4-aminoazobenzene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

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 publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Evaluation of the rodent micronucleus assay in the screening of IARC carcinogens (groups 1, 2A and 2B). The summary report of the 6th collaborative study by CSGMT/JEMS MMS

Author:

Morita T, et al.

Year:

1997

Bibliographic source:

Mutat Res 389: pp. 3-122

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4-aminoazobenzene

EC Number:

200-453-6

EC Name:

4-aminoazobenzene

Cas Number:

60-09-3

Molecular formula:

C12H11N3

IUPAC Name:

4-[(E)-2-phenyldiazen-1-yl]aniline

Details on test material:

no data

Test animals

Species:

mouse

Strain:

other: ddY

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 to 10 weeks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: olive oil

Duration of treatment / exposure:

0-72 hours

Frequency of treatment:

1 to 2 treatments

Post exposure period:

24 hour to 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 100, 150, 200, 300 mg/kg body weight
Basis:
other: nominal dose

No. of animals per sex per dose:

6 male mice per dose for group 1 (one treatment and analysis of bone marrow)
5 male mice per dose for group 2 (two treamtents at 24 hour interval and analysis of peripheral blood)
5 male mice per dose for group 2 (wo treamtents at 24 hour interval and analysis of bone marrow)

Control animals:

yes, concurrent no treatment

yes, concurrent vehicle

Positive control(s):

mitomycin C
- Route of administration: i.p.
- Doses / concentrations: once 0.5 mg/kg b.w.

Examinations

Tissues and cell types examined:

Both bone marrow polychromatic erythrocytes (PEC) and peripheral blood reticulocytes (RET) were used for analysis. Micronucleated PET and RET frequencies were based on the observation of at least 1000 PET or RET per animal.

Statistics:

Increase in micronucleus frequency was evaluated against the concurrent negative control using a conditional binominal test. Dose-response relationship was evaluated using the Cochran-Armitage trend test. When both tests were significant the test was declared positive. If neither step showed significance the data was judged negative, and all other cases were called inconclusive. Biological significance was also evaluated by an expert committee.

Results and discussion

Test results

Sex:

male

Genotoxicity:

positive

Toxicity:

yes

Remarks:

maximum tolerance dose: 200mg/kg

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Dose dependent increase in MN frequencies in bone marrow and peripheral blood.

			% of MNPCE or MNRET (after the final treatment)
tissue	number of treamtent	dose (mg/kg b.w.)	0h	24h		48h		72h
			mean ± SD	mean ± SD	p	mean ± SD	p	mean ± SD	p
bone marrow	1	0		0.22 ± 0.12
		50		0.17 ± 0.12	0.798
		100		0.28 ± 0.18	0.292
		200		1.40 ± 0.73	0.000
		300		1.00*	0.000
					(0.000)
peripheral blood	2	50	0.26 ± 0.13	0.40 ± 0.29	0.148	0.46 ± 0.28	0.068	0.22 ± 0.15	0.729
		100	0.22 ± 0.23	0.70 ± 0.21	0.000	0.70 ± 0.25	0.000	0.26 ± 0.15	0.419
		150	0.14 ± 0.13	1.14 ± 0.50	0.000	0.98 ± 0.32	0.000	0.74 ± 0.44	0.000
					(0.000)		(0.000)		(0.000)
bone marrow	2	0		0.14 ± 0.05		0.16 ± 0.05
		50		0.20 ± 0.23	0.315	0.14 ± 0.09	0.696
		100		0.32 ± 0.08	0.047	0.08 ± 0.05**	0.930
		200		0.70 ± 0.38	0.000	0.40 ± 0.23	0.018
					(0.000)		(0.015)

*: 4 dead

**: 1 dead

MNPCE: Micronucleated polychromatic erythrocytes

MNRET: Micronucleated reticulocytes

p: p value of pairwise comparisons and that of the Cochran-Amitage trend test in parentheses.