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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Acute toxicity (oral):

- Oral (gavage) administration of fusidic acid or spiked fusidic acid at 2000 mg/kg/day to female mice of the Crl:CD1(ICR) strain for 15 days was well tolerated and fusidic acid and spiked fusidic acid can be considered comparable in terms of their toxicological potential to mice. Based on the results from this study, an LD50 > 2000 mg/kg bw/d could be established.

- 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.

Acute toxicity (dermal):

- In a cutaneous absorption study using 8 rabbits, 1g of 2% triated fusidin in fusidin salve (without lanolin) corresponding to 6.4-10 mg/kg bw was applied to the rabbit skin. 4 rabbits were treated with sodium lauryl sulphate in vaseline (to damage skin) / 4 served as control and were not treated (undamaged skin). 24 h later all animals were treated with fusidin salve (1g) and after 0, 2, 4,6, 8,24 and 48 h blood samples were taken. Absorption was measured in serum samples. This test method is comparable to recognised guideline for acute dermal toxicity testing in terms of application. Based on the results form the cutaneous absorption study using up to 10 mg/kg bw, an LD50 for dermal toxicity can be established to > 10 mg/kg bw.      

Acute toxicity (inhalation):

- No data available

Acute toxicity (other routes):

- 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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting 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
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
Test type:
other:
Limit test:
yes
Specific details on test material used for the study:
Batch number: 830517
Assay 99.9%
Related substances <0.1%
Water 1.7%
Species:
other: Both rat 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: 90-110 g obtained from Møllegaard Breeding Center Ltd. Ejby Denmark
Mice: 19-22 g LEO Pharma A/S breeding laboratory
Room temperature: 19-23 °C
Relative humidity: 30-40%

Animals were labeled; rats ear notching by and mice by ear tags

Route of administration:
oral: drinking water
Vehicle:
water
Doses:
5000 mg/kg bw.
No. of animals per sex per dose:
5 males and 5 female were used per dose level
Details on study design:
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%
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
Mice
Remarks on result:
other: oral
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
Rats
Remarks on result:
other: oral
Mortality:
No mortality observed
Clinical signs:
No effects
Body weight:
No effect
Interpretation of results:
GHS criteria not met
Conclusions:
In a 2-week study, rats and mice were exposed orally to fusidic acid (5000 mg/kg bw). No mortalities observed. Based on the results form this study, LD50 > 5000 mg/kg bw for both rat and mice can be established.
Executive summary:

In a 2-week study, rats and mice were exposed orally to fusidic acid (5000 mg/kg bw).

No mortalities observed. There were no effects on body weight and clinical signs, only reduced activity up to 4 hous after exposure was observed but was normal for the rest of the study. Based on the results form this study, LD50 > 5000 mg/kg bw for both rat and mice can be established.

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".
Qualifier:
according to guideline
Guideline:
other: CPMP/SWP/1042/99 guideline
GLP compliance:
no
Test type:
other: 1 week dose-finding 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.
Species:
mouse
Sex:
not specified
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
Preliminary study:
This study is a preliminary study for dose level setting for a 2 week study.
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
2 key studies available (Klimich score 1)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Eight male rabbits were shaved on their backs (area = 6*10cm)
4 rabbits were treated with sodium lauryl sulphate in vaseline / 4 served as control and were not treated.
24 h later all animals were treated with fusidin salve (1g) and after 0, 2, 4,6, 8,24 and 48 h blood samples were taken.

Serum was prepared from the blood samples and 1 ml samples mixed with a little water and 10 ml dimilume assed and counted up to 50min. each in Beckman CPM-100 liquid scintillation counter.

Test method is comparable to recognised guideline for acute dermal toxicity testing.
GLP compliance:
not specified
Limit test:
yes
Specific details on test material used for the study:
2% tritiated fusidin in fusidin salve (without lanolin). The salve contained 0.68MCi/g.
Total concentration of fusidic acid in salve was 2%.
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
weight: 2.55-3.05kg
Vehicle:
not specified
Details on dermal exposure:
Eight male rabbits were shaved on their backs (area = 6*10cm)
4 rabbits were treated with sodium lauryl sulphate in vaseline (to damage the skin) / 4 served as control (undamaged skin).
24 h later all animals were treated with fusidin salve (1g)
Duration of exposure:
24h
Doses:
1g of 2% triated fusidin in fusidin salve (without lanolin) corresponding to 6.4-10 mg/kg bw.
No. of animals per sex per dose:
4 males (only one dose)
Control animals:
yes
Details on study design:
please refer to section "principels of method if other than guideline"
Statistics:
NA
Key result
Sex:
male
Dose descriptor:
other:
Effect level:
> 10 mg/kg bw
Based on:
test mat.
Remarks on result:
other: serum levels were measured over time. In exposure groups levels were 3-45 times blank counts. Animals with intact skin had substantially lower levels.
Mortality:
No mortality
Clinical signs:
NA
Body weight:
NA
Gross pathology:
NA
Other findings:
Serum levels showed no effects from application of fucidin salve on intact skin.
Interpretation of results:
study cannot be used for classification
Conclusions:
In this cutaneous absorption study using 8 rabbits, 1g of 2% triated fusidin in fusidin salve (without lanolin) corresponding to 6.4 -10 mg/kg bw was applied to the rabbit skin. 4 rabbits were treated with sodium lauryl sulphate in vaseline (to damage skin) / 4 served as control and were not treated (undamaged skin). 24 h later all animals were treated with fusidin salve (1g) and after 0, 2, 4,6, 8,24 and 48 h blood samples were taken. Absorption was measured in serum samples.
This test method is comparable to recognised guideline for acute dermal toxicity testing in terms of application. Bsed on the results form the cutaneous absorption study using up to 10 mg/kg bw, an LD50 for dermal toxicity can be established to > 10 mg/kg bw.



Executive summary:

In this cutaneous absorption study using 8 rabbits, 1g of 2% triated fusidin in fusidin salve (without lanolin) corresponding to 6.4-10 mg/kg bw was applied to the rabbit skin.

Eight male rabbits were shaved on their backs (area = 6*10cm). 4 rabbits were treated with sodium lauryl sulphate in vaseline (to damage skin) / 4 served as control and were not treated (undamaged skin). 24 h later all animals were treated with fusidin salve (1g) and after 0, 2, 4,6, 8,24 and 48 h blood samples were taken. Absorption was measured in serum samples.

This test method is comparable to recognised guideline for acute dermal toxicity testing in terms of application. Bsed on the results form the cutaneous absorption study using up to 10 mg/kg bw, an LD50 for dermal toxicity can be established to > 10 mg/kg bw.      

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 mg/kg bw

Additional information

Justification for classification or non-classification

Based on the available data showing low potential for acute toxicity, no classification for acute toxicity is proposed.