D-2-hydroxy-2-phenylacetic acid

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 limited documentation / justification

Justification for type of information:

1. SOFTWARE
KOWWIN v1.68 (US EPA)

2. MODEL (incl. version number)
HANSCH,C ET AL. (1995)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
OC(C(=O)O)c1ccccc1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
KOWWIN (the Log Octanol-Water Partition Coefficient Program) estimates the logarithmic octanol-water partition coefficient (log P) of organic compounds.
The KOWWIN program and estimation methodology were developed at Syracuse Research Corporation. A journal article by Meylan and Howard (1995) describes the program 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. For example, aromatic carbon, aromatic oxygen and aromatic sulfur atoms have nothing but general connections; i.e., the fragment is the same no matter what is connected to the atom. In contrast, there are 5 aromatic nitrogen fragments: (a) in a five-member ring, (b) in a six-member ring, (c) if the nitrogen is an oxide-type {i.e. pyridine oxide}, (d) if the nitrogen has a fused ring location {i.e. indolizine}, and (e) if the nitrogen has a +5 valence {i.e. N-methyl pyridinium iodide}; since the oxide-type is most specific, it takes precedence over the other four. The aliphatic carbon atom is another example; it does not matter what is connected to -CH3, -CH2-, or -CH< , the fragment is the same; however, an aliphatic carbon with no hydrogens has two possible fragments: (a) if there are four single bonds with 3 or more carbon connections and (b) any other not meeting the first criteria. Two separate regression analyses were performed.

5. APPLICABILITY DOMAIN
KOWWIN has been tested on an external validation dataset of 10,946 compounds (compounds not included in the training set). The validation set includes a diverse selection of chemical structures that rigorously test the predictive accuracy of any model. It contains many chemicals that are similar in structure to chemicals in the training set, but also many chemicals that are different from and structurally more complex than chemicals in the training set. The average molecular weight of compounds in the validation set is 258.98 versus 199.98 for the training set.

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.

6. ADEQUACY OF THE RESULT
The estimate value has been generated by a valid model. The model is applicable to the substance D-2-hydroxy-2-phenylacetic acid with the necessary level of reliability and is sufficiently relevant for the regulatory purpose.

Data source

Reference

Title:

KOWWIN v.1.68 (September 2010)

Year:

2012

Bibliographic source:

EPI Suite version 4.11

Materials and methods

Principles of method if other than guideline:

Predicted data by EPI Suite v4.11.

GLP compliance:

no

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

D-2-hydroxy-2-phenylacetic acid

EC Number:

241-240-8

EC Name:

D-2-hydroxy-2-phenylacetic acid

Cas Number:

17199-29-0

Molecular formula:

C8H8O3

IUPAC Name:

hydroxy(phenyl)acetic acid

Test material form:

solid: particulate/powder

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

0.62

Remarks on result:

other: Temperature and pH not available