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Physical & Chemical properties

Water solubility

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Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2008-10-09 to 2008-12-19
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Remarks:
It is not clear from the study report, if the volatility of the substance was taken into consideration, therefore, the reliability of the measured data is questionable
Qualifier:
according to
Guideline:
EU Method A.6 (Water Solubility)
Deviations:
not specified
Qualifier:
according to
Guideline:
OECD Guideline 105 (Water Solubility)
Deviations:
not specified
GLP compliance:
no
Other quality assurance:
ISO/IEC 17025 (General requirements for the competence of testing and calibration laboratories)
Type of method:
flask method
Key result
Water solubility:
ca. 283 mg/L
Temp.:
20 °C
pH:
ca. 7.35

The concentrations of the test item measured in at least the two last vessels do not differ by more than ±15 % and there is no trend in the values, thus the test is satisfactory.

The relative standard deviation (repeatability) of the concentrations in all six samples was smaller than 15% and the three duplicate sets of samples showed no tendency of increasing concentration values. Thus the test was satisfactory.

Conclusions:
The water solubility of the test item was determined according to OECD guideline no. 105 [adopted on 27 July 1995] and EU test method A.6 [Directive 92/69/EEC, Official Journal L 383 A 1992] with the flask method.
Water solubility (at 20 °C): 283 mg/L
Endpoint:
water solubility
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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:
1. SOFTWARE
EpiSuite v4.11, US EPA, 2012

2. MODEL (incl. version number)
WSKOW v1.42 and WATERNT v1.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
see attachment (watersolubility_QSAR justification.pdf)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: water solubility
- 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 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.

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).

WSKOWWIN estimates water solubility for any compound with one of two possible equations. The equations are equations 19 and 20 from Meylan and Howard (1994a) or equations 11 and 12 from the journal article (Meylan et al., 1996). The equations are:

log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + ΣCorrections
log S (mol/L) = 0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + ΣCorrections

- Defined domain of applicability:
Currently there is no universally accepted definition of model domain. However, users may
wish to consider the possibility that property estimates are less accurate for compounds
outside the Molecular Weight 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.

WATERNT
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)

- Appropriate measures of goodness-of-fit and robustness and predictivity:
training set of 1128 compounds
r² = 0.940
std deviation = 0.537
avg deviation = 0.355

validation dataset of 4,636 compounds not included in the training set
r² = 0.815
std deviation = 1.045
avg deviation = 0.796


WSKOW
Range of water solubilities in the Training set:
Minimum = 4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)
Maximum = completely soluble (various)

Range of Molecular Weights in the Training set:
Minimum = 27.03 (hydrocyanic acid)
Maximum = 627.62 (hexabromobiphenyl)

Range of Log Kow values in the Training set:
Minimum = -3.89 (aspartic acid)
Maximum = 8.27 (decachlorobiphenyl)

- Appropriate measures of goodness-of-fit and robustness and predictivity:
training set of 1450 compounds
r² = 0. 934
std deviation = 0. 585
avg deviation = 0. 442

validation dataset of 817 compounds not included in the training set
r² = 0. 902
std deviation = 0.615
avg deviation = 0. 480


5. APPLICABILITY DOMAIN
- Descriptor domain: The components of the substance are within the molecular weight range of the training set compounds, and all fragments are represented in the training set. Thus, it is concluded, that the substance is within the applicability domain.
- Similarity with analogues in the training set: several linear and branched alkanes and alkenes, which are considered to be similar, are present in the training set.

6. ADEQUACY OF THE RESULT
The QSAR prediction is valid and of good reliability. Thus, the result is adequate for chemical safety assessment.
Principles of method if other than guideline:
Estimation of the water solubility of the components by QSAR (EpiSuite v4.11, US EPA, 2012; WSKOW v1.42, WATERNT v1.01)
GLP compliance:
no
Remarks:
not applicable for in silico study
Type of method:
other: QSAR
Water solubility:
16.2 mg/L
Conc. based on:
test mat.
Remarks:
weighted mean
Temp.:
25 °C
Remarks on result:
other: fragment method
Water solubility:
>= 0.87 - <= 1 887.7 mg/L
Conc. based on:
test mat.
Remarks:
range for constituents
Temp.:
25 °C
Remarks on result:
other: fragment method
Water solubility:
15.5 mg/L
Conc. based on:
test mat.
Remarks:
weighted mean
Temp.:
25 °C
Remarks on result:
other: Kow method
Water solubility:
>= 1.152 - <= 1 485 mg/L
Conc. based on:
test mat.
Remarks:
range for constituents
Temp.:
25 °C
Remarks on result:
other: Kow-method
Conclusions:
Using the fragment method (WATERNT v1.01) the water solubility of the constituents of Oxooil LS9 ranges from 0.87 to 1887.7 mg/L at 25°C, with a weighted mean of 16.2 mg/L. Using the Kow method (WSKOW v1.42), the water solubility of the constituents ranges from 1.152 to 1485 mg/L at 25°C with a weighted mean of 15.5 mg/L. Since the fragment method showed better correlation with the measured data available in the experimental data base for some of the constituents, the QSAR results obtained with this method were selected as key values.

Description of key information

Using the fragment method (WATERNT v1.01) the water solubility of the constituents of Oxooil LS9 ranges from 0.87 to 1887.7 mg/L at 25°C, with a weighted mean of 16.2 mg/L.

Using the Kow method (WSKOW v1.42), the water solubility of the constituents ranges from 1.152  to 1485 mg/L at 25°C with a weighted mean of 15.5 mg/L

Since the fragment method showed better correlation with the measured data available in the experimental data base for some of the constituents, the QSAR results obtained with this method were selected as key values.

Key value for chemical safety assessment

Water solubility:
16.2 mg/L
at the temperature of:
25 °C

Additional information

The water solubility for Oxooil LS9 was measured to be 283 mg/L at 20° C.

However, it is not clear from the study report, if the volatility of the substance was taken into consideration, therefore, the reliability of the measured data is questionable. In addition, no compound specific analytics were performed. Thus, a calculation of the weighted mean water solubility based on QSAR (EpiSuite, WATERNT v1.01 / WSKOW v1.42) was performed, which is used as key value for chemical safety assessment.

Using the fragment method (WATERNT v1.01) the water solubility of the constituents of Oxooil LS9 ranges from 0.87 to 1887.7 mg/L at 25°C, with a weighted mean of 16.2 mg/L. Using the Kow method (WSKOW v1.42), the water solubility of the constituents ranges from 1.152  to 1485 mg/L at 25°C with a weighted mean of 15.5 mg/L.

Further experimental testing is ongoing, which also addresses the substance specific difficulties. The dossier will be updated accordingly.