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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test conditions are similar to the OECD test guideline. The test conditions and the results are well described. Only one dose level was tested by oral route and no positive control was used. Compliance with GLP was not mentioned.
Cross-reference
Reason / purpose:
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:
Mutation Research, 370, 1-9

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
only one dose level was used
GLP compliance:
not specified
Type of assay:
mammalian germ cell cytogenetic assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): salicylic acid from Sigma Chemical Co. (St, Louis, MO)
No other data

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Division of laboratory animals, Central drug research institute, Lucknow
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 30 g
- Assigned to test groups randomly: no data
- Fasting period before study: no data
- Housing: no data
- Diet : ad libitum, standard rodent pellet diet (Gold Mohor, Lipton India Ltd., Chandigarh, India)
- Water : ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 28 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: solution of gum acacia in water at 2 %
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data
Details on exposure:
Salicylic acid was suspended with 2% gum acacia in distilled water and gavaged (350 mg/kg bw) to a group of 5 mice (0.3 ml/mouse). Negative control mice were gavaged only 2 % gum acacia in distilled water.
Duration of treatment / exposure:
24 hours
Frequency of treatment:
once
Post exposure period:
24 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
350 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
5 male mice per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
None

Examinations

Tissues and cell types examined:
Cells from the bone marrow were examined.
Details of tissue and slide preparation:
After 22 hr of chemical treatment, the animals were injected with  colchicine (2 mg/kg) and 2 hr later they were killed by cervical  dislocation. Bone marrow chromosomes were prepared and slides were stained with Giemsa.  All the slides were coded and 100 well spread metaphase cells 
were scored  per animal. Mitotic indices (MI) were calculated from 1000 cells/animal.  CA were scored. 
Evaluation criteria:
Statistically significant dose-related increase in the number of CA.
Statistics:
Student's t-test was used to compare the results.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined
Additional information on results:
none

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under the condition of this test, salicylic acid did not induce a genotoxic effect.
Executive summary:

In an in vivo chromosome aberration assay (Giri et al., 1996), Swiss albino male mice were treated with salicylic acid, suspended with 2% gum acacia in distilled water (0.3 ml/mouse), by gavage at the dose of 350 mg/kg. Five mice were used for treated group along with a negative control. Negative control mice were gavaged with 2% gum acacia in distilled water. No significant increase in CA was observed for salicylic acid when compared with solvent control. A significant increase in MI was observed for salicylic acid. This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 475.