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EC number: 226-033-2 | CAS number: 5235-82-5
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2017
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 4-[3-(1-naphthylamino)propyl]morpholine
- EC Number:
- 226-033-2
- EC Name:
- 4-[3-(1-naphthylamino)propyl]morpholine
- Cas Number:
- 5235-82-5
- Molecular formula:
- C17H22N2O
- IUPAC Name:
- N-[3-(morpholin-4-yl)propyl]naphthalen-1-amine
- Test material form:
- solid: granular
- Details on test material:
- Colour: Dark Brown to Black
GLP Characterized: January 21, 2016
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- a metabolically active extract of rat liver (treated with Aroclor 1254)
- Test concentrations with justification for top dose:
- 31.25, 62.5, 125, 250, 500 and 1000 µg 4-(3-(1-Naphthylamino)propyl)morpholine/plate both in the absence and presence (10% v/v S9 mix) of metabolic activation
Basis for top dose selection was inhibition of the bacterial lawn at 1500 and 5000 µg in the initial toxicity mutation assay. - Vehicle / solvent:
- Dimethyl sulphoxide
Controls
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- other: 2-Aminoanthracene (613-13-8)
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
Any other information on results incl. tables
Negative Controls
The results of the study indicate that the revertant colony numbers for the negative controls (DMSO) in all strains were within limits of historical range.
Positive Controls
2-Aminoanthracene was used as the positive control in the presence of metabolic activation for all the tester strains during the Initial Toxicity Mutation Assay and Confirmatory Mutation Assay. Historical control data of this laboratory proved the efficiency and suitability of 2-aminoanthracene as a positive control in the presence of metabolic activation.
Positive controls (both in the absence and presence of metabolic activation during both the trials) exhibited a clear increase in the number of revertants when compared with the concurrent negative control and were within the historical ranges .This demonstrated the efficiency of the test system and suitability of the procedures employed in the assay.
An increase in the mean number of revertants was not observed in Salmonella typhimurium tester strain TA100 (Initial Toxicity Mutation Assay and Confirmatory Mutation Assay) treated with 2-aminoanthracene in the absence of metabolic activation, but a clear increase was observed in the presence of metabolic activation. This demonstrated the efficiency of the S9 fraction used in this assay.
Initial Toxicity Mutation Assay
Bacterial cultures were exposed to 4-(3-(1-Naphthylamino)propyl)morpholine at concentrations of 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate (two plates/concentration) both in the absence and presence of metabolic activation (5% v/v S9 mix). Precipitation was not observed up to the tested concentration of 5000 µg/plate. Complete inhibition of background lawn was observed at tested concentrations 1500 and 5000 µg/plate in all the tester strains both in absence and presence of metabolic activation. Partial inhibition of background lawn was observed at tested concentration of 500 µg/plate in all the tester strains both in absence and presence of metabolic activation. No inhibition of background lawn was observed up to the tested concentration of 150 µg/plate in all the tester strains both in absence and presence of metabolic activation. Reduction in number of revertant colonies of 44-56 % in the absence of metabolic activation in all the tester strains and 48-54 % [TA1535, TA98, TA100, and Escherichia coli WP2 uvrA (pKM101)] in the presence of metabolic activation (5% v/v S9 mix) was observed at tested concentration of 500 µg/plate. In tester strain TA1537, no appreciable reduction in revertant colonies was observed at the tested concentration of 500 µg/plate in the presence of metabolic activation (5% v/v S9 mix). Normal growth was observed up to the tested concentration of 150 µg/plate in all tester strains both in the absence and presence of metabolic activation (5% v/v S9 mix). No increase in the number of revertant colonies was observed in any of the tester strains at any of the tested concentrations when compared with the concurrent negative control. Hence, 1000 µg 4-(3-(1-Naphthylamino)propyl)morpholine/plate was selected as the highest concentration to be tested in the Confirmatory Mutation Assay both in the absence and presence of metabolic activation (10% v/v S9 mix).
Confirmatory Mutation Assay
In the Confirmatory Mutation Assay, bacterial cultures were exposed to 4-(3-(1-Naphthylamino)propyl)morpholine at concentrations of 31.25, 62.5, 125, 250, 500 and 1000 µg/plate (three plates/concentration) both in the absence and presence of metabolic activation (10% v/v S9 mix). Precipitation was not observed up to the tested concentration of 1000 µg/plate. Partial inhibition of background lawn was observed at tested concentrations of 500 and 1000 µg/plate in all the tester strains both in absence and presence of metabolic activation. No inhibition of background lawn was observed up to the tested concentration of 250 µg/plate in all the tester strains both in absence and presence of metabolic activation. Reduction in number of revertant colonies of 63-72 % in the absence of metabolic activation and 52-70 % in the presence of metabolic activation (10% v/v S9 mix) was observed at tested concentration of 1000 µg/plate in all the tester strains. Reduction in number of revertant colonies of 43-50 % in the absence of metabolic activation and 47-49 % in the presence of metabolic activation (10% v/v S9 mix) was observed at tested concentration of 500 µg/plate in all the tester strains.
Normal growth was observed up to the tested concentration of 250 µg/plate in all tester strains. No increase in the number of revertant colonies was observed in any of the tester strains at any of the tested concentrations when compared with the concurrent negative control.
Applicant's summary and conclusion
- Conclusions:
From the results of this study, under the specified experimental conditions, 4-(3-(1-Naphthylamino)propyl)morpholine was concluded to be non-mutagenic in the Bacterial Reverse Mutation Assay using Salmonella typhimurium and Escherichia coli WP2 uvrA (pKM101).- Executive summary:
The potential of 4-(3-(1-Naphthylamino)propyl)morpholine to induce reverse mutations in Salmonella typhimurium strains TA1537, TA1535, TA98 and TA100 anda tryptophan deficient strain, Escherichia coli WP2uvrA (pKM101) was evaluated in the bacterial reverse mutation test using the pre-incubation method.
4-(3-(1-Naphthylamino)propyl)morpholinewas tested in the absence and presence of metabolic activation using dimethyl sulfoxide (DMSO) as the solvent. In the Initial Toxicity Mutation Assay, bacterial cultures were exposed to 4-(3-(1-Naphthylamino)propyl)morpholine at concentrations of 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate (two plates/concentration). Precipitation was not observed up to the concentration of 5000 µg/plate. Complete inhibition of background lawn was observed at the tested concentrations of 1500 and 5000 µg/plate in all the tester strains both in absence and presence of metabolic activation (5% v/vS9 mix). Partial inhibition of background lawn was observed at tested concentration of 500 µg/plate in all the tester strains both in absence and presence of metabolic activation. Normal background lawn pattern without reduction in number of revertant colonies was observed up to the tested concentration of 150 µg/plate in all the tester strains in both absence and presence of metabolic activation (5% v/vS9 mix). No increase in the number of revertant colonies was observed in any of the tester strains with the test item at any of the tested concentrationsin the absence or presence ofmetabolic activationwhen compared with the concurrent negative control.
In the Confirmatory Mutation Assay, bacterial cultures were exposed to 4-(3-(1-Naphthylamino)propyl)morpholine at concentrations of 31.25, 62.5, 125, 250, 500 and 1000 µg/plate (three plates/concentration) both in the absence and presence of metabolic activation (10% v/vS9 mix). Precipitation was not observed up to the concentration of 1000 µg/plate. Partial inhibition of background lawn was observed at the tested concentrations of 500 and 1000 µg/plate in all the tester strains both in absence and presence of metabolic activation. No inhibition of background lawn was observed up to the tested concentration of 250 µg/plate in all the tester strains in both absence and presence of metabolic activation. No increase in the number of revertant colonies was observed in any of the tester strains with the test item at any of the tested concentrations in the absence or presence of metabolic activation when compared with the concurrent negative control.
All the values for the negative controls were within historical control ranges of the laboratory and positive controls showed an increase in the number of revertant colonies, demonstrating the efficiency of the test system.
The 4-(3-(1-Naphthylamino)propyl)morpholine stock concentrations 312.5, 625, 1250, 2500, 5000 and 10000 µg/mL were found to be within acceptable range of ± 15% of nominal concentrations during the Confirmatory Mutation Assay. The 0 hour concentrations of 4-(3-(1-Naphthylamino)propyl)morpholine in the dose formulation were found to be 108%, 106%, 107%, 103%, 97.4%, 96.9% of the nominal concentrations of dose level T1 (312.5 µg/mL), T2 (625 µg/mL), T3 (1250 µg/mL), T4 (2500 µg/mL), T5 (5000 µg/mL) and T6 (10000 µg/mL), respectively. The concentrations of 4-(3-(1-Naphthylamino)propyl)morpholine in the dose formulation after 4 hours were found to be 99.3% and 99.1% of the 0 hour concentrations of dose level T1 (312.5 µg/mL) and T6 (10000 µg/mL), respectively. Therefore, the doses complied with the presence of test item for claimed concentration (± 15 %) of active ingredient.
All criteria for a valid study were met as described in the protocol. From the results of this study, under the specified experimental conditions, 4-(3-(1-Naphthylamino)propyl)morpholine is concluded to be non-mutagenic in the Bacterial Reverse Mutation Assay using Salmonella typhimurium and Escherichia coli WP2uvrA (pKM101).
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