(E)-3-methyl-5-cyclopentadecen-1-one

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:

2001-01-23 to 2001-03-08

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to an internationally recognised method, and under GLP. Purity and isomers composition are available from the notifier. However, the flask method is not the most suitable for substances of low solubility, and concentrations were determined versus a single calibration point. Therefore validation applies, but with restrictions.

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Version / remarks:

Commission Directive 92/69/EEC

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 28 February 2000. Signed on 26 April 2000

Type of method:

flask method

Key result

Water solubility:

0.899 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

0.2 g/L

Incubation duration:

72 h

Temp.:

20 °C

pH:

6.33

Preliminary test

The preliminary estimate of water solubility was 5.17 x 10^-4 g/L.

Definitive test

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

Sample number	Time shaken at ca 30°C(hours)	Time equilibrated at 20°C(hours)	Concentration(g/L)	Solution pH
1	24	24	8.90 x 10^-4	6.27
2	48	24	8.93 x 10^-4	6.31
3	72	24	9.13 x 10^-4	6.41

Mean concentration: 8.99 x 10^-4 g/L at 20.0 +/-0.5°C

Discussion

The water solubility has been calculated using the three main isomers of the test material (information provided by the sponsor). Recoveries of analysis (in triplicate) were undertaken at a nominal concentration of 1 mg/L and produced a mean recovery of 98.4%.

The preliminary water solubility test indicated that the column elution method should have been performed as the solubility was less than 1x10^-2 g/L. However, due to the physical nature of the test material, it was not possible to use this method; experience has shown that liquid test materials coated onto glass beads cause these beads to adhere together forming a plug within the column and thus preventing water circulation.

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)

Executive summary:

The water solubility of the test substance was measured under GLP, according to EU A6 guideline, flask method.

Measurements were performed by GC analysis. Results at 24, 48 and 72h were considered to be constant, so the mean value was retained.

The water solubility of the test substance is ca 0.9 mg/L at 20°C.

Reference 2

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 2002-09-03 to 2003-01-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

The study is not designed for water solubility measurement, but sufficient information is provided to consider it as reliable. Purity and isomers composition are available from the notifier. However, due deviations regarding water quality and equilibration time compared to the guideline, validation applies, but with restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

yes

Remarks:

reconstituted water; equilibration for 24h at 25°C only

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 28 February 2000. Signed on 26 April 2000

Type of method:

flask method

Water solubility:

0.69 mg/L

Temp.:

21 °C

pH:

7.8

Remarks on result:

other: Mean of individual results of fresh saturated stock solutions; SD +/- 0.12 mg/L

Sample	Nominal concentration (mg/L)	Concentration found (mg/L)	Expressed as a percent of the nominal concentration (%)
Day 0	1.0	0.833	83
Day 2	1.0	0.639 / 0.691*	64 / 69*
Day 5	1.0	0.776 / 0.733*	78 / 73*
Day 7	1.0	0.765 / 0.747*	77 / 75*
Day 9	1.0	0.619 / 0.587*	62 / 59*
Day 12	1.0	0.886	89
Day 14	1.0	0.542 / 0.653*	54 / 65 *
Day 16	1.0	0.520 / 0.526*	52 / 53*
Day 19	1.0	0.822	82

* analysis of duplicate frozen sample

Chemical analysis of the freshly prepared saturated solutions on Days 0, 2, 5, 7, 9, 12, 14, 16 and 19 showed measured concentrations to range from 0.523 mg/l to 0.886 mg/I (equivalent to 58% to 98% of the nominal concentration and the range quoted including the mean results from duplicate analysis). The variability in the measured test concentrations of the saturated solution was considered to be due to slight variations in preparation of the saturated solution, such as small differences in stirring rate and water quality (pH and dissolved salts). During production of the saturated solution, the head space in the stirring vessel was minimised and the stirrer was sealed onto the vessel to prevent losses due to the suspected volatile nature of the test material. In order to reduce such losses the test vessels were also covered with perspex lids. However, the suspected volatile nature of the test material may also have been a factor in the variability observed. Calculation of Henry's Law Constant gave a value of 10.5 thus indicating the potential for losses due to volatility.

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)

Executive summary:

The water solubility of the test substance was measured when preparing saturated stock solution, in reconstituted water, for ecotoxicity testing.

The sample was equilibrated for 24h, and measurements were performed by GC analysis. Several fresh stock solutions were prepared, so the mean value was retained.

The water solubility of the test substance was determined as ca 0.69 mg/L at 21°C.

Reference 3

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2008-01-21 to 2008-02-27 and 2011-01-28 to 2011-04-01

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

The study was conducted according to non-standard methods, however, the protocols are well described, and some validation elements are provided for the analytics. Moreover, purity is specified, with certificate of analysis provided, except for one batch. Therefore validation applies, but with restrictions.

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method A.6 (Water Solubility)

Qualifier:

no guideline followed

Principles of method if other than guideline:

Solubilisation by direct addition was measured in both deionised water and artificial media.
Solubilisation by headspace was measured in deionised water.

GLP compliance:

no

Type of method:

other: headspace

Water solubility:

0.94 mg/L

Temp.:

23.5 °C

Remarks on result:

other: direct addition, in both deionised and reconstituted water

Water solubility:

0.92 mg/L

Temp.:

20 °C

Remarks on result:

other: headspace technique, in deionised water

1. Direct addition

1.1 Preliminary experiments

In deionised water, after 4 days, the concentration of 4 replicate samples varied by 3%, compliant with an homogenous solution. Solubilisation of the test substance into reconstituted water led to homogeneous solutions after 48 hours. The homogeneity of the solution obtained lead to conclude that the test substance does not from any droplet into water. Direct addition in excess can therefore be used to obtained a saturated water solution which solubilised part can be quantified.

The 0.8 µL spiked solution took one week to reach 0.57 mg/kg. A better stirring accelerated the dissolution of the 0.5 µL test substance and the final concentration of 0.34 mg/kg was reached after 48 hours. In both cases, the final concentration did not correspond to the introduced amount, which illustrates the limits of this approach to generate solutions with a known concentration. It can be explained by the precision of the syringe and/or adsorption to the glass wall of the bottle.

1.2 Main test

In both waters, the concentrations reached saturation after 3 days, and remained constant over a few more days.

The average concentration measured after three days of equilibrium (day 3.5 to day 8) was 0.94 +- 10% mg/L for deionized water and synthetic water at 23.5°C.

day	ppb in deionised water	ppb in reconstitued water
1	681	742
2	905	785
3	870	938
3.5	972
6	958	897
7	910	972
8	912	951
Average (last 4 points)	938	940
confidence interval (alpha=0.05)	5%	10%

2. Headspace

Considering the stability of the signal after day 4 (range 3.4%, rsd=1.9%), saturation of the test substance in water was achieved.

The solubility of test substance in water was 0.92 mg/kg (±10 %) calculated as the average of both experiment results.

Experiment 1	0.99
Experiment 2	0.85
Average	0.92
	+/-10%

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)

Executive summary:

The water solubility of the test substance was measured by two different methods: direct addition, quite similar to OECD 105/EU A6 flask method, and headspace, i.e. solubilisation through a saturated gas phase in a closed system.

Extraction was performed with micro-techniques or with solvent, and concentrations were analysed by GC. Measurements as a function of time lead to the saturation plateau after 3 or 5 days, and the solubility results were very consistent, with 0.94 and 0.92 mg/L at room temperature respectively for direct addition and headspace. The mean value will be retained.

The water solubility of the test substance was determined as ca 0.93 mg/L at room temperature.

Reference 4

Endpoint:

water solubility

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

2008-12-15 to 2009-03-23

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

The study was conducted according to an internationally recognised method, and under GLP. No deviation affected the quality of the study. However, some experimental details are missing.

Justification for type of information:

Based on structural similarity (the source substance is one of the constituents of the target substance, together with isomers), both substances are not expected to have significantly different water solubility. Therefore the result of the study will be considered for the target substance.
Further information is included in IUCLID Section 13.

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 14 September 2009. Signed on 07 February 2011.

Type of method:

flask method

Specific details on test material used for the study:

Storage condition of test material: room temperature

Water solubility:

999 µg/L

Conc. based on:

test mat.

Loading of aqueous phase:

110 mg/L

Incubation duration:

>= 24 - <= 144 h

Temp.:

20 °C

Remarks on result:

other: pH was not recorded

Individual results are shown in the following table.

Stirring time*	Concentration [μg/L]				Mean -15%	Mean +15%
at 20°C [h]	vessel 1	vessel 2	vessel 3	mean	[μg/L]	[μg/L]
24	(796.2)**	971.5	923.3	947.4	805.3	1089.5
48	916.9	1048.9	1061.9	1009.3	857.9	1160.6
72	1001.1	960.1	1042.7	1001.3	851.1	1151.5
144	1101.8	953.8	1006.7	1020.8	867.7	1173.9
Overall mean (calc. from single values):				999.0

*after initial stirring time of 24 h at 30°C ** outlier (value not considered)

The results obtained at the 4 sampling times were in agreement (did not differ by more than 15 %). No tendency to increasing values with increasing equilibration times was observed. So the equilibration times used were long enough according to the test guideline and the test was satisfactory.

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L) (from analogue)

Executive summary:

The water solubility of the test substance was measured according to the OECD 105/EU A6 guideline, flask method.

Triplicate vessels were incubated with ca 110 mg/L at 30°C for 24h, then equilibrated at 20°C for 24 to 144h, with slow-stirring. Samples were extracted and analysed by GC-AED, calibrated with 6 standard solutions and an internal standard substance. Results were consistent (repeatability < 15%), so equilibrium was considered to be reached.

The water solubility (mean of 4 sampling times) was determined as 0.999 mg/L at 20°C.

Description of key information

The substance is considered to be slighlty soluble in pure water, with equilibrium reached from 24h. pH of saturated solution: 6.3.

Slightly less soluble in natural medium: 0.69 mg/L at 20°C. (used for ERA)

Key value for chemical safety assessment

Water solubility:

0.9 mg/L

at the temperature of:

20 °C

Additional information

Four reliable and consistent studies are presented:

- (Safepharm 2001), conducted according to EU guideline, flask method, and under GLP, was considered as the key study; the result is relevant for physico-chemical characterisation with standard testing, and is considered as key value for CSA;

- (Safepharm 2003) was designed for ecotoxicity testing, however preparation of saturated stock solution was sufficiently documented, and resulted in a solubility of 0.69 mg/L in reconstituted natural medium; for purpose of ERA, this value is considered more relevant that the above solubility in pure water;

- (Firmenich 2012) performed non-standard testing, but with robust scientific background, and supported the magnitude of order found above, with results ranging between 0.92 and 0.94 mg/L;

- (Fraunhofer 2011) was conducted on a similar substance, i.e. single isomer of the present multiconstituent, so the read-across was considered justified; it confirmed a solubility just below 1 mg/L.