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EC number: 200-609-3 | CAS number: 65-45-2
Toxicological information
Genetic toxicity: in vivo
Currently viewing:
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study published in a peer-reviewed journal, according to scientific standards. Experimental details well documented, no explicit reference to guideline.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Comparative genotoxicity of six salicylic acid derivatives in bone marrow cells of mice
- Author:
- Giri AK, Adhikari N & Khan KA
- Year:
- 1 996
- Bibliographic source:
- Mutat. Res., 1996, 370, 1-9
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- Housing temperature (28+-2°C) too high. Only male mice tested (5 per dose) - no justification given.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.5385 (In Vivo Mammalian Cytogenetics Tests: Bone Marrow Chromosomal Analysis)
- Deviations:
- yes
- Remarks:
- Only male mice tested (4 per dose i.p., 5 for oral gavage----) - no justification given.
- GLP compliance:
- not specified
- Type of assay:
- chromosome aberration assay
Test material
- Reference substance name:
- Salicylamide
- EC Number:
- 200-609-3
- EC Name:
- Salicylamide
- Cas Number:
- 65-45-2
- Molecular formula:
- C7H7NO2
- IUPAC Name:
- salicylamide
- Details on test material:
- - Substance type: pure active substance
- Physical state: solid
- Supplier: Sigma Chemical Co, St. Louis MO, USA
- Analytical purity: no data
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Division of Laboratory animals, Central Drug Res. Institute, Lucknow, India
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 30 g
- Assigned to test groups randomly: no data
- Fasting period before study: no
- Housing: five per cage, husk bedding
- Diet: Standard rodent pellet diet, Gold Mohor, Lipton India Ltd, Chandigarh, India (ad libitum)
- Water: ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 28 +/- 2 °C
- Humidity (%): 60 +/- 5 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12 hours
IN-LIFE DATES: no data
Administration / exposure
- Route of administration:
- other: intraperitoneal (3 dose levels); or oral (gavage) 1 dose level
- Vehicle:
- - Vehicle(s)/solvent(s) used: DMSO (for i.p. application), suspension in 2% gum acacia in distilled water (for gavage application)
- Justification for choice of solvent/vehicle: solubility of the test substance
- Concentration of test material in vehicle: dose-dependent: approx. 20, 40, and 80 mg/mL (i.p.), 35 mg/mL (gavage)
- Amount of vehicle (if gavage or dermal): DMSO 75 microliter/mouse for i.p., 2% gum acacia in water 0.3 mL per mouse for gavage
- Type and concentration of dispersant aid (if powder): 2% gum acacia
- Lot/batch no. (if required): no data
- Purity: no data - Duration of treatment / exposure:
- i.p. administration: 24 hours, gavage administration: 24 hours
colchicine: 2 hours before sacrifice - Frequency of treatment:
- single treatment
- Post exposure period:
- none (time between administration and sacrifice: i.p. 24 hours, gavage 24 hours)0
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
i.p. 50, 100, 200 mg/kg body weight
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
oral (gavage) 350 mg/kg body weight
Basis:
nominal conc.
- No. of animals per sex per dose:
- 4 males per dose, i.p. administration
5 males, oral administration - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide:
- Justification for choice of positive control(s): no data
- Route of administration: i.p. only
- Doses / concentrations: 25 mg/kg
Examinations
- Tissues and cell types examined:
- Bone marrow cells
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
i.p.: based on the results of the Sister Chromatid Exchange (SCE) dose-response study: one higher dose was selected, since chromosome aberration is less sensitive than SCE
oral/gavage: 1/3 of approx. oral LD50
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
- i.p. injection and gavage 22 h before colchicine, 24 hours before sacrifice
- colchicine (2 mg/kg) 2 h before sacrifice
- sacrifice and expelling of bone marrow 24 hours after treatment
DETAILS OF SLIDE PREPARATION:
- bone marrow chromosomes prepared according to Preston RJ et al (1987) Mutation Res. 198: 157-165
- staining of chromosomes on slide with Giemsa
METHOD OF ANALYSIS:
- 100 well-spread metaphase cells scored per animal
- mitotic indices (MI) calculated from 1000 cells / animal, expressed as percentage
- chromosome aberrations (CA) scored according to WHO method (Preston et al, see above)
- aberration frequencies of chromatid and chromosome type per cell calculated
- gaps recorded but not included in the frequency of aberrations per cell - Evaluation criteria:
- Significant increase in chromosome aberration
Gaps recorded but not included in the frequency of aberrations per cell - Statistics:
- Statistical calculations carried out from percentages of aberrant cells
Student's t-test, to compare results at each dose with control
Results and discussion
Test results
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Remarks:
- no mortality
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
Any other information on results incl. tables
No significant increase in aberrations / cell and aberrant cells (%) for all doses tested, when compared to solvent control.
No significant difference in mitotic indices, when compared to control.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
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