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EC number: 205-792-3 | CAS number: 151-50-8
- 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: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Guideline study on a structurally-similar substance, potassium cyanide. Experimental data was reviewed by the ECETOC Task Force, author of the JACC Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)”, 2007. The report is a weight of evidence approach to an extensive body of literature, much of which was undertaken prior to development of guidelines. The report was peer reviewed by the scientific non-governmental organization (NGO), which judged the data to be reliable with restrictions.
Data source
Reference
- Reference Type:
- other company data
- Title:
- Unnamed
- Year:
- 1 989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Potassium cyanide
- EC Number:
- 205-792-3
- EC Name:
- Potassium cyanide
- Cas Number:
- 151-50-8
- Molecular formula:
- CKN
- IUPAC Name:
- potassium cyanide
- Details on test material:
- The test material administered in water is potassium cyanide (CAS No. 151-50-8), but is present as hydrogen cyanide in the GI tract. The pKa is approximately 9, so at physiological pH and 37 °C, all cyanide species are present in the non-ionized form of hydrogen cyanide.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Rats, age 35 days at the start of quarantine, weighed 100-188 g. Animals were numbered according to a differentiated number scheme and assigned to groups. Standard diet Altromin 1321 was served as food, ad libitum. Animals were kept singly in Macrolon cages, Type III, at a room temperature of 21 oC, with relative humidity at 55% ± 5. The room was alternately illuminated (150 lux) and darkened for periods of 12 hours each. Bedding material was grandulated textured wood, type A2. Cages were cleaned and bedding material changed once weekly. Analysis of food, water and bedding material for contaminants was performed peiodically, at least once annually, with results being within admissible limits according to EPA/USA Proposed Health Effects Test Standards for TSCA Test Rules, 1979.
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on oral exposure:
- Adjustment of the dose to the body weight, or the amount of drinking water to be offered, was carried out once each week.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Random sample aliquots were taken from water bottles of the various experimental groups during weeks, 1,3,5,7,9,11 and 13, and tested analytically for cyanide content, according the method of Lundquist, et al, 1985.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Water was administered ad libitum in 250 ml glass bottles.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
40, 80 and 140-160 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- There was an extra control group of animals receiving the amount of water ingested by the high dose KCN group during the week prior.
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- Clinical and ophthalmologic examinations were performed. Animals were observed daily for behaviour and external appearance. Consistency of faeces and intake of drinking water were monitored daily. Drinking water consumption per animal was measured and recorded twice a week by measuring the amount of water remaining in the containers. Food consumption per animals was observed daily and estimated weekly by weighing the food residue.
- Sacrifice and pathology:
- Autopsy, gross pathology and histopathology were performed.
- Statistics:
- For urinalysis and organ weights: Student's t-test (p ≤ 0.01)
For body weight, food consumption, haematology and clinical biochemistry: Dunnett's test, 1955. p ≤ 0.01).
For histopathology: Exact test of RA Fisher p ≤ 0.05).
Dunnett's,
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- The animals in the high dose group and the paired drinking group were severely emaciated. All othe animals showed no substance-related changes in behaviour and external appearance. Food consumption was reduced in relation to increasing dose of KCN, and this reduction was significant in the high dose group. Food consumption for the paired drinking group and the high dose group was similar. The higher the KCN dose, the lower the consumption of drinking water. In all groups, the difference was significantly different from the standard control group. Development of body weight was significantly reduced in the mid and high dose groups. In the high dose group, toxicity developed so that the dose was lowered from 160 to 140 at the beginning of the 12th week. There were no substance-related differences between treated and untreated rats in ophthalmology or examination of hearing or dentition. There were no statistically significant differences in haematology or clinical chemistry parameters between treated and untreated group. Proteinuria occurred, and amount of protein in the urine showed a clear correlation with increasing dose of KCN. Urine pH was shifted toward the acidic in all groups except the standard control. The absolute weights of the adrenals, heart, kidneys, lungs, and thymus were slightly lower in the medium dose group, and significantly lower in the high dose group. The weights of the brain, pituitary gland and liver were signficantly reduced in the high dose group. The absolute weight of the testes indicated a slight tendency to decrease in the medium dose group, and was significantly reduced in the high dose group. Except for the thymus, all other organs in the high dose group showed an increase in relative organ weight. Gross pathology examination revealed no abnormalities except for haemorrhagic centers in the stomach, mostly in animals given high doses of KCN. Histopathologic examination revealed no major findings, especially in the brain, liver, testes, thyroid or kidneys. Histopathological examination of the animals which died prematurely indicated single to multiple erosive defects in the stomachs of animals, primarily those receiving the high dose of KCN.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 40 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: 40 mg/kg bw/d corresponds to 16 mg CN-/kg bw/d.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- This is an oral subchronic study of KCN in drinking water undertaken in male CD rats at doses of 40, 80 and 140 mg/kg bw/day for 13 weeks. Test material was also administered in the drinking water at 80 mg/kg bw/day supplemented with 10% alcohol. Three control groups were included: normal drinking water, a “paired-drinking” group, and drinking water with 10% alcohol. Body weight gain, and water and food consumption were measured. After 13 weeks the animals were euthanized, organs weighed and examined histopathologically. KCN in the drinking water resulted in decreased consumption of water and food, especially in the high dose group. In this group, toxicity developed so that the dose was lowered from 160 to 140 at the beginning of the 12th week. No toxic effects caused by KCN were observed in the low dose group. Histopathologicial examination of the kidneys, heart, liver, testes and thyroid, and especially the brain, revealed no substance-related changes. The NOAEL was 40 mg/kg bw/day.
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