N-phenyl-N-piperidin-4-ylpropionamide

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-05-09 to 2016-06-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N-phenyl-N-piperidin-4-ylpropionamide

EC Number:

216-543-3

EC Name:

N-phenyl-N-piperidin-4-ylpropionamide

Cas Number:

1609-66-1

Molecular formula:

C14H20N2O

IUPAC Name:

N-phenyl-N-piperidin-4-ylpropionamide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-1594255-AAA (T000425)
- Physical state: solid (powder)
- Appearance: white

Specific details on test material used for the study:

- Name of test material (as cited in study report): T000425
- Substance type: no data
- Physical state: white solid
- Analytical purity: 100%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 00454795
- Expiration date of the lot/batch: 2005-12-31
- Stability under test conditions: no data
- Storage condition of test material: room temperature
- Other: solubility: 43 g/L in water, 500 g/L in ethanol

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

- Concentrations final test: 10, 18, 32, 56, 100 mg/L
- Sampling method: samples for possible analysis were taken form all test concentrations and the control at t=0 and t=48h. 1.4 mL of volume was taken from the approximate centre of the test vessels. At the end of the exposure period, the replicates were pooled at each concentration before sampling
- Sample storage conditions before analysis: the samples were stored in a freezer. Additionally, reserve samples of 1.4 mL were taken for possible analysis

Test solutions

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: Preparation of test solutions started with the highest test concentration of 100 mg/L. No special treatment other than vigorous shaking and a 5 minute treatment period with ultrasonic waves were needed to fully dissolve the test item in the test medium. The pH was adjusted with HCl (1 mol/L, Merck, Darmstadt, Germany) from 9.5 to 7.8 and from 9.4 to 8.0 in the combined limit/range-finding and the final test, respectively. Lower test concentrations were prepared by subsequent dilutions of the highest concentration in test medium.
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no, final test solutions were clear and colourless

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water-flea
- Source: in-house laboratory culture with a known history
- Age at study initiation (mean and range, SD): <24h (from parental daphnids of more than 2 weeks old)
- Method of breeding: 250 newborn daphnids (i.e. less than 3 days old) are placed into 5 litres of medium in an all-glass culture vessel. Medium is M7. After 7 days of cultivation half of the medium is renewed twice a week.
- Feeding during test: no

ACCLIMATION
- Acclimation period: max. 4 weeks
- Acclimation conditions (same as test or not): yes
- Type and amount of food: fresh water algae.
- Feeding frequency: daily
- Health during acclimation (any mortality observed): no

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Test conditions

Hardness:

180 mg/L as CaCO3

Test temperature:

20-21°C

pH:

At t= 0h: 8.0 - 8.1
At t= 48h: 7.9-8.0

Dissolved oxygen:

At t= 0h: 8.7-8.8 mg/L
At t= 48h: 8.9-9.0 mg/L

Salinity:

not relevant

Nominal and measured concentrations:

Final test
Nominal concentrations (mg/L): 10, 18, 32, 56, 100
Measured concentrations (mg/L) at t=0h: 9.72, 17.5, 31.6, 54.4, 99.5
Measured concentrations (mg/L) at t=48h: 9.56, 17.3, 31.2, 54.2, 98.1

Samples taken from the control and all concentrations were analysed. The measured concentrations were in agreement with the nominal concentrations throughout the test duration (96-99% relative to the nominal concentrations).

Details on test conditions:

TEST SYSTEM
- Test vessel: beaker
- Material, size, headspace, fill volume: 100 mL, glass beaker filled with 80mL
- Aeration: not during the test
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Adjusted ISO medium

OTHER TEST CONDITIONS
- Photoperiod: 16h light daily
- Adjustment of pH: no
- Light intensity: no data

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Immobility was defined as those organisms which are not able to swim within 15 seconds after gentle agitation of the test container and was monitored after 24 and 48 hours of continuous treatment with the test substance.

TEST CONCENTRATIONS
- Spacing factor for test concentrations: x1.8
- Range finding study
- Test concentrations: 0.10, 1.0 and 10 mg/L
- Results used to determine the conditions for the definitive study: yes

Reference substance (positive control):

yes

Remarks:

Potassium dichromate

Results and discussion

Effect concentrations

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

73 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% C.L.: 62-86 mg/L

Details on results:

- Mortality of control: none
- Other adverse effects control: no
- Abnormal responses: none
- 24-h EC50: > 100 mg/L (95% C.L.: not determined)

Results with reference substance (positive control):

- Results with reference substance valid? yes
- Concentrations: 0.10, 0.18, 0.32, 0.56, 1.0 and 1.8 mg/L and control.
- EC50/LC50: 48-h EC50 = 0.29 mg/L with a 95% confidence interval between 0.26 and 0.31 mg/L.
- Dose/response: The actual responses were below the ranges of the expected responses at the different concentrations, i.e. the 48h-EC50 was just below the expected range of 0.3
to 1.0 mg/L. Hence, the sensitivity of this batch of Daphnia magna was slightly above the sensitivity of batches previously tested at WIL Research Europe.

Reported statistics and error estimates:

The 24-h EC50 could not be calculated because the observed effects were below 50%. The 48h-EC50 value was calculated from the logits of the percentages of affected daphnids and the logarithms of the corresponding test item concentrations (nominal) using the maximum likelihood estimation method.
ToxRat Professional v. 3.2.1 (ToxRat Solutions® GmbH, Germany) was used to perform the analyses.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of T000425 to Daphnia magna was determined in a 48-hour static test according to the OECD guideline 202.
Based on analytically confirmed nominal concentrations, the 48-h EC50 was determined to be 73 mg T000425/L (95% CL 62-86 mg/L). The results of the test can be considered reliable without restriction.