Hydroxychloroquine

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study to GLP certification with no deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxychloroquine

EC Number:

204-249-8

EC Name:

Hydroxychloroquine

Cas Number:

118-42-3

Molecular formula:

C18H26ClN3O

IUPAC Name:

2-({4-[(7-chloroquinolin-4-yl)amino]pentyl}(ethyl)amino)ethan-1-ol

Test material form:

solid

Remarks:

white solid powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
HYDROXYCHLOROQUINE (CAS N°118-42-3) – Batch 5U054 (Synonym: PLAQUENIL)

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

- Concentrations:
Nominal concentrations were 6.25, 12.5, 25, 50, 100 mg/l
Geometric mean concentrations were 6.76, 11.9, 21.8, 44.8, 105.0 mg/l

- Sampling method:
The quantification of Hydroxychloroquine was performed according to the validated analytical
method to check test item concentrations at T0 and T48h

Test solutions

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
A stock solution of test item was prepared by ultrasonic dissolution
of the test item in the test media.

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water flea
- Age at study initiation (mean and range, SD): Between 6 and 24 hours old

Study design

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

None

Post exposure observation period:

None

Test conditions

Hardness:

No data

Test temperature:

20°C +/- 2°C across the test concentrations, replicates and test duration.

pH:

7.8 to 9 across the test concentrations, replicates and test duration.

Dissolved oxygen:

7.5 to 8.3 across the test concentrations, replicates and test duration.

Salinity:

Not applicable

Conductivity:

No data

Nominal and measured concentrations:

Nominal concentrations were 6.25, 12.5, 25, 50, 100 mg/l
Geometric mean concentrations were 6.76, 11.9, 21.8, 44.8, 105.0 mg/l

Details on test conditions:

TEST SYSTEM
- Test vessel: Tests were performed in 10 mL polystyrene multiwell plate.
- Volume of solution: 10 ml
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4

OTHER TEST CONDITIONS
- Adjustment of pH: Not performed
- Photoperiod: Test conducted in dark

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

48 h

Dose descriptor:

LOEC

Effect conc.:

11.9 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Effect concentrations 2

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

6.76 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Effect concentrations 3

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

8.47 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Effect concentrations 4

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

14 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

None

Results with reference substance (positive control):

EC50-24h K2Cr2O7 between 0.6 and 2.1 mg/L:
March 23rd, 2016 : EC50-24h = 1.39 mg/L [1.31 – 1.47]

Reported statistics and error estimates:

The EC50 at 48h for immobilisation with confidence limits and graphs of the fitted model
used for their calculation, the slopes of the dose-response curves are reported. Data was analysed by an appropriate statistical method (Probit analysis
to calculate the slopes of the curves and the EC50 with 95% confidence limits (p = 0.95)).

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The reliable (K1) OECD 202 Guideline study found that acute toxicity was observed in Daphnia magna resulting in a 48-hr EC50 of 14.0 mg/l based on measured geometric mean.

Executive summary:

The reliable (K1) OECD 202 Guideline study was performed to GLP standards and met validity criteria. The study was performed using five test concentrations ranging from 6.25 to 100 mg/L nominal concentration. The measured concentrations were between 72.7 % and 107.4 % of the nominal concentration at T0, and between 104.6 % and 109.1 % of nominal at 48 hrs. Therefore, the determination of the results was based on the geometric mean of the measured concentrations.

Results according to OECD 202 test guideline:

	HYDROXYCHLOROQUINE BPL15-0032.001
EC50-48h Confidence limits 95%	14.0 mg/L (12.9-15.1 mg/L)
EC10-48h Confidence limits 95%	8.47 mg/L (7.78-9.16 mg/L)
NOEC	6.76 mg/L
LOEC	11.9 mg/L

ECX-48h: Effective Concentration corresponding to X% of mobility inhibition in the 48-hours test.
NOEC: No Observed Effect Concentration.
LOEC: Lowest Observed Effect Concentration.