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EC number: 639-263-7 | CAS number: 200575-15-1
- 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
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:
- August 1997
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- EEC Methods for Determination of Toxicity, Annex to Directive 92/69/EEC, (OJ No.
L3 83A, 29.12.92), Part B, Method B.14. Other effects - Mutagenicity: Salmonella
typhimurium - Reverse Mutation Assay,
- GLP compliance:
- yes
- Remarks:
- Good Laboratory Practice in the testing of Chemicals OECD, ISBN 92-64-12367-9, Paris 1982
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 4-[2-Ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamido]-1-3-propyl-1H-pyrazole-5-carboxamide
- EC Number:
- 639-263-7
- Cas Number:
- 200575-15-1
- Molecular formula:
- C22H32N6O5S
- IUPAC Name:
- 4-[2-Ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamido]-1-3-propyl-1H-pyrazole-5-carboxamide
- Test material form:
- solid: particulate/powder
1
- Specific details on test material used for the study:
- Off white powder with 95% purity
Method
- Target gene:
- four histidine requiring strains
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 lliver fraction - Aroclor 1254 induced rats
- Test concentrations with justification for top dose:
- In the preliminary toxicity test with dose levels of up to 5000 ug/plate no toxicity was observed. A top dose level of 5000 ug/plate was chosen for the subsequent mutation study. Other dose levels used in the mutation assays were: 1500, 500, 150 and 50 ug/plate.
- Vehicle / solvent:
- dimethyl sulphoxide
Controls
- Untreated negative controls:
- yes
- Remarks:
- The chosen solvent, dimethyl sulphoxide, was used as the negative control.
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- N-ethyl-N-nitro-N-nitrosoguanidine
- other: 2-Aminoanthracene
- Remarks:
- 2-Nitrofluorene, 9-Aminoacridine and N-Ethyl-N'-nitro-N-nitrosoguanidine positive controls tested in the absence of S9 mix and diluted in Dimethyl sulphoxide solvent
- Details on test system and experimental conditions:
- Four concentrations of test substance were assessed for toxicity using the four tester strains. The highest concentration was 50 mg/ml of test substance in the chosen solvent, which provided a final concentration of 5000 ug/plate. Three 10-fold serial dilutions of the highest concentration were also tested. The chosen solvent, dimethyl sulphoxide, was used as the negative control. An aliquot of 0.1 ml of a 10 hour bacterial culture and 0.5 ml S-9 mix or 0.5 ml 0.1 M phosphate buffer (pH 7.4) were placed in glass bottles. An aliquot of 0.1 ml of the test solution was added, followed immediately by 2 ml of histidine deficient agar. The mixture was thoroughly shaken and overlaid onto previously prepared petri dishes containing 25 ml minimal agar. A single petri dish was used for each dose level. Plates were also prepared without the addition of bacteria in order to assess the sterility of the test substance, S9 mix and phosphate buffer. All plates were incubated at 37°C for 3 days. After this period the appearance of the background bacterial lawn was examined.
Revertant colonies were counted using a Seescan Automatic Colony Counter.
Any toxic effects of the test substance can be detected by a substantial reduction in revertant colony counts or by the absence of a complete background bacterial lawn. In the absence of any toxic effects the top concentration used in the main tests is the same as that used in the preliminary toxicity test.
If toxic effects are observed a lower concentration may be chosen for the main assays. Ideally the concentrations chosen for the mutation tests should include a minimum of three non-toxic
concentrations - Evaluation criteria:
- The mean number of revertant colonies for all treatment groups is compared with those obtained for solvent control groups. The mutagenic activity of a test substance is assessed by applying the following criteria:
(a) If treatment with a test substance produces an increase in revertant colony numbers of at least twice the concurrent solvent controls, with some evidence of a positive dose-relationship, in two separate experiments, with any bacterial strain either in the presence or absence of S9 mix, it is considered to show evidence of mutagenic activity in this test system. No statistical analysis is performed.
(b) If treatment with a test substance does not produce reproducible increases of at least 1.5 times the concurrent solvent controls, at any dose level with any bacterial strain, it is considered to show no evidence of mutagenic activity in this test system. No statistical analysis is performed.
(c) If the results obtained fail to satisfy the criteria for a clear "positive" or "negative" response given in paragraphs (a) and (b), the following approach is taken in order to resolve the issue of the test substance's mutagenic activity in this test system.
(i) Repeat tests may be performed using modifications of the experimental method. These modifications include (but are not restricted to), the use of a narrower dose range than that already tested; the use of different levels of liver homogenate S-9 fraction in the S9 mix.
Should an increase in revertant colony numbers be observed which satisfies paragraph (a) the test substance is considered to show evidence of mutagenic activity in
this test system. No statistical analysis is performed.
Results and discussion
Test results
- Species / strain:
- other: S. typhimurium TA 1535 hisG46 tia uvrB S. typhimurium TA 1537 hisC3076 tfa uvrB S. typhimurium TA98 hisD3052 tja uvrB pla1101 S. typhimurium TA100 hisG46 tfa uvrB pI(M101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- up to a concentration of 5000ug/plate
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- All strains tested negative with and without metabilic activation
Applicant's summary and conclusion
- Conclusions:
- When tested in dimethyl sulphoxide, UK-220,955 shows no evidence of mutagenic activity in this bacterial system.
- Executive summary:
In this in vitro assessment of the mutagenic potential of UK-220,955, histidine dependent auxotrophic mutants of Salmonella typhimurium (strains TA1535, TA1537, TA98 and TA100) were exposed to the test substance, diluted in dimethyl sulphoxide which was also used as a negative control. Two independent mutation tests were performed, in the presence and absence of liver preparations from Aroclor 1254-induced rats. In the preliminary toxicity test with dose levels of up to 5000 yg/plate no toxicity was observed. A top dose level of 5000 yg/plate was chosen for the subsequent mutation study. Other dose levels used in the mutation assays were: 1500, 500, 150 and 50 Ag/plate. No evidence of mutagenic activity was seen at any dose level of UK-220,955 in either mutation test. The concurrent positive control compounds demonstrated the sensitivity of the assay and the metabolising activity of the liver preparations. It is concluded that, when tested in dimethyl sulphoxide, UK-220,955 shows no evidence of mutagenic activity in this bacterial system.
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