Registration Dossier

Administrative data

Endpoint:
biodegradation in soil: simulation testing
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Oct 2009 - Mar 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted with Sorafenib tosylate according to OECD guideline under GLP
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 307 (Aerobic and Anaerobic Transformation in Soil)
Deviations:
no
Principles of method if other than guideline:
not relevant
GLP compliance:
yes (incl. certificate)
Test type:
laboratory

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sorafenib Tosylate C14
- Analytical Purity: 99.5%
- Lot/batch No.: PLS 0356-1-18 A
- Radiochemical purity (if radiolabelling): 100%
- Specific activity (if radiolabelling): 3.09 MBq/mg
Radiolabelling:
yes

Study design

Oxygen conditions:
aerobic
Soil classification:
USDA (US Department of Agriculture)
Soil properties
Soil type:
sandy loam
% Clay:
10.3
% Silt:
31.5
% Sand:
58.2
% Org. C:
2.21
pH:
7.1
CEC:
12.6
Duration of test (contact time)
Duration:
120 d
Initial test substance concentration
Initial conc.:
1 000 other: ug/kg dry soil
Based on:
test mat.

Results and discussion

% Degradation
% Degr.:
31.7
Parameter:
radiochem. meas.
Sampling time:
120 d
Half-life / dissipation time of parent compound
Half-life:
187 d
Type:
(pseudo-)first order (= DT50)
Remarks on result:
other: DT90 622 d

Any other information on results incl. tables

In the soil an average of 103% of the applied radioactivity

was extractable on day 0. Thereafter, the extractable residue

in the soil decreased steadily to an average of 66.4% at day

120. The non-extractable radioactivity increased constantly

from an average of 1.4% at test start to an average of 31.7%

at day 120.

HPLC analysis of the extracts showed that all extractable

radioactivity consisted of [14C]BAY 54-9085.

No volatile organic compounds were found in the ethylene

glycol traps throughout the study. The 14CO2 measured in

the KOH traps increased from an average of 0.01% on day 3

to an average of 0.54% on day 120

The DT50, DT75 and DT90 of the parent compound were

calculated to be 187, 375 and 622 days, respectively.

The biomass was determined to be 1.3, 1.0 and 0.8% of the

organic carbon content at test start, mid-study and test end

respectively.

Applicant's summary and conclusion

Conclusions:
The DT50 of [14C]BAY 54-9085 in the aerobic sandy loam soil Sevelen was calculated to be 187 days. The soil was
determined to be microbially viable throughout the study. No major metabolites were detected and only minor
mineralization to CO2 was observed throughout the study.
The degradation of [14C]BAY 54-9085 is accompanied by increasing levels of non-extractable residues in soil.
Overall, [14C]BAY 54-9085 is only slowly degraded in soil under aerobic conditions.
Executive summary:

This study about aerobic rate of degradation in soil is intended to provide information on:

(1) the route of degradation (transformation pathway) of the parent compound in one

representative soil,

(2) the nature and rate of formation and decline of transformation products.

In the soil an average of 103% of the applied radioactivity

was extractable on day 0. Thereafter, the extractable residue

in the soil decreased steadily to an average of 66.4% at day

120. The non-extractable radioactivity increased constantly

from an average of 1.4% at test start to an average of 31.7%

at day 120. HPLC analysis of the extracts showed that all extractable

radioactivity consisted of [14C]BAY 54-9085.

No volatile organic compounds were found in the ethylene

glycol traps throughout the study. The 14CO2 measured in

the KOH traps increased from an average of 0.01% on day 3

to an average of 0.54% on day 120

The DT50, DT75 and DT90 of the parent compound were

calculated to be 187, 375 and 622 days, respectively.

The biomass was determined to be 1.3, 1.0 and 0.8% of the

organic carbon content at test start, mid-study and test end

respectively.