3-acetoxymethylen-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE
Aqueous Hydrolysis Rate Program (HYDROWIN), included in the EpiSuite tool of the US EPA.

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
N12C(=O)C(N)C1SCC(COC(=O)C)=C2C(=O)O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
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.  Structures are entered into HYDROWIN by SMILES (Simplified Molecular Input Line Entry System) notations.

Half-Life Estimates:
HYDROWIN estimates a half-life based upon the total base- or acid-catalyzed rate constant.  When a compound contains more than one hydrolyzable 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 (or 0.000001) is the OH- 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 OH- 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.  For example, if the base-catalyzed half-life at pH 8 is 1.0 day, it will be 10 days at pH 7, 100 days at pH 6, and 0.1 days at pH 9.  If the acid-catalyzed half-life at pH 7 is 1.0 day, it will be 10 days at pH 8, 100 days at pH 9, and 0.1 days at pH 6.

5. APPLICABILITY DOMAIN
The prediction methodology was developed for esters, carbamates, epoxides, halomethanes and alkyl halides.  
It must be remembered that the overall hydrolysis rate constant is equal to the acid-catalyzed  +  the base-catalyzed  + the neutral hydrolysis rate constants.  If the neutral hydrolysis rate constant is the dominant constant, the acid- or base-catalyzed estimate made by HYDROWIN will not give the true indication of the environmental hydrolysis rate!  
In many instances, the pH of the water will determine which rate constant is dominant.  This situation applies especially to epoxides, halomethanes and alkyl halides.
In addition to predicting hydrolysis rate constants, the version of HYDROWIN identifies a variety of chemical structure classes that hydrolyze and gives relevant experimental data.

6. ADEQUACY OF THE RESULT
The result is adequate for a first assessment of the hydrolysis rate of the substance. An experimental study will follow.

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR estimation of the half-life of the test item in water, applying the programme HYDROWIN v2.00 within the EpiSuite tool of the US EPA.

GLP compliance:

no

Specific details on test material used for the study:

CC(=O)OCC1=C(N2C(SC1)C(N)C2=O)C(=O)O

Transformation products:

not measured

pH:

7

Temp.:

25 °C

DT50:

231 d

Type:

not specified

pH:

8

Temp.:

25 °C

DT50:

23.1 d

Type:

not specified

Details on results:

Printout of the programme:
Input:
SMILES : N12C(=O)C(N)C1SCC(COC(=O)C)=C2C(=O)O
CHEM : 7-ACA
MOL FOR: C10 H12 N2 O5 S1
MOL WT : 272.28
------------------------------ EPI SUMMARY (v4.11) --------------------------
Physical Property Inputs:
Log Kow (octanol-water): -3.40
Boiling Point (deg C) : ------
Melting Point (deg C) : ------
Vapor Pressure (mm Hg) : 2E-007
Water Solubility (mg/L): 611
Henry LC (atm-m3/mole) : ------

Output:
Aqueous Base/Acid-Catalyzed Hydrolysis (25 deg C) [HYDROWIN v2.00]:
Total Kb for pH > 8 at 25 deg C : 3.467E-001 L/mol-sec
Kb Half-Life at pH 8: 23.141 days
Kb Half-Life at pH 7: 231.410 days
(Total Kb applies only to esters, carbmates, alkyl halides)

Conclusions:

Half-Life at pH 8:      23.1  days  
Half-Life at pH 7:     231  days  

Executive summary:

The hydrolysis rate at 25 °C of the test item was estimated by the QSAR programme HYDROWIN v2.00.

Half-Life at pH 8:      23.1  days

Half-Life at pH 7:     231  days

 

Description of key information

The hydrolysis rate at 25 °C of the test item was estimated by the QSAR programme HYDROWIN v2.00.

Half-Life at pH 8:      23.1  days  

Half-Life at pH 7:     231  days  

Key value for chemical safety assessment

Half-life for hydrolysis:

231 d

at the temperature of:

25 °C