4-isocyanato-2-methyl-1-{4-[(trifluoromethyl)thio]phenoxy}benzene

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance was initially screened with one plate per dose using the Salmonella/microsome plate incorporation test for point mutagenic effects on the Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 (similar to OECD TG 471) up to and including 500 µg per plate. The independent repeat was performed as preincubation for 20 minutes at 37°C up to and including 3200 ug per tube. Other conditions remained unchanged.

There was no indication of a bacteriotoxic effect of the substance at doses of up to and including 200 μg per plate. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. Higher doses had only a weak, strain-specific bacteriotoxic effect. At 500 μg per plate, the substance started to precipitate, so that at 5000 μg per plate no further evaluation was possible.

None of the five strains concerned showed in the plate incorporation test a dose related and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9 mix and was confirmed by the results of the preincubation trials.

The positive controls increased mutant counts to well over those of the negative controls, and thus demonstrated the system's sensitivity and the activity of the S9 mix.

Therefore, the substance was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Nov. 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

- screening version (only one plate per dose and strain investigated, purity of test item not specified)

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine gene locus

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced male rat liver S9 mix

Test concentrations with justification for top dose:

Plate incorporation test: 0, 16, 50, 160, 500 (P), 1600 (P), 5000 (P) µg/plate
Independent preincubation test: 0, 100, 200, 400, 800 (B), 1600 (P), 3200 (P) µg/tube


B = background lawn reduced
P = precipitate

Vehicle / solvent:

Ethylene glycol dimethylether (EGDE) dried with a molecular sieve, 0.4 nm.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: sodium azide (only TA 1535), nitrofurantoin (only TA 100), 4-nitro-1,2-phenylene diamine (TA 1537 and TA 98), cumene hydroperoxide (only TA 102), 2-aminoanthracene.

Remarks:

The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine and cumene hydroperoxide were only used without S9 mix; the positive control 2-aminoanthracene was only used with S9 mix.

Details on test system and experimental conditions:

METHOD: Standard plate test and preincubation test; only one plate per dose and strain investigated

Evaluation criteria:

A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas for TA 1537 at least a threefold increase should be reached. For TA 102 an increase of about 150 mutants should be reached. Otherwise, the result is evaluated as negative. However, these criteria may be overruled by good scientific judgment. In case of questionable results, investigations should continue, possibly with modifications, until a final evaluation is possible.

Statistics:

not specified

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

starting at 400 µg/plate; preceipitation started at 500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

There was no indication of a bacteriotoxic effect of the substance at doses of up to and including 200 μg per plate. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. Higher doses had only a weak, strain-specific bacteriotoxic effect. At 500 μg per plate, the substance started to precipitate, so that at 5000 μg per plate no further evaluation was possible.

None of the five strains concerned showed in the plate incorporation test a doserelated and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9 mix and was confirmed by the results of the preincubation trials.

The positive controls increased mutant counts to well over those of the negative controls, and thus demonstrated the system's sensitivity and the activity of the S9 mix.

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

The substance was initially screened with one plate per dose using the Salmonella/microsome plate incorporation test for point mutagenic effects on the Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535 and TA 1537 (similar to OECD TG 471) up to and including 500 µg per plate. The independent repeat was performed as preincubation for 20 minutes at 37°C up to and including 3200 ug per tube. Other conditions remained unchanged.

There was no indication of a bacteriotoxic effect of the substance at doses of up to and including 200 μg per plate. The total bacteria counts consistently produced results comparable to the negative controls, or differed only insignificantly. No inhibition of growth was noted as well. Higher doses had only a weak, strain-specific bacteriotoxic effect. At 500 μg per plate, the substance started to precipitate, so that at 5000 μg per plate no further evaluation was possible.

None of the five strains concerned showed in the plate incorporation test a dose related and biologically relevant increase in mutant counts over those of the negative controls. This applied both to the tests with and without S9 mix and was confirmed by the results of the preincubation trials.

The positive controls increased mutant counts to well over those of the negative controls, and thus demonstrated the system's sensitivity and the activity of the S9 mix.

Therefore, the substance was considered to be non-mutagenic without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the study result for Genetic toxicity in vitro no classification according to Regulation (EC) No. 1272/2008 (CLP), ANNEX I, is warranted.