(1R)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-ethanol

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:

02 October 2012 - 10 October 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

The determination of the water solubility was performed using the OECD 105 guideline (elution column). This study was considered as reliable with restrictions because not enough details on quantification of the substance were reported in the study report.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

(27 July 1995)

Deviations:

no

Principles of method if other than guideline:

This method is based on the elution of a test substance with water from a micro-column which is charged with an inert support material (celite), previously coated with an excess of the test substance. The water solubility is given by the mass concentration of the eluate when this has reached a plateau as a function of time. A second experiment is performed at half the flow rate of the first. If the results of the two runs are in agreement, the test is satisfactory. If the measured solubility is higher with the lower flow rate, then the halving of the flow rate must continue until two successive runs give the same solubility.

GLP compliance:

no

Type of method:

column elution method

Key result

Water solubility:

ca. 334.81 mg/L

Temp.:

20 °C

pH:

>= 5 - <= 9

Remarks on result:

other: Measured pH : pH=5 at the beginning of the both experiment and pH=9.0 at the end of the both experiment. The relative difference between the results of the two experiments is 0.88%, less than 30% as required by the OECD 105 - elution column method.

Details on results:

Mean of two solubility values obtained in two different experiments.
Concentrations observed at 25 mL/h: mean of the five last samples = 333.34 mg/L (The relative difference = 2.33% : less than 30% as required by the OECD 105 - elution column method)
Concentrations observed at 12.5 mL/h: mean of the five last samples = 336.29 mg/L (The relative difference = 2.48% : less than 30% as required by the OECD 105 - elution column method)

Preliminary test

The approximate solubility determined by the preliminary test was between 100 mg/L and 1g/L.

First experiment at a flow rate of 25 mL/h

The concentrations obtained as a function of time during this first experiment at 25 mL/h are presented in graph 1 : "Concentrations observed at 25 mL/h"

Measured pH :

-       at the beginning of the experiment : 5

-       at the end of the experiment : 9

The mean ± standard deviation of the five last samples is 333.34 ± 3.40 mg/L (The relative difference = 2.33% : less than 30% as required by the OECD 105 - elution column method)

 

The maximum difference observed in the five last samples is

           337.92 - 330.15 = 7.77 mg/L

 

The mean of these two maximum values is

           (337.92 + 330.15) / 2 = 334.04 mg/L

 

The relative difference, corresponding to the ratio of the maximum difference and the mean of the two maximum values is

           7.77 / 334.04 = 2.33 %

 

The five last sample concentrations do not differ by more than ± 30%, which means that equilibrium was established.

Second experiment at a flow rate of 12.5 mL/h

The concentrations obtained as a function of time during this second experiment are presented in graph 2 : "Concentrations observed at 12.5 mL/h".

Measured pH :

-       at the beginning of the experiment : 5

-       at the end of the experiment : 9

 

The mean ± standard deviation of the five last samples is 336.29 ± 3.00 mg/L (The relative difference = 2.48 % : less than 30% as required by the OECD 105 - elution column method)

 

The maximum difference observed in the five last samples is

           340.74 – 332.40 = 8.34 mg/L

 

The mean of these two maximum values is

           (340.74 + 332.40) / 2 = 336.57 mg/L

 

The relative difference, corresponding to the ratio of the maximum difference and the mean of the two maximum values is

8.34 / 336.57 = 2.48 %

 

The five last sample concentrations do not differ by more than ± 30%, which means that equilibrium was established.

Conclusions:

The mean of the two water solubility values obtained in the two different experiments is: (333.34 + 336.29) / 2 = 334.81 mg/L
The relative difference between the results of the two experiments is: (336.29 – 333.34) / 334.81 = 0.88 %
The mean values obtained from two experiments did not differ by more than 30%, so these results are valid.

Executive summary:

The determination of the water solubility of NOPOL was performed using the column elution method (OECD Guideline No 105).

Due to the physicochemical properties of the test item (stability, volatility, adsorption on glass), the samples were analyzed as soon as possible after sampling. This precaution is crucial in order to avoid underestimation and variations of the measured concentrations.

Two independent experiments were carried out. The concentration of the substance was regularly measured by HPLC-UV (High Performance Liquid Chromatography with UV detector). The water solubility of test item was recorded when the concentration reached a plateau.

The water solubility of NOPOL was 334.81 mg/L. This value is the mean of two independent measurements.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 October 2012 - 03 October 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other:

Remarks:

The determination of water solubility was performed using the slow stirring method adapted from OECD Guideline No 123. This study was considered as reliable with restrictions because not enough details on quantification of the substance were reported in the study report.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

other: adapted from OECD Guideline 123

Deviations:

no

Principles of method if other than guideline:

In a stirring vessel maintained at 20°C, ultra-pure water covered by a thin layer of the test item is slow stirred. The aim of this method is to prevent the formation of emulsions when saturating water. That can occur with the shake flask method and lead to a solubility overestimation. The water solubility is given by the mass concentration in water when this has reached a plateau as a function of time. A second experiment is performed in the same conditions.

GLP compliance:

no

Type of method:

other: slow-stirring method

Key result

Water solubility:

ca. 332.15 mg/L

Temp.:

20 °C

pH:

5

Remarks on result:

other: Mean of two solubility values obtained in two different experiments.

Details on results:

First experiment : mean of the five last samples = 333.62 mg/L. The relative difference = 2.94%. The five last sample concentrations do not differ by more than 30%, which means that equilibrium was established.
Second experiment : mean of the five last samples = 330.69 mg/L. The relative difference = 3.16%. The five last sample concentrations do not differ by more than 30%, which means that equilibrium was established.

Preliminary test

The approximate solubility determined by the preliminary test was between 100 mg/L and 1 g/L.

First experiment

The concentrations obtained as a function of time during this first experiment are presented in graph 1 : "Concentrations observed- first experiment"

Measured pH :

-       at the beginning of the experiment : 5

-       at the end of the experiment : 5

The mean ± standard deviation of the five last samples is 333.62 ± 3.98 mg/L (The relative difference = 2.94%)

 

The maximum difference observed in the five last samples is

           339.92 - 330.07 = 9.85 mg/L

 

The mean of these two maximum values is

           (339.92 + 330.07) / 2 = 335.00 mg/L

 

The relative difference, corresponding to the ratio of the maximum difference and the mean of the two maximum values is

           9.85 / 335.00 = 2.94 %

Second experiment

The concentrations obtained as a function of time during this second experiment are presented in graph 2 : "Concentrations observed- second experiment".

Measured pH :

-       at the beginning of the experiment : 5

-       at the end of the experiment : 5

 

The mean ± standard deviation of the five last samples is 330.69 ± 4.28 mg/L (The realtive difference = 3.16%)

 

The maximum difference observed in the five last samples is

           333.59 – 323.20 = 10.39 mg/L

 

The mean of these two maximum values is

           (333.59 + 323.20) / 2 = 328.40 mg/L

 

The relative difference, corresponding to the ratio of the maximum difference and the mean of the two maximum values is

10.39 / 328.40 = 3.16 %

 

Conclusions:

The mean of the two solubility values obtained in the two different experiments is: (330.69 + 333.62) / 2 = 332.15 mg/L
The relative difference between the results of the two experiments is: (333.62 – 330.69) / 332.15 = 0.88 %
The mean values obtained from two experiments did not differ by more than 30%, so these results are valid.

Executive summary:

The determination of the water solubility of NOPOL was performed using the slow stirring method adapted from OECD 123 guideline.

Due to the physicochemical properties of the test item (stability, volatility, adsorption on glass), the samples were analyzed as soon as possible after sampling. This precaution is crucial in order to avoid underestimation and variations of the measured concentrations.

Two independent experiments were carried out. The concentration of the substance was regularly measured by HPLC-UV (High Performance Liquid Chromatography with UV detector). The water solubility was recorded when the concentration reached a plateau.

The water solubility of NOPOL obtained by the slow-stirring method is 332.15 mg/L. This value is the mean of two independent measurements.

Description of key information

The water solubility was determined by two methods: the column elution method and the slow-stirring method. 
A mean value was calculated to give a representative estimation of the water solubility of the substance. 
The water solubility of nopol is 333.50 mg/L at 20°C.

Key value for chemical safety assessment

Water solubility:

333.5 mg/L

at the temperature of:

20 °C

Additional information

Two key studies were conducted: the first one according to OECD 105 Guideline (column elution method) and the second one adapted from OECD 123 Guideline (slow-stirring method).

The results are scientifically acceptable but not obtained under GLP (reliable with restrictions). The arithmetical mean value of the results of these 2 experiments can be retained as key value.