2,4-dihydro-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one

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:

2017-01-06 to 2017-01-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Guidance document on aquatic toxicity testing of difficult items and mixtures, OECD series on testing and assessment number 23, December 14, 2000.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dihydro-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one

EC Number:

278-009-6

EC Name:

2,4-dihydro-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-3H-1,2,4-triazol-3-one

Cas Number:

74853-07-9

Molecular formula:

C19H21N5O2

IUPAC Name:

4-{4-[4-(4-METHOXYPHENYL)PIPERAZIN-1-YL]PHENYL}-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study reports): JNJ-1802905-AAA (T001328)
- Physical state: solid
- Appearance: Purple powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: I16AB0441
- Expiration date of the lot/batch: 2018-01-30 (retest date)
- Purity test date: 2016-02-18

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: not indicated
- Solubility and stability of the test substance in the solvent/vehicle: < 0.001 g/L in water
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

- Sampling method: samples for possible analysis were taken form all test concentrations and the control at t=0 and t=48h. 3.0 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. Additonally, reserve samples of 3.0 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: Due to an expected low water solubility of the test item, a saturated solution (SS) was prepared. The preparation of test solutions started with a loading rate of 100 mg/L applying a three-day period of magnetic stirring at room temperature to ensure maximum dissolution of the test item in test medium. This resulted in a hazy dispersion containing undissolved material. The obtained dispersion was filtered through a 0.45 µm membrane filter (Whatman; RC55). The filter was pre-conditioned with a small volume of test solution that was discarded. The resulting SS was used as the highest test concentration. Lower test concentrations were prepared by subsequent dilutions of the SS in test medium.
- Evidence of undissolved material (e.g. precipitate, surface film, etc): All 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: M7. After 7 days of cultivation half of the medium is renewed twice a week.
- Feeding during cultivation: fresh water algae, daily
- Feeding during test: no

ACCLIMATION
- Acclimation period: not relevant

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Test conditions

Hardness:

180 mg/L expressed as CaCO3

Test temperature:

20°C

pH:

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

Dissolved oxygen:

At t= 0h: 9.3-9.5
At t= 48h: 8.8

Salinity:

not relevant

Nominal and measured concentrations:

Range finder:
Nominal concentrations (mg/L): 1.0, 10 and 100% of a SS prepared at 100 mg/l
Nominal concentration tested (mg/L): 100
Measured concentrations (mg/L) at t=0h: 0.0777
Measured concentrations (mg/L) at t=48h: 0.0.0778
Samples taken from undiluted SS prepared at 100 mg/L were analysed. The actual concentration was 0.078 mg/L at the start of the test. The measured concentration was at the level of 100% of initial at the end of the test.
Based on these results, the effect parameters were expressed in terms of measured concentrations.

Details on test conditions:

TEST SYSTEM
- Test vessel: beaker
- Material, size, headspace, fill volume: 100 mL, glass beaker filled with 80mL
- Aeration: no aeration of the test solutions
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates):
* 4 for the 100 mg/L concentration
* 2 for the 1.0 and 10 mg/L concentration
- No. of vessels per control (replicates): 4

OTHER TEST CONDITIONS
- Photoperiod: 16h light daily

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: x10
- Range finding study: combined/range finding study was performed
- Test concentrations: 1.0, 10 and 100% of a SS prepared at a loading rate of 100 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.:

> 0.078 mg/L

Nominal / measured:

meas. (initial)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Mortality of control: none
- Other adverse effects control: no
- Abnormal responses: none
- 24h and 48h EC50 > 0.078 mg/L measured test item, is equal to 100 % of saturated solution prepared at 100 mg/L

Results with reference substance (positive control):

- Results with reference substance valid? yes
- Mortality:
- EC50/LC50: 48-h EC50 = 0.58 mg/L with a 95% C.L. between 0.49 and 0.67 mg/L. The sensitivity of the daphnia was within the range determined with the historical data collected at Charles River Laboratories Den Bosch.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of T001328 to Daphnia magna was determined in a 48-hour static test according to the OECD guideline 202. The 48h-EC50 was beyond the concentration range tested, i.e. exceeded a measured exposure concentration of 0.078 mg/L, being considered the maximum solubility of test item in test medium.
The results of the test can be considered reliable without restriction.