Fusidic acid

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Remarks:

Interperitoneal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Principles of method if other than guideline:

Sprague-Dawley rats 5 of each sex placed in cages.
NMRI mice 5 of each sex placed in cages.
Animals were identified, mice by ear tags and rats by ear notching.

Test substance suspended in water for injection with methocel and administrated orally 0.5 ml in mice and 1.0 ml in rats. And 1 ml intraperitoneally.
Clinically observations were performed after 0,5, 1, 1,5 and 2 hours and hereafter daily.
Time of death was recorded and the following observations were made:
Skin and fur
Eyes
Mucous membrane
Respiration
Circulatory system
Diarrhoea
Salivation
Behaviour
Tremors
Convoulsion
Weight loss
Lethargy longevity
Coma longevity
After 14 days animals were killed and autopsied and histological examinations performed

GLP compliance:

no

Limit test:

yes

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 830517
Assay 99.9%
Related substances <0.1%
Water 1.7%

Test animals

Species:

other: Both rats and mice were tested

Strain:

Sprague-Dawley

Remarks:

mice: NMRI strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

Rat: Pathogen free Sprague-Dawley (mol: SPRD (Syn. Sprague-Dawley)), 90-110 g obtained from Møllegaard Breeding Center Ltd. Ejby Denmark - kept in microlon cages with 5 of one sex in each cage.
Mice: 19-22 g supplied from LEO Pharma A/S breeding laboratory and kept in microlon cages with 5 of one sex in each cage.
Conventional conditions, room temperature 17-23 °C, relative humidity 30-40%

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Remarks:

injected with 0.25% w/v methocel

Details on exposure:

Intraperitoneal administration was 1 ml.

Doses:

Rats: 2000; 3000; 4000 and 5000 mg/kg bw
Mice: 3000; 4000 and 5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 female were used per dose level

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 900 mg/kg bw

Based on:

test mat.

Remarks:

Mice

95% CL:

> 3 111 - < 4 440

Remarks on result:

other: intraperitoneal

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 550 mg/kg bw

Based on:

test mat.

Remarks:

Rats

95% CL:

> 2 554 - < 4 934

Remarks on result:

other: Intraperitoneal

Mortality:

Observed mortality:
Rats: 2000 mg/kg - no mortality; 3000 mg/kg - 4 of 10 animals; 4000 mg/kg 6 of 10 animals; 5000 mg/kg 7 of 10 animals
Mice: 3000 mg/kg 3 of 10 animals; 4000 mg/kg 5 of 10 animals; 5000 mg/kg 9 of 10 animals

Clinical signs:

Reduced spontaneous activity. After 2-3 hours following exposure, intraperitoneally treated mice exhibited reduced spontaneous activity. From here onwards no abnormal behaviour. Interperitoneally treated rats exhibited reduced spontaneous activity up to 24 hours. From here onwards no abnormal behaviour.

Body weight:

Depression in bodyweight

Gross pathology:

Minor hemorrhages in the small intestines and ascites were observed in animals dying within 48 hours. Residues of the test preparation were seen on the surface of the liver, intestine and other organs within the peritoneal cavity in animals exposed to the high dose of fusidic acid.

Applicant's summary and conclusion

Conclusions:

Acute toxicity of fusidic acid was determined for intraperitoneal administration to mice and rats. LD50 values were determined to be > 3900 mg/kg bw (3111-4440) for mice and > 3550 mg/kg bw (2554-4934) for rats.

Executive summary:

In an acute toxicity study, Fusidic acid was dosed by intraperitoneal administation to mice (3000 -5000 mg/kg bw) and rats (2000 -5000 mg/kg bw). The following results were obtained: LD50 > 3900 mg/kg bw (3111-4440) for mice and > 3550 mg/kg bw (2554-4934) for rats. Depression in body weight was observed after the intraperitoneal administration of fusidic acid. Reduced spontaneous activity was noted in mice after 2 -3 hours and up to 24 hours in rats. From here onwards no abnormal behaviour. Minor hemorrhages in the small intestines and ascites were observed. In the high dose animals, residues of the test preparation were seen on the surface of the liver, intestine and other organs within the peritoneal cavity.