Loperamide

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:

From August 11 to August 13, 2015

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Loperamide

EC Number:

258-416-5

EC Name:

Loperamide

Cas Number:

53179-11-6

Molecular formula:

C29H33ClN2O2

IUPAC Name:

4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide

Details on test material:

Name Loperamide base (CAS 53179-11-6)
Batch no. 02742200215
Appearance White solid
Purity 99.5 %
Homogeneity homogeneous
Expiry date 20. Aug. 2015

Sampling and analysis

Analytical monitoring:

yes

Test solutions

Details on test solutions:

During validation, solubility in daphnia medium was estimated as 0.6 mg/L. Therefore in this daphnia study the concentration 0.6 mg/L was tested. A stock solution containing 6000 mg/L in acetone was prepared. For the solvent control, acetone in a concentration of 0.1 mL/L was used.

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

Strain Berlin
Sex female
Age between 0 and 24 hours
Origin Umweltbundesamt Berlin

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Test conditions

Hardness:

250 mg CaCO3/l

Test temperature:

19.5 – 20.7 °C

pH:

7.6

Nominal and measured concentrations:

At the start and at the end of the test, the content of the test item in the test solutions was
determined using HPLC. The measured concentration was 86°% the nominal concentration
at the start of the test.
At the end of the test significant amounts of the test item were detected in the blank and
the solvent control. This was probably caused by contamination during the sample preparation
before measurement via HPLC. As the detected value in the solvent control was
higher than in the blank control, this value was subtracted from the determined concentration
in treatment at the end of the test.
Thus the measured concentration was 53 % of the nominal concentration at the end of the
test.
Therefore the geometric mean of the measured concentration was used for the determination of the results.

Reference substance (positive control):

yes

Remarks:

Potassium dichromate

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 0.41 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.:

>= 0.41 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Effect concentrations 3

Duration:

48 h

Dose descriptor:

LOEC

Effect conc.:

>= 0.41 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

In the blank control, solvent control and the treatment none of the Daphnia were immobilised.

Results with reference substance (positive control):

The 24h-EC50 value was determined as 1.6 mg/L, lying within the demanded range of 0.6 – 1.7 mg/L.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

One valid experiment was performed.
20 Daphnia were exposed to the test item for the blank control, the solvent control and the treatment for 48 hours in a static test system.
The treatment showed no toxicity. None of the animals were immobilised in the control and in the solvent control.