4-[(6-chloro-2-[(4-cyanophenyl)amino]-4-pyrimidinyl]oxy]-3,5-dimethylbenzonitrile

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-06-13 to 2003-07-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Deviations:

no

Remarks:

: There were no amendments made to the study plan.

Qualifier:

according to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

Deviations:

no

Remarks:

: There were no amendments made to the study plan.

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Name of test material (as cited in study report): T002615
- Substance type: not applicable
- Physical state: solid white
- Analytical purity: > 98%
- Purity test date: no data
- Lot/batch No.: 00403487
- Expiration date of the lot/batch: December 2003 (retest date)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: no data
- Storage condition of test material: at room temperature at about 20 °C, away from direct sunlight

Analytical monitoring:

yes

Details on sampling:

- Concentrations: 100 mg/L (loading rate); 0.19 ug/L (mean measured concentration). Just before test start: duplicate samples from the test medium and control. After 48 and 96 hours (stability samles): duplicate samples from the test medium and control.
- Sampling method: All samples were taken from the center o fthe aquaria without mixing the test medium.
- Sample storage conditions before analysis: the samples were analyzed directly after the sampling procedure.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: A filtrate of a saturated dispersion of the test item was prepared. The undiluted filtrate was tested as the only test concentrations. Before the start of the test, a supersaturated dispersion with a loading rate of 100 mg/L was prepared by mixing 603 mg of the test item into 6 L of test water.. The test item was mixed into the test water as homogeneously as possible using ultrasonic treatment for 15 minutes and by intense stirring for 24 hours at room temperature in the dark. No auxiliary solvent or emulsifier was used. the supersaturated dispersion of the test item was filtered through a membrane filter (Schleicher & Schuell, Type NC45, pore size 0.45 µm) just before the start of the test (= introduction of the fish).
- Controls: yes
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no remarkable observations, clear test substance solutions

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

TEST ORGANISM
- Common name: Zebra fish
- Strain: Brachydanio rerio
- Source: Zoohaus Schaub, Ch-4410 Liestal Switzerland
- Age at study initiation (mean and range, SD): no data
- Length at study initiation (length definition, mean, range and SD): 3.0 ± 0.2 cm
- Weight at study initiation (mean and range, SD): 0.18 ± 0.04 g
- Feeding during test: No

ACCLIMATION
- Acclimation period: one week
- Acclimation conditions (same as test or not): same as test
- Type and amount of food: commercial fish diet (TETRA MIN Hauptfutter, supplied by tetra-Werke, D-49304 Melle, Germany)
- Feeding frequency: no data
- Health during acclimation (any mortality observed): no mortalities

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

96 h

Post exposure observation period:

no data

Hardness:

- Hardness: 2.5 mmol/L (= 250 mg/L CaCO3)
- Alkalinity: 0.8 mmol/L

Test temperature:

22-23 °C

pH:

7.9-8.0

Dissolved oxygen:

8.2-8.7

Salinity:

not relevant

Conductivity:

not indicated

Nominal and measured concentrations:

Nominal: 100 mg/L
Measured: 0.15 -0.20 µg/L (0.19 µg/L mean of measured concentrations)

Details on test conditions:

TEST SYSTEM
- Test vessel: glass aquarium
- Type (delete if not applicable): no data
- Material, size, headspace, fill volume: 7L
- Aeration: The test water was aerated prior to the preparation of the test media until oxygen saturation was reached. The test media and the control were slightly aerated during the test period.
- No. of organisms per vessel: 7
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- Biomass loading rate: less than 1 g fish wet weight per liter test medium

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: reconstituted water
- Alkalinity: 0.8 mmol/L
- Ca/mg ratio: 4:1 (based on molarity)
- Intervals of water quality measurement: 0, 48, 96 h

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16h light and 8 h darkness
- Light intensity: 50-500 Lux

EFFECT PARAMETERS MEASURED (with observation intervals if applicable): mortality and visible abnormalities

TEST CONCENTRATIONS
- Spacing factor for test concentrations: not applicable
- Justification for using less concentrations than requested by guideline: not applicable
- Range finding study: Yes (not GLP)
- Test concentrations: not reported
- Results used to determine the conditions for the definitive study: range finding study and guideline (limit test)

Reference substance (positive control):

no

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

>= 0.19 µg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

>= 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

- Behavioural abnormalities: no
- Mortality of control: no
- Other adverse effects control: no
- Abnormal responses: no
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: no remarcable observations, clear test medium.
- Effect concentrations exceeding solubility of substance in test medium: not applicable

Reported statistics and error estimates:

The LOEC, LC100 and LC50 could not be quantified due to the absence of a toxic effect of the test substance at the tested concentration.

Validity criteria fulfilled:

yes

Conclusions:

The acute toxicity of T002615 to zebra fish was determined in a 96-hour static limit test according to OECD guideline 203. Under the conditions of the preent study, the 96-h LC50 exceeded the nominal concentration of 100 mg/L (mean measured 0.19 µm/L). The results of the test can be considered reliable without restriction.

Description of key information

The study of Seyfried (2003), investigating the acute toxicity of T002615 in Danio rerio according to OECD guideline 203, was considered as the key study for endpoint coverage. A LC50 > 100 mg/L (based on nominal test concentrations) was obtained after an exposure of 96 hours in a static test in freshwater. Based on the results it can be considered that T002615 is not harmful to fish.