OASIS Catalogic v5.14.1.5

2. MODEL (incl. version number)
CATALOGIC 301C v.11.16

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
7 representative structures of the UVCB
CCCCCCCCCCC(C)c1cc(C)cc(N2Nc3ccccc3N2)c1O
CCCCCCCCCCC(C)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(C)CCCCCCCCCC
CCCCCCC(CCCCC)c1cc(C)cc(N2Nc3ccccc3N2)c1O
CCCCCCC(CCCCC)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(CCCCC)CCCCCC
CCCCCCCCCCC(C)c1c(O)c(cc(C)c1C(CCCCC)CCCCCC)N2Nc3ccccc3N2
CCCCCCCCCCC(C)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(CCCCC)CCCCCC
CCCCCCCCCCCCCCCCCCCCCCC(C)c1cc(C)cc(N2Nc3ccccc3N2)c1O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRFs

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the biodegradability of a substance and identifies its degradation betabolites.
- See attached QPRF for reliability assessment.
Principles of method if other than guideline:
Estimation of ready biodegradation in water using CATALOGIC v5.14.1.5 BOD 28 days MITI (OECD 301C) v.11.16
GLP compliance:
no
Oxygen conditions:
aerobic
Inoculum or test system:
other: Model calculation
Duration of test (contact time):
28 d
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
16
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
C12 linear: CCCCCCCCCCC(C)c1cc(C)cc(N2Nc3ccccc3N2)c1O; within parameter domain, out of structural fragment domain, within metabolic domain
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
21
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
2x C12 linear: CCCCCCCCCCC(C)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(C)CCCCCCCCCC; within parameter domain, out of structural fragment domain, within metabolic domain
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
2
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
C12 branched: CCCCCCC(CCCCC)c1cc(C)cc(N2Nc3ccccc3N2)c1O; within parameter domain, out of structural fragment domain, within metabolic domain
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
3
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
2x C12 branched: CCCCCCC(CCCCC)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(CCCCC)CCCCCC; within parameter domain, out of structural fragment domain, within metabolic domain
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
12
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
C12 linear, C12 branched: CCCCCCCCCCC(C)c1c(C(CCCCC)CCCCCC)c(C)cc(N2Nc3ccccc3N2)c1O; within parameter domain, out of structural fragment domain, within metabolic domain
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
12
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
C12 branched, C12 linear: CCCCCCCCCCC(C)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(CCCCC)CCCCCC; within parameter domain, out of structural fragment domain, within metabolic domain
Parameter:
% degradation (O2 consumption)
Remarks:
QSAR model: based on OECD TG 301 C
Value:
22
Sampling time:
28 d
Remarks on result:
not readily biodegradable based on QSAR/QSPR prediction
Remarks:
C24 linear: CCCCCCCCCCCCCCCCCCCCCCC(C)c1cc(C)cc(N2Nc3ccccc3N2)c1O; within parameter domain, out of structural fragment domain, within metabolic domain
Details on results:
Structure 1, C12 linear:
CCCCCCCCCCC(C)c1cc(C)cc(N2Nc3ccccc3N2)c1O
 
Predicted value (model result):
0.16 ± 0.0543
Concomitant predictions :
Not ready degradable
Primary Half Life = 1m 4d
Ultimate Half Life = 3m 19d
 

 
Structure 2, 2x C12 linear:
CCCCCCCCCCC(C)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(C)CCCCCCCCCC
 
Predicted value (model result):
0.21 ± 0.0613
Concomitant predictions :
Not ready degradable
Primary Half Life = 18.65 days
Ultimate Half Life = 2m 22d
 

 
Structure 3, C12 branched:
CCCCCCC(CCCCC)c1cc(C)cc(N2Nc3ccccc3N2)c1O
 
Predicted value (model result):
0.02 ± 0.0146
Concomitant predictions :
Not ready degradable
Primary Half Life = 2m 30d
Ultimate Half Life = 2y 5m 29d
 

 
Structure 4, 2x C12 branched:
CCCCCCC(CCCCC)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(CCCCC)CCCCCC
 
Predicted value (model result):
0.03 ± 0.0183
Concomitant predictions :
Not ready degradable
Primary Half Life = 1m 22d
Ultimate Half Life = 2y 0m 30d
 
 

Structure 5, C12 linear – C12 branched:
CCCCCCCCCCC(C)c1c(O)c(cc(C)c1C(CCCCC)CCCCCC)N2Nc3ccccc3N2
 
Predicted value (model result):
0.12 ± 0.0356
Concomitant predictions :
Not ready degradable
Primary Half Life = 27.59 days
Ultimate Half Life = 5m 3d
 
 

Structure 6, C12 branched – C12 linear:
CCCCCCCCCCC(C)c1c(C)cc(N2Nc3ccccc3N2)c(O)c1C(CCCCC)CCCCCC
 
Predicted value (model result):
0.12 ± 0.0355
Concomitant predictions :
Not ready degradable
Primary Half Life = 27.59 days
Ultimate Half Life = 5m 3d
 

 
Structure 7, C24 linear:
CCCCCCCCCCCCCCCCCCCCCCC(C)c1cc(C)cc(N2Nc3ccccc3N2)c1O
 
Predicted value (model result):
0.22 ± 0.0753
Concomitant predictions :
Not ready degradable
Primary Half Life = 1m 4d
Ultimate Half Life = 2m 20d
Interpretation of results:
not readily biodegradable
Remarks:
representative structures of UVCB
Conclusions:
The representative structures of the UVCB are not readily biodegradable. In total 126 metabolites (including the parents) at a quantity >=0.1% and a logKow of >4 could be identified.
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
biodegradation in water: sediment simulation testing
Remarks:
study currently running
Study period:
2019 - 2020
Data waiving:
other justification
Justification for data waiving:
other:
Qualifier:
according to
Guideline:
OECD Guideline 308 (Aerobic and Anaerobic Transformation in Aquatic Sediment Systems)
Version / remarks:
Organisation for Economic Cooperation and Development - OECD
Guidelines for Testing of Chemicals
Aerobic and Anaerobic Transformation in Aquatic Sediment Systems No. 308:
24 Apr 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Radiolabelling:
yes
Remarks:
14C-2-(2H-benzotriazole-2-yl)-4-methyl-6-(1-methylundecyl)phenol was used as test material. A representative Isomer was synthesized and labeled.
Oxygen conditions:
aerobic
Inoculum or test system:
natural water / sediment: freshwater
Details on study design:
As the study is still running a final study report is not yet available. Therefore, only the information of the study plan is presented.

EXPERIMENTAL PROCEDURE
Number of test assays
For every water/sediment system the following number and type of test assays will be prepared:
a.) 16 test assays with test item for regular sampling (6 sampling times, in double determinations). The sampling times depend on the dissipation rate in the water phase (day 0 and at the end of exposure are fixed).
b.) 2 additional test assays with test item, only for water phase sampling on additional sampling points. This will be sacrificed together with the other assays only at the termination.
c.) 2 test assays without test item as control. One of these test assays will be used for determination the parameters in the acclimation phase.
d.) 2 test assays with test item for checking the toxic or inhibition effects of the test substance on the microbial community.
e.) 2 additional control units with the solvent (same solvent volume that was used to apply the test substance) to measure adverse effects on the microbial activity of the test system.
Acclimation of the test system
The test system used in the test will be configured and acclimated for about 1 to 2 weeks but not longer than 4 weeks. During this time, the scheduled parameters will be measured one time a week.
Therefore, the needed number of cylindrical glass flasks with a volume of 1000 ml will be used as test vessels. The test vessels will be filled with water and sediment volume in a ratio between 3:1 to 4:1 and with a sediment layer of at least 2.5 ± 0.5 cm. This sediment layer should have a minimum amount of sediment of about 50 g/100g dry weight. The test vessel will be aerated so that the air bubbles are as small as possible, and the water layer will be lightly moved. The test vessels will be protected from light and incubated at 22 ± 2°C. The blending of the water layer will be assured by lightly aerating the water surface. A distinct phase separation and stable test system parameters should be seen at the end of acclimation.

Application of the test item
The required amount of the test substance will be added to the test vessels after the acclimation phase by aliquots of a test substance stock solution. The scheduled test concentration in the water layer should be about 140 µg in 500 ml water (nominal concentration). The amount of test substance is calculated to a volume of water phase of 500 ml. A suitable volume of test substance aliquots of the test item stock solution will be administered into the test vessel water phase. Following addition of the test substance, a gently mixing of the water phase should be done by not disturbing the sediment. Weight of the test vessels at the beginning of test after test substance addition will be noted.

Determination of the start concentration of TAR (base value)
For determination the amount of the total applied radioactivity at the start of exposure, suitable aliquots of the stock solution 14G0118/18G275/SP2/0 will be dosed to 500 ml deionized water. This will be done in two replicates. The activity will be measured by liquid scintillation measurement. The mean value will be used for the base value of total applied radioactivity (TAR).

Exposure
After addition of the test substance to the scheduled test vessels 5x 250 ml absorption flasks will be connect with the test vessels. The first absorption flask is empty and will be used to collect any back flow of liquid or condensation liquid. Second and third trap will be filled with 50 ml 2 M sodium hydroxide solution for the adsorption of carbon dioxide from biodegradation processes. Fourth trap consists of 50 ml ethylene glycol to absorb volatile organic substances, and the last flask will be filled with 50 ml 0.1 m sulphuric acid for volatile alkali substances. After application of the test substance the test vessels will be connected with the air supply. Aeration with a tube pump will be adjusted so that the air bubbles are as small as possible and the water layer in the test vessels will be lightly moved. The test vessels will be protected from light and incubated at 22 ± 2°C.

Test duration
The scheduled test duration is 100 days. The test duration should be continued until the transformation way and the water/sediment distribution pattern are established or when the removal of test substance by degradation or by volatilization is >90% (if test vessels are available).

Sampling times
Sampling times are fixed for the start of exposure (day 0) and for the end of exposure. Other sampling points are decided depending on the development of transformation. As the test substance is hydrophobic test substances, additional sampling points during the initial period of the study is necessary in order to determine the rate of distribution between water and sediment phases. This will be derived through the water phase sampling of two additional replicates set up under same conditions.


SAMPLING PROCEDURE
Prior to sampling, weight of the test bottles will be noted. At the sampling times the whole test vessels with test substance (replicates) are removed for analysis.
Sampling for evolved 14CO2 radioactivity measurement
Radioactivity will be measured in the LSC on the sampling days in the test assays in the dissolved phase and from the absorption solution for 14CO2. After stopping the aeration and closing the valve in the gas transferring tubes, the second and third trap with NaOH solution are removed for sampling. Duplicate subsamples of 1 ml from each of the removed traps with NaOH solution will be transferred to scintillation vials and combined with a suitable scintillation cocktail and analyzed by LSC. This procedure is repeated until the last day of exposure.
Sampling for volatiles radioactivity measurement
After removing the NaOH traps, the volatile traps (ethylene glycol and H2SO4) will be removed and duplicate samples will be analyzed by LSC after mixing with the scintillation cocktail.
Radioactivity in water phase by direct LSC measurement
Samples of approximately 2 ml will be taken from all test substance assays (double determinations) on each sampling points into corresponding labelled tubes containing about 15 ml of Ultima Gold scintillation cocktail and are analyzed directly by LSC to quantify the radioactivity remaining in each treatment over time. These measurements are used to confirm that the recovery of radioactivity from the extracted samples is acceptable and to monitor for volatilization. Quench effects due to particulates in the samples will be checked and minimized if necessary, by appropriate quench correction methods available.
Wet extraction of sediment phase
After this, water and sediment phase will be treated separately. The bottles will be opened, and water phase is decanted into a separate tube. Water phase will be extracted with appropriate solvents and will be send for radio HPLC analysis. After decantation, the wet sediment phase will be extracted three times with methanol, each time with 100 ml methanol by shaking at 5 minutes on a shaker at 150 rpm. Extracts from each extraction will be measured by LSC for differences in the extractability and at the end, all three extracts will be combined (pooled extract) and measured by LSC. Only the pooled extract LSC will be reported. The bottles will be washed by adding appropriate solvent and the radioactivity will be determined on the washed fraction with LSC.
Radioactivity in sediment phase
The sediment phase obtained after wet extraction will be dried at 60° until weight constant. If there is significant radioactivity (more than 10%) in the sediment after extraction, the non-extractable activity in the sediments will be further characterized in selected samples by separation into fulvic acid, humic acid and humins. For each sample, about 20 g of the dried sediment will be weighed into a centrifuge vessel and extracted 3 times with about 50 ml of 0.5 M NaOH overnight. The sediment will be finally extracted and rinsed with 20 ml water respectively. All extracts will be measured by LSC and specific analysis, if reasonable. The corresponding extracts per sample will be combined, the activity will be measured and then acidified with conc. HCI to pH 1-2 to precipitate the acid-insoluble humic acid. For precipitation, the samples will be kept over weekend in a refrigerator. After centrifugation at the next workday, the radioactivity in the supernatant will be determined by LSC and the remaining fraction will be sent for radio HPLC analysis when radioactivity >10% TAR. The precipitates will be dissolved in 40 ml 0.5 M NaOH and the solutions will be measured by LSC. The remaining non-extractable activity in the residual sediments will be determined by LSC after combustion. If there are additional investigations for nonextractable activity in the sediment required, this will be described in a notice to the raw data.

ANALYTICS
The measurement of radioactivity of the absorption liquid, water phase, extraction phases and sediment phases will be conducted in the department "Radio Isotope Laboratory and Analytics" of BASF SE under the responsibility of the personal of the Degradation lab of "Experimental Toxicology and Ecology". The apparatus, materials and reagents are inspected facility based in regular intervals by the QAU of the department Crop Protection, 67116 Limburgerhof, BASF SE. The nature of the radioactivity (test substance or metabolites) will be analyzed by suitable methods. The structure of metabolites in an amount of ~10% of the inserted radioactivity will be investigated by suitable methods. Metabolites with a continuous increasing concentration in the test vessel during the test will be identified also if the concentration is lower than ~10% of the inserted radioactivity. It can be necessary to concentrate the samples for structure elucidation. The analytical investigations of the test substance and the structural elucidation of potential metabolites in the extraction phases of the liquid phase, if possible in sediments after extraction (when a radioactivity > 10 % of the total applied radioactivity (TAR) is found with the extracted solids) will be carried out. The analytical investigations of the test substance preparations (substance specific analysis) and identification and structural elucidation of potential metabolites, when appropriate will be carried out as a separate study at Noack Laboratorien GmbH, KathePaulus- Stral5e 1, 31157 Sarstedt, Germany under the responsibility of a Study Director of this test facility. If analytically possible, identification, stability, behavior, molar quantity of metabolites relative to the parent compound will also be evaluated at the same test facility. This study will be carried out in compliance with the Principles of Good Laboratory Practice. The Analytical Report will be included in the study report as an appendix. A justification of the analytical method must be provided. The control vessels will be used for determination of chemical and physical parameters, in acclimation phase, during and at the end of exposure.
Transformation products:
not specified
Remarks:
study is currently running
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
biodegradation in water: ready biodegradability
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985/11/22 - 20/12/1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, study was conducted under GLP like quality assurance.
Qualifier:
according to
Guideline:
OECD Guideline 301 B (Ready Biodegradability: CO2 Evolution Test)
Deviations:
no
GLP compliance:
no
Remarks:
but GLP like quality assurance
Oxygen conditions:
aerobic
Inoculum or test system:
activated sludge, non-adapted
Details on inoculum:
- Source of inoculum/activated sludge:
Bacteria collected from activated sludge of the sewage treatment plant of CH-4153 Reinach on 19/11/85. The preparation was carried out according to the method described in the guideline.
Duration of test (contact time):
28 d
Initial conc.:
10 mg/L
Based on:
test mat.
Initial conc.:
20 mg/L
Based on:
test mat.
Parameter followed for biodegradation estimation:
CO2 evolution
Details on study design:
TEST CONDITIONS
- Composition of medium:The test medium was prepared according to the method described in the guideline.
- Test temperature: 22 + or - 2 degrees
- Aeration of dilution water: Approx. 50 mL/min free of carbon dioxide.

TEST SYSTEM
- Culturing apparatus: 2 liters flasks equipped with gas inlet and magnetic stirrer.
- Number of culture flasks/concentration: 1

SAMPLING
- Sampling frequency: day 4 / 7 / 10 / 13 / 17 / 24 / 27 and 28
Reference substance:
aniline
Parameter:
% degradation (CO2 evolution)
Value:
13
Sampling time:
28 d
Remarks on result:
other: 20 mg/L test substance
Parameter:
% degradation (CO2 evolution)
Value:
19
Sampling time:
28 d
Remarks on result:
other: 10 mg/L test substance
Details on results:
The test item is not is not biodegradable in this test.
The biodegradation of the reference substances was calculated as 91 % in 28 days
Interpretation of results:
other: not readily biodegradable
Reason / purpose:
data waiving: supporting information
Reference
Endpoint:
biodegradation in water: screening tests
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1986-02-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, study was performed predated GLP.
Qualifier:
equivalent or similar to
Guideline:
other: "Deutsche Einheitsverfahren zur Wasseruntersuchung" H 41 December 1980 DIN 38 409
Principles of method if other than guideline:
Determination of the chemical oxygen demand by oxydation of the test substance with potassium dichromate.
GLP compliance:
no
Remarks:
but GLP like quality assurance
Oxygen conditions:
other: not relevant
Inoculum or test system:
other: not applicable
Duration of test (contact time):
2 h
Details on study design:
TEST CONDITIONS
- Test temperature: 148 +/- 3 degrees.
Reference substance:
other: Potassium hydrogen phthalate
Parameter:
COD
Value:
2.15 g O2/g test mat.
Results with reference substance:
Reference substance : 201 mg COD/L (limit: 192 - 208 mg COD/L)

Result: 2.15 g O2/g test item

Data source

Materials and methods

Results and discussion

Transformation products:
not specified
Remarks:
the degradation products have been identified in section 5.2.1

Applicant's summary and conclusion