Carvacrol-rich essential oil obtained from the leaves of Origanum spp., Labiatae, by distillation

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

22-30 March 2018

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:

iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship (HA-QSAR) based on a holistic approach for predicting physicochemical and ecotoxicological endpoints: Water solubility

1. SOFTWARE
iSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.4

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.8

3. IDENTIFIERS USED AS INPUT FOR THE MODEL
logKOW of the constituents predicted using the iSafeRat® Log KOW module with the molecular structure (SMILES code) as the input (see attached QPRF).

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

yes

Remarks:

QSAR model

Principles of method if other than guideline:

A calculation method prediction was performed to assess the water solubility of the consituents of test item. This calculation method predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 105, "Water Solubility" adapted for testing as a mixture using the WAF method. The criterion predicted was the solubility in pure water in mg.L-1 at 25°C.

The water solubility of each constituent was determined using an algorithm based on Quantitative Structure-Property Relationship (QSPR) models which have been validated as QSAR models to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004). The determination was performed using regression method in which validated log KOW values are plotted against the log of subcooled liquid water solubility from studies of high quality. These have been carried out using one of the methods recommended in the OECD 105 guideline or an adaptation of these. Further to this the water solubility of the WAF is determined by using a calculation method based on equilibrium thermodynamic principles.

GLP compliance:

no

Type of method:

other: QSAR

Key result

Water solubility:

492 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 1

Key result

Water solubility:

39.7 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 2

Key result

Water solubility:

1.6 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 3

Key result

Water solubility:

0.785 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 4

Key result

Water solubility:

9.48 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 5

Key result

Water solubility:

0.002 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 6

Key result

Water solubility:

0.001 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 7

Key result

Water solubility:

0.095 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 8

Key result

Water solubility:

0.112 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 9

Key result

Water solubility:

0.117 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 10

Key result

Water solubility:

1.06 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 11

Key result

Water solubility:

0.045 mg/L

Temp.:

25 °C

Remarks on result:

other: Constituent 12

Details on results:

None

None

Conclusions:

The water solubility of 12 constituents of the test item is predicted as follows (mg test item/L):
Constituant 1: 492
Constituant 2: 39.7
Constituant 3: 1.60
Constituant 4: 0.785
Constituant 5: 9.48
Constituant 6: 0.00196
Constituant 7: 0.000877
Constituant 8: 0.095
Constituant 9: 0.112
Constituant 10: 0.117
Constituant 11: 1.06
Constituant 12: 0.0449

Executive summary:

A calculation method prediction was performed to assess the water solubility of the test item. This calculation method predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following Guideline for Testing of Chemicals No. 105, "Water Solubility" adapted for testing as a mixture using the WAF method. The criterion predicted was the solubility in pure water in mg.L-1 at 25°C.

The water solubility determination of the individual constituents of the mixture was performed using regression method in which validated log Kow values are plotted against the log of sub-cooled liquid water solubility from studies of high quality. These have been carried out using one of the methods recommended in the OECD 105 guideline or an adaptation of these. Further to this the water solubility of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics.

Finally the water solubility of 12 components (covering more than 94% of the composition of the substance) has been determined to be between 0.000877 and 492 mg/L each at 25°C.

Description of key information

The apparent water solubilities of the constituents of the substance at ambient temperature (12 components covering more than 94% of the composition) were determined to be between 0.000877 and 492

mg/L each at 25°C (estimations based on valid QSAR estimations).

Additional information

No study was conducted on the oil itself.

The test item is a natural complex substance (NCS). It is a mixture of several constituents, but 12 of them represent more than 94% of that mixture.

Water solubility of the 12 constituents of the test item were calculated using valid QSAR estimations.

Finally, apparent water solubility of each of these 12 constituents was reported below:

Constituent 1   :  492 mg/L at 25°C

Constituent 2   : 39.7 mg/L at 25°C

Constituent 3   :  1.60 mg/L at 25°C

Constituent 4   :  0.785 mg/L at 25°C

Constituent 5   :  9.48 mg/L at 25°C

Constituent 6   :  0.00196 mg/L at 25°C

Constituent 7   :  0.000877 mg/L at 25°C

Constituent 8   :  0.095 mg/L at 25°C

Constituent 9   :  0.112 mg/L at 25°C

Constituent 10 :  0.117 mg/L at 25°C

Constituent 11 :  1.06 mg/L at 25°C

Constituent 12 :  0.0449 mg/L at 25°C

As the substance is a UVCB with constituents of different solubility, the global solubility of the substance will depend on the composition and the loading rate (with varying ratio of constituents in the dissolved phase). Therefore we reported the water solubility of the 12 components of the substance in the range between 0.000877 and 492 mg/L each at 25°C and no single key value was retained (nor calculated weighted WS nor worst-case).