Fusidic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23-Aug-2006 (animal arrival) to 8-Sep- 2006 (necropsy).

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was conducted in accordance with the principles mentioned in the CPMP/SWP/1042/99 guideline “Note for guidance on repeated dose toxicity".

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: CPMP/SWP/1042/99 guideline

GLP compliance:

no

Test type:

other: 1 week dose-finding study

Test material

Test material information

Constituent 1

Reference substance name:

Fusidic acid

EC Number:

230-256-0

EC Name:

Fusidic acid

Cas Number:

6990-06-3

Molecular formula:

C31H48O6

IUPAC Name:

2-[(1Z,2S,3aS,3bS,5aS,6S,7R,9aS,9bS,10R,11aR)-2-(acetyloxy)-7,10-dihydroxy-3a,3b,6,9a-tetramethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-1-ylidene]-6-methylhept-5-enoic acid

Test material form:

solid: crystalline

Details on test material:

Details are given for each individual study

Specific details on test material used for the study:

Batch no. 06 265 151 used in oral suspension for group 2, 100 mg/mL
Batch no. 06 268 150 used in oral suspension for group 3, 200 mg/mL
No CoA available as the study is a non-GLP dose-finding study.

Test animals

Species:

mouse

Sex:

not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

Fusidic acid is tested in the following vehicle: Methylcellulose 15 cps 10 mg Polysorbate 80 4 mg Water purified ad 1 mL containing methylcellulose and polysorbate 80.

Doses:

Two mice were treated orally by gavage daily for 7 days with 1000 mg/kg of fusidic acid.
Another two mice were treated likewise with 2000 mg/kg of fusidic acid
The dose volume was 10 ml of suspension/kg/day.

Control animals:

no

Details on study design:

2 concentrations (1000 mg/kg bw. and 2000 mg/kg bw.)
2 mice per concentration tested
Duration: 1 week

Statistics:

No statistical calculations were made in this study as no control group of animals were used

Results and discussion

Preliminary study:

This study is a preliminary study for dose level setting for a 2 week study.

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Remarks:

7 days

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

No clinical findings were observed

Body weight:

Only a transient and minor weight loss was observed in the beginning of the treatment period in one mouse receiving 2000 mg/kg/day of fusidic acid. However, on the last days of the treatment period this effect was not so pronounced,
suggesting an adaptation to the treatment.

Any other information on results incl. tables

A dose level of up to 2000 mg/kg/day of fusidic acid given orally by gavage for 7 days were well tolerated in mice in this study

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A dose level of up to 2000 mg/kg/day of fusidic acid given orally by gavage for 7 days were well tolerated in mice in this study. Based on the results from this study, an LD50 > 2000 mg/kg bw/d could be established.

Executive summary:

Two mice were treated orally by gavage daily for 7 days with 1000 mg/kg of fusidic acid. Another two mice were treated likewise with 2000 mg/kg of fusidic acid

The dose volume was 10 ml of suspension/kg/day. A dose level of up to 2000 mg/kg/day of fusidic acid given orally by gavage for 7 days were well tolerated in mice in this study. Based on the results from this study, an LD50 > 2000 mg/kg bw/d could be established.