Fusidic acid

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Alga, Growth Inhibition Test)

Version / remarks:

1984_06_07

Deviations:

no

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%

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:

Subsamples (25 mL) were withdrawn for chmical analysis after 0, 24, 48 and 72 hours of exposure. Samples were stored at -20°C until analysis at LEO Pharma A/S. Please also refer to section on result displaying the results from the chemical analysis.

Vehicle:

no

Test organisms (species):

Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum)

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

72 h

Post exposure observation period:

not included

Test temperature:

23.5+/-0.2°C

pH:

7.9 (stock solution)

Salinity:

freshwater

Nominal and measured concentrations:

0; 0.1; 0.3; 1; 3; 10; 30; 100; 300 (nominal concentrations)

Details on test conditions:

Cell density at start: 7500 cells/mL
Cells were incubated under continuous shaking and illuminated from a panal of fluorecent light at an intensity of approximately 3.5-7*10E15 quanta x cm-2 x sec-1. Density was meassured in the control mixture as an in vivo fluorescence at the beginning of the test and after 24, 48 and 72 hours of incubation in triplicate test flasks and six controls. Fluorescence was meassured with a TD-700 Laboratory Fluorometer.

Reference substance (positive control):

yes

Remarks:

Potassium dichromate

Key result

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

0.7 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

4.3 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Key result

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

0.3 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Details on results:

Sampling time, hours 0 24 48 72 Mean+/-Std. dev.
Nominal concentrations (mg/L) Measured concentration (mg sodium fusidate/L)
1 ≤1 ≤1 ≤1 2 ≤1
3 3 2 2 4 3+/-1
10 11 9 9 9 10+/-1
30 30 29 29 29 29+/-1


90-110% of the initially added sodium fusidate was recovered during 0-72 hours, the test substance was considered stable during the test and results were therefore reported as nominal concentrations

Results with reference substance (positive control):

The EC50 value calculated for the reference substance potassium dichromate was 1 (0.95-1.04) mg/L

Validity criteria fulfilled:

yes

Conclusions:

The resulting EC10; EC50 and NOEC values (72h) for sodium fusidate were: 0.7 mg/L 4.3 mg/L and 0.3 mg/L respectively.

Executive summary:

The toxicity of sodium fusidate towards algae was studied according to the OECD Guideline no 201 "Algae growth inhibition test".

The study was performed according to GLP.

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.

90-110% of the initially added sodium fusidate was recovered during 0-72 hours, the test substance was considered stable during the test and results were therefore reported as nominal concentrations

The resulting EC10; EC50 and NOEC values (72h) were:  0.7 mg/L 4.3 mg/L and  0.3 mg/L respectively based on growth rate.

The EC50 value calculated for the reference substance potassium dichromate was 1 (0.95-1.04) mg/L

Description of key information

The toxicity of sodium fusidate towards algae (Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum)) was studied according to the OECD Guideline no 201 "Algae growth inhibition test". The study was performed according to GLP. 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 resulting EC10; EC50 and NOEC values (72h) were:  0.7 mg/L 4.3 mg/L and  0.3 mg/L respectively (nominal concentration, based on growth rate).

Key value for chemical safety assessment

EC50 for freshwater algae:

4.3 mg/L

EC10 or NOEC for freshwater algae:

0.3 mg/L