Salicylamide

Genetic toxicity: in vivo

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:

1996

Bibliographic source:

Mutat. Res., 1996, 370, 1-9

Materials and methods

Test guideline

Test guideline 1

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.

Test guideline 2

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

Test material information

Constituent 1

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

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
i.p. 50, 100, 200 mg/kg body weight
Basis:
nominal conc.

Doses / concentrations 2

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