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

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Remarks:

adsorption

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Individual model KOCWIN included in the Estimation Programs Interface (EPI) Suite.
2. MODEL (incl. version number)
KOCWIN v2.00 included in EPISuite v 4.11, 2000-2012.
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Input data to allow calculation can be CAS No., SMILES notation or chemical name (followed by substance selection in a shown list). In the structure window, the molecular weight, structural formula and the structure of the input SMILES notation is shown.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Log Kow method: For estimation of the Log Koc according to the Log Kow method an experimentally determined Log Kow of 3.3 was used (BIS, 2004). Further the following fragment corrections were applied:
 

No. of Fragments Fragment Fragment Description
2 N Nitrogen to non-fused aromatic ring
1 (-C-O-C-) Ether, aromatic
1 (N-CO-N) Urea
1 (-N-C) Nitrogen to Carbon (aliphatic)
1 Misc (C=O) Group Ketone (aliphatic attach)
1 Pyridine ring

MCI method: For the Log Koc estimation of Bay 43-9006 according to the MCI method the following fragment corrections were applied:
No. of Fragments Fragment Fragment Description
2 N Nitrogen to non-fused aromatic ring
1 (-C-O-C-) Ether, aromatic
1 (N-CO-N) Urea
1 (-N-C) Nitrogen to Carbon (aliphatic)
1 Misc (C=O) Group Ketone (aliphatic attach)
1 Pyridine ring

5. APPLICABILITY DOMAIN
a) Domains:
i. Molecular weights:
With a molecular weight of 464.83 g/mole the substance is within the range of the training set (32 665 g/mole) as well as in the range of the validation set (27 – 991 g/mole ).
ii. Structural fragment domain:
Regarding the structure of Bay 43-9006, the fragment descriptors found by the program are complete and listed in Appendix D (KOCWIN Fragment and Correction Factor descriptors).
iii. Mechanism domain:
No information available.

iv. Metabolic domain, if relevant:
Not relevant.
b) Structural analogues:
No information available.
c) Considerations on structural analogues:
No information available.
The uncertainty of the prediction (OECD principle 4)
The substance is not highly complex and the rules applied for the substance appear appropriate. But an individual uncertainty for the investigated substance is not available.
The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5).
No information available.

6. ADEQUACY OF THE RESULT
Regulatory purpose:
The data may be used under any regulatory purpose.
Approach for regulatory interpretation of the model result:
If no experimental data is available, the estimated value may be used to fill data gaps needed for hazard and risk assessment. Further the value is used for other calculations.
Outcome:
The prediction of organic carbon partition coefficient yields a useful result for further evaluation.
Conclusion:
The result is considered as useful for regulatory purposes.

Guideline:

other: REACH guidance QSARs R6, May/July 2008

Principles of method if other than guideline:

Estimation Program Interface EPI-Suite version 4.11: KOCWIN (v2.00) for the estimation of the organic carbon-normalized sorption coefficient for soil and sediment (Koc).
The Estimation Program Interface was developed by the US Environmental Agency's Office of Pollution Prevention and Toxics, and Syracuse Research Corporation (SRC). © 2000 - 2012 U.S. Environmental Protection Agency for EPI SuiteTM (Published online in November 2012).

GLP compliance:

no

Type of method:

other: Estimation

Media:

soil

Radiolabelling:

no

Type:

log Koc

Value:

2.68

Remarks on result:

other: calculation (log Kow method)

Type:

log Koc

Value:

3.64

Remarks on result:

other: calculation (MCI method)

Phase system:

other: Koc

Type:

other: Koc

Value:

476.7 L/kg

Remarks on result:

other: calculation (log Kow method)

Phase system:

other: Koc

Type:

other: Koc

Value:

4 414 L/kg

Remarks on result:

other: calculation (MCI method)

Validity of the model:

1. Defined Endpoint: Organic carbon partition coefficient, given as logarithmic Koc and Koc

2. Unambigous algorithm: The molecule is first classified as a polar substance. Based on structure of the molecule, the following fragments were applied: Nitrogen to non-fused aromatic ring, ether (aromatic), urea, nitrogen to carbon (aliphatic), ketone (aliphatic attach) and a pyridine ring. The number of times of the fragments that occurs in the structure of the substance applied by the program is verified. For estimation of logKoc according to the logKow method an experimental logKow of 3.3 by the program was used.

3. Applicable domain: With a molecular weight of 464.83 g/mole the substance is within the range of the training set (32 - 665 g/mole) as well as in the validation set (27 - 991 g/mole). Regarding the structure of the substance, the fragment descriptors found by the program are complete.

4a. Statistical characteristics (MCI method): N training set without corrections = 69; N training set with correction = 447; N validation set = 158; Correction coefficient of the total training set without corrections r² = 0.967; Correlation coefficient of the total training set with corrections r² = 0.900; Correlation coefficient of the total validation set r² = 0.850.

4b.Statistical characteristics (Kow method): N training set without corrections = 68; N training set with correction = 447; N validation set = 150; Correction coefficient of the total training set without corrections r² = 0.877; Correlation coefficient of the total training set with corrections r² = 0.855; Correlation coefficient of the total validation set r² = 0.778.

5. Mechanistic interpretation: Log Koc is estimated based on the likeliness of a substance for sorption to surfaces of soil/sediment particles. The log Koc is a physical inherent property used extensively to describe a chemical's likeliness to adsob to organic carbon.

Adequacy of prediction:

The result for the substance falls within the applicability domain described above and the estimation rules applied for the substance appear appropriate.

Conclusions:

The QSAR determination of the carbon partition coefficient for the substance using the model KOCWIN included in the Estimation Program Interface (EPI) Suite v4.11 revealed values of 476.7 L/kg (logKow method) and 4414 L/kg (MCI method) for the unaffected molecule of the substance as any decomposition (e.g. hydrolysis) of the substance is not taken into account by the program.

Executive summary:

The organic carbon partition coefficient (Koc) for the substance was predicted using the QSAR calculation of the Estimation Program Interface (EPI) Suite v 4.11. The Koc was estimated to be 476.7 L/kg (logKow method), and 4414 L/kg (MCI method). The results relate to the unaffected molecule of the substance as any decomposition (e.g. hydrolysis) of the substance is not taken into account by the program.

Description of key information

The QSAR determination of the carbon partition coefficient revealed values of 476.7 L/kg (logKow method) and 4414 L/kg (MCI method) for the unaffected molecule of the substance as any decomposition (e.g. hydrolysis) of the substance is not taken into account by the program. Since the substance is expected to be hydrolytically stable under environmental conditions the adsorption potential of the test substance is considered to be moderate to high with a logKoc=3.64. Therefore, the target compartment of the test substance is expected to be soil and sediment.

Key value for chemical safety assessment

Koc at 20 °C:

4 414