7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The available study was not conducted to the tiered structure of guideline OECD 111. During the analytical method development loss of the test substance was observed. However, the study provides adequate details to address this data point.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

Please see below

Principles of method if other than guideline:

A definitive rate of hydrolysis could not be calculated by QSAR. This estimation is based upon work performed under the analytical method development and determination of water solubility study. The half-life at environmentally relevant conditions is likely to be in the range of circa 1-2 days.

GLP compliance:

yes

Test material

Test material information

1

Reference substance name:

Cycloaliphatic Epoxy Resin ERL-422 1

IUPAC Name:

Cycloaliphatic Epoxy Resin ERL-422 1

Specific details on test material used for the study:

- Name of test material (as cited in study report): Cycloaliphatic Epoxide Resin ERL-4221
- Physical state: Colourless, almost transparent slightly viscous liquid
- Lot/batch No.: 87068
- Storage condition of test material: in the dark, at ambient temperature, in the container in which it was received.

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

Each tube was covered in aluminium foil and then tightly stoppered. Tubes were then placed on magnetic stirrers and heated in a water bath to approximately 30°C and continuously stirred. After 24 hours, solutions were removed at intervals and placed in a 20°C waterbath to equilibrate for approximately 24 hours (except for one flask, equilibrated for 43 hours) after which small known volumes were taken, centrifuged and the supernatant analysed for Cycloaliphatic Epoxide Resin ERL-4221.

Buffers:

Buffer solutions were prepared according to the OECD Guideline for Testing of Chemicals Method 111. Solutions were prepared at pH 4, 7 and 9 by dilution of 5000 uL of a 10,000 mg L-1 stock in acetone with 100 mL of the appropriate buffer to give a nominal concentration of 50 mg-1.

Estimation method (if used):

Hydrolysis as a function of pH is normally measured using the following procedure. Buffered solutions of the test substance at pH 4, 7 and 9 are prepared at a concentration not exceeding the lesser of 0.1 M or half the saturation concentration. Where the test substance is known to be unstable, investigations are made at 2 temperatures at each pH. Each reaction is analysed in time intervals to provide a minimum of 6 spaced data points between 20 and 70 % hydrolysis. Temperatures should be maintained to at least ± 0.1 °C.

Assuming that the reaction is pseudo-first order, the observed rate constant is given by the relationship,
Kobs= k.[H20]
and can be determined from the expression
Kobs = 2.303/t(log10 C0/Ct)
where t = time
and Co, Ct = concentrations of test substance at times O and t.
The units of this constant have the dimension of (time)-1 and the half-life of the reaction is given by:

t1/2= 0.693/Kobs

Where the log10 of the concentration is plotted against time, the slope of the resulting line gives the rate constant from the formula
Kobs = - slope 2.303

During the analytical method development of Cycloaliphatic Epoxide Resin ERL-4221, loss of test substance was observed. As photolysis was eliminated by comparison of solutions stored in dark and light, the rate of loss was attributed to hydrolysis. Solutions had been prepared to examine pH 4, 7 and 9 buffers for analytical interferences and were also analysed at 0 and 72 hours to give an approximate stability. This data was used to give an approximate half-life at each pH.

Details on test conditions:

A total of 20 solutions were prepared at a nominal 5000 mg L-1 by accurately weighing into 30 ml stoppered tubes approximately 125 mg Cycloaliphatic Epoxide Resin EKL-4221. A 25 ml volume of deionised water together with a magnetic follower were then added to each tube. Each tube was covered in aluminium foil and then tightly stoppered. Tubes were then placed on magnetic stirrers and heated in a water bath to approximately 30°C and
continuously stirred. After 24 hours, solutions were removed at intervals and placed in a 20°C waterbath to equilibrate for approximately 24 hours (except for one flask, equilibrated for 43 hours) after which small known volumes were taken, centrifuged and the supernatant analysed for Cycloaliphatic Epoxide Resin ERL-4221.

Duration of test

Duration of test 1

Duration:

72 h

pH:

4

Initial conc. measured:

50 mg/L

Duration of test 2

Duration:

72 h

pH:

7

Initial conc. measured:

50 mg/L

Duration of test 3

Duration:

72 h

pH:

9

Initial conc. measured:

50 mg/L

Number of replicates:

20

Positive controls:

not specified

Negative controls:

not specified

Statistical methods:

No details given

Results and discussion

Preliminary study:

No details supplied

Test performance:

No details supplied

Transformation products:

not specified

Details on hydrolysis and appearance of transformation product(s):

Estimation by QSAR:
A QSAR containing the exact structural rules for this substance does not currently exist. The most appropriate program was therefore selected. Due to the correct structural fragments not being available from the fragment library, the QSAR program substituted straight chain alkane fragments for the carbon rings in the molecule. The half-life for the substituted molecule (acid-catalysed) at 25OC was estimated to be 324 days at pH 7. The rate constant estimated did not include the neutral hydrolysis rate constant. For some epoxides, the neutral rate constant is the dominant hydrolysis rate at environmental pHs. If the neutral rate constant is important, the program under-estimates the actual rate. The half life of Cycloaliphatic Epoxide Resin ERL-4221 could therefore not be accurately obtained from the QSAR program.

Estimation using analytical method development data:
The measured conccntrations of Cycloaliphatic Epoxide Resln ERL4221 of each pH buffered solution at 0 and 72 hours for the analytical rnethod development are detailed inTable 1. All measured concentrations for the solutions are quoted to significant figures. The measured concentrations are plotagainst time. After 72 hours pH 4 demonstrated 91 %I loss; pH 7, 65 % loss; and pH 9, 69 % loss.

Estimation of half-life:
The log10 of the concentration for each pH was plotted against time. A straight line was fitted to the data, with the assumption that the rate of loss is pseudo-first order. From the slope of the resulting graphs, and using the equations, the half-life of Cycloaliphatic Epoxide Resin ERL-4221
at pHs 4,7 and 9 was estimated to be 21,47 and 42 hours respectively.

Other kinetic parameters:

No details given

Details on results:

Data interpretation:
The use of data from the analytical method development provides information for pH 4, 7 and 9 at room temperature. Temperatures were not maintained to within +/- 0.lC by use of a water bath. Results are based on two data points and use of this information also assumes the rate of loss to be linear. At 72 hours, the pH 4 concentration uses the limit of detection of 3.0 mg L-1, so will give the minimum rate of decay. Estimation from the method development data will therefore provide only an approximate rate of hydrolysis at each pH and must be treated with caution.

Estimation using solubility data:
The measured concentrations of Cycloaliphatic Epoxide Resin ERL-4221 in each flask for Run 1 of the solubility study are detailed in Table 2. All measured concentrations for the solutions are quoted to 3 significant figures.

The measured concentrations are plotted against time. The concentration of one of the flasks was not measured at 0 hours due to the requirement of the guideline to equilibrate at the lower test temperature, After equilibration of the first nominal 5000 mg 1.' flask for 24 hours at 20°C, the measured concentration had dropped to 3630 rng I"', ie
27 96 1 ~ ) s ~A.f ter 147.25 hours, the measured concentration had drnppcd to 200 mg I-', ie
96 5% loss. Run 1 of the study was terminated at this point, after 9 flasks had been
analysed.

Any other information on results incl. tables

Table1: Measured concentrations- Analytical Method Development

Time (Hours)	pH of vessel	Nominal Concentration (mg/L-1)	Measured Nominal Concentration (mg/L-1)	Log10Nominal Concentration (mg/L-1)	% Loss
0	4	50	33	1.52	-
72	4	50	3.0*	0.48	91
0	7	50	49	1.69	-
72	7	50	17	1.23	65
0	9	50	59	1.77	-
72	9	50	18	1.26	69

Measured concentrations are quoted to 2 significant figures

Note * Limit of detection of analytical method

Table 2: Measured concentrations – Run 1 of solubility study

Time (Hours)	pH of vessel	Nominal Concentration (mg/L-1)	Measured Nominal Concentration (mg/L-1)	Log10Nominal Concentration (mg/L-1)	% Loss
24	7.14	5000	3630	3.56	27
44	7.48	5000	2320	3.37	54
52	7.36	5000	3090	3.49	38
69	7.30	5000	875	2.94	82
76	7.36	5000	1360	3.13	73
93	7.32	5000	1310	3.12	74
101	7.25	5000	1520	3.18	70
116	7.32	5000	610	2.79	88
143	7.26	5000	200	2.30	96

Measured concentrations quoted to 3 significant figures

Each flask equilibrated for approximately 24 hours at 20°C, except for the 101 and 143 hour samples, equilibrated for 43 and 46 hours respectively, at 20°C

Applicant's summary and conclusion

Validity criteria fulfilled:

not specified

Remarks:

The half-life of Cycloaliphatic Epoxide Resin ERL-4221 was estimated to be 21,47 and 42 hours at pHs 4,7 and 9 respectively (method development) and 33 hours at pH 7 (solubility study). Half-life at environmentally relevant conditions, therefore, is likel

Conclusions:

The half-life of Cycloaliphatic Epoxide Resin ERL-4221 was estimated to be 21,47 and 42 hours at pHs 4,7 and 9 respectively (method development) and 33 hours at pH 7 (solubility study). Half-life at environmentally relevant conditions, therefore, is likely to be in the range of circa 1-2 days.

Executive summary:

The study was conducted according to OECD Guideline 111.

The half-life of Cycloaliphatic Epoxide Resin ERL-4221 was estimated by the QSAR program to be 324 days at pH 7. This value was not used due to the inability of the QSAR program to use the correct structural fragments in its calculation.

On the basis of other work performed on the test substance, it was apparent that hydrolysis proceeded at a much quicker rate. The half-life is thought to be more accurately estimated by use of information from the analytical method development and water solubility studies. The half-life of Cycloaliphatic Epoxide Resin ERL-4221 was estimated to be 21,47 and 42 hours at pHs 4,7 and 9 respectively (method development) and 33 hours at pH 7 (solubility study). Half-life at environmentally relevant conditions, therefore, is likely to be in the range of circa 1-2 days.