p-tolyl isocyanate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genotoxicity studies for p-tolyl isocyanate are available.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: guideline study - only 4 strains tested

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The mutagenic potential of m-tolylisocyanate was examined in the Salmonella/microsome test. Bacteria of four histidineauxotrophic Salmonella typhimurium LT2 mutant strains (TA 98, TA 100, 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

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:

plate incorporation assay: 0, 8, 40, 200, 1000, 5000 µg/plate
preincubation assay: 0, 62.5, 125, 250, 500, 1000, 2000 µg/tube

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: sodium azide, nitrofurantoin, 4-nitro- 1,2-phenylene diamine, 2-aminoanthracene

Details on test system and experimental conditions:

IUCLID4 Type: Ames test

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: Doses up to and including 200 pg 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 and TA 100

Remarks:

Migrated from field 'Test system'.

Doses up to and including 200 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no growth inhibition was observed. The substance revealed weak, strain-specific bacteriotoxic effects at higher doses yet doses up to 1000 µg per plate could still be used for assessment purposes. Substance precipitation occurred at the dose of 500 µg per plate and above. Plates containing 2000 or 5000 µg of the test substance could not be used for assessment purposes.

Conclusions:

Interpretation of results (migrated information):
negative

Executive summary:

The mutagenic potential of m-tolylisocyanate was examined in the Salmonella/microsome test. Bacteria of four histidineauxotrophic Salmonella typhimurium LT2 mutant strains (TA 98, TA 100, 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.

Doses up to and including 200 µg per plate did not cause any bacteriotoxic effects: Total bacteria counts remained unchanged and no growth inhibition was observed. The substance revealed weak, strain-specific bacteriotoxic effects at higher doses yet doses up to 1000 µg per plate could still be used for assessment purposes. Substance precipitation occurred at the dose of 500 µg per plate and above. Plates containing 2000 or 5000 µg of the test substance could not be used for assessment purposes.

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

In a valid Ames test m-tolyl isocyanante (as a structural analogue or surrogate for p-tolyl isocyanate) was negative

Justification for selection of genetic toxicity endpoint
The materials/methods and results are described in detail und are sufficient for evaluation

Justification for classification or non-classification

From the available data a classification is not justified