Reaction mass of stereoisomers of 4-METHYLENE-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-TETRAHYDRO-PYRAN and; 4-METHYL-6-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN and; 4-METHYL-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

January 24th, 2019 to July 31st, 2019

Reliability:

1 (reliable without restriction)

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
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. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
isomer 1: CC1=CCC(CC2CC(CCO2)=C)C(C)1C
isomer 2: CC1=CCC(CC2C=C(C)CCO2)C(C)1C
isomer 3: CC1=CCC(CC2CC(C)=CCO2)C(C)1C

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

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

not applicable

Remarks:

QSAR model

Principles of method if other than guideline:

The purpose of the holistic study was to determine the water solubility of test item in pure water at 25°C. The holistic approach consisted in using simultaneously the iSafeRat® QSAR models which are interconnected by the water solubility as the common descriptor. The objective is to predict a parameter, i.e. water solubility by using different QSAR models and then, to compare the output values to ensure the input values are consistent between each other. Provided the input values are considered to be reliable, the holistic approach can provide a set of values for the parameter to be predicted. Therefore, the determination of the water solubility was performed by combining the different QSAR models available with iSafeRat® for which the input values are already known and considered to be reliable.

GLP compliance:

no

Type of method:

other: QSAR models holistic approach

Specific details on test material used for the study:

not applicable

Water solubility:

72 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: input log KOW (experimental)

Water solubility:

44 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: input log KOW (calculated, isomer 1)

Water solubility:

17.2 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: input log KOW (calculated, isomer 2 and 3)

Key result

Water solubility:

44.4 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: mean

method	water solubility (mg test item.L^-1) at 25°C	95% confidence limits (mg test item.L^-1)
from experimental log KOW(3.75)	72.0	61.9 – 83.7
from calculated log KOW(3.9) for isomer 1	44.0	37.4 – 51.7
from calculated log KOW(4.3) for isomers 2 and 3	17.2	14.3 – 20.6
mean	44.4	N/A

No ionisation, therefore no pH-dependency, is expected from structure.

Executive summary:

A holistic approach has been performed in order to determine the water solubility of the test item in pure water at 25°C, by using several Quantitative Structure-Property Relationship (QSPR) or Quantitative Structure-Activity Relationship (QSAR) models, to independently calculate the water solubility. Experimental values considered as reliable are used as input to obtain a set of predictions of water solubility. The test item falls within the applicability domain of each model used. Therefore the predictions are considered to be reliable for water solubility.

The experimental study on log Kow, as well as the fragment approach used to calculate the log K_OW from the structures, were both considered to be reliable and were therefore used as input. As a result, three values of water solubility were obtained, ranging between 17.2 and 72.0 mg/L (Table 1). The result of the holistic approach is given as the mean of the different values.

The water solubility at 25°C of the test item was determined as 44.4 mg/L.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

23 January to 21 March 2007

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

The determination was conducted with the column elution method, which is not suitable for a liquid test substance.

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Type of method:

column elution method

Water solubility:

4.2 mg/L

Temp.:

20 °C

pH:

6.55 - 6.69

Executive summary:

The water solubility of the test substance was determined according to EU A.6 guideline, column elution method.

As this method is considered not suitable for liquid test items, the solubility result was not retained.

But the information on the pH of the solution is considered of scientific interest : ca 6.6 at 4.2 mg/L.

Description of key information

Calculated water solubility ca 44.4 mg/L at 25°C.

pH of a 4.2 mg/L solution ca 6.6.

Key value for chemical safety assessment

Water solubility:

44.4 mg/L

at the temperature of:

25 °C

Additional information

An experimental study was available, but the result was disregarded, as the elution method, not suitable for liquids, was used. However the pH of the resulting solution was included as supporting scientific information of interest.

Therefore, the water solubility was reliably estimated by QSAR, using a holistic approach with independant calculations. Three results were obtained, from experimental logKow, and structures of the isomers, ranging between 17.2 and 72.0 mg/L. The average value was retained as key.