2,4,6-trinitrotoluene

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: genome mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 Feb 1975 - 28 Feb 1978

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

no

Remarks:

The studies were conducted in 1978, before implemenation of OECD Guidelines (1981) and EU Guidelines (1988) as well as GLP principles. The studies were probably conducted according to TSCA guidelines.

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

TNT

IUPAC Name:

TNT

Constituent 2

Reference substance name:

2,4,6-trinitrotoluene

EC Number:

204-289-6

EC Name:

2,4,6-trinitrotoluene

Cas Number:

118-96-7

Molecular formula:

C7H5N3O6

IUPAC Name:

2-methyl-1,3,5-trinitrobenzene

Details on test material:

Purity >99%.

Specific details on test material used for the study:

Test material was dissolved in DMSO at different concentrations.

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

The S-9 fraction from rat liver prepared according to the procedure of Ames Test.

Metabolic activation:

with

Metabolic activation system:

The microsomal activation system used for mutagenic assay contained per ml: S-9 fraction (0.08 ml), NADP (4 uM), glucose-6-phosphate (5 uM), KCl (33 uM), MgCl2 (8 uM), and sodium phosphate buffer (100 uM), pH 7.4.The system was prepared fresh daily.

Test concentrations with justification for top dose:

1000, 300, 100, 30 and 10 ug/plate (0.1 ml)

Details on test system and experimental conditions:

all strains/cell types tested

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

300 ug/plate

Cytotoxicity / choice of top concentrations:

not determined

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

10 ug/plate of TNT

Cytotoxicity / choice of top concentrations:

not determined

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

10 ug/plate of TNT

Cytotoxicity / choice of top concentrations:

not determined

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

300 ug/plate

Cytotoxicity / choice of top concentrations:

not determined

Test results 5

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

10 ug/plate of TNT

Cytotoxicity / choice of top concentrations:

not determined

Remarks on result:

other: Potential mutagen.

Any other information on results incl. tables

TNT exhibited significant increase in the number of revertants at 10 and 30 ug/plate.It produced both base-pair substitution and frame-shift mutations. As little as 10 ug/plate of TNT was mutagenic in the TA-98, TA-1538 and TA-1537 strains. When 30 ug/plate were used, TNT was positive in four test strains; at 300 ug/plate, TNT was positive in all five tester strains.

 

Conclusion: Potential mutagen.

Applicant's summary and conclusion

Conclusions:

Potential mutagen. Further testing is necessary.