Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
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
Remarks:
Value for this mono-constituent was calculated using a validated QSAR. This mono-constituent falls within the applicability domain of the QSAR.
Justification for type of information:
1. The software used: see attached QMRF
2. The model(s) used: see attached QPRF

1. SOFTWARE
Kowwin v 1.67a, part of Estimation Programs Interface Suite™ for
Microsoft® Windows, v 4.00 QSAR for octanol-water partition coefficient
(logP) also referred to as log Kow Dr. Robert Boethling, U.S. Environmental
Protection Agenc,y 1200 Pennsylvania Ave., N.W. (Mail Code 7406M)
Washington, DC 20460, USA, Phone # (202) 564-8533, e-mail:
b o e t h l i n g . b o b @ e p a . g o v
h t t p : / / w w w . e p a . g o v / o p p t i n t r / e x p o s u r e / p u b s / e p i s u i t e . h t m

2. MODEL (incl. version number)

Model or submodel name: KOWWIN
Model version: Version 1.67
Reference to QMRF: QSAR for octanol-water partition coefficient (LogP) also referred to as Log Kow
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
other: QSAR model
Title:
KOWWIN v1.67a
Author:
U.S. Environmental Protection Agency
Year:
2008
Bibliographic source:
US EPA. [2008]. Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.00. United States Environmental Protection Agency, Washington, DC, USA

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: REACH Guidance on QSARs R.6
Deviations:
not applicable
Principles of method if other than guideline:
Calculated and measured data on the constituent is obtained from Kowwin v1.67. The relevance and reliability of the used QSAR for this constituent is shown in the attached QMRF and QPRF.
GLP compliance:
no
Type of method:
other: Calculation by estimation / QSAR
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
3.69
Remarks on result:
other: The log Kow for MNK
Details on results:
0 % of the NCS has a log Kow >= 4.0.

Any other information on results incl. tables

Substance CAS Estimated log Kow
 undecan-2 -one  112 -12 -9  3.69

Kowwin v1.67a model details

Reference to the type of model used

KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method.

 

Description of the applicability domain

The applicability domain is based on the maximum number of instances of that a fragment can be used in a chemical and molecular weight. The minimum and maximum values for molecular weight are the following:

 

Training Set Molecular Weights:

Minimum MW: 18.02

Maximum MW: 719.92

Average MW: 199.98

 

Validation Molecular Weights:

Minimum MW: 27.03

Maximum MW: 991.15

Average MW: 258.98

Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that log P estimates are less accurate for compounds outside the MW range of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed. These points should be taken into consideration when interpreting model results.

 

Description and results of any possible structural analogues of the substance to assess reliability of the prediction

External validation with a dataset containing 10946 substances resulted in a correlation coefficient (r2) of 0.943, a standard deviation of 0.479 and an absolute deviation of 0.358.

Predictivity assessment of the external validation set:

Validation Set Estimation Error:

within <= 0.20 - 39.6%

within <= 0.40 - 66.0%

within <= 0.50 - 75.6%

within <= 0.60 - 82.5%

within <= 0.80 - 91.6%

within <= 1.00 - 95.6%

within <= 1.20 - 97.7%

within <= 1.50 - 99.1%

Uncertainty of the prediction

All constituents for which estimations were made fall within the applicability domain of the model.

Mechanistic domain

KOWWIN (the Log Octanol-Water Partition Coefficient Program) estimates the logarithmic octanol-water partition coefficient (log P) of organic compounds. KOWWIN requires only a chemical structure to estimate a log P. The octanol-water partition coefficient is a physical property used extensively to describe a chemical's lipophilic or hydrophobic properties. It is the ratio of a chemical's concentration in the octanol-phase to its concentration in the aqueous phase of a two phase system at equilibrium. Since measured values range from less than 10^-4 to greater than 10^8 (at least 12 orders of magnitude), the logarithm (log P) is commonly used to characterize its value.

KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s™s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values.

As all regular and common fragments are included in this method, and the constituents for which this method was applied do not contain exotic fragments, there are no limits to the mechanistic domain.

Applicant's summary and conclusion

Conclusions:
The log Kow of MNK (undecan-2-one) is 3.69.
Executive summary:

The partition coefficient for undecan-2-one was calculated using the KOWWIN v1.67 QSAR by US-EPA.

The log Kow of undecan-2-one was found to be 3.69.