Reaction mass of (2Z)-5-[(1R,3R,6S)-2,3-dimethyltricyclo[2.2.1.02,6]hept-3-yl]-2-methyl-2-penten-1-ol and (2Z)-2-methyl-5-[(1S,2R,4R)-2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl]-2-penten-1-ol

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:

Experimental Dates (main test): January 7-27, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted according to an internationally recognised method, with no deviation, and under GLP. The substance is adequately characterised, with isomers composition. Therefore full validation applies.

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

27 July 1995

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

Commission Regulation (EC) No 440/2008 on test methods, Method A.6: “Water Solubility” (as amended by Regulation (EU) No 260/2014
An adaptation of the standard method will be performed taking into account the findings of Letinski, D.J., Connolly, M.J., Peterson, D.R. and Parkerton, T.F. (2002) “Slow-stir water solubility measurements of selected alcohols and diesters”, Chemosphere 48, 257-265.
The OECD guideline for the Testing of Chemicals No 123 “Partition Coefficient (1-Octanol/Water): Slow-Stirring Method”, 11 July 2006, was also considered.

GLP compliance:

yes (incl. QA statement)

Remarks:

signed on 15 Nov. 2018

Type of method:

flask method

Remarks:

with slow-stirring adaptation

Key result

Water solubility:

5.6 mg/L

Conc. based on:

other: constituent 1

Loading of aqueous phase:

50 mg/L

Incubation duration:

336 h

Temp.:

20 °C

pH:

>= 5.3 - <= 6

Key result

Water solubility:

3.6 mg/L

Conc. based on:

other: constituent 2

Loading of aqueous phase:

50 mg/L

Incubation duration:

336 h

Temp.:

20 °C

pH:

>= 5.3 - <= 6

Preliminary test

The test item was not solubilized by a water volume of 100 mL after 24 hours, corresponding to a solubility inferior to 200 mg/L.

An ecotoxicity range-finding test was recently carried out on this test item (“Daphnia sp., Acute Immobilisation Test”). Solutions of the test item were prepared at 1 mg/L, 10 mg/L, 32 mg/L and 100 mg/L by weighing the test item on glass slides and introducing them in about 5 L of test water (daphnia Elendt M4 medium). After 24 hours of slow-stirring, the maximum measured concentration of constituent 1 was about 3.9 mg/L and the maximum concentration of constituent 2 was about 1.6 mg/L. These results mean that the solubility of the test item is below 10 mg/L.

It was observed during this preliminary test that the test item is less dense than water.

Main test

Ultrapure water :

The following table presents the concentrations (in mg/L) obtained during the study. Equilibrium was considered achieved after an equilibration time of ca 336h.

	Constituent 1			Constituent 2
	Rep.1	Rep.2	Mean	Rep.1	Rep.2	Mean
vessel 1	5.83	5.26	5.55	3.62	3.33	3.48
vessel 2	6.09	5.55	5.82	3.71	3.42	3.57
vessel 3	5.69	5.37	5.53	3.72	3.55	3.64
mean			5.6 ± 0.3 mg/L (maximum difference: 5 %)			3.6 ± 0.1 mg/L (maximum difference: 4 %)

The pH values measured in the systems were:

- 6.03 in vessel 1, and 5.64 in vessels 2 and 3 at the beginning of the experiment;

- 5.99 in vessel 1, and 5.34 in vessels 2 and 3 at the end of the experiment.

The pH controlled with the indicator strips for each specimen was 5 for all the samples. The pH variation did not exceed 2 pH units.

The surface tension was measured at the beginning (without test item) and at the end of the experiment. The values were to 69.9 mN/m at the beginning and to 51.8 mN/m at the equilibrium time.

The temperature variations were included in the range 19.6°C - 20.4°C.

Daphnia Elendt M4 medium:

The following table presents the concentrations (in mg/L) obtained during the study. Equilibrium was considered achieved after an equilibration time of ca 336h.

	Constituent 1			Constituent 2
	Rep.1	Rep.2	Mean	Rep.1	Rep.2	Mean
vessel 1	5.39	5.40	5.40	3.43	3.40	3.42
vessel 2	6.21	5.34	5.78	3.94	3.40	3.67
vessel 3	6.50	5.95	6.23	4.10	3.79	3.95
mean			5.8 ± 0.5 mg/L (maximum difference: 14 %)			3.7 ± 0.3 mg/L (maximum difference: 14 %)

The pH values measured in the systems were:

- 7.30 in vessel 1, and 8.45 in vessels 2 and 3 at the beginning of the experiment;

- 7.41 in vessel 1, 7.77 in vessel 2, and 7.92 in vessel 3 at the end of the experiment.

The pH controlled with the indicator strips for each specimen was 7 for all the samples. The pH variation did not exceed 2 pH units.

The surface tension was measured at the beginning (without test item) and at the end of the experiment. The values were to 70.9 mN/m at the beginning and to 52.3 mN/m at the equilibrium time.

The temperature variations were included in the range 19.6 °C - 20.4 °C.

Executive summary:

The water solubility of the test substance was measured, under GLP, according OECD 105 guideline, modified with slow-stirring adaptation from Lentinski et al (2002).

Three vessels were prepared, at 20°C. Quantification was performed with a validated GC-FID method. The first vessel was used to determine the equilibration time. When achieved, test item concentration was determined in the other two vessels.

The water solubility was calculated as the average of the three vessels at the final sampling time: 5.6 mg/L + 3.6 mg/L for constituents 1 and 2, respectively (at 20°C and pH 5.3 -6.0) in pure water.

The test was conducted in duplicate in reconstituted daphnia Elendt M4 medium: 5.8 + 3.7 mg/L (at 20°C, pH 7.4 -7.9)

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 2019-08-08

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

Justification for type of information:

1. SOFTWARE
EPI Suite (US EPA)

2. MODEL (incl. version number)
WSKOWWIN v1.42 (September 2010)
WATERNT v1.01 (September 2010)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
OCC(=CCCC(C(C1C2)(C1C3)C)(C23)C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
generally acknowledged source

5. APPLICABILITY DOMAIN
The model is considered suitableas all fragments are described and for MW < 1000 g/mol.

6. ADEQUACY OF THE RESULT
The estimation is provided to demonstrate that low water solubility is anticipated, based on magnitude of order.

Principles of method if other than guideline:

QSAR calculation

GLP compliance:

no

Water solubility:

ca. 3.07 - ca. 10.1 mg/L

Temp.:

25 °C

pH:

ca. 0 - ca. 14

WSKOW v1.42 Results

Log Kow  (estimated)  :  4.96

Log Kow (experimental):  not available from database

Log Kow used by Water solubility estimates:  4.96

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) = 0.00 deg C (Use Tm = 25 for all liquids)

     Correction(s): Alcohol, aliphatic    0.424

Log Water Solubility  (in moles/L) :  -4.339

Water Solubility at 25 deg C (mg/L):  10.1

Water Sol (v1.01 est)

Log Water Sol (moles/L) at 25 dec C  =   -4.8556

Water Solubility (mg/L) at 25 dec C  =   3.0731

Conclusions:

The constituent has low water solubility.

Executive summary:

The water solubility of the constituent was modelled with the both the WSKowWin and WaterNT Estimation tools, which are part of the US EPA Episuite modelling tool box.

The substance was characterised with its SMILES code.

The predicted water solubilities at 25 °C were low, respectively between 10.1 and 3.07 mg/L.

Description of key information

Considered as slightly soluble, with solubility of the two major constituents as 5.6 + 3.6 mg/L in pure water at 20°C (measured).

Equilibrium reached at 336h. pH of saturated solution: 5.3 - 6.0.

Additional information

A new, fully reliable, experimental study was conducted on the registered substance, with quantification of the two major constituents. Therefore it is considered as the key data.

No single key value was derived for the multi-constituent substance, result expressed as a range was prefered, having more scientific sense.

As a qualitative assessement, the substance as a whole is regarded as having low water solubility.

These results are consistent with predictions calculated for the analogue and major constituent alpha-Santalol, with EpiSuite QSAR models Wskowwin and WaterNT, respectively 10.1 and 3.07 mg/L.