2-nitroaniline

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Acceptable, well documented publication which meets basic scientific principles (neither Escherichia coli strain WP2 uvrA pKM101a nor S. typhimurium strain TA102 were employed in this study for the detection of oxidising mutagens and cross-linking agents)

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity evaluation of nitroanilines and nitroaminophenols in Salmonella typhimurium.

Author:

Shahin MM

Year:

1985

Bibliographic source:

International Journal of Cosmetic Science 7: 277-289

Materials and methods

Principles of method if other than guideline:

The test procedure described by Maron and Ames (1983) was followed.

Maron & Ames (1983). Mutation Res. 113: 173-215

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2-nitroaniline

EC Number:

201-855-4

EC Name:

2-nitroaniline

Cas Number:

88-74-4

Molecular formula:

C6H6N2O2

IUPAC Name:

2-nitroaniline

Details on test material:

- Name of test material (as cited in study report): o-Nitroaniline
- Analytical purity: > 98 % (HPLC, TLC)

Method

Target gene:

His +/-

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9 mix prepared from liver microsomal fractions from male Wistar rats pretreated with 500 mg/kg bw Aroclor 1254

Test concentrations with justification for top dose:

5-1000 µg/plate (8 concentrations)

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1,2-diamono-4-nitrobenzene, 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS: 3 plates/dose; two separate experiments

Evaluation criteria:

A dose-dependent two-fold increase in the number of revertants per plate was used as the criterion for genetic activity of the compounds tested. A 2.5-fold increase over the spontaneous level, even without clear evidence of dose-dependence, was also considered to be an indication of genetic activity if found in repeated experiments.

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Compound/control	TA1535		TA100		TA1537		TA1538		TA98
	- S9	+ S9	- S9	+ S9	- S9	+ S9	- S9	+ S9	- S9	+ S9
	Revertants/nmol
o-nitroaniline	-	-	-	-	-	-	-	-	-	-
	Revertant colonies/plate**
Negative control	18.5	17.5	166.0	159.5	25.0	34.0	30.0	45.0	47.5	61.5
Solvent control	17.5	18.0	146.0	147.5	28.5	36.0	31.0	45.5	47.0	57.0
1,2-diamino-4-nitrobenzene	40.5	34.5	639.0	400.0	194.0	67.0	1990.0	1794.0	3018.5	2311.5
2-aminoanthracene	21.0	220.0	168.0	1649.0	23.5	258.0	29.5	1133.0	40.0	2050.0

* All values were determined from the linear portion of the dose response curves.

** Average of at least 30 independent controls.

The data reported in the present publication clearly show that not all compounds with a nitro group in their structure are genetically active. The three nitroanilines (ortho, meta, para) are isomers. The mutagenic properties of some members of this group therefore seem to have structural requirements beyond simple membership in this class of chemicals. Rather mutagenicity or non-mutagenicity seems to depend on the position of the electron donating amino (NH₂) and hydroxy (OH) groups and the electron accepting nitro (NO₂)group in the structure of these compounds. The authors have found o-nitroaniline not to be mutagenic in Salmonella typhimurium. Moreover, the addition of a hydroxy group to m-nitroaniline either diminished its mutagenic activity (e.g., 2-nitro-6-aminophenol, 2-nitro-4-aminophenol) or altered its activity (e.g., 4-nitro-2-aminophenol).