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Biodegradation in water and sediment: simulation tests

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Reference
Endpoint:
biodegradation in water: simulation testing on ultimate degradation in surface water
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 October 2018 - 31 May 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 309 (Aerobic Mineralisation in Surface Water - Simulation Biodegradation Test)
Version / remarks:
April 2004
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Name: Omnirad TPO
Chemical Name: 2,4,6-Trimethylbenzoyl-diphenyl phosphine oxide
CAS Number: 75980-60-8
Molecular Formula: C22H21O2P
Molecular Weight: 348.4 g/mol

Non-radiolabelled reference standard was supplied by the Sponsor. Information on the supplied material is presented in the following table:

Name: Omnirad TPO
Purity: 99.3%
Storage: Ambient
Radiolabelling:
yes
Remarks:
14C-phosphinophenyl]-Omnirad TPO and [14C-benzoyl]-Omnirad TPO were used on this study. These metabolically stable positions of radiolabelling were chosen to provide the maximum amount of information for elucidation of the biotransformation pathway.
Oxygen conditions:
aerobic
Inoculum or test system:
natural water: freshwater
Details on source and properties of surface water:
The study was conducted using surface water sampled at Calwich Abbey Lake, Staffordshire, England. The water was collected from the lake and passed through a 100 μm filter bag at the time of sampling by Land Research Associates. Full details of the sampling dates and the locations are given in Table 1.
Details on source and properties of sediment:
Not applicable: surface water simulation test.
Details on inoculum:
Not applicable: surface water simulation test.
Duration of test (contact time):
>= 60 - <= 62 d
Initial conc.:
10 µg/L
Based on:
other: Phosphinophenyl
Remarks:
dpm per vessel: 192,862
Initial conc.:
95 µg/L
Based on:
other: Phosphinophenyl
Remarks:
dpm per vessel: 1,777,900
Initial conc.:
10 µg/L
Based on:
other: Benzoyl
Remarks:
dpm per vessel: 171,611
Initial conc.:
95 µg/L
Based on:
other: Benzoyl
Remarks:
dpm per vessel: 1,640,350
Parameter followed for biodegradation estimation:
radiochem. meas.
Details on study design:
- Study Design:
Incubation groups are shown in the table below.

Preliminary tests were carried out to establish suitable experimental conditions and determine appropriate timepoints for the main test. Summary data from these are provided in Appendix 6. The definitive experimental design is summarised in the following table and a diagram illustrating the aerobic flow and volatile traps system is provided in Figure 1:

- Study Parameters:
Duration of the test: 60/62 days
Water condition: Fresh, passed through 100 µm filter bag prior to use
Sample size (mL per test vessel): 100 mL (b)
Control conditions: Treated with non-labelled Omnirad TPO, for measurement of water quality parameters
Number of replicates: 2
Test apparatus: Glass flask (a), moist air flow through system, connections made with glass and PVC tubing
Incubation conditions: Aerobic, moist air, dark and 12 ± 2ºC. Continuous agitation by shaking.
Traps for CO2 & organic volatiles: 2M NaOH for 14CO2
Test material application:
- Identity of solvent: Acetonitrile
- Volume of test solution used/treatment: 200 µL for 10 µg/L samples; 200 µL for 95 µg/L samples
- % of co-solvent per sample: 0.2%
- Application method: Pipette
Indication of test material adsorbing to walls of test apparatus: No
(a) The protocol states that 250 mL flasks will be used. The size of the flask was not recorded in that data, but is deemed to have no impact on the study.
(b) The protocol states that the water level of the sample will be marked on the flasks to check for any losses. This was not carried out for all flasks. As the weight of water is recorded at the time of sampling and no significant losses were observed, this is deemed to have no effect on the results of the study.

- Preparation of Test Systems:
A total of 18 test flasks were prepared for each radiolabel and each concentration, this included 14 test flasks and 4 contingency flask. A total of 21 control flasks were prepared, this includes 12 sterile controls, 4 reference controls and a blank control, as detailed in the table below.

Aliquots (100 mL) of the surface water were dispensed into pre-labelled glass flasks . These vessels were labelled with the study number and a code representing the incubation group.
Sterile samples were prepared by autoclaving vessels containing surface water, at 121°C for 15 or 20 min. Sterile in-line air filters were attached to the inlet and outlet tubing connected to sterile control vessels to maintain sterility. Samples were only opened in a laminar flowhood under sterile conditions.

The protocol states that the samples will be autoclaved, and then autoclaved again 24 hours later. In error, for the benzoyl labelled samples, both were carried out on the same day. As the sterility checks at the final timepoint were acceptable, this is deemed to have no effect on the final timepoint.

For the sterility check of the controls treated alongside the benzoyl labelled samples, the sterility check was carried out for ca 96 h. This is a deviation from the protocol, however is deemed to have no impact on the results as the results showed the samples were sterile after 96 h.

- Radiochemical Purity:
The radiochemical purity of stock [14C-phosphinophenyl]-Omnirad TPO and [14C benzoyl] Omnirad TPO were determined by HPLC using methods detailed above and in Appendix 4. The radiochemical purity of [14C-phosphinophenyl]-Omnirad TPO and [14C benzoyl]-Omnirad TPO in treatment solution were determined by HPLC immediately prior to application. Due to time constraints, no stock RCP was carried out for the repurified benzoyl material. As the treatment solution purity is acceptable, this was not deemed necessary.

- Preparation of Treatment Solutions:
For the phosphinophenyl labelled treatment solution, approximately 0.8 mg of [14C phosphinophenyl]-Omnirad TPO was weighed and dissolved in 15 mL acetonitrile. The homogeneity and radioactive content of the solution was determined by LSC analysis. The concentration of this solution was determined as 60.5 µg/mL. This solution was used to treat the high treatment concentration samples.

For the phosphinophenyl labelled low treatment concentration samples, 1.613 mL of the high treatment concentration solution was diluted to a final volume of 15 mL, using acetonitrile. The homogeneity and radioactive content of the solution was determined by LSC analysis. The concentration of this solution was determined as 5.1 µg/mL.

For the benzoyl label, the entire test item was dissolved in acetonitrile, to give a stock solution with a concentration of 990.3 µg/mL. The high concentration treatment solution was prepared by diluting 720 µL of stock solution to a final volume of 15 mL. The homogeneity and radioactive content of the solution was determined by LSC analysis. The concentration of this solution was determined as 46.1 µg/mL.

For the benzoyl labelled low treatment concentration samples, 1.6 mL of the high treatment concentration solution was diluted to a final volume of 15 mL, using acetonitrile. The homogeneity and radioactive content of the solution was determined by LSC analysis. The concentration of this solution was determined as 4.9 µg/mL.

A stock solution of non-labelled Omnirad-TPO was prepared by dissolving 3.1 mg of Omnirad TPO in 3 mL acetonitrile. A 47.5 µg/mL solution was prepared by diluting 95 µL of stock solution to a final volume of 2 mL. A 5 µg/mL solution was prepared by diluting 10 µL of stock solution to a final volume of 2 mL.

All Omnirad TPO solutions were wrapped in aluminium foil to exclude light.

A reference control solution was prepared by dispensing 52.3 µL of [14C]-sodium benzoate into a 2 mL volumetric flask and making this to a final volume of 2 mL with ultra-pure water. The homogeneity and radioactive content of the solution was determined by LSC analysis.

- Application of [14C]-Omnirad TPO:
A Rainin MR250 pipette was used to apply the test item treatment solution to the study samples. Treatment solution (200 µL) was applied to each sample. All test samples were treated under reduced light. Following application, each flask was wrapped in aluminium foil to exclude light and reconnected to the flow through apparatus.

To accurately quantify the amount of test item applied to each sample, additional aliquots (200 μL) of treatment solution for both the low treatment concentration and high treatment concentration samples for both radiolabels were dispensed directly into 5/10 mL volumetric flasks at regular intervals during each treatment. Each was made up to volume with acetonitrile and aliquots (3 x 100/200 μL) taken for LSC analysis.

Treatment solution (200 µL) was applied to each sterile control sample in a laminar flowhood. In-line filters were then attached to each side of the flask before each flask was wrapped in aluminium foil to exclude light and reconnected to the flow through apparatus.

Full details of the treatment calculations are provided in Appendix 7.

The phosphinophenyl labelled samples were treated on 20 November 2018 and benzoyl labelled samples were treated on 22 March 2019. Full details of key dates for the study are provided in Appendix 8.

- Application of [14C]-Sodium Benzoate:
A Rainin pipette (MR250) was used to apply the [14C]-sodium benzoate treatment solution to the control samples. Treatment solution (200 μL) was applied to each sample. Following application, each flask was reconnected to the flow through apparatus. Solvent control samples had 200 μL of acetonitrile added alongside the [14C]-sodium benzoate treatment solution.

- Incubation, Monitoring and Parameters Measurement:
Flasks used for measurement of water parameters had an aliquot (200 μL) of non-labelled Omnirad TPO added to give overall concentration of 10 μg/L for low concentration samples or 95 μg/L for high concentration samples.

Incubation Temperature: 12 ± 2ºC
Measurement Intervals:
- pH: At each sampling interval
- Dissolved Oxygen: At each sampling interval
- Redox(a): At each sampling interval
(a) The protocol states that the pH and dissolved oxygen measurements would be taken at each sampling interval. In addition to this redox measurements were taken at the same time. This was not included in the protocol, but is deemed to have no effect on the study and results are included in this report.

- Sampling:
Sampling intervals by treatment:
- [14C-phosphinophenyl]-Omnirad TPO(a): Duplicate samples 0, 1, 3, 7, 14, 30 and 62 DAT. For flasks not sampled, additional trap changes carried out at 14, 30 and 62 DAT.
- [14C-benzoyl]-Omnirad TPO(a): Duplicate samples 0, 1, 3, 7, 14, 30, 62 DAT. For flasks not sampled, additional trap changes carried out at 14, 30 and 64 DAT.
- [14C-phosphinophenyl]-Omnirad TPO – sterile samples(a): Duplicate samples 0, 14 and 62 DAT. For flasks not samples, additional trap changes carried out at 14 and 30 DAT.
- [14C-benzoyl]-Omnirad TPO – sterile samples(a): Duplicate samples 0, 14 and 60 DAT. For flasks not samples, additional trap changes carried out at 14 DAT. (b)
- [14C]-sodium benzoate – incubated with phosphinophenyl samples: Samples collected at 62 DAT
- [14C]-sodium benzoate – incubated with benzoyl samples: Samples collected at 63 DAT
Sampling procedures: Duplicate vessels were removed at each sampling interval. The amount of radioactivity in the surface water was quantified by LSC. Empty vessels were washed with 125 mL acetonitrile, the flasks sonicated for ca 5 minutes and the amount of radioactivity in the apparatus wash determined by LSC.
Quantification of radioactivity in trapping solutions: Weights of solutions measured and aliquots taken for LSC
Sample storage before analysis: Samples analysed on day of sampling. 2 mL aliquots of surface water were snap frozen using an acetone/dry ice mixture and stored frozen.
(a) Includes both low and high concentration samples.
(b) The protocol states that the NaOH traps should be sampled and replenished at 30 days. In error this was not carried out for the benzoyl labelled sterile samples. As the LSC results of the Day 60 NaOH traps are below the limit of quantification and the the mass balance is >90%AR, this is deemed to have no effect on the overall results of the study.

- Preparation of Samples for Analysis:
- Surface Waters:
Surface waters were analysed directly by HPLC without concentration.

- Concentration of Apparatus Washes:
For apparatus washes which contained >5% AR, samples were concentrated prior to analysis. 50 mL of apparatus wash was concentrated to a small volume using a Turbovap sample concentrator. The sample was then transferred to a glass vial, 2 x 5 mL washes of the Turbovap vessel carried out and combined in the vial. The samples were then placed under a gentle stream of N2 gas and concentrated to a small volume. Samples were made to a final volume of 2 mL with acetonitrile and the radioactive content of the samples determined by LSC analysis.

- Preparation of Samples for LC-MS Analysis:
A single surface water replicate for days 30 and 60 were subject to solid phase extraction (SPE) using SUPELCO ENVI-18 (6 mL, 500 mg) cartridges. 15 mL of surface water was loaded and washed with 5 mL of ultra-pure water to yield Eluent 1. The cartridge was then subject to three successive wash steps using 2 mL of MeCN:ultra-pure water (30:70 v/v), 2 mL of MeCN:ultra-pure water (1:1 v/v) and 2 mL of MeCN yielding Eluent 2, 3 and 4, respectively. Eluents were made to known volumes and the radioactive content determined by LSC analysis.

Eluent 1 was concentrated to ca 1 mL using a Turbovap sample concentrator and the radioactive recovery determined by LSC analysis.

Eluents 2, 3 and 4 were combined and concentrated to ca 1 mL under a gentle stream of N2 gas. 1 mL of MeCN was added to yield a total volume of ca 2 mL and the radioactive recovery was determined by LSC analysis.

- Chromatographic Analysis:
Surface waters and concentrated apparatus washes were by HPLC Method 1.

- Structural Assignment
Structural assignments for parent, Omnirad TPO and degradates 2,4,6-trimethylbenzoic acid and diphenylphosphinic acid were made by co chromatography with putative metabolite standards by reverse phase HPLC (Method 1). Assignments were confirmed by co chromatography with authenticated reference standards by normal phase TLC (Method 1). Confirmation of the presence of parent and degradation products, where co-chromatography was demonstrated, was by LC-MS. Full details of LC-MS equipment and conditions are provided in Appendix 4. As no reference standard was available for diphenylphosphinous acid, this assignment is tentative and determined by LC-MS analysis.

- Calculations:
- General Calculations:
A full example calculation for this study is described in Appendix 7. The Limit of Quantification (LOQ) is described in Appendix 5. An example output from the database used to acquire and process total radioactivity data (Debra Version 5.7; LabLogic, UK) is provided in Appendix 9.

- Calculation of DT50 for [14C]-Omnirad TPO:
The degradation rate (DegT50) of Omnirad TPO was determined using non-linear regression and a single first order kinetic model (CAKE Version 3.3) as detailed in Appendix 10. Appropriate administrative and procedural controls were implemented to assure quality and integrity of the data.

Reference substance:
benzoic acid, sodium salt
Remarks:
[14C]
Test performance:
- Physical Conditions:
The temperature of the incubation room in which the test system were housed was in the range 12 ± 2ºC and maintained this temperature throughout the incubation of the samples. On 4 occasions, the temperature was briefly out with this temperature range. On the 17th and 18th of January 2019, the temperature reched a minimum temperature of 8 ºC. On the 17th and 21st of April 2019 the temperature reached a maximum of 16 and 15ºC, respectively. This is deviation to the protocol, but is deemed to have no effect on the overall results of the study. Samples were placed on a flatbed shaker and wrapped in aluminium foil to exclude light.

- Radiochemical Purity:
The radiochemical purity and identity of [14C-phosphinophenyl]-Omnirad TPO and [14C benzoyl]-Omnirad TPO were confirmed by HPLC using the conditions detailed above and in Appendix 4. The purity value of stock [14C-phosphinophenyl]-Omnirad TPO was 96.2%. The purity value of stock [14C-benzoyl]-Omnirad TPO was 92.9%. This was deemed suitable for carrying out the preliminary investigations and preliminary test. As [14C benzoyl]-Omnirad TPO degraded further on storage, this was sent for repurification before treatment of the main test samples.

The radiochemical purity of the [14C-phosphinophenyl]-Omnirad TPO and [14C benzoyl] Omnirad TPO in the treatment solutions were determined immediately prior to application by HPLC using the conditions detailed above and in Appendix 4. The purity value was 96.3% and 97.9% by HPLC, for [14C-phosphinophenyl]-Omnirad TPO and [14C benzoyl]-Omnirad TPO, respectively. Representative chromatograms are provided in Figure 2.

Radiochemical purity results are summarised in Table 3.
Compartment:
natural water: freshwater
% Recovery:
91.9
St. dev.:
0.78
Remarks on result:
other: Mean recovery at 0 DAT
Remarks:
10 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
93.2
St. dev.:
7.64
Remarks on result:
other: Overall recovery (all samples)
Remarks:
10 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
94
St. dev.:
3.18
Remarks on result:
other: Sterilised Samples – overall recovery
Remarks:
10 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
95.8
St. dev.:
6.01
Remarks on result:
other: Reference Controls
Remarks:
10 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
91.4
St. dev.:
1.2
Remarks on result:
other: Mean recovery at 0 DAT
Remarks:
95 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
93.9
St. dev.:
10.53
Remarks on result:
other: Overall recovery (all samples)
Remarks:
95 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
96.2
St. dev.:
4.74
Remarks on result:
other: Sterilised Samples – overall recovery
Remarks:
95 µg/l Phosphinophenyl Label
Compartment:
natural water: freshwater
% Recovery:
91.3
St. dev.:
2.19
Remarks on result:
other: Mean recovery at 0 DAT
Remarks:
10 µg/l Benzoyl Label
Compartment:
natural water: freshwater
% Recovery:
105.8
St. dev.:
11.59
Remarks on result:
other: Overall recovery (all samples)
Remarks:
10 µg/l Benzoyl Label
Compartment:
natural water: freshwater
% Recovery:
96.5
St. dev.:
8.69
Remarks on result:
other: Sterilised Samples – overall recovery
Remarks:
10 µg/l Benzoyl Label
Compartment:
natural water: freshwater
% Recovery:
90.8
St. dev.:
1.2
Remarks on result:
other: Mean recovery at 0 DAT
Remarks:
95 µg/l Benzoyl Label
Compartment:
natural water: freshwater
% Recovery:
96.3
St. dev.:
7.56
Remarks on result:
other: Overall recovery (all samples)
Remarks:
95 µg/l Benzoyl Label
Compartment:
natural water: freshwater
% Recovery:
92.8
St. dev.:
3.54
Remarks on result:
other: Sterilised Samples – overall recovery
Remarks:
95 µg/l Benzoyl Label
% Degr.:
0
St. dev.:
0
Parameter:
CO2 evolution
Sampling time:
60 d
Remarks on result:
other: Volatile degradation
Remarks:
Phosphinophenyl label
% Degr.:
6.5
Parameter:
CO2 evolution
Sampling time:
60 d
Remarks on result:
other: Volatile degradation
Remarks:
Benzoyl label 10 µg/l
% Degr.:
1.1
Parameter:
CO2 evolution
Sampling time:
60 d
Remarks on result:
other: Volatile degradation
Remarks:
Benzoyl label 95 µg/l
Compartment:
natural water: freshwater
DT50:
16.8 d
Type:
(pseudo-)first order (= half-life)
Temp.:
12 °C
Remarks on result:
other: 10 µg/l
Compartment:
natural water: freshwater
DT50:
15.2 d
Type:
(pseudo-)first order (= half-life)
Temp.:
12 °C
Remarks on result:
other: 95 µg/l
Transformation products:
yes
No.:
#1
No.:
#2
No.:
#3
Details on transformation products:
Proposed Degradation Pathway:
In phosphinophenyl labelled samples, following incubation for 62 days, Omnirad TPO degraded quickly with diphenylphosphinic acid and diphenylphosphinous acid being the major degradation products observed.
In benzoyl labelled samples, following incubation for 62 days, Omnirad TPO degraded quickly with 2,4,6-trimethylbenzoic acid being the major degradation product observed.
Evaporation of parent compound:
yes
Remarks:
See % degradation above
Volatile metabolites:
not specified
Residues:
yes
Remarks:
A summary of the characterisation/identification of radioactive residues in surface water is shown in Table 12 to Table 19, Appendix 12, and Figures 11 to 14.
Details on results:
Samples Treated with [14C-Phosphinophenyl]-Omnirad TPO
In samples treated with [14C-phosphinophenyl]-Omnirad TPO, Omnirad TPO was detected at all timepoints. Two radioactive components were detected which were assigned by LC-MS analysis and are assigned as Diphenylphosphinic acid and Diphenylphosphinous acid.

Low Rate Samples Treated with [14C-Phosphinophenyl]-Omnirad TPO
For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 80.2% AR at 0 DAT, to 8.9% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 9.4% AR at 0 DAT and a maximum mean of 37.9% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 4.2% at 1 DAT and increased to a maximum mean of 49.6% AR at 30 DAT. Diphenylphosphinous acid decreased to 48.9% AR at 62 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 6.9% AR (range 2.3% AR – 6.9% AR), Diphenylphosphinic acid accounted for maximum mean of 0.7% AR (range 0.1% AR – 0.7% AR) and Diphenylphosphinous acid accounted for mean of 0.1% AR at a single timepoint.
In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 80.2% AR at 0 DAT, to 8.9% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 9.4% AR at 0 DAT and a maximum mean of 37.9% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 4.2% at 1 DAT and increased to a maximum mean of 49.6% AR at 30 DAT. Diphenylphosphinous acid decreased to 48.9% AR at 62 DAT.

High Rate Samples Treated with [14C-Phosphinophenyl]-Omnirad TPO
For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 80.6% AR at 0 DAT, to 10.1% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 7.9% AR at 0 DAT and a maximum mean of 36.1% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 6.1% at 1 DAT and increased to a maximum mean of 50.3% AR at 30 DAT. Diphenylphosphinous acid decreased to 48.0% AR at 62 DAT. Minor unknown components were combined and accounted for a maximum mean of 2.1% AR at 62 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 13.7% AR (range 5.6% AR – 13.7% AR), Diphenylphosphinic acid accounted for maximum mean of 2.4% AR (range 0.4% AR – 2.4% AR) and Diphenylphosphinous acid accounted for mean of 0.8% AR at a single timepoint. Minor unknown components were combined and accounted for a maximum mean of 0.4% AR at 7 DAT.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 80.6% AR at 0 DAT, to 10.1% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 7.9% AR at 0 DAT and a maximum mean of 36.1% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 6.1% at 1 DAT and increased to a maximum mean of 51.1% AR at 30 DAT. Diphenylphosphinous acid decreased to 48.0% AR at 62 DAT.

Sterile Samples Treated with [14C-Phosphinophenyl]-Omnirad TPO
For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 80.8% AR at 0 DAT, to 17.9% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 9.4% AR at 0 DAT and a maximum mean of 37.2% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 22.5% at 14 DAT and increased to a maximum mean of 38.3% AR at 62 DAT.

For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 78.5% AR at 0 DAT, to 12.3% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 12.2% AR at 0 DAT and a maximum mean of 40.0% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 24.6% at 14 DAT and increased to a maximum mean of 42.5% AR at 62 DAT. Minor unknown components were combined and accounted for a maximum mean of 1.9% AR at 62 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 3.2% AR (range 0.6% AR – 3.2% AR), Diphenylphosphinic acid accounted for maximum mean of 0.8% AR (range 0.3% AR – 0.8% AR) and Diphenylphosphinous acid accounted for mean of 0.4% AR at a single timepoint.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 81.7% AR at 0 DAT, to 12.3% AR at 62 DAT. Diphenylphosphinic acid accounted for a mean of 12.5% AR at 0 DAT and a maximum mean of 40.0% AR at 62 DAT. Diphenylphosphinous acid accounted for a mean of 25.0% at 14 DAT and increased to a maximum mean of 42.5% AR at 62 DAT. Minor unknown components were combined and accounted for a maximum mean of 1.9% AR at 62 DAT.

Samples Treated with [14C-Benzoyl]-Omnirad TPO
In samples treated with [14C-benzoyl]-Omnirad TPO, Omnirad TPO was detected at all timepoints. One significant radioactive component was detected which were assigned by LC MS analysis as 2,4,6-trimethylbenzoic acid. Commercially available 2,4,6 trimethylbenzoic acid was obtained for use on this study as a reference standard.

Low Rate Samples Treated with [14C-Benzoyl]-Omnirad TPO
For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 78.4% AR at 0 DAT, to 9.4% AR at 62 DAT. 2,4,6 trimethylbenzoic acid accounted for a mean of 1.7% AR at 0 DAT and increased to a maximum mean of 84.6% AR at 62 DAT. In the 0 DAT samples, individual unknown components accounted for 5.1% AR and 9.5% AR in Replicates A and B, respectively. As these only appeared in a single timepoint, no identification work was carried out on this component. No other unknown component accounted for >3.4% AR.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 6.1% AR (range 2.9% AR – 6.1% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 0.7% AR (range 0.2% AR – 0.7% AR). Minor unknowns accounted for a maximum mean of 0.9% AR.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 81.3% AR at 0 DAT, to 9.4% AR at 62 DAT. 2,4,6-trimethylbenzoic acid accounted for a mean of 1.9% AR at 0 DAT and increased to a maximum mean of 84.6% AR at 62 DAT. In the 0 DAT samples, individual unknown components accounted for 5.1% AR and 6.1% AR in Replicates A and B, respectively. As these only appeared in a single timepoint, no identification work was carried out on this component. No other unknown component accounted for >3.4% AR.

High Rate Samples Treated with [14C-Benzoyl]-Omnirad TPO
For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 82.2% AR at 0 DAT, to 10.4% AR at 62 DAT. 2,4,6 trimethylbenzoic acid accounted for a mean of 2.7% AR at 0 DAT and increased to a maximum mean of 82.9% AR at 62 DAT. Minor unknowns accounted for a maximum mean of 2.7% AR.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 5.8% AR (range 2.5% AR – 5.8% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 0.6% AR (range 0.3% AR – 0.6% AR). Minor unknowns accounted for a maximum mean of 0.4% AR.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 84.7% AR at 0 DAT, to 10.4% AR at 62 DAT. 2,4,6-trimethylbenzoic acid accounted for a mean of 3.0% AR at 0 DAT and increased to a maximum mean of 82.9% AR at 62 DAT. Minor unknowns accounted for a maximum mean of 2.7% AR.

Sterile Samples Treated with [14C-Benzoyl]-Omnirad TPO
For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 84.2% AR at 0 DAT, to 40.5% AR at 60 DAT. 2,4,6 trimethylbenzoic acid accounted for a mean of 3.6% AR at 0 DAT and increased to a maximum mean of 54.4% AR at 60 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 4.0% AR (range 2.4 % AR – 4.0% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 1.5% AR (range 0.1% AR – 1.5% AR). Minor unknowns accounted for a maximum mean of 0.8% AR.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 86.7% AR at 0 DAT, to 40.5% AR at 60 DAT. 2,4,6-trimethylbenzoic acid accounted for a mean of 3.6% AR at 0 DAT and increased to a maximum mean of 54.4% AR at 60 DAT. Minor unknowns accounted for a maximum mean of 0.8% AR.
For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 83.1% AR at 0 DAT, to 24.7% AR at 60 DAT. 2,4,6 trimethylbenzoic acid accounted for a mean of 3.1% AR at 0 DAT and increased to a maximum mean of 64.1% AR at 60 DAT. Minor unknowns accounted for a maximum mean of 2.7% AR.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 5.5% AR (range 2.4-5.5% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 0.6% AR (range 0.5 – 0.6% AR).

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 83.1% AR at 0 DAT, to 27.1% AR at 60 DAT. 2,4,6-trimethylbenzoic acid accounted for a mean of 3.1% AR at 0 DAT and increased to a maximum mean of 64.6% AR at 60 DAT. Minor unknowns accounted for a maximum mean of 2.7% AR.

Structural Assignments
Structural assignment for Omnirad TPO, 2,4,6-trimethylbenzoic acid and diphenylphosphinic acid was achieved by co-chromatography using normal phase TLC (HPLC Method 1) analysis as detailed in Appendix 4. Representative chromatograms are provided in Figure 15. Assignments were confirmed qualitatively using selected samples from each matrix and incubation group using LC-MS analysis as detailed in Appendix 13.

Structural Assignment Using LC-MS
Full details of structural assignment using LC-MS can be found in Appendix 13.

Proposed Degradation Pathway
In phosphinophenyl labelled samples, following incubation for 62 days, Omnirad TPO degraded quickly with diphenylphosphinic acid and diphenylphosphinous acid being the major degradation products observed.

In benzoyl labelled samples, following incubation for 62 days, Omnirad TPO degraded quickly with 2,4,6-trimethylbenzoic acid being the major degradation product observed.

DegT50 and DegT90 of Omnirad TPO in Surface Water Systems
The degradation of [14C]-Omnirad TPO in surface water (DegT50 and DegT90) was determined using non-linear regression and a single first order kinetic model (SFO, CAKE, Version 3.3). A detailed description of the kinetic model and the results of the kinetic analysis are given in Appendix 10. The single first order dissipation and DegT50 for all incubation groups are summarised in Table 20.

SFO kinetics describes the dissipation and degradation of Omnirad TPO well with a Chi square (χ2) error value of less than or equal to 6.9 in all cases and R2 values ranged from 0.9276 – 0.9831.

The DegT50 of Omnirad TPO was 16.8 and 15.2 days, for samples treated at 10 and 95 µg/L, respectively.
Results with reference substance:
Results for reference controls conducted for the low and high treatment concentration experiments are detailed in Table 10 and Table 11. Total radioactivity was calculated from the sum of radioactivity in the surface water, NaOH traps and apparatus wash. Radioactivity of each component is presented as a percentage of the total radioactivity recovered.

Reference controls demonstrated degradation of [14C]-sodium benzoate to 14CO2 in surface water used for the phosphinophenyl labelled samples. Degradation rates were comparable in both the reference control and solvent control samples, with 14CO2 accounting for a mean of 92.1% AR and 85.6% AR, respectively (62 DAT) indicating that a viable microbial population was established.

Reference controls demonstrated degradation of [14C]-sodium benzoate to 14CO2 in surface water used for the benzoyl labelled samples. Degradation rates were comparable in both the reference control and solvent control samples, with 14CO2 accounting for a mean of 88.4% AR and 83.4% AR, respectively, at 63 DAT) indicating that a viable microbial population was established.
Validity criteria fulfilled:
yes
Conclusions:
The mineralisation rate and route of degradation of [14C]-Omnirad TPO was investigated in Calwich Abbey surface water at nominal rates of 10 and 95 µg/L under aerobic conditions and maintained in dark conditions at ca 12ºC for up to 62 days.

The overall mean mass balance for the low and high treatment concentration surface water samples treated with [14C-phosphinophenyl]-Omnirad TPO and [14C-benzoyl]-Omnirad TPO was 93.6% and 94.9% applied radioactivity, respectively. Analysis of reference control samples demonstrated that the surface water had a viable microbial population.

Omnirad TPO degraded quickly with Diphenylphosphinic acid and diphenylphosphinous acid being major degradation products observed in the phosphinophenyl labelled samples and 2,4,6-trimethylbenzoic acid being observed as the major degradation product in benzoyl labelled samples.

The DegT50 of Omnirad TPO was 16.8 and 15.2 days in the 10 and 95 µg/L concentrations, respectively.
Executive summary:

The extent of mineralisation and the rate and route of degradation of phosphinophenyl and benzoyl labelled [14C]-Omnirad TPO was investigated in Calwich Abbey surface water at ca 12 ± 2ºC.  [14C]-Omnirad TPO was applied to the water at nominal rates of 10 and 95 µg/L (low and high concentrations, respectively).  The systems were incubated under aerobic conditions and maintained in the dark at ca 12 ± 2ºC for 60/62 days.  Volatile radioactivity was continuously flushed from the vessels and collected in NaOH traps.  For each test system and radiolabel, duplicate samples were taken for analysis at 7 intervals.

Sterilised test systems were also treated with Omnirad TPO at the low and high application rates.  Duplicate samples were taken for analysis at 0, 14 and 62 days or 0, 14 and 60 days for the phosphinophenyl and benzoyl labelled samples, respectively.

At each sampling time, the quantity of radioactivity in the water, apparatus wash and NaOH traps was determined by liquid scintillation counting (LSC).  A mass balance was determined for each sample.

Separate reference control samples (treated with [14C]-sodium benzoate at 10 μg/L) of surface water were prepared and incubated alongside the test samples to determine whether a viable microbial population was present in the test system.

Control samples treated with non-labelled Omnirad TPO were similarly incubated to allow water quality measurements at each sampling interval.

- Mass Balance:

The overall mean mass balance for the low and high treatment concentration surface water samples treated with [14C-phosphinophenyl]-Omnirad TPO was 93.6% applied radioactivity (AR) with ranges of 88.1% to 98.9% AR and 85.7% to 100.6% AR, respectively.  For the low treatment concentration, a single sample had a mass balance <90% (88.1% AR) and for the high concentration samples, two samples had a mass balance <90% (Range 85.7% - 86.6% AR), although no declining trend was observed.

The overall mean mass balance for the low and high treatment concentration surface water samples treated with [14C-benzoyl]-Omnirad TPO was 94.8% applied radioactivity (AR) with ranges of 87.7% to 104.1% AR and 89.9% to 100.6% AR, respectively.  For the low treatment concentration, three samples had a mass balance <90% (Range 87.7% AR - 88.4% AR) and for the high concentration samples, one samples had a mass balance <90% (89.9%), although no declining trend was observed.  A second sample from the high treatment concentration samples had a mass balance significantly below 90% AR (77.1%).  This sample was not included in any mean values and was excluded from further calculations.

Levels of 14CO2 evolved throughout the study were low for all samples, reaching a maximum of 6.5% AR and 1.1% AR in the benzoyl labelled samples, respectively.  Levels of 14CO2 evolved were below the limit of quantification for all phosphinophenyl samples.

The overall mean mass balance for the low and high treatment concentration sterile surface water samples treated with [14C-phosphinophenyl]-Omnirad TPO was 95.1% applied radioactivity (AR) with ranges of 91.8% to 96.3% AR and 93.3% to 100.0% AR, respectively.  

The overall mean mass balance for the low and high treatment concentration sterile surface water samples treated with [14C-benzoyl]-Omnirad TPO was 94.7% applied radioactivity (AR) with ranges of 91.8% to 105.8% AR and 90.8% to 96.3% AR, respectively.  

- Radioactive Residues – Phosphinophenyl Labelled Samples:

For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 80.2% AR at 0 DAT, to 8.9% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 9.4% AR at 0 DAT and a maximum mean of 37.9% AR at 62 DAT.  Diphenylphosphinous acid accounted for a mean of 4.2% at 1 DAT and increased to a maximum mean of 49.6% AR at 30 DAT.  Diphenylphosphinous acid decreased to 48.9% AR at 62 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 6.9% AR (range 2.3% AR – 6.9% AR), Diphenylphosphinic acid accounted for maximum mean of 0.7% AR (range 0.1% AR – 0.7% AR) and Diphenylphosphinous acid accounted for mean of 0.1% AR at a single timepoint.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 80.2% AR at 0 DAT, to 8.9% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 9.4% AR at 0 DAT and a maximum mean of 37.9% AR at 62 DAT.  Diphenylphosphinous acid accounted for a mean of 4.2% at 1 DAT and increased to a maximum mean of 49.6% AR at 30 DAT.  Diphenylphosphinous acid decreased to 48.9% AR at 62 DAT.

For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 80.6% AR at 0 DAT, to 10.1% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 7.9% AR at 0 DAT and a maximum mean of 36.1% AR at 62 DAT.  Diphenylphosphinous acid accounted for a mean of 6.1% at 1 DAT and increased to a maximum mean of 50.3% AR at 30 DAT.  Diphenylphosphinous acid decreased to 48.0% AR at 62 DAT.  Minor unknown components were combined and accounted for a maximum mean of 2.1% AR at 62 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 13.7% AR (range 5.6% AR – 13.7% AR), Diphenylphosphinic acid accounted for maximum mean of 2.4% AR (range 0.4% AR – 2.4% AR) and Diphenylphosphinous acid accounted for mean of 0.8% AR at a single timepoint.  Minor unknown components were combined and accounted for a maximum mean of 0.4% AR at 7 DAT.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 80.6% AR at 0 DAT, to 10.1% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 7.9% AR at 0 DAT and a maximum mean of 36.1% AR at 62 DAT.  Diphenylphosphinous acid accounted for a mean of 6.1% at 1 DAT and increased to a maximum mean of 51.1% AR at 30 DAT.  Diphenylphosphinous acid decreased to 48.0% AR at 62 DAT.

- Radioactive Residues – Benzoyl Labelled Samples:

For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 78.4% AR at 0 DAT, to 9.4% AR at 62 DAT.  2,4,6 trimethylbenzoic acid accounted for a mean of 1.7% AR at 0 DAT and increased to a maximum mean of 84.6% AR at 62 DAT.  In the 0 DAT samples, individual unknown components accounted for 5.1% AR and 9.5% AR in Replicates A and B, respectively.  As these only appeared in a single timepoint, no identification work was carried out on this component.  No other unknown component accounted for >3.4% AR.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 6.1% AR (range 2.9% AR – 6.1% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 0.7% AR (range 0.2% AR – 0.7% AR).  Minor unknowns accounted for a maximum mean of 0.8% AR.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 81.3% AR at 0 DAT, to 9.4% AR at 62 DAT.  2,4,6-trimethylbenzoic acid accounted for a mean of 1.9% AR at 0 DAT and increased to a maximum mean of 84.6% AR at 62 DAT.  In the 0 DAT samples, individual unknown components accounted for 5.1% AR and 6.1% AR in Replicates A and B, respectively.  As these only appeared in a single timepoint, no

identification work was carried out on this component.  No other unknown component accounted for >3.4% AR.

For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 82.2% AR at 0 DAT, to 10.4% AR at 62 DAT.  2,4,6 trimethylbenzoic acid accounted for a mean of 2.7% AR at 0 DAT and increased to a maximum mean of 82.9% AR at 62 DAT.  Minor unknowns accounted for a maximum mean of 2.7% AR.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 5.8% AR (range 2.5% AR – 5.8% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 0.6% AR (range 0.3% AR – 0.6% AR).  Minor unknowns accounted for a maximum mean of 0.4% AR.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 84.7% AR at 0 DAT, to 10.9% AR at 62 DAT.  2,4,6-trimethylbenzoic acid accounted for a mean of 3.0% AR at 0 DAT and increased to a maximum mean of 82.9% AR at 62 DAT.  Minor unknowns accounted for a maximum mean of 2.7% AR.

- Radioactive Residues – Phosphinophenyl Labelled Sterile Samples:

For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 80.8% AR at 0 DAT, to 17.9% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 9.4% AR at 0 DAT and a maximum mean of 37.2% AR at 62 DAT.  Diphenylphosphinous acid accounted for a mean of 22.5% at 14 DAT and increased to a maximum mean of 38.3% AR at 62 DAT.

For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 78.5% AR at 0 DAT, to 12.3% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 12.2% AR at 0 DAT and a maximum mean of 40.0% AR at 62 DAT.  Diphenylphosphinous acid accounted for a mean of 24.6% at 14 DAT and increased to a maximum mean of 42.5% AR at 62 DAT.  Minor unknown components were combined and accounted for a maximum mean of 1.9% AR at 62 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 3.2% AR (range 0.6% AR – 3.2% AR), Diphenylphosphinic acid accounted for maximum mean of 0.8% AR (range 0.3% AR – 0.8% AR) and Diphenylphosphinous acid accounted for mean of 0.4% AR at a single timepoint.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 81.7% AR at 0 DAT, to 12.3% AR at 62 DAT.  Diphenylphosphinic acid accounted for a mean of 12.5% AR at 0 DAT and a maximum mean of 40.0% AR at 62 DAT.  

Diphenylphosphinous acid accounted for a mean of 25.0% at 14 DAT and increased to a maximum mean of 42.5% AR at 62 DAT.  Minor unknown components were combined and accounted for a maximum mean of 1.9% AR at 62 DAT.

- Radioactive Residues – Benzoyl Labelled Sterile Samples:

For the low rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 84.2% AR at 0 DAT, to 40.5% AR at 60 DAT.  2,4,6 trimethylbenzoic acid accounted for a mean of 3.6% AR at 0 DAT and increased to a maximum mean of 54.4% AR at 60 DAT.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 4.0% AR (range 2.4 % AR – 4.0% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 1.5% AR (range 0.1% AR – 1.5% AR).  Minor unknowns accounted for a maximum mean of 0.8% AR.

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 86.7% AR at 0 DAT, to 40.5% AR at 60 DAT.  2,4,6-trimethylbenzoic acid accounted for a mean of 3.6% AR at 0 DAT and increased to a maximum mean of 54.4% AR at 60 DAT.  Minor unknowns accounted for a maximum mean of 0.8% AR.

For the high rate treatment concentration samples, levels of Omnirad TPO in the surface water decreased from a mean of 83.1% AR at 0 DAT, to 24.7% AR at 60 DAT.  2,4,6 trimethylbenzoic acid accounted for a mean of 3.1% AR at 0 DAT and increased to a maximum mean of 64.1% AR at 60 DAT.  Minor unknowns accounted for a maximum mean of 2.7% AR.

In the apparatus washes that were analysed, Omnirad TPO accounted for a maximum mean of 5.5% AR (range 2.4-5.5% AR) and 2,4,6-trimethylbenzoic acid accounted for a maximum mean of 0.6% AR (range 0.5 – 0.6% AR).

In the total system, levels of Omnirad TPO in the surface water decreased from a mean of 83.1% AR at 0 DAT, to 27.1% AR at 60 DAT.  2,4,6-trimethylbenzoic acid accounted for a mean of 3.1% AR at 0 DAT and increased to a maximum mean of 64.6% AR at 60 DAT.  Minor unknowns accounted for a maximum mean of 2.7% AR.

- Reference Samples:

Reference controls demonstrated degradation of [14C]-sodium benzoate to 14CO2 in surface water used for the phosphinophenyl labelled samples.  Degradation rates were comparable in both the reference control and solvent control samples, with 14CO2 accounting for a mean of

92.1% AR and 85.6% AR, respectively (62 DAT), indicating that a viable microbial population was established.

Reference controls demonstrated degradation of [14C]-sodium benzoate to 14CO2 in surface water used for the benzoyl labelled samples.  Degradation rates were comparable in both the reference control and solvent control samples, with 14CO2 accounting for a mean of 88.4% AR and 83.4% AR, respectively, at 63 DAT) indicating that a viable microbial population was established.

- Degradation Rates:

The dissipation/degradation rates of Omnirad were estimated using CAKE software by fitting single first-order kinetics (SFO) to the data.  The results are summarised in the following table:

Test Concentration (µg/L) * SFO
DegT50(Days) DegT90(Days) K_Parent χ2 R2 Prob > t
10 16.8 55.8 0.04 2.8 0.9831

1.29 x 10-18

95 15.2 50.4 0.05 6.9 0.9276 1.64 x 10-10

SFO       =       Single first order kinetics (non-linear method) calculated using CAKE software (Version 3.3).

DegT50       =              Calculated degradation half-life of parent (Time taken for 50% degradation of parent compound).

DegT90       =              Time taken for 90% degradation of parent compound.

K_Parent =       Rate constant.

χ2       =       Chi-square statistical value.

R2       =              Linear regression coefficient relating goodness of fit as value approaches unity.

Prob> t       =              Statistical probability value related to a statistical t-test calculation.

*       =       kinetic results are calculated using values from both labels.

- Conclusions:

The mineralisation rate and route of degradation of [14C]-Omnirad TPO was investigated in Calwich Abbey surface water at nominal rates of 10 and 95 µg/L under aerobic conditions and maintained in dark conditions at ca 12ºC for up to 62 days.

The overall mean mass balance for the low and high treatment concentration surface water samples treated with [14C-phosphinophenyl]-Omnirad TPO and [14C-benzoyl]-Omnirad TPO was 93.6% and 94.9% applied radioactivity, respectively.  Analysis of reference control samples demonstrated that the surface water had a viable microbial population.

Omnirad TPO degraded quickly with Diphenylphosphinic acid and diphenylphosphinous acid being major degradation products observed in the phosphinophenyl labelled samples and 2,4,6-trimethylbenzoic acid being observed as the major degradation product in benzoyl labelled samples. The DegT50 of Omnirad TPO was 16.8 and 15.2 days in the 10 and 95 µg/L concentrations, respectively.

Description of key information

Study conducted to recognised testing guideline with GLP certification.

Key value for chemical safety assessment

Half-life in freshwater:
16.8 d
at the temperature of:
12 °C

Additional information