1-[([[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl)oxy]pyrrolidine-2,5-dione

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-09-20 to 2017-10-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 301 B (Ready Biodegradability: CO2 Evolution Test)

Deviations:

yes

Remarks:

See section "Any other information on materials and methods incl. tables"

Qualifier:

according to guideline

Guideline:

EU Method C.4-C (Determination of the "Ready" Biodegradability - Carbon Dioxide Evolution Test)

Deviations:

yes

Remarks:

See section "Any other information on materials and methods incl. tables"

Qualifier:

according to guideline

Guideline:

other: ISO International Standard 9439

Version / remarks:

Water Quality - Evaluation of ultimate aerobic biodegradability of organic compounds in aqueous medium - carbon dioxide evolution test (1999)

Deviations:

yes

Remarks:

See section "Any other information on materials and methods incl. tables"

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: I16FD3167
- Expiration date of the lot/batch: 2018-06-30 (retest date)
- Purity test date: 2016-10-19

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refrigerator (2-8°C)
- Stability under test conditions: not stable
- Solubility of the test substance in the solvent/vehicle: solubility in water: not specified

Oxygen conditions:

aerobic

Inoculum or test system:

activated sludge, non-adapted

Details on inoculum:

- Source: municipal sewage treatment plant receiving predominantly domestic sewage, 'Waterschap Aa en Maas', 's-Hertogenbosch, The Netherlands.
- Storage conditions: the freshly obtained sludge was used immediately
- Preparation of inoculum for exposure: Before use, the sludge was allowed to settle (30 minutes) and the supernatant liquid was used as inoculum.
- Pretreatment: no
- Concentration of sludge: the concentration of suspended solids was determined to be 4.9 g/L in the concentrated sludge.
- Water filtered: Tap-water purified by reverse osmosis (Milli-RO) and subsequently passed over activated carbon.

Duration of test (contact time):

28 d

Initial conc.:

24.5 mg/L

Based on:

test mat.

Initial conc.:

12 mg/L

Based on:

TOC

Parameter followed for biodegradation estimation:

CO2 evolution

Details on study design:

TEST CONDITIONS
- Composition of medium: test water prepared according to test guidelines, analytical grade salts dissolved in tap-water purified by reverse osmosis (Milli-RO) and subsequently passed over activated carbon.
* mineral stock solution A: 8.5 g KH2PO4, 21.75 g K2HPO4, 67.20 g Na2HPO4.12H2O, 0.5 gNH4Cl dissolved in 1 L Milli-Q water, pH 7.4 ± 0.2
* mineral stock solution B: 22.50 g MgSO4.7H2O dissolved in 1 L Milli-Q water
* mineral stock solution C: 36.4 g CaCl2.2H2O dissolved in 1 L Milli-Q water
* mineral stock solution D: 0.25 g FeCl3.6H2O dissolved in 1 L Milli-Q water
* Final test medium: 10 mL of solution A and 1 mL of solutions B, C and D per L of test medium
- Additional substrate: no
- Test temperature: 22.2-23.5°C
- pH: 7.4-7.6 (measured prior to testing in each test flask before addition of inoculum) and 7.4-7.8 (in each test flask at the end of the incubation period)
- pH adjusted: no
- Aeration of dilution water: yes
- Continuous darkness: yes

TEST SYSTEM
- Test flasks: 2 L all-glass brown coloured bottles
- Number of culture flasks/concentration: 2
- Method used to create aerobic conditions: A mixture of oxygen (~20%) and nitrogen (~80%) was passed through a bottle, containing 0,5 - 1 L 0,0125 M Ba(OH)2 solution to trap CO2. The synthetic air was sparged through the scrubbing solutions at a rate of ~1-2 bubbles per second ( ~30-100 mL/min).
- Details of trap for CO2 and volatile organics if used: 3 CO2-absorbers (bottles filled with 100 mL 0,0125 M Ba(OH)2) were connected in series to the exit air line of eache bottle. The CO2 produced in each test botle reacted with the barium hydroxide in the gas scrubbing bottle and precipitated out as barium carbonate. The amount of CO2 produced was determined by titrating the remaining ba(OH)2 with 0,05 M standardized HCl.

SAMPLING
- Sampling frequency: every second or third day during the first 10 days, and thereafter at least every fifth day until the 28th day
- Sampling method: the absorber bottle closest to the incubation system was sampled each time, the second and third bottle were moved one position closer to the system and a new bottle was added at the end
- On the 28th day, pH of test suspensions was measured and 1 mL of concentrated HCl was added to each bottle. Bottles were aerated overnight to drive off CO2 present in the test suspension. The final titration was made on day 29.

CONTROL AND BLANK SYSTEM
- test substance and inoculum: 2 replicates
- Inoculum blank: two replicates with only inoculum.
- Toxicity control: one replicate with test item, reference substance, and inoculum.
- Procedure control: 1 replicate with reference item and inoculum

Reference substance:

acetic acid, sodium salt

Test performance:

- The positive control substance was biodegraded by at least 60% (81%) within 14 days.
- The difference of duplicate values for %-degradation of the test item was always less than 20% (<=4%).
- The total CO2 release in the blank at the end of the test did not exceed 40 mg/L (48.8 mg CO2 per 2 litres of medium, corresponding to 24.4 mg CO2/L).
- The inorganic Carbon content (IC) of the test item (suspension) in the mineral medium at the beginning of the test was less than 5% of the Total Carbon content (TC).

Key result

Parameter:

% degradation (CO2 evolution)

Value:

ca. 33

Sampling time:

28 d

Remarks on result:

other: Mean of test bottles A and B

Details on results:

T002632 was biodegraded significantly (31% and 35% in bottle A and B respectively) during the test period. However, since at least 60% biodegradation was not reached within 10 days immediately following the attainment of 10% biodegradation (10-day window), the criterion for ready biodegradability was not met.

Results with reference substance:

The positive control substance was biodegraded by at least 60% (81%) within 14 days confirming the suitability of the inoculum and test conditions.

Validity criteria fulfilled:

yes

Interpretation of results:

not readily biodegradable

Conclusions:

A 28-d ready biodegradability test (OECD 301B, modified sturm test) using unadapted activated sludge from a predominantly domestic waste water treatment plant indicated that JNJ-26144612-AAA (T002632) was not readily biodegradable under the conditions of the test (initial test concentration 24.5 mg/L). The test substance showed significant biodegradation (31% and 35%, test bottle A and B, respectively). However, since at least 60% biodegradation was not reached within 10 days immediately following the attainment of 10% biodegradation (10-day window), the criterion for ready biodegradability was not met. The test substance did not inhibit microbial activity at the concentration used in the test. The results of the test can be considered reliable without restriction.

Description of key information

A 28-d ready biodegradability test (OECD 301B, modified sturm test) using unadapted activated sludge from a predominantly domestic waste water treatment plant indicated that JNJ-26144612-AAA (T002632) was not readily biodegradable under the conditions of the test (initial test concentration 24.5 mg/L). The test substance showed significant biodegradation (31% and 35%, test bottle A and B, respectively). However, since at least 60% biodegradation was not reached within 10 days immediately following the attainment of 10% biodegradation (10-day window), the criterion for ready biodegradability was not met. The test substance did not inhibit microbial activity at the concentration used in the test.

Key value for chemical safety assessment

Biodegradation in water:

under test conditions no biodegradation observed

Type of water:

freshwater