2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]-3-fluorophenoxy]-N-methyl-, hydrochloride (1:1)

Toxicity to soil microorganisms

Administrative data

Endpoint:

toxicity to soil microorganisms

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan - Feb 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted with the base (BAY 73-4605) according to OECD guideline under GLP

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 216 (Soil Microorganisms: Nitrogen Transformation Test)

Deviations:

no

Principles of method if other than guideline:

not relevant

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}-3-fluorophenoxy)-N-methylpyridine-2- carboxamide

IUPAC Name:

4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}-3-fluorophenoxy)-N-methylpyridine-2- carboxamide

Details on test material:

- Name of test material (as cited in study report): Regorafenib (BAY 73-4605)
- Analytical purity: 100.2%
- Lot/batch No.: BXR3JPV

Sampling and analysis

Analytical monitoring:

no

Test substrate

Vehicle:

no

Test organisms

Test organisms (inoculum):

soil

Study design

Total exposure duration:

28 d

Test conditions

Moisture:

The moisture content of the soil used for the definitive test was 26.1% based on dry weight, corresponding to 43.5% of the maximum water holding
capacity (WHC) of 60 g /100 g dry soil.
On test day 7 the moisture content of the samples was increased to approximately 28.4% which is equal to 47.3% of the maximum WHC.

Results and discussion

Effect concentrations

Duration:

28 d

Dose descriptor:

NOEC

Effect conc.:

1 000 mg/kg soil dw

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

nitrate formation rate

Any other information on results incl. tables

Table 1: Mean nitrate transformation in the test concentrations determined on day 28 of the soil microflora study with BAY 73-4506

Treatment group	Mean Nitrate (mg N03-/kg dry soil)
With Lucerne Meal	Without Lucerne Meal	Contribution of the Test Item	N03- Transformation corrected for Test Item	Inhibition(%)
Day 28 ¿ Day 0	Day 28 ¿ Day 0
Control	206	51,1	NA	NA	NA
1000 mg a.i./kg dry soil	196	59,4	8,2	188	8,9

NA Not Applicable.

Note: all results are based on unrounded numbers

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

BAY 73-4506 shows no effects on the nitrification of soil microflora. Owing to the outcome of the test, no calculation of the ECx values is possible.
The NOEC is 1000 mg a.i./kg.

Executive summary:

This study was conducted to assess the effects of BAY 73-4506 on major microbiological processes of a sandy loam soil. Based on preliminary testing, a limit test with a concentration of 1000 mg a.i./kg dry soil was performed.

The study was conducted according to the OECD Guideline # 216, Soil Microorganisms: Nitrogen Transformation Test (OECD, 2000).

Each test concentration was performed in triplicates, resulting in a total of 12 systems. An amount of approximately 189 g of soil (150 g dry weight) was weighed into each of the 12 flasks. After addition of the soil, the replicates of the Control and the 1000 mg a.i./kg were amended with 0.75 g of lucerne meal. To the nitrification controls no lucerne meal was added. The samples were incubated at a temperature of 20 ± 2°C in an environmental climate chamber. The temperature was recorded continuously. The moisture content of the soil samples was checked and adjusted on days 7, 14, 21 and 28. On test day 7 the moisture content of the samples was increased to approximately 28.4% which is equal to 47.3% of the maximum WHC.

On day 0, all replicates (with and without lucerne meal) showed similar nitrate concentrations, ranging from 53.5 to 70.7 mg NO3-/kg dry soil. In the NC control samples (no test item, without lucerne meal) the nitrate formation showed an increase of 51.1 mg NO3-/kg dry soil after 28 days of incubation. For the NC 1000 mg a.i. samples (1000 mg a.i./kg dry soil, without lucerne meal) the formed amount was 59.4 mg/kg dry soil. The contribution of the test item was therefore 8.2 mg NO3-/kg dry soil.

In the control samples (no test item, with lucerne meal) the nitrate formation showed an increase of 206 mg NO3-/kg dry soil after 28 days of incubation. For the 1000 mg a.i. samples (1000 mg a.i./kg dry soil, with lucerne meal) the formed amount was 196 mg/kg dry soil. With respect to the contribution of the test item, the formed amount in the samples with 1000 mg a.i./kg dry soil was 188 mg NO3-/kg dry soil, which is 91.1% of the amount formed in the control (based on unrounded numbers). The % inhibition is therefore 8.9%.

Based on the results of the preliminary study and the definitive study, the test item has no significant effect on the soil microflora responsible for nitrification.