2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Sorafenib Tosylate was used as an analogue.

Qualifier:

according to guideline

Guideline:

OECD Guideline 301 F (Ready Biodegradability: Manometric Respirometry Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Oxygen conditions:

aerobic

Inoculum or test system:

activated sludge, domestic, non-adapted

Duration of test (contact time):

ca. 28 d

Initial conc.:

200 mg/L

Based on:

ThOD/L

Parameter:

% degradation (O2 consumption)

Value:

0

Sampling time:

28 d

Interpretation of results:

under test conditions no biodegradation observed

Conclusions:

In accordance with the OECD 301F (1), the test compound sorafenibtosylate is not readily
biodegradable under the conditions of the test and it was not toxic to the microbes of activated
sludge.

Executive summary:

The test substance sorafenibtosylate was incubated in an aqueous solution including nutrients

with microorganisms from a municipal sewage treatment plant for 28 days (start of

treatment = day 1). The nutrient solutions were made up of phosphates, magnesium sulphate,

iron chloride, ammonium chloride and calcium chloride.

The test substance sorafenibtosylate was incubated in triplicate at a concentration of 200 mg

theoretical oxygen demand (ThOD) per liter. Additionally, a reference substance (sodium

acetate) was tested in a single set according to the same procedure, in order to verify the viability

and activity of the degrading microorganisms. One further set was incubated with sodium acetate

at 100 mg ThOD/L (reference substance) plus sorafenibtosylate at 100 mg ThOD/L representing

a toxicity control. Furthermore, a blank control was tested in triplicate without any test or

reference substance.

The biological degradation of the test and reference substances was evaluated by measurement of

the O2 consumption during the test period. O2 consumption was continuously monitored and

recorded by an automated device. The O2 consumption was calculated as the percentage of total

O2 that the test material could theoretically have consumed, based on the molecular formula. The

blank O2 consumption was subtracted for correction.

The test compound sorafenibtosylate was degraded to 0 % on day 29 (¿ 28 days of incubation).

The reference compound sodium acetate was degraded to 88.3 % on day 29

(= 28 days of incubation). 60 % degradation was reached on day 7.

In the toxicity control, the reference compound (sodium acetate) plus the test compound

sorafenibtosylate, was degraded to 57.3 % on day 29 (= 28 days of incubation), which reflected

the degradation in the individual sets.

Reference 2

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method C.4-D (Determination of the "Ready" Biodegradability - Manometric Respirometry Test)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 301 F (Ready Biodegradability: Manometric Respirometry Test)

Deviations:

no

Principles of method if other than guideline:

The samples for NOx-determination at test start were erroneously not measured directly. As the respective samples did not have any influence on the results of the study, the following procedure was followed. The stored samples (0 h) were analysed with a delay of 29 days. To verify the respective results new samples for NOx determination after 0 hours were prepared and measured.
A the end of the study the concentration of the test item in the aqueous solution has been determined by specific accompanying chemical analysis. After 28 days 2.598 mg/L of the test item BAY 43-9006 were detected. The amount of the test item at test start has been 100 mg/l. The difference between the initial amount of the test item and the concentration at the end of the study is mainly caused by the water solubility of the test item and not by degradation processes.

GLP compliance:

yes (incl. QA statement)

Oxygen conditions:

aerobic

Inoculum or test system:

activated sludge, domestic (adaptation not specified)

Details on inoculum:

TEST ORGANISM:
- mixed population of aquatic microorganisms, origin from an aeration tank of a waste water plant treating predominantly domestic sewage (Wupper area water authority, Germany)
- pretreatment: none
- concentration: 30 mg/L suspendid solids

Duration of test (contact time):

28 d

Initial conc.:

100 mg/L

Based on:

test mat.

Parameter followed for biodegradation estimation:

O2 consumption

Details on study design:

PRETREATMENT OF THE TEST ITEM:
- 25 mg of the test item were weighed out on aluminium foil
- substance inclusive the aluminium foil was added to the test vessels to give a test concentration of 100 mg test item/L

EXPOSURE CONDITION:
- test volume: 250 mL
- incubation temperature: 22 +/- 2 °C
- performed in the dark
- mixing: 1 magnetic stirrer per test vessel
- test apparatus: Voith Sapromat

Reference substance:

benzoic acid, sodium salt

Remarks:

Purity 99% (Fluka-BioChemika); Batch-no. 450273/1 35103269

Parameter:

% degradation (O2 consumption)

Value:

2

Sampling time:

8 d

Parameter:

% degradation (O2 consumption)

Value:

3

Sampling time:

14 d

Parameter:

% degradation (O2 consumption)

Value:

3

Sampling time:

20 d

Parameter:

% degradation (O2 consumption)

Value:

2

Sampling time:

28 d

Remarks on result:

other: pH = 7.6

Details on results:

The test item is an N-containing substance. Therefore the BOD values of the test item after 28 days were corrected for the oxygen consumed by nitrification. The oxygen consumed by nitrification was 5 mg/L. This oxygen consumption by nitrification has been substracted from the respective 28 days measurements of the test item. Further the used concentration of the test item did not show toxic effects to bacteria.

Results with reference substance:

The reference compound showed 86% degradation after 14 days.

Valdity criteria:

- The reference compound has reached the level for ready biodegradability by 14 days

- No toxicity of the test item has been observed in the toxicity control

- The difference of extremes of replicate values of the removal of test chemical at the end of the test is less than 20 %

- The oxygen uptake of the inoculum blank was 60 mg/L

- The pH is between 6.0 and 8.5 in the test vessels at the end of the test (if degradation is less than 60 %).

- Oxygen uptake by nitrification has been determined

Validity criteria fulfilled:

yes

Remarks:

see "Any other information on results incl. tables"

Interpretation of results:

under test conditions no biodegradation observed

Conclusions:

In the study on ready biodegradability a degradation rate of 2 % was determined within 28 days for the test substance.

Executive summary:

The study was conducted in accordance with the Council Directive 92/69/EEC Method C.4-D "Manometrie Respirometry Test". This test method is in assential parts identical with OECD Guideline 301 F. A solution of the substance in a mineral medium was inoculated and incubated for 28 d under aerobic conditions. During this period the ready biodegradability was determined. The substance showed 2 % degradation after 28 days. The reference compound showed 86% degradation after 14 days.

Therefore the substance has to be classified as "Not Readily Biodegradable".

Description of key information

A guideline study was conducted in accordance with the Council Directive 92/69/EEC Method C.4-D "Manometrie Respirometry Test" under GLP conditions to assess the biodegradation of BAY 43-9006 in water over 28 days. This test method is in essential parts identical with OECD Guideline 301 F. The nominal test concentration at test start was 100 mg/L. A the end of the study the concentration of the test item in the aqueous solution has been determined by specific accompanying chemical analysis. After 28 days 2.598 mg/L of the test item were detected. The difference between the initial amount of the test item and the concentration at the end of the study is mainly caused by the water solubility of the test item and not by degradation processes. The test item is an N-containing substance. Thus, the oxygen consumed by nitrification is calculated and the values of the test item after 28 days were corrected for the oxygen consumed by nitrification. Further the used concentration of the test item did not show toxic effects to bacteria. During the study on ready biodegradability a degradation rate of 3% after 14 days and 2% after 28 days was determined for the test substance. In a study according to the OECD 301F (Ready Biodegradability: Manometric Respirometry Test), sorafenib tosylate was used as an analogue. The test substance sorafenib tosylate was incubated in an aqueous solution including nutrients with microorganisms from a municipal sewage treatment plant for 28 days (start of treatment = day 1). The test substance sorafenib tosylate was degraded to 0 % on day 29 (28 days of incubation) and it was not toxic to the microbes of activated sludge. Overall, the test substance has to be classified as "Not Readily Biodegradable".

 

Key value for chemical safety assessment

Biodegradation in water:

not biodegradable

Type of water:

freshwater

Additional information

The test substance showed 2 % biodegradation after 28 days and therefore has to be classified as "Not Readily Biodegradable".