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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation toxicity study was performed to determine the mutagenic nature of p-nitro-m-phenylenediamine (p-NO2-m-PD). The study was performed by the Ames method with the suspension assay using Salmonella typhimurium strain TA98 with and without of S9 activation system. The test chemical dissolved in DMSO was used at dose levels of 0, 10 or 30 µg/plate in triplicate. Concurrent solvent and positive controls were included in the study.

 

p-nitro-m-phenylenediamine (p-NO2-m-PD) did not induce a dose dependent increase in the number of revertnats/plate as compared to controls using Salmonella typhimurium strain TA98 in the presence and absence of S9 activation system and hence the chemical is not likely to classify as a gene mutant in vitro.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
Gene mutation toxicity study was performed to determine the mutagenic nature of p-nitro-m-phenylenediamine (p-NO2-m-PD)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
- Name of test material : 4-nitro-m-phenylenediamine
- IUPAC name: 4-nitrobenzene-1,3-diamine
- Molecular formula : C6H7N3O2
- Molecular weight : 153.14 g/mol
- Substance type: organic
- Physical state: No data
- Purity: No data available
- Impurities (identity and concentrations): No data available
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
The postmitochondrial fraction (S9) was prepared from the liver of male Sprague-Dawley rats induced with PCB.
Test concentrations with justification for top dose:
0, 10 or 30 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The chemical was soluble in DMSO
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
2-acetylaminofluorene
4-nitroquinoline-N-oxide
Details on test system and experimental conditions:
METHOD OF APPLICATION: in suspension

DURATION
- Preincubation period: No data
- Exposure duration: No data
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: Triplicate

NUMBER OF CELLS EVALUATED: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: No data
Rationale for test conditions:
No data
Evaluation criteria:
The plates were observed for a dose dependent increase in the number of revertants/plate
Statistics:
No data
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
No data

Table: Mutagenicity for the test compoundp-nitro-m-phenylenediamine (p-NO2-m-PD)

Sample

Histidine revertants/dose

-S9

+S9

p-NO2-m-PD

17/10

25/10

28/30

32/30

DMSO

18

21

4NQO

411

-

AAF

-

470

Conclusions:
p-nitro-m-phenylenediamine (p-NO2-m-PD) did not induce a dose dependent increase in the number of revertnats/plate as compared to controls using Salmonella typhimurium strain TA98 in the presence and absence of S9 activation system and hence the chemical is not likely to classify as a gene mutant in vitro.
Executive summary:

Gene mutation toxicity study was performed to determine the mutagenic nature of p-nitro-m-phenylenediamine (p-NO2-m-PD). The study was performed by the Ames method with the suspension assay using Salmonella typhimurium strain TA98 with and without of S9 activation system. The test chemical dissolved in DMSO was used at dose levels of 0, 10 or 30 µg/plate in triplicate. Concurrent solvent and positive controls were included in the study.

 

p-nitro-m-phenylenediamine (p-NO2-m-PD) did not induce a dose dependent increase in the number of revertnats/plate as compared to controls using Salmonella typhimurium strain TA98 in the presence and absence of S9 activation system and hence the chemical is not likely to classify as a gene mutant in vitro.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Gene mutation in vitro:

Various peer reviewed publications were reviewed to determine the mutagenic nature of . The studies are as mentioned below:

Gene mutation toxicity study was performed by Watanabe et al (Mutation Research, 1989) to determine the mutagenic nature of p-nitro-m-phenylenediamine (p-NO2-m-PD; CAS no 5131 -58 -8; IUPAC name: 4-nitrobenzene-1,3-diamine). The study was performed by the Ames method with the suspension assay using Salmonella typhimurium strain TA98 with and without of S9 activation system. The test chemical dissolved in DMSO was used at dose levels of 0, 10 or 30 µg/plate in triplicate. Concurrent solvent and positive controls were included in the study. p-nitro-m-phenylenediamine (p-NO2-m-PD) did not induce a dose dependent increase in the number of revertnats/plate as compared to controls using Salmonella typhimurium strain TA98 in the presence and absence of S9 activation system and hence the chemical is not likely to classify as a gene mutant in vitro.

Watanabe et al (Mutation Research, 1991) also performed gene mutation toxicity study to determine the mutagenic nature of p-nitro-m-phenylenediamine (p-nitro-m-PD; CAS no 5131 -58 -8; IUPAC name:4-nitrobenzene-1,3-diamine). The study was performed by the Ames method using Salmonella typhimurium strain TA98 with and without of S9 activation system. p-nitro-m-phenylenediamine (p-nitro-m-PD) failed to induce gene mutation in Salmonella typhimurium strain TA98 in the presence and absence of S9 activation system and hence the chemical is not likely to classify as a gene mutant in vitro.

Based on the data available for the target chemical, p-nitro-m-phenylenediamine did not induce gene mutation in vitro. Hence the chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Based on the data available for the target chemical, p-nitro-m-phenylenediamine did not induce gene mutation in vitro. Hence the chemical is not likely to classify as a gene mutant in vitro.