Registration Dossier

Diss Factsheets

Environmental fate & pathways

Hydrolysis

Currently viewing:

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
hydrolysis
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 October 2014 to 06 November 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: New study performed to GLP and to internationally accepted guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 111 (Hydrolysis as a Function of pH)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method C.7 (Degradation: Abiotic Degradation: Hydrolysis as a Function of pH)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Radiolabelling:
no
Analytical monitoring:
yes
Details on sampling:
- Sampling intervals for the parent:
Preliminary test 0, 2.4, 48, 120 hrs;
Main test - sufficient time points to show linearity during 10-90% degradation at 50°, 60° and 70°C at pH7 and 20°C, 30°C and 40°C at pH9

- Sampling method: at each sampling time, two samples were removed from the constant temperature water bath bath

- Other observation, if any (e.g.: precipitation, color change etc.): no changes to test solution reported
Buffers:
pH 4: 0.2M aqueous potassium dihydrogen orthophosphate (110 ml) was mixed with 0.07M aqueous disodium hydrogen orthophosphate dodecahydrate (250 ml) and purified water (640 ml). The pH was adjusted to 4.0 ± 0.05 with orthophosphoric acid.
pH 7: 0.2M aqueous potassium dihydrogen orthophosphate (250 mL) was mixed with 1M sodium hydroxide (30 mL) and purified water (720 mL). The pH was adjusted to 7.0 ± 0.05 with 1M hydrochloric acid.
pH 9: 0.1M boric acid in 0.1M aqueous potassium chloride (500 mL) was mixed with 1M sodium hydroxide (21 mL) and purified water (480 mL). The pH was adjusted to 9.0 ± 0.05 with 1M hydrochloric acid.
Number of replicates:
2
Positive controls:
no
Negative controls:
no
Preliminary study:
The preliminary study showed that at pH 4 and 50 ± 0.5°C, less than 10% hydrolysis had occurred after 120 hours (5 days), equivalent to an environmental (25°C) half-life (te½) of greater than 1 year. No further testing was therefore necessary at this pH value.

At pH 7 and pH 9 and 50 ± 0.5°C, however, more than 10% hydrolysis had occurred after 120 hours (5 days), indicating a te½ value of less than 1 year. This necessitated proceeding to definitive testing at these pH values.
Test performance:
At pH 7, definitive tests were conducted at temperatures of 50, 60 and 70°C and the hydrolysis rate constant (k) and te½ at 25°C were extrapolated from the measured values of log10k at the selected temperatures using the Arrhenius relationship. A te½ value of 386 days was obtained at this pH value.
At pH 9, definitive tests were conducted at temperatures of 20, 30 and 40°C and the hydrolysis rate constant (k) and te½ at 25°C were interpolated from the measured values of log10k at the selected temperatures using the Arrhenius relationship. A te½ value of 9 days was obtained at this pH value.
The hydrolysis reactions for PGDB at each of pH 7 and pH 9 were shown to follow pseudo-first order behaviour.
Transformation products:
not measured
Key result
pH:
9
Temp.:
25 °C
DT50:
ca. 9 d
Type:
(pseudo-)first order (= half-life)
Details on results:
TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: Yes
- Anomalies or problems encountered: none

There were no significant changes in pH with time

Validity criteria fulfilled:
yes
Conclusions:
PGDB was determined to be hydrolytically stable under acidic and neutral conditions, but unstable under basic conditions with a half-life of 9 days.
Executive summary:

PGDB was determined to be hydrolytically stable under acidic and neutral conditions, but unstable under basic conditions with a half-life of 9 days.

Description of key information

PGDB was determined to be hydrolytically stable under acidic and neutral conditions, but unstable under basic conditions with a half-life of 9 days in an OECD Guideline 111 (hydrolysis  as a function of pH) test performed to GLP guidelines (Huntingdon Life Sciences, 2014b; Klimisch score = 1).

Key value for chemical safety assessment

Half-life for hydrolysis:
386 d
at the temperature of:
25 °C

Additional information

At pH 7, definitive tests were conducted at temperatures of 50, 60 and 70°C and the hydrolysis rate constant (k) and te½ at 25˚C were extrapolated from the measured values of log10k at the selected temperatures using the Arrhenius relationship. A te½ value of 386 days was obtained at this pH value. At pH 9, definitive tests were conducted at temperatures of 20, 30 and 40°C and the hydrolysis rate constant (k) and te½ at 25°C were interpolated from the measured values of log10k at the selected temperatures using the Arrhenius relationship. A te½ value of 9 days was obtained at this pH value. The hydrolysis reactions for PGDB at each of pH 7 and pH 9 were shown to follow pseudo-first order behaviour.