Fusidic acid

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2006-01-17 to 2006-01-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to GLP

Principles of method if other than guideline:

OECD Guideline no 202

GLP compliance:

yes

Specific details on test material used for the study:

Sodium Fusidate NOS (011060; Lot. no. A4620; Afd. 221 ompd.)
Manufacturing date: 22-03-2006
Expiry date: 22-03-2006
Form: White powder
Purity: 99.3% (w/w)

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:

In order to verify test concentrations throughout the test, subsamples (2*10mL) were withdrawn at the start of the test, after 24 hours (before and after renewal) and at 48 hours. Samples were stored at -20°C and sent for analysis of sodium fusidate at LEO Pharma A/S.

Details on test solutions:

A stock solution of 600 mg/L was prepared by weighing out 0.180 gof the test substance and adding 300 mL of the test medium. The stock solution was used to prepare a dilution series of the test substance in the test medium.
Nominal concentrations of sodium fusidate were: 0 (control); 30; 60; 300 and 600 mg/L

Test organisms (species):

Daphnia magna

Details on test organisms:

Daphnia magna was cultured at DHI. Young animals < 24hours old were applied for the test.

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Post exposure observation period:

Not included

Hardness:

250+/-25 mg/L expressed as CaCO3

Test temperature:

19.5+/-0,2 °C

pH:

7.8+/-0.2

Dissolved oxygen:

98-100%

Salinity:

NA

Conductivity:

NA

Nominal and measured concentrations:

Time
Nominal concentration T = 0h(new solution) T =24h(old solution) T = 24h(new solution) T =48 h(old solution)
Control na na na na
30 mg/L 29 na na na
100 mg/L na na na na
300 mg/L 297 309 301 309
600 mg/L 591 610 614 615

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Key result

Duration:

48 h

Dose descriptor:

LC10

Effect conc.:

225 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

367 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Results with reference substance (positive control):

EC10 (24h) = 1.05 (0.274 -1.25)
EC50 (24h) = 1.74 (1.56 -1.98)

Validity criteria fulfilled:

yes

Conclusions:

EC10 (48h) = 225 (124-284)
EC50 (48h) = 367 (294-443)

Executive summary:

The acute toxicity of Sodium fusidate was tested during a Daphnia immobilization test (according to OECD guideline no 201). 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 test was performed with Daphnia magna, as a semi static test (renewal of test solutions after 24 hours) and was performed according to GLP. Test concentrations were analysed and as recovery was 97 -103% the test substance was considered stable during the test and concentrations reported as nominal concentrations.

The resulting EC10 and EC 50 values were:

EC10 (48h) = 225 (124-284)

EC50 (48h) = 367 (294-443)

Description of key information

The acute toxicity of Sodium fusidate was tested during a Daphnia immobilization test (according to OECD guideline no 201).

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 test was performed with Daphnia magna, as a semi static test (renewal of test solutions after 24 hours) and was performed according to GLP. Test concentrations were analysed and as recovery was 97 -103% the test substance was considered stable during the test and concentrations reported as nominal concentrations.

The resulting EC10 and EC 50 values were:

EC10 (48h) = 225 (124-284)

EC50 (48h) = 367 (294-443)

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

367 mg/L