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EC number: 230-256-0 | CAS number: 6990-06-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Spiked Fusidic Acid was assayed for mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium, both in the absence and in the presence of metabolic activation (S-9) , in two separate experiments. The study was performed in accordance to OECD 471 (AMES test). No toxicological significant increases in the frequecy of revertant colonies with treatments at concentrations up to or approaching the lower limit of toxicity, in the absence and in the presence of a rat liver metabolic activation system (S-9). Hence, Spiked Fusidic Acid was found to be non-mutagenic.
Spiked Fusidic Acid was assayed for its ability to induce mutation at the tk locus (5-trifluorothymidine resistance) in mouse lymphoma cells using a fluctuation protocol (OECD 476). The study consisted of a cytotoxicity range-finding experiment followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254 induced rat liver post-mitochondrial fraction (S-9). Spiked Fusidic Acid did not induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. The study was considerd to be valid based on the results from negative and positive controls. Thus, Spiked Fusidic Acid was found to be non-mutagenic under the conditions of this study.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Experimental work started on 24-Jan-2007 and was completed on 20-Feb-2007.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 1997
- Deviations:
- yes
- Remarks:
- plate counts were slightly above the historical ranges, they were all sufficiently comparable to be considered as characteristic and acceptable for demonstrating the correct strain and assay functioning.
- Qualifier:
- according to guideline
- Guideline:
- other: UKEMS Guideline
- Version / remarks:
- 1990
- Deviations:
- yes
- Remarks:
- plate counts were slightly above the historical ranges, they were all sufficiently comparable to be considered as characteristic and acceptable for demonstrating the correct strain and assay functioning.
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Harmonised Tripartite Guideline
- Version / remarks:
- 1997
- Deviations:
- yes
- Remarks:
- plate counts were slightly above the historical ranges, they were all sufficiently comparable to be considered as characteristic and acceptable for demonstrating the correct strain and assay functioning.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Spiked Fusidic acid, batch number 0704514701
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- both in the absence and in the presence of metabolic activation by an Aroclor 1254-induced rat liver post-mitochondrial fraction (S-9), in two separate experiments
- Test concentrations with justification for top dose:
- Concentrations based on range-finding study where toxicity was observed at a concentration of 200 ug/plate or higher
Experiment 1, using final concentrations of Spiked Fusidic Acid at 0.032, 0.16, 0.8, 4, 20, 100 and 500 μg/plate
Experiment 2, concentration ranges of 5.12 to 500 or 1250 μg/plate - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Remarks:
- Negative controls comprised treatments with the vehicle sterile anhydrous analytical grade dimethyl sulphoxide (DMSO).
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Positive controls:
- yes
- Positive control substance:
- other:
- Remarks:
- 2-aminoanthracene (AAN)
- Details on test system and experimental conditions:
- Bacteria Strain Type of mutation in the histidine gene
S. typhimurium TA98 frame-shift
S. typhimurium TA100 base-pair substitution
S. typhimurium TA1535 base-pair substitution
S. typhimurium TA1537 frame-shift
S. typhimurium TA102 base-pair substitution - Statistics:
- The m-statistic was calculated to check that the data were Poisson-distributed (10), and Dunnett's test was used to compare the counts at each concentration with the control.
The presence or otherwise of a concentration response was checked by linear regression analysis (10). As multiple regression analysis calculations are
performed (at each concentration level), there is an increased incidence of values which will fall outside the 95 or 99% probability range, but are not due to compound related increases.
Therefore, a statistically significant regression analysis is not considered as a biologically relevant event unless accompanied by a statistically significant Dunnett’s test. - Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxicity was only observed in experiment 2
- Untreated negative controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies on negative control plates were all considered acceptable,
- Positive controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies were significantly elevated by positive control treatments.
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxicity was only observed at the highest concentration tested (500 ug/plate and/or 1250 ug/plate)
- Untreated negative controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies on negative control plates were all considered acceptable,
- Positive controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies were significantly elevated by positive control treatments.
- Key result
- Species / strain:
- S. typhimurium TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxicity was only observed at the highest concentration tested (500 ug/plate and/or 1250 ug/plate)
- Untreated negative controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies on negative control plates were all considered acceptable,
- Positive controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies were significantly elevated by positive control treatments.
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxicity was only observed at the highest concentration tested (500 ug/plate and/or 1250 ug/plate)
- Untreated negative controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies on negative control plates were all considered acceptable,
- Positive controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies were significantly elevated by positive control treatments.
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- toxicity was only observed at the highest concentration tested (500 ug/plate and/or 1250 ug/plate)
- Untreated negative controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies on negative control plates were all considered acceptable,
- Positive controls validity:
- valid
- Remarks:
- The mean numbers of revertant colonies were significantly elevated by positive control treatments.
- Conclusions:
- Spiked Fusidic Acid was assayed for mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium, both in the absence and in the presence of metabolic activation (S-9) , in two separate experiments. The study was performed in accordance to OECD 471. No toxicological significant increases in the frequecy of revertant colonies were recorded, thus it was concluded that Spiked Fusidic Acid does not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium when tested under the conditions of this study. These conditions included treatments at concentrations up to or approaching the lower limit of toxicity, in the absence and in the presence of a rat liver metabolic activation system (S-9). Hence, Spiked Fusidic Acid was found to be non-mutagenic.
- Executive summary:
Spiked Fusidic Acid was assayed for mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium, both in the absence and in the presence of metabolic activation (S-9) , in two separate experiments. The study was performed in accordance to OECD 471.
Two experiments (refered to as experiment 1 and 2) were conducted:
Experiment 1, using final concentrations of Spiked Fusidic Acid at 0.032, 0.16, 0.8, 4, 20, 100 and 500 μg/plate, plus negative (vehicle) and positive controls. Following these treatments, evidence of toxicity was observed in the absence and presence of S-9 at 500 μg/plate in all strains except TA98. Although no clear evidence of toxicity was seen in strain TA98, treatments in this strain were considered to have been performed at concentrations approaching toxic levels, based on the observations seen in the other tester strains.
Following Experiment 2 treatments, clear evidence of toxicity was observed at either 500 μg/plate or 1250 μg/plate in all strains in the absence of S-9, and at either 200 μg/plate and above or 500 μg/plate (and above where applicable) in all strains in the presence of S-9.
No toxicological significant increases in the frequecy of revertant colonies were recorded, thus it was concluded that Spiked Fusidic Acid does not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium when tested under the conditions of this study. These conditions included treatments at concentrations up to or approaching the lower limit of toxicity, in the absence and in the presence of a rat liver metabolic activation system (S-9). Hence, Spiked Fusidic Acid was found to be non-mutagenic.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Experimental work started on 23-Jan-2007 and was completed on 13-Mar-2007.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- 1997
- Qualifier:
- according to guideline
- Guideline:
- other: UKEMS Guideline
- Version / remarks:
- 1990
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Tripartite Harmonised Guideline on Genotoxicity S2A: Specific Aspects of Regulatory Tests
- Version / remarks:
- 1995
- Qualifier:
- according to guideline
- Guideline:
- other: ICH Requirements for Registration of Pharmaceuti-cals for Human Use S2B, Genotoxicity: a Standard Battery for Genotoxicity Testing of Pharmaceuticals
- Version / remarks:
- Step 4, recommended for adoption 16 July 1997
- GLP compliance:
- yes
- Type of assay:
- other: gene mutation study in mammalian cells
- Specific details on test material used for the study:
- Batch number 0704514701
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- The mammalian liver post-mitochondrial fraction (S-9) used for metabolic activation
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Negative controls comprised treatments with the vehicle, sterile anhydrous analytical grade dimethyl sulphoxide (DMSO) diluted 100-fold in the treatment medium.
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Details on test system and experimental conditions:
- positive control chemicals:
Chemical Source Stock* concentration (mg/mL) Final concentration (μg/mL) S-9
4-nitroquinoline Sigma-Aldrich Chemical 0.0150 0.150# -
1-oxide (NQO) Co, Poole, UK 0.0200 0.200# -
benzo(a)pyrene (BP) Sigma-Aldrich Chemical 0.200 2.00 +
Co, Poole, UK 0.300 3.00 +
* All solutions were prepared in anhydrous analytical grade dimethyl sulphoxide (DMSO). NQO
and BP solutions, if not used immediately, were stored as frozen aliquots at –80ºC nominal in the
dark.
# For Experiment 2 -S-9 (24 hour treatment), final NQO concentrations of 0.05 and 0.1 μg/mL
were tested. - Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- The mutant frequency of the all the test concentrations were less than the sum of the mean control mutant frequency plus GEF, thus indicating a negative result.
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Exp.1 134 μg/mL (+/- S-9) yielded 13% and 43 % RTG respectively. Exp. 2 (+ S-9): Complete tox. At 134.4 μg/mL. The highest conc. tested that provided >10% RTG was 67.19 μg/mL, which yielded 22% RTG.
- Untreated negative controls validity:
- valid
- Remarks:
- For the negative controls, the proportion of small colony mutants in the absence and presence of S-9 ranged from 35% to 36% in Experiment 1 and from 29% to 31% in Experiment 2
- Positive controls validity:
- valid
- Remarks:
- Marked increases in the number of both small and large colony mutants were observed following treatment with the positive control chemicals NQO and BP
- Additional information on results:
- Negative controls comprised treatments with the vehicle, sterile anhydrous analytical grade dimethyl sulphoxide (DMSO) diluted 100-fold in the treatment medium.
Positive control chemicals: 4-nitroquinoline 1-oxide (NQO) and benzo(a)pyrene (BP)
In the cytotoxicity range-finding experiment, 3 hour treatment, six concentrations of Spiked Fusidic Acid were tested in the absence and presence of S-9, separated by two fold intervals and ranging from 67.19 to 2150 μg/mL (maximum concentration limited by supplied formulation). Upon addition of the test article to the cultures, precipitate was observed at the highest three concentrations tested (537.5 to 2150 μg/mL). After the 3 hour treatment incubation period, precipitate was observed at the highest concentration tested (2150 μg/mL). The highest four concentrations tested (268.8 to 2150 μg/mL) were not plated due to excessive toxicity (based on cell count data).
In the cytotoxicity range-finding experiment, 24 hour treatment, nine concentrations of Spiked Fusidic Acid were tested in the absence of S-9, separated by two fold intervals and ranging from 8.398 to 2150 μg/mL. Upon addition of the test article to the cultures, precipitate was observed at the highest three concentrations tested (537.5 to 2150 μg/mL). After the 24 hour treatment incubation period, precipitate was observed at the highest concentration tested (2150 μg/mL). The highest four concentrations tested (268.8 to 2150 μg/mL) were not plated due to excessive toxicity (based on cell count data). Complete toxicity was observed at the highest concentration plated (134.4 μg/mL). The highest concentration tested that provided >10% RTG was 67.19 μg/mL, which yielded 22% RTG. - Conclusions:
- Spiked Fusidic Acid was assayed for its ability to induce mutation at the tk locus (5-trifluorothymidine resistance) in mouse lymphoma cells using a fluctuation protocol (OECD 476). Based on the results, it is concluded that Spiked Fusidic Acid did not induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. These conditions included treatments up to toxic concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system (S-9). The study was considerd to be valid based on the results from negative and positive controls. Thus, Spiked Fusidic Acid was found to be non-mutagenic under the conditions of this study.
- Executive summary:
Spiked Fusidic Acid was assayed for its ability to induce mutation at the tk locus (5-trifluorothymidine resistance) in mouse lymphoma cells using a fluctuation protocol (OECD 476). The study consisted of a cytotoxicity range-finding experiment followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254 induced rat liver post-mitochondrial fraction (S-9).
The mutant frequency at all the test concentrations were less than the sum of the mean control mutant frequency plus GEF, thus indicating a negative result. No significant linear trend occurred with any experiment in the presence of S-9, and for treatments in the absence of S-9 in Experiment 2, but a very weak linear trend was observed in the absence of S-9 in Experiment 1. As no significant increase in mutant frequency occurred at any treatment concentration in Experiment 1, this observation alone is not considered sufficient to be indicative of any biologically relevant event.
It is concluded that Spiked Fusidic Acid did not induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. These conditions included treatments up to toxic concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system (S-9). The study was considerd to be valid based on the results from negative and positive controls. Thus, Spiked Fusidic Acid was found to be non-mutagenic under the conditions of this study.
Referenceopen allclose all
Experiment 1, using final concentrations of Spiked Fusidic Acid at 0.032, 0.16, 0.8, 4, 20, 100 and 500 μg/plate, plus negative (vehicle) and positive controls. Following these treatments, evidence of toxicity was observed in the absence and presence of S-9 at 500 μg/plate in all strains except TA98. Although no clear evidence of toxicity was seen in strain TA98, treatments in this strain were considered to have been performed at concentrations approaching toxic levels, based on the observations seen in the other test strains.
Following Experiment 2 treatments, clear evidence of toxicity was observed at either 500 μg/plate or 1250 μg/plate in all strains in the absence of S-9, and at either 200 μg/plate and above or 500 μg/plate (and above where applicable) in all strains in the presence of S-9.
Following Spiked Fusidic Acid treatments of all the tester strains, both in the absence and in the presence of a rat liver metabolic activation system (S-9), only Experiment 1 treatments of strain TA102 in the presence of S-9 resulted in any increase in revertant numbers that was statistically significant.
As the increase in Experiment 1 was neither doserelated nor reproducible, it was not considered to have been a biologically relevant or compound-related effect.
As no other strain treatments resulted in an statistically significant increases in revertant numbers, this study was considered to have provided no evidence of any Spiked Fusidic Acid mutagenic activity in this assay system.
In the cytotoxicity range-finding experiment, 3 hour treatment, concentrations of Spiked Fusidic Acid were tested in the absence and presence of S-9 ranging from 67.19 to 2150 μg/mL (maximum concentration limited by supplied formulation). Due to extreme toxicity, the highest concentration plated was 134.4 μg/mL, which yielded 13% relative total growth (RTG) in the absence of S-9 and 47% RTG in the presence of S-9.
In the cytotoxicity range-finding experiment, 24 hour treatment, concentrations of Spiked Fusidic Acid were tested in the absence of S-9, ranging from 8.398 to 2150 μg/mL (maximum concentration limited by supplied formulation). The highest concentration to provide >10% RTG was 67.19 μg/mL, which yielded 22% RTG.
Accordingly, for the first experiment (3 hour treatment) concentrations of Spiked Fusidic Acid were chosen ranging from 20 to 150 μg/mL in the absence of S-9, and from 60 to 240 μg/mL in the presence of S-9. Due to extreme toxicity, the highest concentrations analysed were 120 and 160 μg/mL in the absence and presence of S-9, which yielded 17% and 11% RTG respectively.
In the second experiment concentrations of Spiked Fusidic Acid were tested ranging from 10 to 120 μg/mL in the absence of S-9 (24 hour treatment) and from 60 to 220 μg/mL in the presence of S-9 (3 hour treatment). Due to extreme toxicity, the highest concentrations analysed were 80 μg/mL in the absence of S-9 and 160 μg/mL in the presence of S-9, which yielded 14% and 13% RTG respectively.
Negative (vehicle) and positive control treatments were included in each mutation experiment in the absence and presence of S-9. Mutant frequencies in negative control cultures fell within acceptable ranges, and clear increases in mutation were induced by the positive control chemicals 4-nitroquinoline 1-oxide (without S-9) and benzo(a)pyrene (with S-9). Therefore the study was accepted as valid.
The mutant frequency of the all the test concentrations were less than the sum of the mean control mutant frequency plus GEF, thus indicating a negative result. No significant linear trend occurred with any experiment in the presence of S-9, and for treatments in the absence of S-9 in Experiment 2, but a very weak linear trend was observed in the absence of S-9 in Experiment 1. As no significant increase in mutant frequency occurred at any treatment concentration in Experiment 1, this observation alone is not considered sufficient to be indicative of any biologically relevant event.
It is concluded that Spiked Fusidic Acid did not induce mutation at the tk locus of L5178Y mouse lymphoma cells when tested under the conditions employed in this study. These conditions included treatments up to toxic concentrations in two independent experiments, in the absence and presence of a rat liver metabolic activation system (S-9).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
A micronucleus test in mice was conducted in accordance to OECD Guideline 474 and following GLP. Groups of mice (NMRI strain), containing 10 males and 10 females, were exposed to a single oral dose of either 250 or 500 mg fusidic acid /kg bw. After 24 or 48 hours mice were sacrificed, the femora excised and bone marrow extracted. Sodium fusidate given orally to male and female mice in the fasting state at the dose levels of 250 and 500 mg/kg bw did not show any clastogenic potential in the in vivo micronucleus test.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- micronucleus test in mice
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Specific details on test material used for the study:
- Sodium fusidate
Solid
Lot no. C1728
Purity 99.9 % by HPLC for anhydrate substance, 99.6 by titration for anhydrate substance. - Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Bomholtgaard Breeding and Research Center, Ry, Denmark
Weight: Male 28g and female 25 g at
Number: 50 males and 50 females devided in 4 groups
Animals were placed 3 of one sex per cage. Dust free wood shavings were used for breeding material
Room temperature: 22.5°C
Relative humidity: 40-45%
Light/dark period: 12:12 hours
Free access to commercial rodent diet and tap water - Route of administration:
- oral: unspecified
- Vehicle:
- phosphate buffer solution: (disodium edetate 0.5 mg; disodium hydrogen phosphate19.6 mg; citric acid 1mg; water 1 mL) Lot no. B4049A
- Details on exposure:
- doses given orally to fasted animals. Control given intraperitoneally. Both in a volume of 10 mL/kg
- Duration of treatment / exposure:
- single dose
- Frequency of treatment:
- single dose
- Post exposure period:
- 24/48 hours
- Dose / conc.:
- 0 mg/kg bw (total dose)
- Dose / conc.:
- 250 mg/kg bw (total dose)
- Dose / conc.:
- 500 mg/kg bw (total dose)
- No. of animals per sex per dose:
- 10 males +10 females / group
- Control animals:
- yes
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide 25 mg/kg (6 males and 6 females exposed to positive control)
- Tissues and cell types examined:
- Femora excised and bone marrow extracted.
Polychromatic erythrocyte (PEC)/ Normochromatic erythrocyte (NCE) and Polychromatic erythrocyte (PECM)/ Normochromatic erythrocyte with micronuclei (NCEM) - Details of tissue and slide preparation:
- Extracted bone marrow was centrifugated (1000 rpm). The supernantant was decanted and remaining cells resuspended and smears prepared in duplicate.
Smears were fixed in methanol (5min) and stained in May-GrünWald solution (20min) and Giemsa stain (25min). Hereafter rinsed in phosphate buffer (pH 6.5) and finally rinsed in distilled water. - Statistics:
- Mann-Whitney test p ≤ 0.05 (=significant)
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Conclusions:
- Sodium fusidate given orally to male and female mice in the fasting state at the dose levels of 250 and 500 mg/kg bw did not show any clastogenic potential in an in vivo micronucleus test. Thus, Sodium fusidate was considered to be non-clastogenic.
- Executive summary:
A micronucleus test in mice was conducted in accordance to OECD Guideline 474 and following GLP.
Groups of mice (NMRI strain), containing 10 males and 10 females, were exposed to a single oral dose of either 250 or 500 mg fusidic acid /kg bw. After 24 or 48 hours mice were sacrificed, the femora excised and bone marrow extracted.
Sodium fusidate given orally to male and female mice in the fasting state at the dose levels of 250 and 500 mg/kg bw did not show any clastogenic potential in the in vivo micronucleus test.
Reference
Mean ratio (+SD) of polychromatic to Normochromatic Erythrocytes
Samples male | Samples female | ||||
Group | 24 h | 48 h | 24 h | 48 h | |
Negative control (vehicle) | 1.12 ± 0.27 | 1.03 ± 0.13 | 1.46 ± 0.31 | 1.08 ± 0.26 | |
Sodium fusidate 250 mg/kg bw | 1.02 ± 0.19 | 0.85 ± 0.17 | 0.88 ± 0.07 | 1.05 ± 0.12 | |
Sodium fusidate 500 mg/kg bw | 0.81 ± 0.17 | 0.86 ± 0.18 | 1.03 ± 0.24 | 0.84 ± 0.21 | |
Cyclophosphamide 25 mg/kg bw i.p. | 0.98 ± 0.05 | 0.66 ± 0.14 | 1.13 ± 0.20 | 0.96 ± 0.21 |
Mean incidence in percent (+SD) of micronucleated polychromatic erythrocytes
Samples male | Samples female | ||||
Group | 24 h | 48 h | 24 h | 48 h | |
Negative control (vehicle) | 0.04±0.05 | 0.02±0.04 | 0.04±0.05 | 0.06±0.05 | |
Sodium fusidate 250 mg/kg bw | 0.06±0.09 | 0.04±0.09 | 0.04±0.05 | 0.08±0.08 | |
Sodium fusidate 500 mg/kg bw | 0.04±0.05 | 0.00±0.00 | 0.00±0.00 | 0.06±0.09 | |
Cyclophosphamide 25 mg/kg bw i.p. | 1.77±0.45 | 1.60±0.62 | 0.87±0.31 | 0.53±0.15 |
Mean incidence percent (+SD) of micronucleated normochromatic erythrocytes
Samples male | Samples female | ||||
Group | 24 h | 48 h | 24 h | 48 h | |
Negative control (vehicle) | 0.14±0.11 | 0.02±0.04 | 0.03±0.08 | 0.00±0.00 | |
Sodium fusidate 250 mg/kg bw | 0.10±0.11 | 0.07±0.07 | 0.07±0.01 | 0.07±0.06 | |
Sodium fusidate 500 mg/kg bw | 0.03±0.04 | 0.04±0.05 | 0.00±0.00 | 0.04±0.09 | |
Cyclophosphamide 25 mg/kg bw i.p. | 0.19±0.16 | 1.08±0.29 | 0.04±0.07 | 0.59±0.09 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
Based on the available data base from in vitro and in vivo studies, no classification is proposed.
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