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EC number: 238-914-9 | CAS number: 14852-17-6
- 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 germ cell study: gene mutation
- Remarks:
- Sperm abnormality assay
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data provided is from a peer-reviwed publication.
Data source
Reference
- Reference Type:
- publication
- Title:
- Gene mutation toxicity study of the test chemical
- Author:
- Bruce WR et al.
- Year:
- 1 978
- Bibliographic source:
- Canadian Journal of Genetics and Cytology
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as mentioned below
- Principles of method if other than guideline:
- A significant increase in the proportion of abnormally shaped sperm cells has been observed in mice between four to eleven weeks after exposure to mutagenic agents (Proc. Natl. Acad. Sci. U.S.A. 1975; 72: 4425-4429). The abnormal sperm morphology is likely caused by small deletions, point mutations or both according to data from previous studies
- GLP compliance:
- not specified
- Type of assay:
- other: Sperm abnormality assay
Test material
- Details on test material:
- Name: Codeine phosphate
IUPAC name: 3-methoxy-17-methyl-7,8-didehydro-4,5-epoxymorphinan-6-ol phosphate (salt)
Molecular weight: 397.4 g/mol
Molecular formula: C18H24NO7P
Smiles: COc1ccc2C[C@@H]3[C@@H]4C=C[C@H](O)[C@@H]5Oc1c2[C@]45CCN3C.OP(=O)(O)O
Purity:No data
Impurity:No data
Test animals
- Species:
- mouse
- Strain:
- other: Hybrid mice (C57BL/6 X C3H/He)
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- The rats were housed in suspension, wire bottom cages, in air conditioned rooms with automated light and dark cycles, and were allowed food (Purina Chow) and water ad lib. They were not treated with antibiotics or insecticides.
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- Water
- Details on exposure:
- The highest dose was selected by chosing a convenient value close to the LD50, which was initially established in the study.
- Duration of treatment / exposure:
- Five consecutive days
- Frequency of treatment:
- Once daily
- Post exposure period:
- 30 days
Doses / concentrations
- Remarks:
- 0 (vehicle), 125, 250 and 500 mg/kg bw/day
- No. of animals per sex per dose:
- 3 to 4.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Benzo(a)pyrene
Examinations
- Tissues and cell types examined:
- Sperm cells
- Details of tissue and slide preparation:
- Sperm suspensions were prepared by mincing the cauda epididymis in 2 ml phosphate buffered physiological saline, pipetting the resulting suspension and filtering it through an 80 um stainless steel mesh to remove tissue fragments. A fraction of each suspension was mixed 10:l with 1% eosin-Y in water. Thirty min later smears were made, allowed to dry in air, and mounted under a coverslip with Permount. Three hundred and thirty-three sperm were examined at high magnification from each animal for a total of approx 1000 per treated group.
- Evaluation criteria:
- The results were plotted as percent abnormal sperm after subtraction of the frequency found in the control group. Threshold for biological significance was breached if the treated group exceeded the control group by 1% (10/1000). The test chemical was considered active when positive results were obtained consistently, i.e., when dose response curves could be constructed, or the results could be repeated.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not examined
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
Applicant's summary and conclusion
- Conclusions:
- Based on the presented data, the test chemical is non-mutagenic in mouse sperm cells following intraperitoneal injections at doses up to 500 mg/kg bw.
- Executive summary:
The test chemical was tested for mutagenicity in this sperm abnormality assay by Bruce and Heddle. In brief, the assay was used as an in vivo method to study mutagenicity because it has been shown that mice exposed to mutagenic agents exhibit significantly increased numbers of abnormally shaped sperm cells. The abnormal sperm morphology is likely caused by small deletions, point mutations or both. Three male mice per dose level were exposed to the test chemical via intraperitoneal injection at 0 (vehicle), 125, 250 and 500 mg/kg bw/day for 5 consecutive days. The highest dose level was close to the pre-determined LD50 value. Mice treated with benzo(a)pyrene served as positive controls. All mice were sacrificed 30 days after the last injection. Sperm samples were then prepared accordingly to calculate the number of abnormally shaped sperm cells. A total of 333 sperm cells from each animal were examined under high magnification. The results were plotted as percent abnormal sperm after subtraction of the frequency found in the control group. Threshold for biological significance was breached if the treated group exceeded the control group by 1% (10/1000). The test chemical was considered active when positive results were obtained consistently, i.e., when dose response curves could be constructed, or the results could be repeated. No significant increase in the proportion of abnormal sperm cells could be observed following treatment with the test chemical. In contrast, the positive control group showed a distinct increase in the proportion of abnormal sperm cells at 125 mg/kg bw/day (lowest dose tested). Based on the presented data, the test chemical is non-mutagenic in mouse sperm cells following intraperitoneal injections at doses up to 500 mg/kg bw.
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