Cinnamomum zeylanicum, ext.

Water solubility

Administrative data

Endpoint:

water solubility

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:

QSAR prediction

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

other: QSAR model

Title:

WSKOWWIN v1.41a

Author:

U.S. Environmental Protection Agency

Year:

2008

Bibliographic source:

US EPA. 2009. 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

Guideline:

other: NCS Protocol

Deviations:

no

Principles of method if other than guideline:

NCSs, consisting of a number of constituents, do not have one single water solubility value (Sw). The range of Sw can be given from calculated or measured values of the individual constituents. Calculated and measured data on the constituents are obtained from the WATERNT v1.01 from US-EPA.

GLP compliance:

no

Type of method:

other: Estimation by calculation

Test material

Test material information

Constituent 1

Reference substance name:

Cinnamomum zeylanicum, ext.

EC Number:

283-479-0

EC Name:

Cinnamomum zeylanicum, ext.

Cas Number:

84649-98-9

Molecular formula:

Not Applicable due to UVCB

IUPAC Name:

Cinnamomum zeylanicum, ext.

Details on test material:

- Name of test material (as cited in study report): Cinnamon leaf oil
- Physical state: liquid

Results and discussion

Water solubility

Key result

Water solubility:

>= 0.54 - <= 7 481.5 mg/L

Temp.:

25 °C

Remarks on result:

other: The main constituent, Eugenol has a water solubility > 100 mg/L, 14.4 % of known constituents of the substance have a water solubility < 100 mg/L.

Details on results:

No data

Any other information on results incl. tables

Constituent	CAS-number	Sw [mg/L @ 25ºC]
Eugenol	97-53-0	979.83
beta-Caryophyllene	87-44-5	0.54268
Linalool	78-70-6	709.26
Benzyl benzoate	120-51-4	20.002
alpha-Phellandrene	99-83-2	37.447
Cinnamyl acetate	103-54-8	183.76
Cinnamyl aldehyde	104-55-2	3373.9
5-allyl-1,3-benzodioxole	94-59-7	5.8996
4-allyl-2-methoxyphenyl acetate	93-28-7	48.621
Pin-2(3)-ene	80-56-8	3.4834
para-Cymene	99-87-6	28.93
Humulene	6753-98-6	1.5354
p-mentha-1(7),2-diene	555-10-2	28.156
Camphene	79-92-5	2.6192
D-Limone	5989-27-5	44.388
p-mentha-1-en-8-ol	98-55-5	1767.3
Pin-2(10)-ene	127-91-3	2.6192
Cinnamyl alcohol	104-54-1	7481.5
Benzaldehyde	100-52-7	5128.6
beta-Myrcene	123-35-3	17.814
alpha-Terpinene	99-86-5	59.034
p-mentha-1,4(8)-diene	586-62-9	93.066

WaterNT v1.01 model details

 

Reference to the type of model used

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. The WATERNT™s methodology is further referred to as 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.

 

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 (based on the training and validation set, summarized in appendix D) and on molecular weight. The minimum and maximum values for molecular weight are the following:

 

Training Set Molecular Weights:

Minimum MW: 30.30

Maximum MW: 627.62

Average MW: 187.73

 

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.

 

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

External validation with a dataset containing 4636 substances resulted in a correlation coefficient (r²) of 0.815, a standard deviation of 1.045 and an absolute deviation of 0.796. The external 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.

 

Uncertainty of the prediction

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

 

Mechanistic domain

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.

 

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 QSAR. In total 117 different types of fragments exist.

 

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.

 

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 water solubility of the known constituents of Cinnamon Leaf Oil ranges from 0.54 to 7481.5 mg/L at 25 ºC. The main constituent, Eugenol has a water solubility > 100 mg/L, 14.4 % of known constituents of the substance have a water solubility < 100 mg/L.

Executive summary:

The water solubility of cinnamon leaf oil was estimated by calculation. Water solubilities for the known constiuents were estimated using the QSAR WSKOWWIN v 1.41 according to the fragment method.

The water solubility of the known constituents of Cinnamon Leaf Oil ranges from 0.54 to 7481.5 mg/L at 25 ºC. The main constituent, Eugenol has a water solubility > 100 mg/L, 14.4 % of known constituents of the substance have a water solubility < 100 mg/L.