p-(trifluoromethoxy)phenyl 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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The mutagenic potential of 4-trifluoromethoxyphenyl isocyanate was examined in the Salmonella/microsome test. Bacteria of four histidine auxotrophic Salmonella typhimurium LT2 mutant strains (TA 98, TA 100, TA 1535, and TA 1537) were exposed to doses up to 12500 µg per plate. The plate incorporation method was used.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

p-(trifluoromethoxy)phenyl isocyanate

EC Number:

252-328-0

EC Name:

p-(trifluoromethoxy)phenyl isocyanate

Cas Number:

35037-73-1

Molecular formula:

C8H4F3NO2

IUPAC Name:

1-isocyanato-4-(trifluoromethoxy)benzene

Details on test material:

content: 99.7 %

Method

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other: Firstly, they are deep rough since certain lipopolysaccharide side chains are missing in the bacterial cell wall. Secondly, their reduced ability to repair damage from UV light (e.g. thymidine dimers) allows the phenotypic detection of mutation events

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

first test: 0, 20, 100, 500, 2500, 12500 µg/plate
repeat: 0, 0.16, 0.8, 4, 20, 100 µg/plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: endoxane, trypaflavine, 2-aminoanthracene

Results and discussion

Test results

Test results 1

Species / strain:

E. coli WP2

Metabolic activation:

not applicable

Genotoxicity:

other: not tested

Cytotoxicity / choice of top concentrations:

other: not tested

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Doses up to 4 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no growth inhibition was observed. In higher dose ranges the test substance was bacteriotoxic, maily without S-9 mix. Therefore this range could only be used with limitations up to 500 µg/plate. Substance precipitation occurred at the dose of 2500 µg per plate and above.

Applicant's summary and conclusion

Conclusions:

There was no evidence for mutagenic effects of 4-trifluoromethoxyphenyl isocyanate with and without S9 mix. A biologically relevant increase of revertant colony numbers over control levels was not observed. Therefore, 4-trifluoromethoxyphenyl isocyanate was considered to be non-mutagenic in the Salmonella/microsome test.

Executive summary:

The mutagenic potential of 4-trifluoromethoxyphenyl isocyanate was examined in the Salmonella/microsome test. Bacteria of four histidine auxotrophic Salmonella typhimurium LT2 mutant strains (TA 98, TA 100, TA 1535, and TA 1537) were exposed to doses up to 12500 µg per plate.

There was no evidence for mutagenic effects of 4-trifluoromethoxyphenyl isocyanate with and without S9 mix. A biologically relevant increase of revertant colony numbers over control levels was not observed. Therefore, 4-trifluoromethoxyphenyl isocyanate was considered to be non-mutagenic in the Salmonella/microsome test.