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Short-term toxicity to aquatic invertebrates

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Reference
Endpoint:
short-term toxicity to aquatic invertebrates
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 May 2020 - 21 August 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)
Version / remarks:
13 April 2004
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Analytical monitoring:
yes
Details on sampling:
Duplicate samples from the freshly prepared test media of all test concentrations and the control were taken at the start of the test.
For the determination of the stability of the test item under the test conditions and of the maintenance of the test item concentrations during the test period, duplicate samples from the test media of all test concentrations and the control were collected at the end of the test (after 48 hours) by pouring together the contents of the test beakers of each treatment. An additional intermediate sampling point after 24h was also performed.
All samples were diluted by a factor of 2 with acetonitrile.
Additional samples of the control and the dilution solvent were taken at each sampling date without any sample treatment.
All samples were stored in a freezer (≤ - 20 °C), protected from light, until analysis was performed. Afterwards the samples were again stored deep frozen (≤ -20 °C) and will be kept stored up to the date of the final report.
Vehicle:
no
Details on test solutions:
PREPARATION AND APPLICATION OF TEST SOLUTION
- Method: a supersaturated stock solution of nominal 100 mg test item/L was prepared by suspending 89.9 mg test item in 899 mL test water. The stock suspension was stirred for 48.3 hours at room temperature in the dark to dissolve as much test item as possible. Then, non-dissolved fractions of the test item were separated from the test medium by membrane filtration (0.45 µm cellulose acetate filter). The filtrate with dissolved test item was used to prepare the desired dilutions of 1:50, 1:110, 1:242, 1:532, 1:1171, 1:2577, 1:5669.
Test organisms (species):
Daphnia magna
Details on test organisms:
TEST ORGANISM
- Common name: Water flea
- Strain/clone: clone 5
- Age at study initiation: 1.25 - 17.50 h
- Method of breeding: Parental daphnids in Elendt M4 medium
- Source: in-house culture of Ibacon

ACCLIMATION
- Acclimation period: none, already cultured in test medium
Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
48 h
Test temperature:
20.0 - 20.6
pH:
8.0
Dissolved oxygen:
8.9 - 8.7 mg/L
Nominal and measured concentrations:
Nominal: 1:50, 1:110, 1:242, 1:532, 1:1171, 1:2577 and 1:5660 dolutions of 100 mg/L filtrated solution.
Measured (geometric mean): 1097, 508, 225, 104, 42.5, 15.8, 7.17 µg/L
Details on test conditions:
TEST SYSTEM
- Test vessel: 100 ml glass beaker
- Type: closed
- Material, size, headspace, fill volume:
- Volume of solution: 60 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: no
- Photoperiod: 16:8 (h, light:dark)
- Light intensity: 300-570 lux

EFFECT PARAMETERS MEASURED: immobilisation after 24 and 48h
Reference substance (positive control):
yes
Remarks:
potassium dichromate
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
684 µg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mobility
Duration:
48 h
Dose descriptor:
NOEC
Effect conc.:
225 µg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mobility
Duration:
48 h
Dose descriptor:
EC10
Effect conc.:
474 µg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mobility
Results with reference substance (positive control):
- Results with reference substance valid? yes. The sensitivity of the daphnids was consistent with the level proposed by the OECD 202 guideline (EC50 between 0.6 and 2.1 mg potassium dichromate/L)

Table 1: Effect concentrations

Endpoint

24 hours

48 hours

 

[µg test item/L]

EC50

< 1097

684

95 % CI

n.d.

585 - 800

EC20

< 1097

537

95 % CI

n.d.

449 - 643

EC10

n.d.

474

95 % CI

n.d.

384 - 585

NOEC

508

225

LOEC

1097

508

Table 2: Sumary of immobilised daphnids (%)

Geometric Mean Measured Concentration [µg test item/L]

% of immobilized daphnids after

24 hours

48 hours

Control

0

0

7.17

0

0

15.8

0

0

42.5

0

0

104

0

0

225

0

0

508

0

15

1097

10

95

Validity criteria fulfilled:
yes
Conclusions:
The 48-hour NOEC of (R)-3-Amino-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol L-tartrate was determined to be 225 µg test item/L. The 48-hour LOEC was determined to be 508 µg test item/L and the 48-hour EC50 value was calculated to be 684 µg test item/L.
Executive summary:

The 48–hr-acute toxicity of (R)-3-Amino-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol L-tartrate to Daphnia magna Straus was studied under static conditions. Test species were exposed to control and test chemical at measured concentrations of 0, 7.17, 15.8, 42.5, 104, 225, 508, 1097 µg test item/L for 48 hr.  Immobilisation was observed at 24 and 48 h.  The 48–hour EC50was 684 µg/L.  The 48–hr NOEC based on immobilization was 225 µg test item/L. 

 

This study is classified as acceptable and satisfies the guideline requirements for an acute toxicity study with freshwater invertebrates.

 

Results Synopsis

 

Test Organism Age: 1.75 - 17.50h

Test Type: static

 

NOEC:  225 µg test item/L                       

EC50:  684 µg test item/L                       95% C.I.:  585 to 800 µg test item/L

Endpoint Effected:  immobilisation

Description of key information

In a single key study on the 48–hr-acute toxicity of (R)-3-Amino-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol L-tartrate to Daphnia magna Straus was studied according to OECD guideline 202. The 48–hour EC50was 684 µg/L. The study was conducted under static conditions and fulfilled all criteria for a valid test.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates
Effect concentration:
684 µg/L

Additional information

Daphnia magna were exposed to control and test chemical at measured concentration of 0, 7.17, 15.8, 42.5, 104, 225, 508, 1097 µg test item/L for 48 hr.  Immobilisation was observed at 24 and 48 h.  The 48–hour EC50was 684 µg/L.  The 48–hr NOEC based on immobilization was 225 µg test item/L.