1-Butanone, 3-(dodecylthio)-1-[(1R,2S)-2,6,6-trimethyl-3-cyclohexen-1-yl]-, rel-

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 01 October 2011 to 29 February 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study conducted with different methods not complying with guidelines requirements, but conducted with acceptable scientific reasoning. Purity of test sustance specified but not isomers composition. Therefore reliability applies with restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

flask method

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

slow stirring method

Principles of method if other than guideline:

Six assays were conducted to measure the solubility of the test substance, based on direct introduction with vigorous or slow-stir stirring, or diffusion from a non-miscible phase. As the test substance is estimated to have very low solubility, and easily forms a suspension, the study focused to obtain true solutions; this was checked by turbidity measurement using a nephelometer.

GLP compliance:

no

Type of method:

flask method

Water solubility:

< 0.5 µg/L

Temp.:

25 °C

pH:

ca. 0 - ca. 14

Direct introduction of the test substance in water with vigorous stirring:

Preparation of the 55.2 g/L concentration led immediately to an opalescent suspension. Separation techniques showed:

- Decantation: after 1 month, the suspension looked clearer but stayed opalescent, and was observed to be quite stable, with the presence of both droplets and crystals;

- Crystallization: after cooling the suspension at +4°C, the remaining solution was still opalescent and visually contained suspended materials;

- Centrifugation: 25 mL of suspension was centrifuged at 27000G for 30 minutes, no separation occurred;

- Filtration: after 1 week decantation, the suspension was filtered through a 0.2 μm regenerated cellulose filter; the remaining mixture was not a true solution.

With a lower nominal concentration (1.03 mg/L) with mixing at 45°C, turbidity measurement gave dispersed results which are typical of an unstable suspension, as well as heterogeneity of measured concentrations.

Direct introduction of the test substance in water without stirring or with very gentle stirring:

From the 55.2 g/L mixture, the concentration of the test substance rose rapidly after 15 days in air atmosphere, correlated with release of degradation product delta-damascone. The variability of replicate injections and turbidity values confirmed that a suspension was measured, rather than a true solution.

The static experiment at 50°C led to a 6.6 µg/L concentration of the test substance in water after 23 days and a low turbidity, close to a true solution. However, suspended material was nevertheless present (average diameter 550 nm).

With low concentration, a rapid increase in the concentration followed by a rapid drop (day 2) was observed in dynamic experiments. In static mode without SBSE at ambient temperature (23°C), the concentration of the test substance in water increased rapidly and after 3 days oscillated slightly. Replication of the experiment however led to slightly different concentrations (0.5 µg/L vs. 1.5 µg/L), and the turbidity, despite being low, was still significantly different from that of a true solution.

Diffusion of the test substance in water via an hydrophobic solvent:

With diffusion from polyalphaolefins oil, the concentration of the test substance in the water phase was above the LOD, but below the LOQ (0.5 µg/L). The turbidity indicated the presence of a suspension. However no suspended material was observed by microscopy.

With octanol, it is interesting to notice that whereas the test substance dissolved easily in pure 1-octanol, the solubilisation is more difficult in 1-octanol saturated with water. After 10 days of equilibrium, the concentration of the test substance was similarly above the LOD, but below the LOQ (0.5 µg/L). The turbidity corresponded to that expected for a true solution (0.02 NTU). No suspended material was observed by microscopy. However, the solubilised part of 1-octanol in the water phase certainly increased the solubility of the test substance, and consequently biased the trueness of the result.

Conclusions:

Interpretation of results (migrated information): insoluble (< 0.1 mg/L)
The true solubility of the test substance was estimated to be <0.5 µg/L.
Suspensions are easily formed in water, which cannot be completely separated with usual techniques, so oversaturation is anticipated in actual conditions.

Executive summary:

Different attempts have been conducted to prepare a true saturated solution of the test substance in water.

All direct additions led to a suspension. The microscopic observation of some samples demonstrated that they may contain both droplets and crystals. Decantation, filtration, centrifugation, crystallization were not efficient to prepare true solution.

Adjusting the initial temperature of the solubilization experiment, limiting the stirring and working on the amount of the test substance introduced, did improve the results and tended to lead to a true solution.

Using a hydrophobic phase to act as a limiting transfer medium also gave good results, but with possible overestimation due to slight mutual solubility of the solvents.

Analytical measurements were found to be below the LOQ of the analytical method, therefore the solubility of the test substance can be estimated to be less than 0.5 µg/L.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 16 June 2004 to 03 August 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Testing in accordance with Method A6 of Commission Directive 92/69/EEC. Purity and isomers composition specified.

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on December 02, 2002 / signed on February 13, 2003)

Type of method:

flask method

Remarks:

See important remark in "Overall remarks"

Water solubility:

<= 93 µg/L

Temp.:

20 °C

pH:

>= 5.5 - <= 6.2

Details on results:

See in "Remarks on results including tables and figures"

Results of Preliminary test:The preliminary estimate of water solubility was less than 1.0 x 10^-4g/l.

 

Results of Definitive test:The mean peak areas relating to the standard and sample solutions are shown in the following table:

 

Solution	Mean Peak Area
Standard 2.51 mg/l Standard 2.46 mg/l Sample blank Sample 1A Sample 1B Sample 2A Sample 2B Sample 3A Sample 3B	7.214 x 103 7.420 x 103 1.509 x 103 6.998 x 103 3.379 x 103 5.231 x 103 2.042 x 103 4.935 x 103 4.263 x 103

 

The concentration (g/l) of test material in the sample solutions is shown in the following table:

Sample Number	Time shaken at 30°C (hours)	Time equilibrated at 20°C (hours)	Concentration (g/l)	Solution pH
1	24	24	≤ 9.3 x 10^-5	6.1
2	48	24	≤ 9.3 x 10^-5	5.5
3	72	24	≤ 9.3 x 10^-5	6.2

 

Overall concentration: less than or equal to 9.3 x 10^-5g/l at 20.0 ± 0.5ºC.

Concentrations have not been corrected for recovery of analysis.

Conclusions:

Interpretation of results (migrated information): insoluble (< 0.1 mg/L)
The water solubility of the test material has been determined to be less than or equal to 9.3 x 10-5 g/L of solution at 20.0 ± 0.5°C.

Executive summary:

Introduction. Water solubility of ST 48 C 03 was determined using the Method A6 of Commission Directive 92/69/EEC.

Method.The preliminary water solubility test indicated that the column elution method should have been performed as the solubility was less than 10 mg/L. However, due to the physical nature of the test material, it was not possible to use this method (due to the adherence of the test material to the glass beads and to the formation of a plug in the column). The flask method was more adapted to measure the water solubility of ST 48 C 03 and was therefore used in this test.

Result & Conclusion. The solubility of ST 48 C 03 was less than or equal to 9.3 x 10-5 g/L (or 93 µg/L) at 20.0 ± 0.5°C

Reference 3

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. Moreover, the substance is within the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Water solubility:

84.5 mg/L

Temp.:

25 °C

Remarks on result:

other: unionised form

Water solubility:

27.5 g/L

Temp.:

25 °C

Remarks on result:

other: ionised (Na salt)

SMILES : (acid)

MOL FOR: C15 H24 O3 S1

MOL WT : 284.42

---------------------------------- WSKOW v1.42 Results ------------------------

Log Kow (estimated) : 3.36

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: 3.10 (user entered)

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

(used when Melting Point NOT available)

Correction(s): Value

-------------- -----

Acid, aliphatic 0.395

Log Water Solubility (in moles/L) : -3.527

Water Solubility at 25 deg C (mg/L): 84.53

For information, with default log Kow = 3.36, Water Solubility at 25 deg C (mg/L): 50.9

SMILES : (Na salt)

MOL FOR: C15 H23 O3 S1 Na1

MOL WT : 306.40

---------------------------------- WSKOW v1.42 Results ------------------------

Log Kow (estimated) : -0.45

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: -0.45

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

(used when Melting Point NOT available)

Correction(s): Value

-------------- -----

No Applicable Correction Factors

Log Water Solubility (in moles/L) : -1.048

Water Solubility at 25 deg C (mg/L): 2.746e+004

pH is not considered in this model. However it should be noted that the substance has an estimated pKa of 3.56 (please refer to section 4.21), therefore it will be mainly under its ionised form at environmental pH, and ionised species are known to have higher water solubility, as confirmed by the estimated value for Na salt.

Conclusions:

Expected to be very soluble at environmental pH (ionised form).

Executive summary:

The water solubility of the test substance, as acid and sodium salt, was estimated using the recommended QSAR model WSKowWin v1.42. Both forms are within the applicability domain.

Reference 4

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. Moreover, the substance is within the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Water solubility:

47.3 mg/L

Temp.:

25 °C

Remarks on result:

other: unionised form

Water solubility:

8.64 g/L

Temp.:

25 °C

Remarks on result:

other: ionised (Na salt)

SMILES : (acid)

MOL FOR: C16 H26 O3 S1

MOL WT : 298.44

---------------------------------- WSKOW v1.42 Results ------------------------

Log Kow (estimated) : 3.85

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: 3.30 (user entered)

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

(used when Melting Point NOT available)

Correction(s): Value

---------------- -----

Acid, aliphatic 0.395

Log Water Solubility (in moles/L) : -3.800

Water Solubility at 25 deg C (mg/L): 47.31

For information, with default log Kow = 3.85, Water Solubility at 25 deg C (mg/L): 16.07

SMILES : (Na salt)

MOL FOR: C16 H25 O3 S1 Na1

MOL WT : 320.43

---------------------------------- WSKOW v1.42 Results ------------------------

Log Kow (estimated) : 0.04

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: 0.04

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

(used when Melting Point NOT available)

Correction(s): Value

---------------- -----

No Applicable Correction Factors

Log Water Solubility (in moles/L) : -1.569

Water Solubility at 25 deg C (mg/L): 8641

pH is not considered in this model. However it should be noted that the substance has an estimated pKa of 4.33 (please refer to section 4.21), therefore it will be mainly under its ionised form at environmental pH, and ionised species are known to have higher water solubility, as confirmed by the estimated value for Na salt.

Conclusions:

Expected to be soluble at environmental pH (ionised form).

Executive summary:

The water solubility of the test substance, as acid and sodium salt, was estimated using the recommended QSAR model WSKowWin v1.42. Both forms are within the applicability domain.

Reference 5

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. Moreover, the substance is within the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Water solubility:

40.3 mg/L

Temp.:

25 °C

MOL FOR: C13 H20 O1

MOL WT : 192.30

---------------------------------- WSKOW v1.42 Results ------------------------

Log Kow (estimated) : 4.16

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: 3.60 (user entered)

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.796 - 0.854 log Kow - 0.00728 MW + Correction

(used when Melting Point NOT available)

Correction(s): Value

---------------- -----

No Applicable Correction Factors

Log Water Solubility (in moles/L) : -3.678

Water Solubility at 25 deg C (mg/L): 40.33

For information, with default log Kow = 4.16, Water Solubility at 25 deg C (mg/L): 13.3

pH is not considered in this model.

No ionisation (please refer to section 4.21), therefore no pH-dependency is anticipated for the molecule.

Conclusions:

Expected to be slightly soluble.

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKowWin v1.42. It is within the applicability domain.

Reference 6

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2013-03-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Remarks:

The value is not an experimental result, however the QSAR model is recommended by the ECHA guidance document on information requirements, and is well documented with regard to validation parameters according to OECD principles. However, the substance is not fully within the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Water solubility:

0.085 µg/L

Temp.:

25 °C

MOL FOR: C25 H46 O1 S1

MOL WT : 394.70

---------------------------------- WSKOW v1.42 Results ------------------------

Log Kow (estimated) : 9.51

Log Kow (experimental): not available from database

Log Kow used by Water solubility estimates: 9.50 (user entered)

Equation Used to Make Water Sol estimate: Log S (mol/L) = 0.693-0.96 log Kow-0.0092(Tm-25)-0.00314 MW + Correction

Melting Pt (Tm) = 19.00 deg C (Use Tm = 25 for all liquids)

Correction(s): Value

---------------- -----

No Applicable Correction Factors

Log Water Solubility (in moles/L) : -9.666

Water Solubility at 25 deg C (mg/L): 8.509e-005

pH is not considered in this model.

No ionisation (please refer to section 4.21), therefore no pH-dependency is anticipated for the molecule.

Conclusions:

The model is considered to be of good predictibility for the compound.

Executive summary:

The water solubility of the test substance was estimated using the recommended QSAR model WSKowWin v1.42. It is not fully within the applicability domain, however the estimated value for the outlier parameter, log K, was found to be identical to the experimental value. The estimated solubility was also in line with the experimental result.

Description of key information

The true water solubility of the parent substance is considered to be <0.5 µg/L (experimental).

Suspensions are easily formed in water, which cannot be completely separated with usual techniques, so oversaturation is anticipated in actual conditions.

Metabolites DD-ma and DD-mp are estimated to have a solubility of respectively 85 and 47 mg/L, but anticipated to ionise and to increase up to ca 27 and 8.6 g/L at environmental pH (>=5).

Metabolite DD is estimated to have a solubility of ca 40 mg/L.

Key value for chemical safety assessment

Water solubility:

0.5 µg/L

at the temperature of:

25 °C

Additional information

An experimental study on water solubility measurement of the substance, was conducted under GLP, and considered as fully reliable. In order to refine the previous limit value obtained, another study was conducted, with several non-guideline methods, but nevertheless considered to be scientifically acceptable, with regard to obtaining a solution free of suspended particles. The lower result obtained was retained as the maximum measurable true concentration.

As risk assessment requires a figure in the above "key value" box (no < or > sign accepted), this limit value will be used as default data for CSA purpose.

Moreover, as the parent substance is likely to degrade into DD-ma, DD-mp and DD, supporting information is provided also on the solubility of the metabolites, which are the relevant species for the environmental risk assessment.

The water solubility was estimated using QSAR calculations. Four models, using different methodologies, were tried (WSKowWin, WaterNT, SPARC and VCClab), however three were discarded as not able to handle salts/ionised species, or considered to be of poor reliability for the substances of concern. Therefore only WSKowWin was retained in the present dossier. All compounds were within the applicability domain, and the predictibiity was confirmed by comparison with experimental values (Wsol and logK) from the parent compound.