bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2018-03-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

1. SOFTWARE
HYDROWIN software by US-EPA

2. MODEL (incl. version number)
HYDROWIN v2.00

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The most representative structure, O,O,O',O'-tetra-(2-ethylhexyl) trisulfane-1,3-diylbis(phosphonothioate), was chosen for the present estimation and entered into the model via ist SMILES code: C(CCCC)(CC)COP(=S)(OCC(CCCC)CC)SSSP(=S)(OCC(CCCC)CC)OCC(CCCC)CC.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The complete test sets of experimental data can be downloaded via the Internet at: http://esc.syrres.com/interkow/EpiSuiteData.htm
The Aqueous Hydrolysis Rate Program (HYDROWIN) estimates aqueous hydrolysis rate constants for the following chemical classes: esters, carbamates, epoxides, halomethanes, selected alkyl halides and phosphorus esters. HYDROWIN estimates acid- and base-catalyzed rate constants; with the exception of phosphorus esters, it does NOT estimate neutral hydrolysis rate constants. The estimated acid- and base-catalyzed rate constants are used to calculate hydrolysis half-lives and selected pHs. HYDROWIN requires only a chemical structure to make these predictions.
The prediction methodology for esters, carbamates, epoxides, halomethanes and alkyl halides was developed for the U.S. 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. Menlo Park, CA: SRI International (1987).
The prediction methodology for phosphorus esters is described in a separate help file: The HYDROWIN phoshporus compound update was limited to organic phosphorus compounds with the following structures:
O=PR1R2R3, and S=PR1R2R3
where R1, R2 and R3 are substituents with the first atom being carbon, oxygen, sulfur, nitrogen, or halogen.
- Defined domain of applicability: Estimation Methodology for the HYDROWIN Update: Mill et al. (1987) demonstrated that practical application of Taft steric factors, sigma star constants and Hammett sigma constants is effective in estimating hydrolysis rate constants of carboxylates, carbamates and epoxides. Depending upon the type of structure, Mill et al. (1987) included other descriptors such cyclic versus alicyclic, cis- versus trans-, and other structure-specific descriptors and equations.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Phosphates: The first structure type evaluated was the phosphate group because the database contained more data for phosphates than any other structure type. The final phosphate regressions for base-catalyzed and neutral hydrolysis are presented in the respective data collection. Statistically, the base-regression had a correlation coefficient (r2)of 0.925 and standard deviation of 0.372 while the neutral-regression had a correlation coefficient (r2)of 0.977 and standard deviation of 0.352.
For base-catalyzed hydrolysis of phosphates, the type of substituent to the oxygen (whether alkyl, olefinic or aromatic) was an important descriptor. For neutral hydrolysis, only aliphatic or aromatic was important (olefinic was not). In both cases, it is clear that an "aromatic" descriptor (in addition to the Hammett sigma values on the ring) is required to adequately predict phosphate hydrolysis with aromatic substituents attached to an oxygen.

5. APPLICABILITY DOMAIN
- Descriptor domain / Structural and mechanistic domains: The Aqueous Hydrolysis Rate Program (HYDROWIN) estimates aqueous hydrolysis rate constants for the following chemical classes: esters, carbamates, epoxides, halomethanes, selected alkyl halides and phosphorus esters.
Currently there is no universally accepted definition of model domain. However, 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 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.

6. ADEQUACY OF THE RESULT
The functional groups of most representative structure of the substance of interest are clearly contained in the model. Hence, the estimation is suitable to determine the hydrolysis rates of the substance which cannot be determined experimentally.

Data source

Reference

Reference Type:

other: software application

Title:

US EPA Aqueous Hydrolysis Rate Program (HYDROWIN)

Author:

U.S. Environmental Protection Agency 1200 Pennsylvania Ave., N.W. (Mail Code 7406M) Washington, DC 20460

Year:

2018

Bibliographic source:

http://www.epa.gov/oppt/exposure/pubs/episuite.htm

Materials and methods

Principles of method if other than guideline:

The computer program HYDROWIN (v2.00) by US-EPA is used for this estimation. The Aqueous Hydrolysis Rate Program (HYDROWIN) estimates aqueous hydrolysis rate constants for the following chemical classes: esters, carbamates, epoxides, halomethanes, selected alkyl halides and phosphorus esters.  HYDROWIN estimates acid- and base-catalyzed rate constants; with the exception of phosphorus esters, it does NOT estimate neutral hydrolysis rate constants.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

O,O,O',O'-tetra-(2-ethylhexyl) trisulfane-1,3-diylbis(phosphonothioate)

Molecular formula:

C32H68O4P2S5

IUPAC Name:

O,O,O',O'-tetra-(2-ethylhexyl) trisulfane-1,3-diylbis(phosphonothioate)

Specific details on test material used for the study:

SMILES Code: C(CCCC)(CC)COP(=S)(OCC(CCCC)CC)SSSP(=S)(OCC(CCCC)CC)OCC(CCCC)CC

Study design

Analytical monitoring:

not required

Results and discussion

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

5

DT50:

0.026 s

Dissipation DT50 of parent compound 2

pH:

6

DT50:

0.003 s

Dissipation DT50 of parent compound 3

pH:

7

DT50:

0 s

Dissipation DT50 of parent compound 4

pH:

8

DT50:

0 s

Dissipation DT50 of parent compound 5

pH:

9

DT50:

0 s

Dissipation DT50 of parent compound 6

pH:

10

DT50:

0 s

Applicant's summary and conclusion

Validity criteria fulfilled:

not applicable

Conclusions:

The study report describes a scientifically accepted calculation method for the hydrolysis constants using the US-EPA software HYDROWIN v2.00.No GLP criteria are applicable for the usage of this tool and the QSAR estimation is easily repeatable. The functional groups of most representative structure of the substance of interest are clearly contained in the model. Hence, the estimation is suitable to determine the hydrolysis rates of the substance which cannot be determined experimentally. The estimated half-life of the substance at pH 7 was estimated to be 0.0002567 sec, clearly indicating that the substance is hydrolytically unstable in water.

Executive summary:

The hydrolysis constants of the most relevant structure of the registered substance, i.e. O,O,O',O'-tetra-(2-ethylhexyl) trisulfane-1,3-diylbis(phosphonothioate), were estimated via HYDROWIN v2.00 software by US-EPA. The estimated half-life of the substance at pH 7 was estimated to be 0.0002567 sec, clearly indicating that the substance is hydrolytically unstable in water.