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EC number: 237-198-5 | CAS number: 13684-56-5
- 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 vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Mouse bone marrow micronucleus assay
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1985-02-11 to 1985-03-18
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 985
- Report date:
- 1985
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- Desmedipham
- EC Number:
- 237-198-5
- EC Name:
- Desmedipham
- Cas Number:
- 13684-56-5
- Molecular formula:
- C16 H16 N2 O4
- IUPAC Name:
- ethyl 3´-phenylcarbamoyloxycarbanilate
- Test material form:
- solid: particulate/powder
- Details on test material:
- The test material is Desmedipham.
Constituent 1
- Specific details on test material used for the study:
- Physical appearance light beige coloured fine powder.
Storage The test article and a reserve sample were stored at room temperature, in the dark.
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Details on species / strain selection:
- Standard laboratory species/strain used for this type of study, with background data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: males: 6 weeks, females: 7 weeks
- Weight at study initiation: males: 26-37 g, females: 26-34 g
- Assigned to test groups randomly: yes, Animals mere randomized into the different groups after delivery using a random algorithm.
- Housing: Groups of 6 in Makrolon Type 3, with wire mesh top and granulated softwood bedding.
- Diet: Pelleted standard mouse diet, ad libitum.
- Water: Tap water, ad libitum.
- Acclimation period: 7 days under test conditions, with veterinary examination
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12 per day
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: 2% carboxymethylcellulose, (CMC) in distilled water.
- Amount of vehicle (if gavage or dermal): 20 mL/kg bw - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
A suspension was prepared immediately before application by adding the test article to distilled water containing CMC (2%).
Homogeneity of the suspension was maintained during application using a magnetic stirrer. - Duration of treatment / exposure:
- single dose
- Frequency of treatment:
- single dose
- Post exposure period:
- At 24-, 48- and 72-hour intervals after treatment, six mice per sex and group were sacrificed for examination. The first five animals of each sex were evaluated.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: mg/kg bw
- Remarks:
- Negative Control (2% carboxymethylcellulose, sodium salt (CMC) in distilled water)
- Dose / conc.:
- 5 000 other: mg/kg bw
- Remarks:
- Desmedipham
- No. of animals per sex per dose:
- 18/sex/dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (reference mutagen)
- Doses / concentrations: 50 mg/kg bw
Examinations
- Tissues and cell types examined:
- Bone marrow
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
The maximum tolerated dose was based on acute oral toxicity data. The acute oral LD50 performed with mouse is greater than 5000 mg/kg body weight. The 5000 mg/kg body weight dose was used in this study as the maximum tolerated dose.
TREATMENT AND SAMPLING TIMES: The animals were dosed once, at 24 -, 48 -, and 72 -hour intervals after treatment, six mice per sex and group were sacrificed for examination, bone marrow was collected
DETAILS OF SLIDE PREPARATION:
All mice were sacrificed by cervical dislocation. The femora were removed from each mouse and freed of adherent tissue.
The proximal end of the femur was cut with scissors. The needle of a plastic syringe containing 0.2 ml calf serum was inserted into the proximal part of the marrow canal which was closed at the distal end. The femur was submerged in 1.5 ml calf serum in a labeled centrifuge tube. The bone marrow cells mere dispersed in the calf serum as a homogeneous suspension. The tube containing the bone marrow cells of both femora was centrifuged at 1000 rpm for 5 minutes. The supernatant was removed, leaving a thin layer of serum. The cells of the sediment were suspended by aspiration in a siliconized Pasteur pipette. A small drop of the marrow serum suspension was smeared on the slide, which was identified by project code and the animal number and allowed to dry overnight. Two slides per animal mere prepared. The following day, the smears mere stained using the panoptic stain method developed by Pappenheim
METHOD OF ANALYSIS:
From each animal 1000 polychromatic erythrocytes (PCE) were scored under the microscope for the incidence of micronuclei. The ratio of polychromatic to normochromatic erythrocytes (PCE/NCE), based on scoring 1000 erythrocytes per slide, measured the toxicity of desmedipham. - Evaluation criteria:
- The frequencies of micronuclei of the treated male and female groups were compared with those of the negative control groups at each sampling time. A regression model assuming a Poisson distribution mas applied. Estimation and testing were performed by maximum likelihood method. If a test article produced no statistically significant and reproducible positive response at any one of the test points, it was considered non-mutagenic in this system.
- Statistics:
- Statistical evaluation of the data was made using a regression model assuming a Poisson distribution and the maximum likelihood method.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Sedation was observed in all treated animals for at least 6 hours after dosing.
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
See the Results' tables attached in "Overall remarks, attachments"
Applicant's summary and conclusion
- Conclusions:
- After a single dose of 5000 mg desmedipham /kg bw by gavage, no significant increase of micronucleated polychromatic erythrocytes in the bone marrow was observed in either male or female treated groups at either 24, 48 or 72 hours post-dose.
- Executive summary:
This in vivo study with mice was performed to assess the potential mutagenic activity, induced by DESMEDIPHAM, through damage to the chromosomes or to the mitotic apparatus, according to Schmid (1) with the modifications of Salomone et al.(2). The experiment was performed with three groups, each containing 18 males and 18 females, for a total of 108 mice. The negative control groups received the test article vehicle, i.e. 2% carbaoxymethylcellulose sodium salt in distilled water. The test groups received 5000 mg/kg body weight as the maximum tolerated dose of the test article. The positive control groups received 50 mg/kg body weight cyclophosphamide dissolved in 0.9% saline solution. All animals were given a single application of 20 ml/kg body weight by gavage. Twenty-four (24), 48 and 72 hours after treatment, six mice per sex and group were sacrificed and bone marraw was removed from the femora for examination. The first five animals were used for evaluation. One thousand polychromatic erythrocytes per animal were scored for micronuclei. The ratio of polychromatic to normochromatic erythrocytes was used to assess the toxicity of the test article by counting a total of 1000 erythrocytes. Data was statistically analyzed by means of a regression model assuming a Poisson distribution. Estimation and testing were performed by maximum likelihood method. Sedation was observed in all test article-treated animals for at least 6 hours after application. After single application of the test article at 5000 mg/kg body weight by gavage, no significant test article-related increase of micronucleated polychromatic erythrocytes was observed in either male and female treated groups, when compared with corresponding negative control groups. These results were found at the three examination times, 24, 48 and 72 hours post-application, respectively. The positive control groups, which received cyclophosphamide, exhibited a significant and clear increase in the number of micronucleated polychromatic erythrocytes and thus validated, the test. In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test article induced no chromosome mutations by chromosome-breaking activity or by damage to the mitotic apparatus. Therefore, DESMEDIPHAM is not considered to be mutagenic in this in vivo mouse micronucleus assay.
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