N,N-dimethyloctadecylamine N-oxide

Partition coefficient

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

Justification for type of information:

1. SOFTWARE
and MODEL
EPI Suite version 4.11

Kowwin v1.68 (september 2010)

2. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : C(CCCCCCCCCCCCCCC)CC[N+](C)(C)[O-]
NAME : N,N-Dimethyl-1-octadecanamine-N-oxide
CAS Number : 2571-88-2

3. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
No formal QMRF assessment of the model is currently available, however, the user's guide describes all the information.
- Defined endpoint: Partition coefficient
- Methodology : 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.  Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values.  KOWWIN’s "reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (1979) that is available in the CLOGP Program (Daylight, 1995).  See the Meylan and Howard (1995) journal article for a more complete description of KOWWIN’s methodology.

To estimate log P, KOWWIN initially separates a molecule into distinct atom/fragments.  In general, each non-hydrogen atom (e.g. carbon, nitrogen, oxygen, sulfur, etc.) in a structure is a "core" for a fragment; the exact fragment is determined by what is connected to the atom.  Several functional groups are treated as core "atoms"; these include carbonyl (C=O), thiocarbonyl (C=S), nitro (-NO2), nitrate (ONO2), cyano (-C/N), and isothiocyanate (-N=C=S).  Connections to each core "atom" are either general or specific; specific connections take precedence over general connections.

4. APPLICABILITY DOMAIN
No formal QMRF assessment of the model is currently available, however, the user's guide describes all the information.
- Descriptor domain:
organic chemical
- Structural and mechanistic domains:
Training Set Molecular Weights: Minimum MW:  18.02 Maximum MW:  719.92 Average MW:  199.98
Appendix D of the KOWWIN Help gives the maximum number of fragments that occur in any individual compound of the training set.
- Similarity with analogues in the training set:
The KOWWIN training and validation datasets can be downloaded from the Internet at http://esc.syrres.com/interkow/KowwinData.htm

5. References
Daylight.  1995.  CLOGP Program. Daylight Chemical Information Systems.  Von Karman Ave., Irvine, CA 92715. (web-site as of March 2008: http://www.daylight.com/)
Hansch, C and  Leo, A.J.  1979.  Substituent Constants for Correlation Analysis in Chemistry and Biology;  Wiley: New York, 1979.
Meylan, W.M. and P.H. Howard.  1995.  Atom/fragment contribution method for estimating octanol-water partition coefficients.  J. Pharm. Sci. 84: 83-92.

Data source

Reference

Reference Type:

other: Model

Title:

EPI Suite version 4.11

Author:

U.S Environmental Protection Agency

Year:

2012

Bibliographic source:

KOWWIN - Meylan, W.M and P.H Howard. 1995. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84: 83-92

Materials and methods

Test guideline

Guideline:

other: REACH guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version:
Kowwin v1.68 (september 2010)

- Model(s) used:
Kowwin v1.68 (september 2010)

- Model description: see field 'Justification for type of information"
- Justification of QSAR prediction: see field 'Attached justification'

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethyloctadecylamine N-oxide

EC Number:

219-919-5

EC Name:

N,N-dimethyloctadecylamine N-oxide

Cas Number:

2571-88-2

Molecular formula:

C20H43NO

IUPAC Name:

N,N-dimethyloctadecanamine oxide

Specific details on test material used for the study:

SMILE : C(CCCCCCCCCCCCCCC)CC[N+](C)(C)[O-]

Results and discussion

Partition coefficient

Type:

log Pow

Remarks on result:

not determinable

Remarks:

The surface-active substances have a tendency to partition to interphases between oils/fats and the algorithms are limited. Thee Kowin estimates were found to be of limited accuracy for Kow.

Details on results:

KOWWIN predicted that N,N-Dimethyl-1-octadecanamine-N-oxide has a logKow = 7.62. However the surface-active substances have a tendency to partition to interphases between oils/fats and the algorithms are limited. The Kowin estimates were found to be of limited accuracy for Kow

Applicant's summary and conclusion

Conclusions:

KOWWIN predicted that N,N-Dimethyl-1-octadecanamine-N-oxide has a logKow of 7.62. However the surface-active substances have a tendency to partition to interphases between oils/fats and the algorithms are limited. The Kowin estimates were found to be of limited accuracy for Kow.

Executive summary:

KOWWIN predicted that N,N-Dimethyl-1-octadecanamine-N-oxide has a logKow of 7.62. However the surface-active substances have a tendency to partition to interphases between oils/fats and the algorithms are limited. The Kowin estimates were found to be of limited accuracy for Kow. On the chemical behavior of the other amine oxides which are expected to be very similar.