Isotridecyl 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:

12/4/2017 to 3/1/2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

Adaption to the slow stir 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.

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Remarks:

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.

Specific details on test material used for the study:

The test substance, Isotridecyl 3,5,5-Trimethylhexanoate was allocated the code ESTS 67/17
for reference throughout the study.

Name: Isotridecyl 3,5,5-Trimethylhexanoate
CAS number: 59231-37-7
EC number: 261-675-7
Physical state: Clear colourless liquid
Sponsor lot number: P7639
Purity: Assumed to be 100%*
Molecular weight: 340.59
Arrival date: 1 March 2017
Expiry date: 1 December 2018
Storage conditions: Room temperature (15 to 30°C)

* No supporting information supplied.
Analytical Procedure
The procedure, SMV (PC) 3201859-01V, for determining the content of Isotridecyl 3,5,5Trimethylhexanoate in double-distilled water was developed in this study. The method used was Gas chromatography (GC) with flame ionisation detection (FID). A summary of the analytical procedure is shown in Appendix 2.
The method was assessed against the criteria detailed in the following sections:
Specificity
Blank solutions were prepared and run with the rest of the validation samples, to assess freedom from any interfering (co-chromatographic) peaks.
Sensitivity
The limit of quantification (LOQ) was described as the lowest fortification level where acceptable precision and accuracy data were obtained.
Linearity
The analytical calibration covered a range appropriate for the anticipated concentration of Isotridecyl 3,5,5-Trimethylhexanoate in double-distilled water. The linearity of detector response for standard solutions over the concentration range (minimum of five different concentrations) was determined by least squares linear regression with a 1/x weighting.
Accuracy and Precision (Repeatability)
For procedure SMV (PC) 3201859-01V, the accuracy and precision of the analysis was determined by analysis of five replicates of prepared sample solutions. The sample solutions were prepared at the following concentrations 1, 10 and 100 µg/mL by spiking into double-distilled water from a stock solution of Isotridecyl 3,5,5-Trimethylhexanoate in acetone. The solutions were super saturated with sodium chloride (0.4 g/mL) and then extracted with hexane, centrifuged a speed setting of 2500 rpm for 5 minutes and the hexane layer analysed. The volume of hexane chosen was such that the concentration was within the calibration line.
Acceptance criteria (SANCO/3029/99 rev. 4.) Accuracy (recovery)
The mean recovery values should be within 70 to 110% (ideally with the mean in the range 80 to 100%).
A suitable test for outliers may be applied to the accuracy data, for example the Grubbs or Dixons Tests.
Precision (repeatability)
The precision percent relative standard deviation (%RSD) should be ≤ 20%.

Key result

Water solubility:

< 0.003 µg/L

Conc. based on:

test mat.

Incubation duration:

14 d

Temp.:

20 °C

pH:

> 5.6 - < 6.16

Remarks on result:

other:

Remarks:

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.

Details on results:

In all water solubility samples Isotridecyl 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.
The water solubility was expected to be about 10 µg/mL. Using the conditions in the validated method nothing was detected in the water on the first two sampling occasions. As a consequence the 10 mL of the water was extracted with 0.5 mL of hexane and the calibration line adjusted to 0.05 to 10 µg/mL. Under these conditions nothing was detected in the water.
Surface tension measurements on a 90% solution from Vessel 1 tested in triplicate gave 72.5, 72.5 and 72.5 mN/m at 20°C, compared to the control, three determinations at 73 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 test substance 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 8.07 NTU.
Qualitative analytical assessments were made, first by centrifugation at 2500 rpm and then filtering through a 0.45 µm PTFE filter. A spiked sample of water was also filtered in like manner. Nearly 100% of the test substance was retained on the filter. This would suggest the test substance 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 µg/ml. This was considered unreliable, because of the issue of micro-emulsions and test substance adhering to the sides of the sampling tube that might have been taken up when sampling the centrifuged material. Centrifugation was therefore considered to be inappropriate.
No further testing was performed on the other vessels and it concluded that the water solubility of the slow stir approach was valid. The LOQ for the method was 1 µg/mL and the lowest standard was 0.05 µg/mL (the Limit of detection, LOD). Taking into account the dilution factor of 0.05 the equivalent concentration to the LOD was 0.0025 µg/mL. It was therefore concluded that the water solubility was less than the LOD at 0.0025 µg/mL.
Example chromatograms for the water solubility samples are shown in Figure 14 and Figure 15.

Calculated Values
Calculated values for the water were determined using the WSKOW and WATERNT models in the EPI ver 4.1 software.
The calculated, estimated water solubility values were:
0.00006052 mg/L at 25°C using the WSKOW model.
0.00022436 mg/L at 25°C using the WATERNT model.
The full EPI Ver. 4.1 data are shown in Appendix 3.

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.

Conclusions:

Water solubility OECD 105:
< 0.0025 µg/mL determined experimentally

Executive summary:

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 inFigure 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 10 µg/mL, but might be considerably lower than this due to the possibility of the formation of a micro emulsion.

Due to the characteristics of the test substance, it was not possible to determine experimental values for the partition coefficient (log Pow) or the hydrolysis, in addition the water solubility was below the limit of quantification of the analytical method. It was decided that estimated values would be calculated for the partition coefficient and hydrolysis using appropriate software and as part of this procedure also produced estimated values for water solubility these have also been reported.

The octanol-water partition coefficient (as log Kow), hydrolysis and water solubility are also predicted using the Estimation Program Interface (EPI ver. 4.1) developed by the United States Environmental Protection Agency (US EPA) (US EPA 2012). EPI Suite is used in the US EPA Pollution Prevention framework for the review of pre-manufacturing notice chemicals under the Toxic Substance Control Act (TSCA) and for the evaluation of the potential for chemicals to have persistent, bioaccumulative and toxic properties.

Water solubility OECD 105:

< 0.0025 µg/mL determined experimentally

Reference 2

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)
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 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 0.00022436 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 0.00022436 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 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 0.00006052 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 0.00006052 mg/l at 25 °C.

Description of key information

Water solubility OECD 105 < 0.0025 µg/mL determined experimentally

0.00006052 mg/L at 25°C EPI ver. 4.1 WSKOW

calculated value

0.00022436 mg/L at 25°C EPI ver 4.1 WATERNT

calculated value

Key value for chemical safety assessment

Water solubility:

0 mg/L

at the temperature of:

25 °C

Additional information

Water solubility OECD 105 < 0.0025 µg/mL determined experimentally

0.00006052 mg/L at 25°C EPI ver. 4.1 WSKOW

calculated value

0.00022436 mg/L at 25°C EPI ver 4.1 WATERNT

calculated value