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EC number: 209-676-3 | CAS number: 590-28-3
- 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
Repeated dose toxicity: other routes
Administrative data
- Endpoint:
- sub-chronic toxicity: other route
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- public available literature (non Guideline, non GLP)
Data source
Reference
- Reference Type:
- publication
- Title:
- Pharmacology of cyanate. I. general Effects on experimental animals
- Author:
- Cerami, A.; Allen, T.A..; Graziano, J.H. deFuria, F.G.; Manning, J.M.; Gillette, P.N.
- Year:
- 1 973
- Bibliographic source:
- J. Pharmacol. Exp. Ther. 185: 653-666, 1973
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Public available literature only. No guideline indicated. For details on method see below.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Potassium cyanate
- EC Number:
- 209-676-3
- EC Name:
- Potassium cyanate
- Cas Number:
- 590-28-3
- Molecular formula:
- KOCN
- IUPAC Name:
- potassium cyanate
- Details on test material:
- not indicated.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: B6/D2 F1
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- not indicated.
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- water
- Details on exposure:
- not indicated.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 5 months
- Frequency of treatment:
- daily (5 times a week)
Doses / concentrations
- Remarks:
- Doses / Concentrations:
- Three groups of 20 B6/D2 F1 female mice were injected i.p. once daily (five times a week) for a five-month period with either a) 0.1 ml of saline; b) 0.1 ml of 0.02 M KNCO (6.5 mg/kg); or c) 0,1 of 0.1 M KNCO (32.5 mg/kg).
- single i.p. administration of 91 mg/kg daily
- A group of 20 female B6/D2 F1 mice were injected once daily (five times a week) with 0.1 ml of 0.285 M KNCO; the injections were discontinued when the mice displayed signs of chronic toxicity
- No. of animals per sex per dose:
- 20 females
- Control animals:
- yes
- Details on study design:
- not indicated.
Examinations
- Observations and examinations performed and frequency:
- - body weight
- mortality
- amount of carbamylation of the amino-terminal valine of the hemoglobin - Sacrifice and pathology:
- At intervals some of the animals were sacrificed and examined for gross and histopathological lesions.
- Other examinations:
- not indicated.
- Statistics:
- not indicated.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Three groups of 20 B6/D2 F1 female mice were injected i.p. once daily (five times a week) for a five-month period with either a) 0.1 ml of saline; b) 0.1 ml of 0.02 M KNCO (6.5 mg/kg); or c) 0,1 of 0.1 M KNCO (32.5 mg/kg) without any apparent effects.
The hemoglobin concentration of some of the mice receiving 32 mg/kg of KNCO tends to be approximately 10 to 15% higher than that of the other two groups. The extent of carbamylation of the NH2-terminal valine of hemoglobin of the mice receiving cyanate increases linerarly and plateaus at approximately 0.15 and 0.8 to 1.0 carbamyl residues per hemoglobin tetramer for the 6.5 and 32.5 mg/kg groups, respectively. It should be pointed out that the hemoglobin molecule exists as a tetramer of 2 α- and 2 β-chains and has 4 amino-terminal valine residues; therefore, in the case of the 32.5 mg/kg group this corresponds to reacting an average of 0.8 of the 4 amino-terminal valine residues. The separation of the α- and β-chains of the hemoglobin of a mouse at a plateau value of 0.88 carbamyl group per mole of hemoglobin tetramer revealed an equal distribution of the cyanate between the NH2-terminal valine of the α- and β-chains. In addition, there was no detectable carbamylation of the ε-amino groups of lysine in the sample.
At intervals some of the animals were sacrificed and examined for gross and histopathological lesions. No pathological findings were noted in the cyanate-treated animals. Sodium cyanate has also been administered by i.p. injection to another series of mice for a comparable period of time at dose levels of 6 and 32 mg/kg without adverse effects.
Although a single i.p. administration of 91 mg/kg of KNCO does not kill a mouse, the daily administration of this amount leads to weight loss and eventually to death. A group of 20 female B6/D2 F1 mice were injected once daily (five times a week) with 0.1 ml of 0.285 M KNCO; the injections were discontinued when the mice displayed signs of chronic toxicity. As soon as the cyanate injections were discontinued the surviving animals quickly regained the lost weight.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 32.5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No effects up to this dose level.
Applicant's summary and conclusion
- Conclusions:
- Three groups of 20 B6/D2 F1 female mice were injected i.p. once daily (five times a week) for a five-month period with either a) 0.1 ml of saline; b) 0.1 ml of 0.02 M KNCO (6.5 mg/kg); or c) 0,1 of 0.1 M KNCO (32.5 mg/kg) without any apparent effects. The NOAEL is determined to be > 32.5 mg/kg bw/day.
- Executive summary:
In a subchronic toxicity study potassium cyanate was administered i.p. to 20 female B6/D2 F1 mice /dose in water at dose levels of 0, 6.5 and 32.5 mg/kg bw/day for 5 months.
No apparent effects were observed.
The hemoglobin concentration of some of the mice receiving 32 mg/kg of KNCO tends to be approximately 10 to 15% higher than that of the other two groups. The extent of carbamylation of the NH2-terminal valine of hemoglobin of the mice receiving cyanate increases linearly and plateaus at approximately 0.15 and 0.8 to 1.0 carbamyl residues per hemoglobin tetramer for the 6.5 and 32.5 mg/kg groups, respectively. It should be pointed out that the hemoglobin molecule exists as a tetramer of 2 α- and 2 β-chains and has 4 amino-terminal valine residues; therefore, in the case of the 32.5 mg/kg group this corresponds to reacting an average of 0.8 of the 4 amino-terminal valine residues. The separation of the α- and β-chains of the hemoglobin of a mouse at a plateau value of 0.88 carbamyl group per mole of hemoglobin tetramer revealed an equal distribution of the cyanate between the NH2-terminal valine of the α- and β-chains. In addition, there was no detectable carbamylation of the ε-amino groups of lysine in the sample.
At intervals some of the animals were sacrificed and examined for gross and histopathological lesions. No pathological findings were noted in the cyanate-treated animals. Sodium cyanate has also been administered by i.p. injection to another series of mice for a comparable period of time at dose levels of 6 and 32 mg/kg without adverse effects.
Although a single i.p. administration of 91 mg/kg of KNCO does not kill a mouse, the daily administration of this amount leads to weight loss and eventually to death. A group of 20 female B6/D2 F1 mice were injected once daily (five times a week) with 0.1 ml of 0.285 M KNCO; the injections were discontinued when the mice displayed signs of chronic toxicity. As soon as the cyanate injections were discontinued the surviving animals quickly regained the lost weight.
The NOAEL is > 32.5 mg/kg bw/day .
This subchronic toxicity study (i.p. administration) in the mouse is acceptable as supporting study, although no guideline was followed.
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