Fusidic acid

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:

from 2006-01-16 to 2006-01-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

according to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1992-07-17

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Chemical name: Sodium fusidate
Batch No. Lot A4620
Molecular formula: C31H47O6Na
purity: 93%

The degree of dissociation of fusidic acid can be calculated as a function of pH (α = Ka/(Ka+[H+]) with the pKa for fusidic acid determined to be 4.9:
pH α
6.00 0.93
6.50 0.98
7.00 0.99
7.50 1.00
8.00 1.00
For environmental realistic conditions at pH 7-8, fusidic acid will be almost completely (99-100%) dissociated and will be present in the fusidate form. Due to the dissociation of the substance, it is therefore justified to use environmental data on the fusidate form to describe fusidic acid under these conditions.

Analytical monitoring:

yes

Details on sampling:

Chemical analysis were performed at LEO Pharma A/S. Not according to GLP.

Vehicle:

no

Details on test solutions:

The stock solution was prepared by weighing out 1.600 mg of the test substance and adding 2.0 L of test medium. Stock solution was used to prepare a dilution series of the test medium

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Details on test organisms:

Danio rerio (approximately 2+/-0.5 cm at the beginning of the test)

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Remarks on exposure duration:

According to guideline

Post exposure observation period:

not included

Hardness:

N.a.

Test temperature:

23+/-2°C

pH:

7.7-8.0

Dissolved oxygen:

94-100%

Salinity:

freshwater

Conductivity:

N.a.

Nominal and measured concentrations:

Nominal concentration Meassured concentrations
T = 0 T = 24 (old) T = 24 (new) T = 48 (old) T = 48 (new) T = 72(old) T = 72 (new) T = 96 (old)
Stock (800 mg/L) n.a. n.a. n.a. 807
Control n.a. n.a. n.a. n.a. n.a. n.a. n.a. n.a.
10 mg/L 9 9 n.a. n.a. 9 11 n.a. 9
25 mg/L n.a. 2 n.a. n.a. n.a. n.a. n.a. n.a.
60 mg/L 58 65 n.a. n.a. 64 64 65 65
160 mg/L n.a. n.a. n.a. n.a. n.a. n.a. n.a. n.a.
400 mg/L 411 415 n.a. n.a. 410 416 400 406
n.a. : not analysed

Details on test conditions:

semi static, renewal every 24 hours

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Key result

Duration:

96 h

Dose descriptor:

LC10

Effect conc.:

> 160 - <= 400 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

> 400 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Details on results:

Results are based on nominal concentrations. Sodium Fusidate NOS was considered stable throughout the test (recovery was between 101-122%)

Results with reference substance (positive control):

LC50 =208 mg/L (95% confidence intervals: 133-308)

Reported statistics and error estimates:

Results did not allow statistical analysis as the highest test concentration only resulted in 30% mortality during the exposure period.
Probit analysis was applied for calculating the LC10/LC50 and LC90 values for the reference substance

Validity criteria fulfilled:

yes

Conclusions:

A fish acute toxicity study was conducted with Danio rerio under semi-static conditions (renewal of test media every 24h)
The resulting LC10 (96h) and LC50 (96h) were 160-400mg/L and > 400 mg/L respectively.

Executive summary:

A fish acute toxicity study was conducted with Danio rerio under semi-static conditions (renewal of test media every 24h) on sodium fusidate.

For environmental realistic conditions at pH 7-8, fusidic acid will be almost completely (99-100%) dissociated and will be present in the fusidate form. Due to the dissociation of the substance, it is therefore justified to use environmental data on the fusidate form to describe fusidic acid under these conditions.

The study was conducted according to GLP and according to OECD Guideline no 203.

The resulting LC10 (96h) and  LC50 (96h) were 160-400mg/L and > 400 mg/L respectively. Sodium Fusidate NOS was considered stable throughout the test (recovery was between 101-122%) and results were therefore based on nominal concentrations. Validity criteria were fulfilled

Description of key information

A fish acute toxicity study was conducted with Danio rerio under semi-static conditions (renewal of test media every 24h) on sodium fusidate. For environmental realistic conditions at pH 7-8, fusidic acid will be almost completely (99-100%) dissociated and will be present in the fusidate form. Due to the dissociation of the substance, it is therefore justified to use environmental data on the fusidate form to describe fusidic acid under these conditions. The study was conducted according to GLP and according to OECD Guideline no 203.

Sodium Fusidate NOS was considered stable throughout the test (recovery was between 101-122%) and results were therefore based on nominal concentrations. Validity criteria were fulfilled.

Results did not allow statistical analysis as the highest test concentration (400 mg/L) only resulted in 30% mortality during the exposure period. LC50 is therefore reported as > 400 mg/L

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

400 mg/L