p-fluorophenyl 4-piperidyl ketone hydrochloride

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:

2015-10-05 to 2015-10-31

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:

p-fluorophenyl 4-piperidyl ketone hydrochloride

EC Number:

247-070-0

EC Name:

p-fluorophenyl 4-piperidyl ketone hydrochloride

Cas Number:

25519-78-2

Molecular formula:

C12H14FNO.ClH

IUPAC Name:

4-(4-fluorobenzoyl)piperidine hydrochloride

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Identification JNJ-398099-AAC (T001047)
Appearance White powder (determined by Charles River Den Bosch
at receipt of the test item)
Batch I15DB1484
Purity/Composition: 97%
Test item storage conditions At room temperature
Stable under storage conditions until 19 April 2017 (retest date)

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

- Sampling method: Samples for possible analysis were taken from all test concentrations and the control at t=0 and t=48h. 1.8 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 1.8 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 concentration of 100 mg/L applying a 15-20 minutes of magnetic stirring to accelerate the dissolving of the test item in the test medium. The 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): final solutions were clear and colourless

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water flea
- Strain: STRAUS
- 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 placed into 5 L of medium in all-glass culture vessel.
- Feeding during test: no

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

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Test conditions

Hardness:

180 mg/L expressed as CaCO3

Test temperature:

20-21°C

pH:

At t= 0h: 7.9-8.0
At t= 48h: 7.8-7.9

Dissolved oxygen:

At t= 0h: 9.0-9.1
At t= 48h: 9.0-9.1

Salinity:

not relevant

Nominal and measured concentrations:

Final test
Nominal concentrations (mg/L): 4.6, 10, 22, 46, 100
Measured concentrations (mg/L) at t=0h: n.a., 4.65, 10.2, 22.1, 46.5, 102 (99% - 102% of nominal)
Measured concentrations (mg/L) at t=48h: n.a., 4.59, 10.1, 21.8, 46.3, 101

Details on test conditions:

TEST SYSTEM
- Test vessel: all-glass test vessels
- Material, size, headspace, fill volume: 100 mL, all-glass vessels filled with 80mL of test solution
- Aeration: no aeration
- 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: M7, as prescribed by Dr. Elendt-Schneider

OTHER TEST CONDITIONS
- Photoperiod: 16h light daily

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : immobility

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 2.2
- Range finding study: yes
- Test concentrations: 0.1, 1.0, 10, 100 mg/L
- Results used to determine the conditions for the definitive study: yes

Reference substance (positive control):

yes

Results and discussion

Effect concentrations

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

33 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% CL: 24-43

Details on results:

- Behavioural abnormalities: no data
- Mortality of control: no
- Other adverse effects control: no
- 24h-EC50 > 100 mg/L

Results with reference substance (positive control):

- Results with reference substance valid? yes (should lie between 0.3 and 1.0 mg/L)
- EC50/LC50: 48h-EC50 = 0.39 mg/L

Reported statistics and error estimates:

Calculations of EC50.
The 48h-EC50-value was calculated from the weibits of the percentages of affected daphnids and the logarithms of the corresponding test item concentrations (initially measured) using the maximum likelihood estimation method.
The 24h-EC50 could not be determined because the observed effects were below 50%
ToxRat Professional v 3.0.0. (ToxRat Solutions gmbh, Germany) was used to perform the analyses.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of T001047 to Daphnia magna was determined in a 48-hour static test according to the OECD guideline 202.
The 48h-EC50 was determined to be 33 mg/L (95% CL 24-43 mg/L). The results of the test can be considered reliable without restriction.