α,α,α-trifluoro-3-tolyl isocyanate

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The mutagenic potential of m-trifluoromethylphenylisocyanate was examined in the Salmonella/microsome test. Bacteria of four histidine auxotrophic Salmonella typhimurium LT2 mutant strains (TA 98, TA 100, TA 102, TA 1535, and TA 1537) were exposed to doses up to 5000 pg per plate. Both the plate incorporation method and the preincubation method was used.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α-trifluoro-3-tolyl isocyanate

EC Number:

206-341-3

EC Name:

α,α,α-trifluoro-3-tolyl isocyanate

Cas Number:

329-01-1

Molecular formula:

C8H4F3NO

IUPAC Name:

1-isocyanato-3-(trifluoromethyl)benzene

Constituent 2

Reference substance name:

alpha,alpha,alpha-trifluoro-3-tolyl isocyanate

IUPAC Name:

alpha,alpha,alpha-trifluoro-3-tolyl isocyanate

Details on test material:

content: > 99.3 %

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

other: Firstly, they are deep rough since certain lipopolysaccharide side chains are missing in the bacterial cell wall. Secondly, with the exception of TA 102, all strains have reduced capability to repair DNA-damage

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

Plate incorporation method: up to 5 µl/plate;
Preincubation method: up to 5 µl/plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: sodium azide, anthracene-2-amine, cumene hydroperoxide, mitomycin C, 2-nitro-9H-fluorene, 4-nitro-o-phenylenediamine

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

In the plate incorporation test doses of up to and including 0.009 µl per plate did not cause any bacteriotoxic effects. In the preincubation test doses of up to and including 0.001 µl per plate did not cause any bacteriotoxic effects

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Precipitation was observed at the highest tested dose of 5 µl/plate.

In the plate incorporation test doses of up to and including 0.009 µl per plate did not cause any bacteriotoxic effects. At higher doses, the test item had a strain-specific bacteriotoxic effect. Due to this effect this range could not be used up to 5 µl per plate for assessment purposes.

In the preincubation test doses of up to and including 0.001 µl per plate did not cause any bacteriotoxic effects. At higher doses, the test item had a strain-specific bacteriotoxic effect. Due to this effect this range could not be used up to 5 µl per plate for assessment purposes.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

The test item (m-trifluoromethylphenylisocyanate) was initially investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5 µl per plate on five Salmonella typhimurium LT2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. The independent repeat was performed as preincubation for 60 minutes at 37°C. Other conditions remained unchanged.

Precipitation was observed at the highest tested dose of 5 µl/plate.

In the plate incorporation test doses of up to and including 0.009 µl per plate did not cause any bacteriotoxic effects. At higher doses, the test item had a strain-specific bacteriotoxic effect. Due to this effect this range could not be used up to 5 µl per plate for assessment purposes.

In the preincubation test doses of up to and including 0.001 µl per plate did not cause any bacteriotoxic effects. At higher doses, the test item had a strain-specific bacteriotoxic effect. Due to this effect this range could not be used up to 5 µl per plate for assessment purposes.

Evidence of mutagenic activity of the test item was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed up to assessable doses.

The positive controls sodium azide, anthracene 2 amine, cumene hydroperoxide, mitomycin C, 2 nitro-9H-fluorene and 4 nitro o phenylenediamine showed the ex-pected mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared to the corresponding negative controls.

Therefore, the test item was negative without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.