Ammonium 3-nitrobenzoate

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting 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:

SOFTWARE
EPIWIN software by US-EPA

2. MODEL (incl. version number)
WATERNT v1.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
N(=O)(=O)c1cc(C(=O)ON(H)(H)(H))ccc1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint: The models and the training and validation sets are published by US Environmental Protection Agency (USA). A complete description of the estimation methodology used is available in documents prepared for the U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics (Meylan and Howard, 1994a,b). A database of more than 8400 compounds with reliably measured log Kow values had already been compiled from available sources. Most experimental values were taken from a "star-list" compilation of Hansch and Leo (1985) that had already been critically evaluated (see also Hansch et al, 1995) or an extensive compilation by Sangster (1993) that includes many "recommended" values based upon critical evaluation. Other log Kow values were taken from sources located through the Environmental Fate Data Base (EFDB) system (Howard et al, 1982, 1986). A few values were taken from Section 4a, 8d, and 8e submissions the to U.S. EPA under the Toxic Substances Control Act (see http://www.syrres.com/esc/tscats_info.htm).
Water solubilities were collected from the AQUASOL dATAbASETM of the University of Arizona (Yalkowsky and Dannenfelser, 1990), Syracuse Research Corporation's PHYSPROP© Database (SRC,1994), and sources located through the Environmental Fate Data Base (EFDB) system (Howard et al, 1982, 1986). Water solubilities were primarily constrained to the 20-25oC temperature range with 25oC being preferred.

- Unambiguous algorithm:
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 WATERNTs 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.
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).

- Defined domain of applicability:
In WATERNT, the current fragment constants were developed almost entirely from a sub-set of the 1450 compound database used to train the WSKOWWIN program.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
Training sets were chosen large enough, deviation from prediction with the training set are considered acceptable:
The WATERNT Program training set with 1128 compounds gave an equation for logWSolubility with r² = 0.940 resulted in a std dev = 0.537, acd dev = 0.355

5. APPLICABILITY DOMAIN
The intended application domain is organic chemicals. Inorganic and organometallic chemicals generally are outside the domain.

In WATERNT, the minimum and maximum values for molecular weight are the following:

Training Set Molecular Weights:
Minimum MW: 30.30 (formaldehyde)
Maximum MW: 627.62 (hexabromobiphenyl)
Average MW: 187.73

Training Set Water Solubility Ranges:
Minimum Solubility (mg/L): 0.0000004 (octachlorodibenzo-p-dioxin)
Minimum Solubility (log moles/L): -12.0605 (octachlorodibenzo-p-dioxin)
Maximum Solubility (mg/L): miscible (various)
Maximum Solubility (log moles/L): 1.3561 (acetaldehyde)

Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that water solubility 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.

- Similarity with analogues in the training set:
The following information is available on the structure in question:
MW = 184.1494 g/mol, logPow = -1.5162 (estimated, KOWWIN Program (v1.68)), water solubility = 2981.3 mg/L (estimated, WATERNT) / 4.269e+005 mg/L (estimated, WSKOWWIN); Log Water Sol = -1.7884 moles/L (estimated, WATERNT) / 0.368 moles/L (estimated, WSKOWWIN)

So, the substance fits in the validated molecular weight range of both models, the structure is covered by the validation data sets. Also, the resulting estimated water solubility is covered by the values of the components used in the training set. However it is recommended that users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the training set compounds. Nevertheless a clear magnitude of water solubility is evident.

6. ADEQUACY OF THE RESULT
The prediction fits is purpose to support the conclusions drawn from the experimentally derived values.

Data source

Reference

Reference Type:

other: software application

Title:

US EPA . Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.10 . United States Environmental Protection Agency, Washington, DC, USA ; WATERNT™ Version 1.01 [2010]

Author:

U.S. Environmental Protection Agency 1200 Pennsylvania Ave., N.W. (Mail Code 7406M) Washington, DC 20460

Year:

2013

Bibliographic source:

http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Materials and methods

Test guideline

Guideline:

other: REACH guidance on QSARs Chapter R.6 , May 2008

Principles of method if other than guideline:

The computer program WATERNT v1.01 (EPIWIN software by US-EPA) estimates the water solubility of organic compounds at 25°C. WATERNT uses a "fragment constant" methodology to predict water solubility. To estimate water solubility, WATERNT separates a molecule into distinct atom/fragments. Coefficients for individual fragments and groups in WATERNT were derived by multiple regression of 1000 reliably measured water solubility values.

GLP compliance:

no

Remarks:

(not applicable)

Type of method:

other: QSAR calculation

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium 3-nitrobenzoate

EC Number:

242-965-2

EC Name:

Ammonium 3-nitrobenzoate

Cas Number:

19328-56-4

Molecular formula:

C7H5NO4.H3N

IUPAC Name:

ammonium 3-nitrobenzoate

Test material form:

not specified

Details on test material:

SMILES : N(=O)(=O)c1cc(C(=O)ON(H)(H)(H))ccc1
CHEM : Ammonium-3-nitrobenzoate

Results and discussion

Water solubility

Key result

Water solubility:

2 981.3 mg/L

Temp.:

25 °C

Remarks on result:

other: (calculated with WATERNT v1.01)

Details on results:

No further details on results are available.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: soluble (1000-10000 mg/L)
The study report describes a scientifically accepted calculation method for the water solubility prediction using the US-EPA software WATERNT v1.01 .No GLP criteria are applicable for the usage of this tool and the QSAR estimation is easily repeatable.

Executive summary:

The water solubility of the substance ammonium-3-nitrobenzoate was determined by the computer program WATERNT v1.01 (EPIWIN software) by US-EPA (2010).To estimate water solubility, WATERNT separates a molecule into distinct atom/fragments. Coefficients for individual fragments and groups in WATERNT were derived by multiple regression of 1000 reliably measured water solubility values.

For the chemical a water solubility of 2981.3 mg/L was calculated . Due to this estimation the substance is regarded to be soluble in water.