Trimetazidine

Short-term toxicity to fish

Administrative data

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

27 Sept. 2004 to 1st Oct. 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Deviations:

no

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trimetazidine

EC Number:

225-690-2

EC Name:

Trimetazidine

Cas Number:

5011-34-7

Molecular formula:

C14H22N2O3

IUPAC Name:

1-[(2,3,4-trimethoxyphenyl)methyl]piperazine

Test material form:

liquid

Details on test material:

No details are provided in the study report

Specific details on test material used for the study:

No analytical data are provided on the test material in the study report. Batch N°538271/0124

Sampling and analysis

Analytical monitoring:

not specified

Test solutions

Vehicle:

no

Details on test solutions:

Preparation of the stock solution:
To prepare the stock solution, the test item will be dissolved or dispersed directly in test water. The obtained preparation will be agitated mechanically for up to 24 hours in an attempt to completely dissolve or disperse the test item.
Water: filtered and dechlorinated potable water which is then softened by a Permo® water softening system. Half of the water passes directly into a reservoir tank attached to the water delivery system for culture while the remaining half passes through a deioniser producing ultra-pure water which is then fed into the reservoir tank. This results in a dilution of potable dechlorinated:deionised water giving a supply of the desirable hardness. The pH of the resulting solution is between 6.0 and 8.5 (generally in the range 7.5 - 8.0) and the total hardness is between 10 and 250 mg/L as CaC03 (generally in the range 130 - 170 mg/L as CaC03).

Preparation of the test solutions:
Test solutions were prepared by further dilution of the stock solution with water or directly from the test item. A solution containing a maximum of 100 mg/L of the test item plus two other range-finding concentrations was prepared. Test vessels (aquariums) were filled directly from the test solution containers immediately after preparation. The same vessels were used throughout the test.

Test organisms

Test organisms (species):

Oncorhynchus mykiss (previous name: Salmo gairdneri)

Details on test organisms:

Justification of this choice: the rainbow trout is a fish species generally accepted by regulatory authorities for this type of study and is recommended in OECD and EEC guidelines.
Origin: CIT, BP 563, 27005 Evreux, France; the eggs are obtained from Viviers de France, Pisciculture des Fontaines, 64490 Sarrance, France.
Allocation to study: animals were selected using a hand-net, without preference, and randomly assigned to test vessels.
Number of animals: four groups of seven fish.

Study design

Test type:

static

Water media type:

freshwater

Total exposure duration:

96 h

Test conditions

Hardness:

Between 154 and 155mg/L of CaCO3 in the control flask

Test temperature:

Between 14.0 and 14.8°C

pH:

Between 7.66 and 8.72

Dissolved oxygen:

Between 7.4 and 10.0 mg/L

Salinity:

Not specified (freshwater)

Conductivity:

Not specified

Nominal and measured concentrations:

Nominal concentrations : 0 ; 1 ; 10 & 100 mg/L

Details on test conditions:

Light/dark cycle: 16/8 hours.
Loading: up to 1 g of fish per liter of test solution. The animals were between 4 and 6 cm in length.
Food: During culture, animals were fed trout chow twice daily, ceasing at least 24 hourg before the start of the test. Animals were not fed during the test.

Reference substance (positive control):

not specified

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

24 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 2

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 3

Duration:

72 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Effect concentrations 4

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Any other information on results incl. tables

Sublethal observations / clinical signs:

Table 1: Physicochemical parameters

	Time (hours)	Temperature (°C)			pH		Oxygene rate (mg/L)	Water hardness (mg/L of CaCO3)
	Control
	0*	14,0			7,45		9.9	154
	24	14,5			7,87		8,0
	48	14,6			7,66		7,9
	72	14,3			7,73		7,8
	96	14,3			7,93		7,6	155
Highest nominal concentration : 100mg/L until T96h
0*			14,2	8,72		10,0
24			14,6	8,04		7,8
48			14,8	7,77		8,0
72			14,4	7,77		7,6
96			14,3	7,90		7,4

* Parameter measured between T0 and T2 hours

 

 

Table 2:Summary of mortality

Observation time (hours)	Mortality at each nominal concentration (mg/L) n fishes on 7 fishes
	Control	1	10	100
0	0	0	0	0
24	0	0	0	0
48	0	0	0	0
72	0	0	0	0
96	0	0	0	0

 

  

Table 3: Observation of clinical signs

		N fishes on 7 fishes
Nominal concentration (mg/L)	Time (hours)	NTR	Loss of eq.	fish on the surface	Fish at the bottom of the aquarium	Hyper.	vertical swim	swimming on the back	spasms	Loss of color	quick breathing	Imm.	death
0	0 to 96h	0	0	0	0	0	0	0	0	0	0	0	0
1	0 to 96h	0	0	0	0	0	0	0	0	0	0	0	0
10	0 to 96h	0	0	0	0	0	0	0	0	0	0	0	0
100	0 to 96h	0	0	0	0	0	0	0	0	0	0	0	0

NTR: Nothing to Report

Loss of eq.: Loss of equilibrium

Hyper.: Hyperactive fish

Imm. :Immobilisation

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The highest concentration without clinical effect and mortality at T96h was 100 mg/L.
The lowest concentration with 100% mortality at T96h was > 100 mg / L.
LC50s at 24h, 4811, 72h and 96h were > 100 mg / L.

Executive summary:

An acute toxicity test was performed on rainbow trout under static conditions according the OECD guidline 203. No toxicity on fish of the test item was observed during the test.

The highest concentration without clinical effect and mortality at T96h was 100 mg/L.

The lowest concentration with 100% mortality at T96h was > 100 mg / L.

LC50s at 24h, 4811, 72h and 96h were > 100 mg / L.