Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is highly insoluble in water

Justification for type of information:

In accordance with Annex VIII, column 2, 9.2.2.1 of Regulation (EC) No 1907/2006, a study of Hydrolysis as a funtion of pH dues not need to be conducted as the sbstance is highly insoluble in water.

Reference 2

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

December 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
Program HYDROWIN included in EPISUITE (Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.11)

2. MODEL (incl. version number)
The Aqueous Hydrolysis Rate Program (HYDROWIN) estimates aqueous hydrolysis rate constants for the following chemical classes: carboxylic acid esters, carbamates, epoxides, halomethanes, selected alkyl halides and phosphorus esters (under development). The simulated base- or acid-catalyzed rate constants are used to calculate hydrolysis half-lives at selected pHs.
 
The prediction methodology for esters, carbamates, epoxides, halomethanes and alkyl halides was developed for the Environmental Protection Agency and is outlined in the following document: Mill, T., Haag, W., Penwell, P., Pettit, T. and Johnson, H. "Environmental Fate and Exposure Studies Development of a PC-SAR for Hydrolysis: Esters, Alkyl Halides and Epoxides". EPA Contract No. 68-02-4254: SRI International (1987).
 
HYDROWIN uses linear free energy relationship (LFER) equations. The Taft equation is used in physical organic chemistry in the study of reaction mechanisms:
Log (ks/kCH3) = (ro*)(sigma*) + (delta)(Es),
where sigma* and Es are Taft constant and steric factor, respectively, ks/kCH3is the ratio of the rate of the substituted reaction compared to the reference reaction, ro* is the sensitivity factor for the reaction to polar effects and delta is the sensitivity factor for the reaction of steric effects. In the special case of benzoic acid derivatives with meta- and para- substituents, the reaction takes the form of the Hammett reaction: Log (ks/kCH3) = (roX)(sigmaX),
where sigmaX is the Hammet constant and roX is the reaction constant. In HYDROWIN, sigmaX-Meta and sigmaX-para Hammet values apply only to a phenyl ring that is attached directly to the ester or carbamate function.

 3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
DPE777777 (constituent #1): O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

DPE777779 (constituent #2):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

DPE777799 (constituent #3):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE777999 (constituen #4):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE779999 (constituent #5):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE799999 (constituent #6):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)C

DPE999999 (constituent #7):
O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)


4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL

1. Defined endpoint: log Kb – hydrolysis base-catalyzed rate constant
Epoxides: log Ka – hydrolysis acid-catalyzed rate constant.
For all classes: It is assumed that the calculated rate constant is the predominant rate constant and the other rate constants including the neutral rate constant are negligible.
 
2. Unambiguous algorithm.
Carboxylic acid esters R1-C(=O)-O-R2:
log Kb = 0.92 Es(R1) + 0.31 Es(R2) + 2.16 sigma*(R1) + 2.30 sigma*(R2) + 2.10 sigmaX(R1) + 1.25 sigmaX(R2) + 1.25 sigmaX(R2) + 2.67,
where Es – steric factor at the designated position (R1 or R2), sigma* the Taft constant at R1 or R2, sigmaX the Hammet constant at R1 or R2. A complete list of the parameters is available in the program documentation.
 
For all classes: HYDROWIN estimates a half-life based upon the total base- or acid-catalyzed rate constant. When a compound contains more than one hydrolysable group, individually estimated rate constants are summed to yield the total rate constant. The half-life for base-catalyzed rate constants is calculated at pH 8 from the following equation:
Half-life = 0.6931 / (Kb)(1.0E-6)
where 1.0E-6 is the concentration in water at pH 8. A half-life at pH 7 is also reported. The half-life for acid-catalyzed rate constants is calculated at pH 7 where both the and H+ concentrations are 1.0E-7. Half-lives at different pHs can be determined simply by moving the half-life decimal point one position right or left for each pH unit change.
 
3. Applicability domain: Currently there is no universally accepted definition of model domain. Users may wish to consider the possibility that aqueous hydrolysis estimates are less accurate for compounds that have a functional group(s) or other structural features not represented in the training set.
 
The underlying program methodology is dependent upon accurate values of Taft steric factors, Taft sigma star constants and Hammett sigma constants. HYDROWIN uses a library of 300 fragments for which corresponding values are available. The fragments and values are identified in HYDROWIN’s on-line user guide help file. The library consists primarily of common fragments such as linear alkyl, branched alkyl, cyclo-alkyl, halo-alkyls, phenyl, and common oxygen, nitrogen and sulfur derivatives (such as ethers, thioethers, and alkyl-amines). Realistically, three hundred fragments is only a small fraction of the possible variations of fragments that can exist in chemical structures.
 
When HYDROWIN identifies a fragment that does not occur in the fragment list, it uses an analogous fragment that is in the list. A warning message is provided. The substitute selected by the program is expected to be the best substitute selection.
 
4. Appropriate measures of goodness of fit, robustness and predictivity.
Carboxylic acid esters: N = 124 compounds, R2 = 0.965
 
As yet, the QSAR equations in HYDROWIN have not been rigorously tested with external validation datasets. Currently, the number of chemicals with evaluated hydrolysis rates is relatively small in number, and the available data have been used to train the QSAR regressions.
 
5. Mechanistic interpretation if possible: The model is developed based on profound knowledge of the different reaction pathways and assigns incremental values that are specific for the mechanism under consideration. The HYDROWIN model uses linear free energy relationship (LFER) equations.

5. APPLICABILITY DOMAIN
The functional groups present in the constituents of the substance (ester groups) are included in the model's dataset. Each constituent has the following generic structure: R1-C(=O)-O-R2
R1 = n-hexyl for the n-heptanoic esters. n-Hexyl fragment is included in the fragment library and therefore its contribution to the calculated log Koc is accurate within the model.
R1 = 3,5,5-trimethyloctyl for the 3,5,5-trimethylhexyl esters. This fragment is not included in the fragment library and iso-Butyl fragment is used instead. The substitute is a shorter carbon chain with less branching.
R2 = DPE pentaester. This fragment is not included in the fragment library and -CH2-(t-Bu) fragment is used instead, which contains the same structure than the DPE actual fragment up to the 3 closest carbon atoms.

Principles of method if other than guideline:

Calculation based on HYDROWIN v2.00, Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

pH:

7

Temp.:

25 °C

DT50:

1.766 yr

Remarks on result:

other:

Remarks:

constituent #1

pH:

8

Temp.:

25 °C

DT50:

64.5 d

Remarks on result:

other:

Remarks:

constituent #1

pH:

7

Temp.:

25 °C

DT50:

2.011 yr

Remarks on result:

other:

Remarks:

constituent #2

pH:

8

Temp.:

25 °C

DT50:

73.462 d

Remarks on result:

other:

Remarks:

constituent #2

pH:

7

Temp.:

25 °C

DT50:

2.335 yr

Remarks on result:

other:

Remarks:

constituent #3

pH:

8

Temp.:

25 °C

DT50:

85.297 d

Remarks on result:

other:

Remarks:

constituent #3

pH:

7

Temp.:

25 °C

DT50:

2.784 yr

Remarks on result:

other:

Remarks:

constituent #4

pH:

8

Temp.:

25 °C

DT50:

101.679 d

Remarks on result:

other:

Remarks:

constituent #4

pH:

7

Temp.:

25 °C

DT50:

3.446 yr

Remarks on result:

other:

Remarks:

constitueny #5

pH:

8

Temp.:

25 °C

DT50:

125.849 d

Remarks on result:

other:

Remarks:

constituent #5

pH:

7

Temp.:

25 °C

DT50:

4.52 yr

Remarks on result:

other:

Remarks:

constituent #6

pH:

8

Temp.:

25 °C

DT50:

165.092 d

Remarks on result:

other:

Remarks:

constituent #6

pH:

7

Temp.:

25 °C

DT50:

6.568 yr

Remarks on result:

other:

Remarks:

constituent #7

pH:

8

Temp.:

25 °C

DT50:

239.9 d

Remarks on result:

other:

Remarks:

constituent #7

Details on results:

- Total Kb for pH > 8: 31.244E-001 L/mol-sec
- Temperature for which rate constant was calculated: 25 °C
- Computer programme: HYDROWIN v2.00
- Fragments on this compound are not available from the fragment library. Substitute(s) have been used:
ESTER: R1-C(=O)-O-R2
R1: n-Hexyl-
R2: -CH2-(t-Bu)

Description of key information

Due to the chemical structure and the low water solubility (< 0.1 mg/L) of the substance EC 945 -883 -1, hydrolysis does not contribute to abiotic degradation in the aquatic environment.

Additional information

No experimental studies investigating the abiotic hydrolysis of Dipentaerythritol hexaesters of 3,5,5 -trimethylhexanoic and n-heptanoic acids are available. However, in accordance with Annex VIII, column 2, 9.2.2.1. of Regulation (EC) No 1907/2006, testing is not required since the substance is highly insoluble in water (< 0.1 mg/L).

A supporting QSAR calculation (HYDROWIN v2.00) indicates that hydrolysis is a negligible pathway for the environmental fate of Dipentaerythritol hexaesters of 3,5,5 -trimethylhexanoic and n-heptanoic acids in the environment (DT50 > 1 yr (pH 7).