4H-Pyrido[1,2-a]pyrimidin-4-one, 9-hydroxy-3-(2-hydroxyethyl)-2-methyl-

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:

2015-09-14 to 2015-09-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study performed according to standard test guidelines (OECD, EC) and conform GLP requirements. The results of the study can be considered reliable without restriction.

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:

9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

EC Number:

605-935-3

Cas Number:

181525-38-2

Molecular formula:

C11H12N2O3

IUPAC Name:

9-hydroxy-3-(2-hydroxyethyl)-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): JNJ-200395-AAA (T002416)
- Physical state: solid
- Appearance: light yellow
- Analytical purity: >97.4%
- Batch n°: I14FB2740
- Expiration date: 26 June 2016
- Storage condition: at room temperature

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

- Sampling method: samples (1.9 mL) for possible analysis were taken form all test concentrations and the control at t=0 and t=48h.
At the end of the exposure period, the replicates were pooled at each concentration before sampling. Additionally, reserve samples (1.9 mL) were taken for possible analysis.
- Sample storage conditions before analysis: the samples were stored in a freezer (<-15°C).

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 by dissolving 100 mg of test item in 1L of test water applying 40 minutes of magnetic stirring at room temperature. The lower test concentrations were prepared by subsequent dilutions of the stock solution in test medium.
- Evidence of undissolved material (e.g. precipitate, surface film, etc): final solutions were all 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 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: a supsension 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:

19.5-21.1°C

pH:

At t= 0h: 7.3-7.8
At t= 48h: 7.6-8.1

Dissolved oxygen:

At t= 0h: 8.0-8.2
At t= 48h: 7.4-9.1

Salinity:

not relevant

Nominal and measured concentrations:

Nominal concentrations (mg/L): 0.1, 1.0, 10 and 100
Nominal concentration tested (mg/L): 100
Measured concentrations (mg/L) at t=0h: 98.7
Measured concentrations (mg/L) at t=48h: 64.6

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 for the highest test concentration and 2 for the remaining concentrations
- No. of vessels per control (replicates): 4

OTHER TEST CONDITIONS
- Photoperiod: 16h light daily

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

TEST CONCENTRATIONS
- Spacing factor for test concentrations: none (limit test)
- Justification for using less concentrations than requested by guideline:
- Range finding study
- 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

Remarks:

Potassium dichromate

Results and discussion

Effect concentrations

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 80 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Behavioural abnormalities: no data
- Immobility of control: no
- Other adverse effects control: no
- 24h-EC50 > 80 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:

No EC50 could be calculated

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of T002416 to Daphnia magna was determined in a 48-hour static test according to the OECD guideline 202.
No effects were observed up to and including the nominal test item concentration of 100 mg/L, corresponding to a geometric mean measured concentration of 79.8 mg/L. The 48h-EC50 was determined to be >80 mg/L (geometric mean measured concentration). The results of the test can be considered reliable without restriction.