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EC number: 946-433-7 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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
- Remarks:
- Values for individual constituents of this natural complex substance (NCS) were calculated using a validated QSAR. All constituents fall within the applicability domain of the QSAR.
- Justification for type of information:
- 1. The software used: see attached QMRF
2. The model(s) used: see attached QPRF
1. SOFTWARE
WATERNT v 1.01 QSAR for water solubility in mg/l at 25°C Dr. Robert
Boethling, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave.,
N.W. (Mail Code 7406M) Washington, DC 20460, USA, Phone: # (202) 564-
8 5 3 3 , e - m a i l : b o e t h l i n g . b o b @ e p a . g o v
h t t p : / / w w w . e p a . g o v / o p p t / e x p o s u r e / p u b s / e p i s u i t e d l . h t m
2. MODEL (incl. version number)
Model or Submodel name: WATERNT
Model Version: Version 1.01
Reference to QMRF: QSAR for water solubility in mg/L at 25ºC
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- other: QSAR model
- Title:
- WATERNT v1.01a
- Author:
- U.S. Environmental Protection Agency
- Year:
- 2 010
- Bibliographic source:
- US EPA. [2008]. 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: REACH Guidance on QSARs R.6;
- Version / remarks:
- Replaces OECD Guideline 105 (Water Solubiity)
- 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 QSAR WaterNT v1.01 from US-EPA.
For Sw, two calculation methods are available in Wskowwin: by log Kow and by fragments of the molecule. In the calculation method based on log Kow, the estimated log Kow value is used as input for the estimation of the water solubility. As this method consists of building QSAR on QSAR preference is given to the next method based on fragments. In this method, the calculation is based on the "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 relevance and reliability of the used QSAR for these constituents is shown in the attached QMRF and QPRF. - GLP compliance:
- no
- Type of method:
- other: Estimation by calculation / QSAR
Test material
- Reference substance name:
- Essential oil of Petitgrain obtained from the leaves and twigs of Citrus aurantium (Rutaceae) by distillation
- EC Number:
- 946-433-7
- Cas Number:
- Not available
- Molecular formula:
- Not applicable for a natural complex substance (UVCB)
- IUPAC Name:
- Essential oil of Petitgrain obtained from the leaves and twigs of Citrus aurantium (Rutaceae) by distillation
- Test material form:
- other: not applicable for in silico study
- Details on test material:
- - Name of test material (as cited in study report): Petitgrain oil
- Commercially available test material - not applicable for in silico study
Constituent 1
Results and discussion
Water solubility
- Key result
- Water solubility:
- >= 0.54 - <= 1 767.3 mg/L
- Temp.:
- 25 °C
- Remarks on result:
- other: Data concern lowest and highest value for water solubility for the individual constituents.
- Details on results:
- No data
Any other information on results incl. tables
Substance | CAS | Estimated Water solubility (@25ºC) |
Linalyl acetate | 115 -95 -7 | 40.617 |
Linalool |
78 -70 -6 |
709.26 |
Geraniol |
106 -24 -1 |
1012.6 |
Terpineol alpha |
98 -55 -5 |
1767.3 |
Geranyl acetate | 105 -87 -3 | 57.985 |
Limonene (D+L) | 7705 -14 -8/138 -86 -3 | 44.388 |
Myrcene beta | 123 -35 -3 | 17.814 |
Citral | 5392 -40 -5 | 1101.00 |
cis/trans-ocimene | 3338 -55 -4 | 38.089 |
Nerol | 106 -25 -2 | 1012.6 |
Neryl acetate | 141 -12 -8 | 57.985 |
Beta Pinene | 127 -91 -3 | 2.6192 |
Terpinyl acetate | 80 -26 -2 | 64.197 |
Caryophyllene beta | 87 -44 -5 | 0.54268 |
alpha pinene | 80 -56 -8 | 3.4835 |
Sabinene | 3387 -41 -5 | 2.6192 |
Terpinolene (p-mentha-1,4(8)-diene) |
586 -62 -9 | 4.48 |
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 main constituent, Linalyl acetate, has a solubility < 100 mg/L, 70.59 % of the NCS has a water solubility < 100 mg/L. The range of water solubilities for the known constituents of Petitgrain oil - citrus aurantum is 0.54 - 1767.3 mg/L at 25°C.
- Executive summary:
The water solubility of Petitgrain oil - citrus aurantum was estimated by calculation. Water solubilities for the known constituents were estimated using the QSAR WATERNT v1.01 according to the fragment method.
The range of water solubilities for the known constituents of Petitgrain oil - citrus aurantum was found to be 0.54 - 1767.3 mg/L at 25°C. The main constituent, Linalyl acetate has a water solubility < 100 mg/L, 70.59% of the NCS has a water solubility < 100 mg/L.
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