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Environmental fate & pathways

Hydrolysis

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Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-05-04 to 2011-08-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of inspection 2011-07-19 to 2011-07-21; Date of certificate 2011-08-31
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- The sample solutions were taken at various times and the pH of each solution recorded.
- The concentration of the sample solution was determined by gas chromatography (GC).
Buffers:
See table below
Details on test conditions:
PREPARATION OF SAMPLES
- Sample solutions were prepared in stoppered flasks at a nominal concentration of 3.0 x 10E-3 g/L in three buffer solutions.
- A 1 % co-solvent of acetonitrile was used to aid solubility.
- Test solutions were split into individual vessels for each data point.
- Solutions were shielded from light whilst maintained at the test temperature.

SAMPLES
- Duplicate aliquots (A and B) of sample solution were diluted by a factor of 4 using acetonitrile for pH 4 and pH7 and using acidified acetonitrile for pH 9.

STANDARDS
- Duplicate standard solutions of test material were prepared in acetonitrile:relevant buffer solution (75:25 v/v) for pH 4 and pH7.
- Duplicate standard solutions of test material were prepared in acidified acetonitrile: pH 9 buffer (75:25 v/v) for pH 9.
- Nominal concentrations were 1.5 mg/L.

MATRIX BLANKS
- Acetonitrile: relevant buffer solution (75:25 v/v) for pH 4 and pH7.
- Acidified acetonitrile: pH 9 buffer (75:25 v/v) for pH9.

PRELIMINARY TEST/TIER 1
- Sample solutions at pH 4, 7 and 9 were maintained at 50.0 ± 0.5 ºC.
Duration:
264 h
pH:
4
Temp.:
50 °C
Initial conc. measured:
0.003 g/L
Duration:
264 h
pH:
7
Temp.:
50 °C
Initial conc. measured:
0.001 g/L
Duration:
48 h
pH:
9
Temp.:
50 °C
Initial conc. measured:
0.003 g/L
Duration:
48 h
pH:
9
Temp.:
40 °C
Initial conc. measured:
0.003 g/L
Duration:
29 h
pH:
9
Temp.:
30 °C
Initial conc. measured:
0.003 g/L
Duration:
24 h
pH:
9
Temp.:
30 °C
Initial conc. measured:
0.003 g/L
Duration:
48 h
pH:
9
Temp.:
25 °C
Initial conc. measured:
0.002 g/L
Duration:
96 h
pH:
9
Temp.:
20 °C
Initial conc. measured:
0.003 g/L
Number of replicates:
Two
Positive controls:
no
Negative controls:
no
Statistical methods:
TREATMENT OF RESULTS
- The common logarithm of concentration (g/L) versus time (hours) was plotted for pH 9 at 20, 25, 30, 40 and 50 ºC (see Figures 10.1 to 10.5 inclusive plus Figure 10.7, attached).
- The rate constant and half life were calculated.
- The natural logarithm of the rate constant was plotted against the reciprocal of temperature (K) and the rate constant and half-life at 25 ºC were obtained by extrapolation (see Figure 10.6, attached).

SAMPLE SOLUTION CONCENTRATION
- The main peak area of each standard was corrected to a nominal concentration of 1.5 mg/L and the mean value taken.
- Sample concentration (g/L) was calculated using the equation Cspl = ((Pspl / Pstd) x Cstd) x D x (1 / 1000))
- Sample concentration (g/L) = Cspl
- Mean peak area of sample solution = Pspl
- Mean peak area of standard solution (corrected to nominal standard concentration) = Pstd
- Nominal standard concentration (1.5 mg/L) = Cstd
- Sample dilution factor (4) = D

ESTIMATION OF HALF-LIFE
- From the graph of Log10 concentration (g/L) versus time, the rate constant was calculated using the equation kobs = - slope x 2.303 where kobs = rate constant (hours-1).
The rate constant at 25 ºC was calculated from the Arrhenius plot by taking the anti-log of the result obtained using the equation y = A + E.x
- Natural logarithm of the rate constant (hours-1) at 25 ºC = y
- Intercept of the Arrhenius plot = A
- Slope of the Arrhenius plot = B
- Reciprocal of the temperature (25 ºC) in K (3.354 x 10E-3) = x
- The half-life was obtained from the rate constant using the equation half-life = 0.693 / kobs
- Rate constant (hours-1) = kobs
Preliminary study:
- Results from the preliminary test showed that it was necessary to undertake further testing at pH9, with solutions being maintained at 20.0, 25.0, 30.0 and 40.0 ± 0.5 ºC.
Transformation products:
not measured
pH:
4
Temp.:
25 °C
DT50:
> 1 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: < 10 % hydrolysis over 5 days at 50 ºC
pH:
7
Temp.:
25 °C
DT50:
> 1 yr
Type:
(pseudo-)first order (= half-life)
Remarks on result:
other: < 10 % hydrolysis over 5 days at 50 ºC
pH:
9
Temp.:
25 °C
Hydrolysis rate constant:
0 s-1
DT50:
15.5 h
Type:
(pseudo-)first order (= half-life)

VALIDATION

- Linearity of the detector response with respect to concentration was assessed over the nominal concentration range of zero to 1.5 mg/L for each pH.

- Satisfactory correlation coefficients of 0.998, 0.999 and 1.000 were obtained.

MATRIX BLANKS

- No significant peaks were observed at the approximate retention time of the test material on analysis of any matrix blank solutions.

DISCUSSION

- Preliminary investigations showed that the test material was prone to volatilisation and/or adsorption to glassware.

- Numerous vessels were investigated and the test material concentration monitored over a specific duration.

- Results indicated that when using volumetric glassware with glass stoppers, or other equipment with plastic seals, loss of the test material could not be prevented.

- Overall, it was demonstrated that the most appropriate vessels to use were GC headspace vials.

- Results obtained with headspace vials showed that some loss of test item was inevitable.

- Loss of test material was most apparent in preliminary tests performed at 50 ºC as required by method guidelines.

- At pH 4 and pH 7, test material concentration was shown to decrease via a non-pseudo first order mechanism, followed by a plateau of consistent concentrations during the course of the test.

- Since no additional loss/degradation of the test material was seen over the period of 120 hours to 264 hours (6 days) at 50 ºC, initial loss of the test material was considered to be due to volatilisation and/or adsorption to the glassware rather than hydrolysis.

- This conclusion was further supported by specialised predictive software (HYDROWIN v2.00), which gave an estimated half-life of 7.3 years at pH 7 and 25 ºC.

- Acidification to pH 4 was considered to further stabilise the ester functional group.

- Difficulties were also encountered at pH 9 and extended testing was required.

- The test material contained an ester functional group and, as such, base catalysed hydrolysis was expected, with return to the parent acid and alcohol.

- Upon performing the test, it was evident that hydrolysis was occurring whilst additional losses attributed to volatilisation and/or adsorption to glassware remained.

- Although the test item was determined to degrade following a pseudo first order trend, the rate of apparent hydrolysis correlated poorly with the temperatures at which the individual Tier 2 test were performed.

- It was consequently decided that the definitive test at pH 9 should be performed directly at 25 ºC in line with guidance from the UK Competent Authority, which suggests that testing should be performed at 25 ºC for a maximum period of 30 days for problematic test items, such as those that do not undergo pseudo first order reactions.

- Data obtained from the direct 25 ºC test yielded a pseudo first order correlation.

- It can be reasonably concluded that, at higher test temperatures of 40 ºC and 50 ºC, losses through volatilisation were the underlying interference.

Validity criteria fulfilled:
yes
Conclusions:
The half-life of the test material at 25 ºC was determined to be > 1 year at pH 4 and pH 7. The rate constant at 25 ºC and pH 9 was determined to be 1.24 x 10-5 s-1 and the half-life at 25 ºC and pH 9 was determined to be 15.5 hours.

Description of key information

Half-life at 25 ºC > 1 year at pH 4 (OECD 111)

Half-life at 25 ºC > 1 year at pH 7 (OECD 111)

Rate constant at 25 ºC = 1.24E-05 s-1 at pH 9 (OECD 111)

Half-life at 25 ºC = 15.5 hours at pH 9 (OCED 111)

Key value for chemical safety assessment

Half-life for hydrolysis:
1 yr
at the temperature of:
25 °C

Additional information

Method

The determination was carried out using a procedure designed to be compatible with Method C7 Abiotic Degradation, Hydrolysis as a Function of pH of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 111 of OECD Guidelines for Testing of Chemicals, 13 April 2004.

Conclusion

The rate constant and estimated half-life at 25 °C of the test item are shown in the following table:

pH

Rate constant (s-1)

Estimated half-life at 25 °C

4

-

> 1 year

7

-

> 1 year

9

1.24 x 10-5

15.5 hours