Quinazolin-4(1H)-one

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2007-01-29 to 2007-02-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1992

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Batch no.: LOT S17686-226
Purity: 99.7% (HPLC purity)

Analytical monitoring:

yes

Details on sampling:

For the analysis of the actual test item concentrations the following samples were taken.
Just before the start of the test: duplicate samples from each test medium; duplicate samples from the control.
After 96 hours(stability samples): duplicate samples from each test medium; duplicate samples from the control.

As the stock solution corresponded to the test item solution, no additional sample was taken. All samples were taken from the approximate center of the aquaria without mixing of the test media, and were deep-frozen (at about -20 °C) immediately after sampling. Based on preexperiments for investigation of the storage stability (without GLP) the test item is sufficiently stable in the test water under the storage conditions.

The concentrations of the test item were analyzed in one of the duplicate test medium samples of all test concentrations and of the control from both sampling times.

Vehicle:

no

Details on test solutions:

The following nominal concentrations of test item were tested: 6.3, 13, 25, 50 and 100 mg/L. Additionally, a control was tested in parallel (test water without test item).
The test media were prepared as follows:
A stock solution of nominal 100 mg/L (= highest test concentration) was freshly prepared in three separate portions by dissolving 1000.0, 1000.9 and 1001.0 mg of the test item in 10 liters of test water each. No auxiliary solvent or emulsifier was used. The test item was mixed into the test water as homogeneously as possible using ultrasonic treatment for 15 minutes and intensive stirring on a magnetic stirrer for 3 hours at room temperature in the dark. Then, these solutions were filtered through a membrane filter (pore size 0.45 μm). After filtration, the three separate portions of the solution were poured together into a 40-liter vessel and thoroughly mixed. This solution was used to prepare the test media with the lower above mentioned test concentrations.
The preparation of the test media and the test concentrations were based on the results of a range-finding test and on the results of a pre-experiment to determine the solubility of the test item (without GLP). Concentrations in excess of nominal 100 mg/L have not been tested according to the guidelines.

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

TEST ORGANISM
- Common name: rainbow trout (Oncorhynchus mykiss)
- Source: P. Hohler, trout breeding station Zeiningen, CH-4314 Zeiningen,Switzerland.
- Length at study initiation (length definition, mean, range and SD): 4.4± 0.2 cm
- Weight at study initiation (mean and range, SD): 0.77 ± 0.09 g
- Method of breeding: fed with a commercial fish diet (HOKOVIT 502,1.2 mm, supplied by H.U. Hofmann AG, CH-4922 Bützberg, Switzerland).
- Maintenance of the brood fish: more than four weeks

ACCLIMATION
- Acclimation period: one week
- Health during acclimation (any mortality observed): no died and all were healthy

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Test temperature:

13°C

pH:

7.3 to 7.4

Dissolved oxygen:

8.9 mg/L

Nominal and measured concentrations:

Measured concentrations of the test item in the test media at test start was 6.3, 13.4, 25.0, 56,1, and 106 mg/L, the nominal values: 6.3, 13, 25, 50 and 100 mg/L

Details on test conditions:

One glass aquarium with 15 liters test medium was used for each test concentration and the control. The test vessels were labeled with the RCC study number and all necessary additional information to ensure unmistakable identification.

At the start of the test 7 fish were introduced into each aquarium in a random order. The loading rate was less than 0.8 g fish wet weight per liter test medium. The test media and the control were slightly aerated during the test period. The fish were not fed during the test.

Test duration: 96 hours
Water temperature: 13 °C during the test period
Light conditions: A 16-hour light to 8-hour dark photoperiod, with a 30-minute transition period (light intensity during the light period was approximately within the range of 50 to 500 Lux).
Test water: Reconstituted water: analytical grade salts were dissolved in deionized water. The test water was aerated prior to the preparation of the test media
until oxygen saturation was reached. The pH of the test water was 7.3.

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

91 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

6.3 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: significant toxic effect

Key result

Duration:

96 h

Dose descriptor:

LOEC

Effect conc.:

13 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: significant toxic effect

Details on results:

In the control and at the lowest test concentration of 6.3 mg/L all fish survived until the end of the test and no visible abnormalities were observed at the test fish.At the next two higher test concentrations of 13 and 25 mg/L, all test fish showed one or several visible abnormalities recorded at observations after 48, 72 and 96 hours (the number of the recorded visible abnormalities increasing with the concentration). At the end of the test, all fish survived at both of these test concentrations. At the two highest test concentrations of 50 and 100 mg/L, all test fish showed still more visible abnormalities recorded at observations after 24, 48, 72 and 96 hours. At the end of the test one of the seven test fish was dead at the concentration of 50 mg/L and four fish were dead at the concentration of 100 mg/L.
Thus, the 96-hour NOEC (highest concentration tested without observable toxic effects after the exposure period of 96 hours) and the 96-hour LC0 of test item to rainbow trout were determined to be 6.3 and 25 mg/L, respectively. The 96-hour LOEC (lowest concentration tested with observable toxic effects) was 13 mg/L.
The 96-hour LC50 of test item was calculated to be 91 mg/L (the 95% confidence interval could not be calculated). The 96-hour LC100 could not be determined due to the low toxicity of the test item up to the concentration of 100 mg/L.
No remarkable observations were made concerning the appearance of the test media. All test media were clear solutions throughout the entire test duration.

Validity criteria fulfilled:

yes

Conclusions:

After exposure of rainbow trout to test item over 96 hours in a dose-response test, the LC50 was determined to be 91 mg/L, the NOEC was determined to be 6.3 mg/L.

Executive summary:

The acute toxicity of the test item to rainbow trout (Oncorhynchus mykiss) was determined in a 96-hour static test according to the EU Commission Directive 92/69/EEC, Part C.1 (1992), and the OECD Guideline for Testing of Chemicals No. 203,(1992), as well as in consideration of the OPPTS Guideline No. 850.1075 (Public Draft, April 1996).

 

The nominal test item concentrations tested were 6.3, 13, 25, 50 and 100 mg/L, and in parallel a control.

 

The analytically determined concentrations of the test item in the test media varied in the range from 97 to 114% of the nominal values. The mean measured test item concentrations (calculated as the average over all measurements per test concentration) ranged from 99 to 113% of the nominal values. The test item was stable under the conditions of the test during the test period of 96 hours. Therefore, all reported biological results are related to the nominal concentrations of the test item.

 

The biological test results after 96 hours test duration:

96-hour LC50: 91 mg/L

95% confidence interval: could not be determined

96-hour LC0: 25 mg/L

96-hour LC100: >100 mg/L

96-hour NOEC: 6.3 mg/L

96-hour LOEC: 13 mg/L

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 1995-01-16 to 1995-01-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1984

Deviations:

yes

Remarks:

The stability of the test substance in the test water was not determined analytically.

GLP compliance:

yes

Specific details on test material used for the study:

Batch No.: Partie 9
Purity: 98.9 %

Analytical monitoring:

no

Vehicle:

no

Details on test solutions:

Preparation of the test solutions / dispersions: Separately for each conc. 0.0999, 0.2154, 0.4640, 1.0001 and 2.1507 g test substance were added to the test water using an ultra-turrax stirrer.

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

TEST ORGANISM
- Common name: Zebra fish
- Strain: Brachydanio rerio HAM. and BUCH.
- Source: West Aquarium GmbH
- Age at study initiation (mean and range, SD): about 4 months
- Length at study initiation (length definition, mean, range and SD): 3.4 cm (range: 3.0 - 4.0)
- Weight at study initiation (mean and range, SD): 0.44 g (range: 0.35 - 0.56)
- Maintenance of the brood fish: The fish were kept in a flow-through tank in tap water, not chlorinated, passed through an active carbon filter and aerated with oil-free air.

ACCLIMATION
- Acclimation period: about 1 month
- Acclimation conditions (same as test or not): same as test
- Type and amount of food during acclimation: "Tetra Min" standard feed ad libitum and on workdays additionally live artemia
- Feeding frequency during acclimation: "Tetra Min" standard feed ad libitum and on workdays additionally live artemia
- Health during acclimation (any mortality observed): Mortality during the last 2 weeks of housing: about 0.1 %

FEEDING DURING TEST
- Withdrawal of food: 1 day before and during exposure

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

about 2.5 mmol/L (= about 250 mg/L)

Test temperature:

22°C

pH:

8.4-8.6

Dissolved oxygen:

7.6-9.3 mg/L

Nominal and measured concentrations:

Nominal: 10.0, 21.5, 46.4, 100 and 215 mg/L.

Details on test conditions:

TEST SYSTEM
- Test vessel: all-glass aquaria (30 cm x 22 cm x 24 cm) , one aquarium for each test group
- Volume of water: 10 liters (water depth about 17 cm)
- Aeration: slight
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- Biomass loading rate: 0.44 g fish/L test water

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: municipal water of the city of Frankenthal
- Total organic carbon: about 2.5 mmol/L (= about 250 mg/L CaC03)
- Acid capacity: about 5.5 mmol/L
- Ca content: about 90 mg/L
- Mg content: about 10 mg/L
- pH: about 8.0 - 8.6
- Intervals of water quality measurement: regularly assayed

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16 hours light and 8 hours darkness
- Light intensity:

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Determination of mortality and symptoms after 1, 4, 24, 48, 72, 96 hours.

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 2.2
- Range finding study
- Results used to determine the conditions for the definitive study: LC 50 after 96 h: between 10 and 100 mg/L

Reference substance (positive control):

no

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

ca. 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

21.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

21.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

215 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

- Symptoms: tumbling

Validity criteria fulfilled:

yes

Conclusions:

The LC50 after 96 hours was determined to be about 100 mg/L.

Executive summary:

The purpose of this study was to determine the acute toxiclty of test item on the Zebra fish, based on the OECD guideline 203.

Zebra flsh were exposed over a 96-hour period to a range of 5 concentrations spaced by a factor of about 2.2: 10.0, 21.5, 46.4, 100 and 215 mg/L and an untreated control.

The study was performed using a static procedure.

The LC 50 after 96 hours was about 100 (mg/L), No observed effect concentration (NOEC) was 21.5 mg/L.

Maximum concentration tested causing no mortality: 21.5 mg/L

Minimum concentration tested causing 100% mortality: 215 mg/L

Description of key information

Two GLP studies are available.

One is conducted on rainbow trout in 2007 according to OECD 203. After exposure of rainbow trout to test item over 96 hours in a dose-response test, the LC50 was determined to be 91 mg/L, the NOEC was determined to be 6.3 mg/L.

Another one is conducted on zebra fish in 1996 according to OECD 203. The LC 50 after 96 hours was about 100 (mg/L), No observed effect concentration (NOEC) was 21.5 mg/L.

The first one study in 2007 is assigned as key study due to measured concentration and lower LC50.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

91 mg/L