Carbazole

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: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Clastogenicity of carbazole in mouse bone marrow cells in vivo

Author:

Jha AM, Sing AC, and Bharti MK

Year:

2002

Bibliographic source:

Mutat Res 521, 11-17

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

: only male animals, reporting of results not meeting requirements

Principles of method if other than guideline:

No guideline stated, but the method used is equivalent to OECD test guideline 475. The test performed is based the method described in Preston et al (1987), Mutat Res 189, 157-165, and Tice et al (1994), Mutat Res 312, 303-312.

GLP compliance:

no

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Carbazole

EC Number:

201-696-0

EC Name:

Carbazole

Cas Number:

86-74-8

Molecular formula:

C12H9N

IUPAC Name:

9H-carbazole

Details on test material:

- Name of test material (as cited in study report): carbazole (purchased from Sigma, USA)
- no further information on test substance

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility
- Amount of vehicle: 0.2 mL of 10% DMSO in phosphate buffered saline
- Test substance was predissolved in DMSO and then diluted with phosphate buffered saline to the concentration required for administration.

Details on exposure:

Doses of test substance were administered dissolved in 0.2 mL of 10% DMSO in phosphate buffered saline by intraperitoneal injection.

Duration of treatment / exposure:

single treatment

Post exposure period:

Bone marrow was collected 14 and 42 hrs after treatment of test animals.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 25, 50, 100, 150, and 200 mg/kg bw
Basis:
other: nominal injected

No. of animals per sex per dose:

12 (2 groups of 6 male animals each)

Control animals:

yes, concurrent vehicle

Positive control(s):

- mitomycin C
- Justification for choice of positive control(s): no data
- Route of administration: i.p. injection
- Doses / concentrations: 1.5 mg/kg bw in 0.2 mL phosphate buffered saline

Examinations

Tissues and cell types examined:

Bone marrow from both femora

Statistics:

students t-test, two-way ANOVA

Results and discussion

Test results

Sex:

male

Genotoxicity:

positive

Remarks:

after 14-h exposure at 150 and 200 mg/kgbw

Toxicity:

yes

Remarks:

at the highest dose, based on pre-tests clinical symptoms

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: single i.p. doses of 200, 300, and 400 mg/kg bw tested in groups of 15 male mice each; observation period 15 days
- Clinical signs of toxicity in test animals: at 400 mg/kg bw, 10 mice died within 2 days. At 300 mg/kg bw, 9 mice out of 15 died after 6 days. At 200 mg/kg, all animals survived. Toxic symptoms such as ataxia and lack of appetite disappeared within 2 hours after treatment. Based on the still apparent toxicity of carbazole at 200 mg/kg bw, this dose was selected as the upper dose limit for the definite study.
- Evidence of cytotoxicity in tissue analyzed: not examined

Any other information on results incl. tables

A general, dose-dependent trend of mitotic depression after carbazole treatment was evident for both, the 14 hr and 42 hr sampling period. But a statistically significant reduction of the mitotic index compared to solvent control was only observed for the 150 and 200 mg/kg bw group after 14 h exposure. In general, mitotic indices at 14 hr sampling time were lower than for the 42 h sampling period.

 

A slight dose-dependent, but not statistically significant increase in chromosome aberration was also observed, ranging from near background values for the 25 mg/kg group to statistically significant increases at 150 mg/kg (sampling time 14 h) and at 200 mg/kg (sampling time 14 and 42 h). Exposure for 14 h resulted in stronger clastogenic effect than the exposure for 42 h. Compared to the positive control (Mitomycin C) and taking into account the different doses, the effect observed for carbazole was at least 200 times lower. More detailed results are presented in the file "Tables results…" attached under "Attached background material".

 

In conclusion, the results of this study demonstrate that carbazole is moderately clastogenic in the bone marrow cells of mouse in vivo under the test conditions used.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive