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

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 November 2018 - 12 December 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

Deviations:

no

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: I18IB2522
- Expiration date of the lot/batch: 19 March 2019 (retest date)
- Purity test date: 9-10-2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refrigerator (2-8°C)

Analytical monitoring:

yes

Details on sampling:

- Concentrations: Samples for possible analysis were taken from all test concentrations and the control.
- Sampling method: Volume: 2.0 mL from the approximate centre of the test vessels
- Sample storage conditions before analysis: Samples were stored in a freezer (≤ -15ºC) until analysis.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The batch of JNJ-26144612-AAA (T002632) tested was a white powder with a purity of 100.1% and completely soluble in test medium at the concentrations tested. No correction was made for the purity/composition of the test item. Preparation of test solutions started with the highest concentration of 100 mg/L applying a three-hour period of magnetic stirring to accelerate complete dissolution and hydrolysis of the test item in test medium. Lower test concentrations were prepared by subsequent dilutions of the highest concentration in test medium.
- Controls: yes
- Evidence of undissolved material (e.g. precipitate, surface film, etc.): All test solutions were clear and colorless at the end of the preparation procedure.

Test organisms (species):

Cyprinus carpio

Details on test organisms:

TEST ORGANISM
- Common name: Carp
- Strain: Carp (Cyprinus carpio, Teleostei, Cyprinidae) Linnaeus, 1758
- Source: Zodiac, proefacc, "De Haar Vissen", Wageningen University and Research Centre, The Netherlands.
- Length at study initiation (length definition, mean, range and SD): 3.5 ± 0.3 cm (mean of 10 fish)
- Weight at study initiation (mean and range, SD): 0.53 ± 0.16 g (mean of 10 fish)
- Method of breeding: F1 from a single parent-pair bred in UV-treated water.

ACCLIMATION
- Acclimation period: At least 12 days after delivery
- Type and amount of food during acclimation: pelleted fish food (Essence (300-500 um), Coppens International bv, Helmond, The Netherlands)
- Feeding frequency during acclimation: daily
- Health during acclimation (any mortality observed): In the batch of fish used for the test, mortality during the seven days prior to the start of the test was less than 5%.

FEEDING DURING TEST
No feeding for 24 hours prior to the test and during the total test period

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

96 h

Hardness:

180 mg/L CaCO3

Test temperature:

20 - 21°C (constant within 2°C)

pH:

6.5 - 8.1 (constant within 1 unit)

Dissolved oxygen:

7.0 - 9.2 mg/L

Salinity:

not applicable

Conductivity:

not applicable

Nominal and measured concentrations:

Nominal concentrations:
1, 10, 100 mg/L

Measured concentrations:
T=0h [100 mg/L nominal] : 101 mg/L
T= 24h [100 mg/L nominal]: 96.8 mg/L
T= 96h [100 mg/L nominal]: 93.1 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: glass container
- Material, size, headspace, fill volume:
Control and limit concentration: 10 litres, all-glass, containing 8 litres of test solution.
Intermediate concentrations: 3.5 litres, all-glass, containing 3 litres of test solution.
- Aeration: The test media were not aerated during the test.
- No. of organisms per vessel:
Control and limit concentration: 0.46 g fish/Litre, i.e. 7 fish per 8 litres of test medium.
Intermediate concentrations: 0.53 g fish/Litre, i.e. 3 fish per 3 litres of test medium.
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- Biomass loading rate:
Control and limit concentration: 0.46 g fish/Litre, i.e. 7 fish per 8 litres of test medium.
Intermediate concentrations: 0.53 g fish/Litre, i.e. 3 fish per 3 litres of test medium.

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Adjusted ISO medium with a hardness of 180 mg CaCO3 per litre and a pH of 7.7 ± 0.3.
- Culture medium different from test medium: no
- Intervals of water quality measurement:
Dissolved oxygen content: Daily in the vessels of the control and the limit concentration, beginning at the start of the test (day 0).
Temperature: Daily in the vessels of the control and the limit concentration, beginning on day 1.
pH: Daily in the vessels of the control and the limit concentration, beginning at the start of the test (day 0). Additionally in the intermediate concentrations after 24 and 48 hours of exposure.

OTHER TEST CONDITIONS
- Photoperiod: 16 hours photoperiod daily
- Light intensity: dimmed light conditions.

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mortality aAt 2.5, 24, 48, 72 and 96 hours following the start of exposure. In addition, every afternoon from day 0 to observe for any dead or severely distressed fish.

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 10

Reference substance (positive control):

yes

Remarks:

pentachlorophenol

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: measured as degradation product

Details on results:

- Behavioural abnormalities: No mortality or symptoms of distress were observed throughout the test.
- Mortality of control: no
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: No remarkable observations were made concerning the appearance of the test media. All test media were clear solutions throughout the entire test duration.

- Study plan deviations:
1. At the start of test, no temperature measurements were documented for any of the test vessels. Evaluation: No mortality or symptoms of distress were observed throughout the test, indicating that this had no impact on the integrity of the test or the interpretation of the results.
2. The pH of the control, 1.0 and 100 mg/L at the start of the test exceeds the maximum tolerance between the holding tank and the test concentration given in the study plan, i.e. was >0.5 units. Evaluation: No mortality or symptoms of distress were observed throughout the test, indicating that this had no impact on the integrity of the test or the interpretation of the results.
3. The test item was not expected to be sensitive to light. Yet, the test was performed under dimmed light conditions. Evaluation: No mortality or symptoms of distress were observed throughout the test, indicating that this had no impact on the integrity of the test or the interpretation of the results

The study integrity was not adversely affected by the deviations

Results with reference substance (positive control):

- Results with reference substance valid? yes

- Mortality:
0.1 mg/L PCP: 0% mortality
0.22 mg/L PCP: 100% mortality
0.46 mg/L PCP: 100% mortality

- LC50: 0.15 mg/L (96h-LC50)

- Other:
Under the conditions of the present test, PCP induced no lethal effects in carp at 0.10 mg/L. The 96h-LC50 for carp exposed to PCP was 0.15 mg/L (95 % confidence interval between 0.10 and 0.22 mg/L). This effect was already reached within 24 hours of exposure.

The range of the 96h-LC50 for carp is generally between 0.10 and 0.46 mg/L based on historical data of reference tests performed approximately every 3 months from April 1988 until the end of 2000, and annually since then. Hence, the sensitivity of carp originating from the present batch for PCP falls within the range of sensitivities generally observed during the past years.

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of T002632 to Cyprinus carpio was determined in a 96 hour static test according to OECD guideline 203.

The test item T002632 was completely soluble in test medium at the concentrations tested. The half-life time of the test item in water was below 1hour, therefore the degradation product of the test item was tested. The measured concentrations of the degradation product were at the level of the nominal concentrations at the start, after 24 hours of exposure and at the end of the test. Based on these results, effect paramaters were based on nominal concentration.

No mortality or symptoms of distress were observed throughout the test. Based on the results, the 96h-EC50 was beyond the range tested, i.e. exceeded a nominal exposure concentration of 100 mg/L. The results of the test can be considered reliable without restriction.

Description of key information

The acute toxicity of T002632 to Cyprinus carpio was determined in a 96 hour static test according to OECD guideline 203. The test item T002632 was completely soluble in test medium at the concentrations tested. The half-life time of the test item in water was below 1hour, therefore the degradation product of the test item was tested. The measured concentrations of the degradation product were at the level of the nominal concentrations at the start, after 24 hours of exposure and at the end of the test. Based on these results, effect paramaters were based on nominal concentration. No mortality or symptoms of distress were observed throughout the test. Based on the results, the 96h-EC50 was beyond the range tested, i.e. exceeded a nominal exposure concentration of 100 mg/L.