Isodecyl 3,5,5-trimethylhexanoate

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

11 April 2017 - 12 July 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

27 July 1995

Deviations:

yes

Remarks:

adapted with the slow stiring method outlined in OECD 123 as the equilibrium shake flask method.

Principles of method if other than guideline:

This procedure conforms to those outlined in OECD Guideline 105, with the adapting of the slow stir method outlined in OECD 123 as the equilibrium shake flask method. A schematic diagram of a slow stir vessel is shown in Figure 1. The slow stir method allows for the determination of the water solubility of liquids less dense than water, without generating emulsions, therefore obviating the need for filtration or centrifugation, as the sample is taken via a tap at the bottom of the vessel. Preliminary work suggested that the water solubility was about 0.05 µg/mL; but might have been considerably lower than this due to the possible formation of a micro emulsion. This adaptation was considered not to effect the reliability of the test result.

GLP compliance:

yes (incl. QA statement)

Type of method:

other: Equilibrium shake flask method

Specific details on test material used for the study:

The test substance, Isodecyl 3,5,5-Trimethylhexanoate was allocated the code ESTS 68/17
for reference throughout the study.
Name: Isodecyl 3,5,5-Trimethylhexanoate
Physical state: Clear colourless liquid
Purity: 100% (provided by Sponsor)
Molecular weight: 298.51
Arrival date: 1 March 2017
Storage conditions: Room temperature (15 to 30°C)
No certificate of analysis was available for the test substance. The purity and expiry date were supplied by the Sponsor via e-mail.

Water solubility:

< 0.01 mg/L

Conc. based on:

test mat.

Incubation duration:

17 d

Temp.:

20 °C

pH:

>= 5.49 - <= 5.97

Remarks on result:

not determinable

Remarks:

The result was below the limit of quantification.

Details on results:

In all water solubility samples Isodecyl 3,5,5-Trimethylhexanoate chromatographic response was not distinguishable from the control sample. The test temperature was 20 ± 0.5°C (min 19.9, max 20.3°C). The sampling times and pH measurements are shown in Table 4.

For the analysis 10 mL of water was taken from the vessels and 4 g of sodium chloride added and extracted with hexane (0.5 mL). The control was treated in like manner. This was a concentration factor of 20.

The chromatograms of the controls and the samples were essentially the same and therefore could not be reliably integrated. The peaks present in the control were due to residual impurities from the sodium chloride, as they are not present in the hexane, but the sodium chloride was required for the partition of the test substance from the water to the hexane. The limit of quantitation was 0.01 µg/mL and with a concentration factor of 20 the response should be 0.2 µg/mL, which would mitigate the peaks present in the control.
This demonstrates the water solubility is lower than 0.01µg/mL. Comparative chromatograms are shown in Figure 14 and Figure 15.

Surface tension measurements on a 90% solution from Vessel 1 tested in triplicate gave a mean value of 72.7 mN/m at 20°C, compared to the control, three determinations at 73.0 mN/m and double-distilled water at 73 mN/m. This adds more evidence supporting very low solubility as even low solubility non-surface active materials would give a small difference in surface tension.

The stirring speed in the vessels was increased to 1000 rpm on 3 July 2017 at 11:30 hrs to induce turbulence. Stirring was stopped on 4 July 2017 at 8:15 hrs. A sample from vessel 1 was taken for some preliminary work after 30 minutes standing, the aqueous layer was an emulsion with TS adhering to the sides of the vessel. The sample was a fine emulsion, which was confirmed when the turbidity was measured and found to be 5.61 NTU. Qualitative analytical assessments were made, first by filtering through a 0.45 µm PTFE filter. A spiked sample of water was also filtered in like manner. About 70% of the TS were retained on the filter. This would suggest the TS is absorbed onto the filter, this avenue was not progressed further.

Centrifugation for 5 minutes at a setting of 2500 rpm, gave what appeared to be a clear solution. Analysis of this solution gave a concentration of about 1.3 µg/ml. This value was orders of magnitude higher than expected. It was considered that centrifugation was not a viable method of separation because of the issue of micro-emulsions and test substance adhering to the sides of the sampling tube. This meant that undissolved test substance could be taken up when sampling most of the centrifuged material.

No further testing was performed on the other vessels and it was concluded that the water solubility of the slow stir approach was valid and the water solubility was less than the LOQ at 0.01 µg/mL.

Table 4: Water solubility

Date	Time	pH
		Vessel 1	Vessel 2	Vessel 3
16-Jun-17	10:35	5.82	5.61	5.78
16-Jun-17	10:50	Test substance added to vessels
19-Jun-17	13:00	5.84	5.68	5.91
23-Jun-17	11:20	5.84	5.69	5.97
26-Jun-17	10:30	5.81	5.64	5.92
27-Jun-17	13:30	Sample taken from vessel 1 for surface tension
03-Jul-17	11:30	5.68	5.49	5.84

Conclusions:

The test material was determined to have a water solubility below the limit of quantification (<0.01 mg/l).

Executive summary:

In this guideline (OECD 105, adapted with OECD 123) study conducted with GLP certification the test material was determined to have a water solubility below the limit of quantification (<0.01 mg/l).

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

11 April 2017 - 12 July 2017

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
EPISUITE

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: O=C(CC(CC(C)(C)C)C)OCCCCCCCC(C)C
NAME: Hexanoic acid, 3,5,5-trimethyl-, isodecyl ester

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Log Water solubility at 25 °C (moles/l) and Water solubility at 25 °C (mg/l)
- Unambiguous algorithm:
Results of two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating water solubility of any organic compound:

log WatSol (moles/L)  = Σ(fi * ni)  + Σ(cj * nj)  +  0.24922

(n = 1128,  correlation coef (r2) = 0.940,  standard deviation = 0.537, avg deviation = 0.355)

where   Σ(fi * ni)   is the summation of  fi  (the coefficient for each atom/fragment)   times  ni  (the number of times the atom/fragment occurs in the structure) and Σ(cj * nj)  is the summation of  cj  (the coefficient for each correction factor) times  nj  (the number of times the correction factor is applied in the molecule).

Appendix D lists (for each fragment and correction factor) the coefficient value, the number of compounds in the training set containing the fragment or correction factor and the maximum number of instances of that fragment in any of the 1128 training set compounds (the minimum number of instances is of course zero, since not all compounds had every fragment).
- Defined domain of applicability: See "Accuracy-Domain.pdf" appended below.


5. APPLICABILITY DOMAIN
See "Accuracy-Domain.pdf" appended below.

6. ADEQUACY OF THE RESULT
The QSAR model was used as the water solubility of the test substance fell below the limit of quantification in an experimental test. The result is of the order of magnitude indicated in the experimental test. The model has been fully validated by a reputable government agency. The result is therefore considered adequatly reliable for use as the basis of the classification and labelling and PBT/vPvB assessment.

Qualifier:

no guideline required

Principles of method if other than guideline:

The QSAR model was used as the water solubility of the test substance fell below the limit of quantification in an experimental test. The result is of the order of magnitude indicated in the experimental test. The model has been fully validated by a reputable government agency. The result is therefore considered adequatly reliable for use as the basis of the classification and labelling and PBT/vPvB assessment.

GLP compliance:

yes (incl. QA statement)

Water solubility:

0.008 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: QSAR: pH not determined

Conclusions:

The QSAR model WATERNT v1.01 calculated the water solubility of the test material to be 0.0080304 mg/l at 25 °C.

Executive summary:

In this validated QSAR (WATERNT) study, conducted with GLP certification, the water solubility of the test material was determined to be 0.0080304 mg/l at 25 °C.

Reference 3

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

11 April 2017 - 12 July 2017

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
EPISUITE

2. MODEL (incl. version number)
WSKOWWIN v1.42 (september 2010)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS NUMBER: 56231-35-5
SMILES: O=C(CC(CC(C)(C)C)C)OCCCCCCCC(C)C
NAME: Hexanoic acid, 3,5,5-trimethyl-, isodecyl ester

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Water Solubility at 25°C
- Unambiguous algorithm:
WSKOWWIN estimates water solubility for any compound with one of two possible equations.  The equations are equations 19 and 20 from Meylan and Howard (1994) or equations 11 and 12 from the journal article (Meylan et al., 1996).  The equations are:

    log S (mol/L)  =  0.796 - 0.854 log Kow - 0.00728 MW + ΣCorrections

    log S (mol/L)  =  0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + ΣCorrections

(where MW is molecular weight, Tm is melting point (MP) in deg C [used only for solids]) ... Summation of Corrections (ΣCorrections) are applied as described in Appendix E.   When a measured MP is available, that equation is used; otherwise, the equation with just MW is used.
- Defined domain of applicability: See "Accuracy-Domain.pdf" appended below.


5. APPLICABILITY DOMAIN
See "Accuracy-Domain.pdf" appended below.

6. ADEQUACY OF THE RESULT
The QSAR model was used as the water solubility of the test substance fell below the limit of quantification in an experimental test. The result is of the order of magnitude indicated in the experimental test. The model has been fully validated by a reputable government agency. The result is therefore considered adequatly reliable for use as the basis of the classification and labelling and PBT/vPvB assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The QSAR model was used as the water solubility of the test substance fell below the limit of quantification in an experimental test. The result is of the order of magnitude indicated in the experimental test. The model has been fully validated by a reputable government agency. The result is therefore considered adequatly reliable for use as the basis of the classification and labelling and PBT/vPvB assessment.

GLP compliance:

yes (incl. QA statement)

Water solubility:

0.002 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

Remarks on result:

other: QSAR: pH not determined

Conclusions:

The QSAR model WSKOWWIN v142 calculated the water solubility of the test material to be 0.001946 mg/l at 25 °C.

Executive summary:

In this validated QSAR (WSKOWWIN) study, conducted with GLP certification, the water solubility of the test material was determined to be 0.001946 mg/l at 25 °C.

Description of key information

Studies conducted to recognised testing guidelines with GLP certification, or using validated QSAR models relevant to this substance type and structure with GLP certification.

Key value for chemical safety assessment

Water solubility:

0.002 mg/L

at the temperature of:

20 °C

Additional information

The water solubility of the test substance was determined to be <0.01 mg/l at 20 °C, under the conditions of the test, which was less than the LOQ. The calculated, estimated water solubility values were:

0.001946 mg/L at 25°C using the WSKOWWIN model.

0.0080304 mg/L at 25°C using the WATERNT model

Both models were run in the EPISUITE software package.

The lowest, and therefore most conservative, result was returned by WSKOWWIN. This value was therefore selected as the key value for the water solubility endpoint.