Fusidic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1971

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Materials and methods

Principles of method if other than guideline:

Fusidin suspended in saccharose solution was administrated to rats six days weekly in doses of 400 mg/kg bw for 5 months.
Growth as well as haemoglobin percentage and count of red and white cells were observed and compared to control animals.

GLP compliance:

no

Limit test:

no

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:

No details on the test material.

Test animals

Species:

rat

Strain:

other: Local LEO strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

35 females and 35 males (weight: 110-120 g at the beginning of the test) of which 10 females and 10 males were control animals.

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

oral sugar solution

Vehicle:

other: saccharose solution

Details on oral exposure:

Six days weekly in doses of 400 mg/kg body weight

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

5 months

Frequency of treatment:

Perorally on six days weekly

Doses / concentrations

Dose / conc.:

400 mg/kg bw/day (nominal)

Remarks:

Dose was given six days weekly

No. of animals per sex per dose:

25

Control animals:

yes

Details on study design:

Control animals were given sugar solution without fusidin.

Positive control:

not included

Examinations

Observations and examinations performed and frequency:

Weekly weighings; Monthly blood examinations; including haemoglobin percentage and red and white blood cell counts

Sacrifice and pathology:

At the end of the test, all animals were sacrified and macroscopic inspections performed. Historical slides were prepared from lung, heart, spleen, lever, kidney, stomach and intestine.

Statistics:

No effects observed, no statistics reported

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

Macroscopic examination revealed nothing abnormal.

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

Analysis of blod samples showed average values within normal compared to the control group.

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Histological slides were prepared from lung, heart, spleen, liver, kidney, stomach and intestine. No pathological changes were found.

Histopathological findings: neoplastic:

not examined

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

>= 400 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

haematology

histopathology: non-neoplastic

Target system / organ toxicity

Key result

Critical effects observed:

no

Organ:

erythrocyte development

heart

intestine

kidney

leucocyte development

liver

lungs

spleen

stomach

Any other information on results incl. tables

No effects on the growth was observed. Body weight within normal range compared to the control group.

Blood samples: average values within normal compared to the control group.

By macroscopic inspection, nothing abnormal was found.

No pathological changes were observed.

Applicant's summary and conclusion

Conclusions:

The subchronic toxicity of fusidin acid from oral administration was evaluated rats at doses of 400 mg/kg bw/day, given six days weekly for 5 months. No toxic effects were observed and no effects on the growth. Analysis of blood samples showed average values within normal compared to the control group and no pathological changes were found. Based on these observations, a NOAEL of 400 mg/kg bw/d could be established.

Executive summary:

In a 5 months oral toxicity study in rats, fusidic acid was suspended in a saccharose solution and administered orally by gavage to one group of 25 male + 25 female rats of the local LEO strain. Daily doses of 400 mg/kg bw were administered six days a week for 5 months. A control group of 10 male + 10 female rats was treated with the sugar solution. No haematological changes and no untoward manifestations of toxicity were apparent throughout the test period. No gross pathological changes were detected. Microscopic examination of lung, heart, spleen, liver, kidney, stomach and intestine did not disclose any morphological alterations that could be attributed to the drug. Based on these observations, a NOAEL of 400 mg/kg bw/d could be established.