Carbazole

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study, limited documentation, basic data given, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of substituted carbazoles in Salmonella typhimurium

Author:

LaVoie EJ, Briggs G, Bedenko V, and Hoffmann D

Year:

1982

Bibliographic source:

Mutat Res 101, 141-150

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

: control substances, unclear if any experiment was performed together with the required controls, limited reporting

Principles of method if other than guideline:

No guideline stated but the investigation was conducted following the method of Ames et al (1975). The mutagenicity of carbazole was tested in the Ames test together with 16 mono- or di-substituted carbazoles.

GLP compliance:

no

Type of assay:

bacterial reverse mutation 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
- test substance was purchased from Aldrich Chemical Company, Metuchen, NJ, USA, and purified by thin-layer or column chromatography prior to bioassay
- no further information on test substance reported

Method

Target gene:

his¯

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA1535, TA1537, TA1538, TA98, and TA100

Metabolic activation:

with and without

Metabolic activation system:

S9-mix from livers of Aroclor 1254 induced male Fischer-344 rats

Test concentrations with justification for top dose:

0, 5, 10, 25, 50, 100, 250 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: quinoline (250 µg), chrysene (20 µg) for all tester strains; N-methyl-N'-nitro-N-nitrosoguanidine (5 µg) for TA1535 and TA100; Picrolonic acid (250 µg) for TA1538 and TA98, 9-aminoacridine (0.5 µg) and 9-aminoanthracene (10µg) for TA1537

Remarks:

no distinct information on the use of positive control substances with and/or without metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: no data
- Expression time (cells in growth medium): no data

DETERMINATION OF CYTOTOXICITY: no data

Evaluation criteria:

Compounds were considered mutagenic when the average number of revertants obtained at any dose level was at least twice that of the solvent control.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA1535, TA1537, TA1538, TA98, and TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: TA1535, TA1537, TA1538, TA98, and TA100

Any other information on results incl. tables

Only carbazole derivatives substituted at the nitrogen atom (9-position) showed graduated mutagenic activity but only in one tester strain (TA100) and with metabolic activation. Only 9-hydroxmethylcarbazole did also induce a relevant increase in revertants without metabolic activation indicating that this substance is an active metabolite of 9 methyl-substituted carbazoles.

 

Parent carbazole did not induce any mutagenic response in any of the bacterial strains tested either with or without metabolic activation.

Only part of the results are reported in detailed form.

 

 

Substance	Dose [µg]	Revertants
		TA100		TA98 + S9
		+ S9	- S9
Solvent control (DMSO)*	50 [µL]	120 ± 5	98 ± 3	43 ± 2
Carbazol	250	111	95	35
	100	112	85	48
	50	132	98	33
	25	123	88	47
	10	129	81	39
	5	138	107	41
MNNG	5	109	1135	-
Quinoline	250	359	88	55
Chrysene	20	221	88	54
Picrolonic acid	250	-	-	741

 

* mean of all control experiments

MNNG: N-Methyl-N'-nitro-N-nitrosoguanidine

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In a bacterial reverse gene mutation assay according to Ames using the five S. typhimurium tester strains TA1535, TA1537, TA1538, TA98, and TA100, carbazole did not induce any mutagenic response either with or without metabolic activation up to the maximum test concentration of 250 µg/plate.