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EC number: 252-328-0 | CAS number: 35037-73-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
There was no evidence for mutagenic effects of 4-trifluoromethoxyphenyl isocyanate with and without S9 mix in S. typhyimurium strains TA 100, TA 98, TA 1535 and TA 1537. 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.
For the strain E. coli WP2 uvrA a read-across analysis with the OECD QSAR Toolbox v4.5 was performed. For Categorization the profiler DNA binding by OECD was used, which showed the following alert: Acylation >> Isocyanates and Isothiocyanates.
All of the seven isocyanates included in the final prediction were negative in Ames Tests with the strain E. coli WP2 uvr A with and without metabolic activation.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Study period:
- 13 Oct 2022
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
OECD QSAR Toolbox v4.5
2. MODEL (incl. version number)
OECD QSAR Toolbox v4.5 - Read-Across Analysis
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
FC(F)(F)Oc1ccc(cc1)N=C=O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The Ames mutagenicity for strain E. coli WP2 uvr A with and without metabolic activation was predicted by read-across analysis with the OECD QSAR Toolbox v4.5. For Categorization the profiler DNA binding by OECD was used, which showed the following alert: Acylation >> Isocyanates and Isothiocyanates. The prediction was then based on the most similar isocyanates having the same alert.
All of the seven isocyanates included in the final prediction were negative in Ames Tests with the strain E. coli WP2 uvr A with and without metabolic activation. Therefore, there is high reliability in the prediction that the registered substance is also negative in E. coli WP2 uvr A.
5. APPLICABILITY DOMAIN
As a Comparison with other substances was performed there is no defined applicability domain - Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Software tool(s) used including version: OECD QSAR Toolbox v4.5
- Model(s) used: OECD QSAR Toolbox v4.5 - Read-Across Analysis
- Model description: see field 'Justification for non-standard information' and 'Attached justification'
- Justification of QSAR prediction: see field 'Justification for type of information' and 'Attached justification' - Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- FC(F)(F)Oc1ccc(cc1)N=C=O
- Species / strain / cell type:
- E. coli WP2 uvr A
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- True negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Remarks on result:
- no mutagenic potential (based on QSAR/QSPR prediction)
- Conclusions:
- All of the seven isocyanates included in the final prediction were negative in Ames Tests with the strain E. coli WP2 uvr A with and without metabolic activation. Therefore, the registered substance is also predicted to be negative for strain E. coli WP2 uvrA.
- Executive summary:
The Ames mutagenicity for strain E. coli WP2 uvr A with and without metabolic activation was predicted by read-across analysis with the OECD QSAR Toolbox. For Categorization the profiler DNA binding by OECD was used, which showed the following alert: Acylation >> Isocyanates and Isothiocyanates.
All of the seven isocyanates included in the final prediction were negative in Ames Tests with the strain E. coli WP2 uvr A with and without metabolic activation.- 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
- 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
- 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 - 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
- Species / strain:
- E. coli WP2
- Metabolic activation:
- not applicable
- Genotoxicity:
- other: not tested
- Cytotoxicity / choice of top concentrations:
- other: not tested
- 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
- 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
- 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
- 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
- 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.
Referenceopen allclose all
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.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect. Under the conditions of the test 4-trifluoromethoxyphenyl isocyanate was negative in the in-vivo micronucleus test.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1981
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Principles of method if other than guideline:
- The micronucleus test was employed to investigate 4-trifluoromethoxyphenyl isocyanate in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, Trenimon, served as positive control. The treated animals received 2 oral application within 24 hoursof the test substance, the positive control was applied intraperitoneal. The femoral marrow of groups treated with 4-trifluoromethoxyphenyl isocyanate was prepared 6 hours after administration.
- GLP compliance:
- no
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- other: Bor: NMRI (SPF Han)
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Duration of treatment / exposure:
- 2 oral treatments within 24 hours
- Frequency of treatment:
- 2 oral treatments within 24 hours
- Post exposure period:
- Animals were sacrificed 6 after the second application
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- 2 x 100 mg/kg bw
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Remarks:
- 2 x 50 mg/kg bw
- No. of animals per sex per dose:
- 5 male and 5 female mice/group
- Control animals:
- yes, concurrent vehicle
- Tissues and cell types examined:
- femoral marrow
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- in the 2 x 50 mg/kg bw no signs of toxicity; in the 2 x 100 mg/kg bw group 11 of 20 animals died
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect. Under the conditions of the test 4-trifluoromethoxyphenyl isocyanate was negative in the in-vivo micronucleus test.
- Executive summary:
The micronucleus test was employed to investigate 4-trifluoromethoxyphenyl isocyanate in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, Trenimon, served as positive control. The treated animals received 2 oral application of the test substance within 24 hours, the positive control was applied intraperitoneal. The femoral marrow of groups treated with 4-trifluoromethoxyphenyl isocyanate was prepared 6 hours after administration.
No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect. Under the conditions of the test 4-trifluoromethoxyphenyl isocyanate was negative in the in-vivo micronucleus test.
Reference
No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Both tests (Ames test and micronucleus test on mice) were negative.
Short description of key information:
A valid bacterial reverse mutation assay (Ames test) and an in-vivo chromosome aberration assay (micronuleus test) on mice are available.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
Due to the results of the Ames test and Micronucleus test a classification according to Regulation (EC) No 1272/2008 is not justified.
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