Paraffin waxes and Hydrocarbon waxes, oxidized

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE
EPISuite 4.11
2. MODEL (incl. version number)
WATERNT 1.01
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The estimation methodology of the WATERNT Program (estimation of water solubility by fragments) was initially described in a document prepared for the US EPA (Meylan, 1995).  This document (and the training and validation data sets) can be downloaded from the Internet at: http://esc.syrres.com/interkow/EpiSuiteData.htm
Data Sets
The current fragment constants were developed almost entirely from a sub-set of the 1450 compound database used to train the WSKOWWIN program (see the WSKOWWIN Help file).
Methodology
WATERNT uses a "fragment constant" methodology to predict water solubility.  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 solubility estimate.   We call WATERNT’s methodology the Atom/Fragment Contribution (AFC) method.  Coefficients for individual fragments and groups in WATERNT were derived by multiple regression of 1000 reliably measured water solubility values.

The exact same methodology is used in the KOWWIN Program (estimation of octanol water partition coefficient ... see the Meylan and Howard (1995) journal article and the KOWWIN Help file for a more complete description of KOWWIN’s methodology).

To estimate water solubility, WATERNT 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.

It became apparent, for various types of structures, that water solubility estimates made from atom/fragment values alone could or needed to be improved by inclusion of  substructures larger or more complex than "atoms"; hence, correction factors were added to the AFC method.  The term "correction factor" is appropriate because their values are derived from the differences between the water solubility estimates from atoms alone and the measured water solubility values.  The correction factors have two main groupings: first, factors involving aromatic ring substituent positions and second,  miscellaneous factors.  In general, the correction factors are values for various steric interactions, hydrogen-bondings, and effects from polar functional substructures.  Individual correction factors were selected through a tedious process of correlating the differences (between solubility estimates from atom/fragments alone and measured solubility values) with common substructures.

Results of two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating water solubility of any organic compound:

log WatSol (moles/L)  = Σ(fi * ni)  + Σ(cj * nj)  +  0.24922
(n = 1128,  correlation coef (r2) = 0.940,  standard deviation = 0.537, avg deviation = 0.355)

where   Σ(fi * ni)   is the summation of  fi  (the coefficient for each atom/fragment)   times  ni  (the number of times the atom/fragment occurs in the structure) and Σ(cj * nj)  is the summation of  cj  (the coefficient for each correction factor) times  nj  (the number of times the correction factor is applied in the molecule).

Appendix D lists (for each fragment and correction factor) the coefficient value, the number of compounds in the training set containing the fragment or correction factor and the maximum number of instances of that fragment in any of the 1128 training set compounds (the minimum number of instances is of course zero, since not all compounds had every fragment).

See the Estimation Accuracy & Domain section for additional information concerning accuracy and domain.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Software tool(s) used including version: EPISuite 4.11
- Model(s) used: WaterNT 1.01

GLP compliance:

no

Type of method:

other: calculation

Key result

Water solubility:

0.453 µg/L

Temp.:

25 °C

Remarks on result:

other: pH not mentioned

SMILES : CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O

CHEM   : Paraffin waxes and Hydrocarbon waxes, oxidized

MOL FOR: C30 H60 O2

MOL WT : 452.81

-------+-----+--------------------------------------------+----------+---------

TYPE  | NUM |    WATER SOLUBILITY FRAGMENT DESCRIPTION   |  COEFF   |  VALUE  

-------+-----+--------------------------------------------+----------+---------

Frag  |  1  |  -CH3    [aliphatic carbon]                |-0.3213   | -0.3213

Frag  | 28  |  -CH2-   [aliphatic carbon]                |-0.5370   |-15.0365

Frag  |  1  |  -COOH   [acid, aliphatic attach]          | 1.1808   |  1.1808

Const |     |  Equation Constant                         |          |  0.2492

-------+-----+--------------------------------------------+----------+---------

NOTE  |     |  Minimum Solubility (log S = -12.00) Applied!         |

-------+-----+--------------------------------------------+----------+---------

                             Log Water Sol (moles/L) at 25 dec C  =  -12.0000

                             Water Solubility (mg/L) at 25 dec C  =4.5281e-007

Description of key information

Calculation

Key value for chemical safety assessment

Water solubility:

0.453 µg/L

at the temperature of:

25 °C