Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 213-554-5 | CAS number: 976-71-6
- 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
Carcinogenicity
Administrative data
Description of key information
Long-term (104-week) rat study with potassium canrenoate: Increased incidence of myelocytic leukaemia at 50 mg/kg bw/day and above; NOAEL = 20 mg/kg bw/day [Wagner 1987]
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- other information
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: short abstract of results on long-term studies with potassium canrenoate
- Principles of method if other than guideline:
- no data
- GLP compliance:
- not specified
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on exposure:
- no data
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Duration of treatment / exposure:
- 52 and 104 weeks
- Frequency of treatment:
- daily
- Post exposure period:
- 13 weeks (52-week study)
- Remarks:
- Doses / Concentrations:
30, 90, 270 mg/kg (52-week study) and 20, 50, 125, 270 mg/kg (104-week study)
Basis:
nominal conc. - No. of animals per sex per dose:
- no data ((52-week study)
50 animals per sex per dose (104-week study) - Control animals:
- yes
- Details on study design:
- no data
- Positive control:
- no data
- Observations and examinations performed and frequency:
- no data
- Sacrifice and pathology:
- no data
- Other examinations:
- no data
- Statistics:
- no data
- Executive summary:
Canrenone is a metabolite of potassium canrenoate, a drug formerly used for therapy of hypertension.
A 52-week study of potassium canrenoate in the rat was conducted. Animals were given oral doses of 30, 90 and 270 mg/kg/day. There was an increased incidence of myelocytic leukaemia at the 90 and 270 mg/kg doses. Leukaemia was observed in the high-dose group after 28 weeks of treatment. There were significant increases in mammary tumours (adenomas, fibroadenomas and adenocarcinomas) and no significant increase of hepatocellular carcinoma, jejunal adenocarcinoma, follicular and medullary adenomas of the thyroid and adenomas of the kidney, pancreas, lung and ear duct. Cellular hypertrophy in the liver, thyroid and adrenal gland were seen after 52 weeks of dosing with potassium canrenoate. However, after 13 weeks of recovery, most of these changes were reversible.
These findings prompted a two-year study of potassium canrenoate in rats. Animals were given doses of 20, 50, 125 and 270 mg/kg/day, with 50 rats of each sex per dose.A dose-related incidence of myelocytic leukaemia, more frequent in males than females, was seen. Leukaemia was observed at dosages of 50 mg/kg/day and above, reaching statistical significance at 125 and 270 mg/kg/day. The first observation of leukaemia was at 32 weeks, eight were diagnosed at post-mortem examination at 52 weeks and there was a total of 30 cases by the end of two years. A statistically significant increase in the incidence of hepatic, thyroid, testicular, skin, brain, histiocytic and mammary tumours was noted. However, the tumour incidence in all organs at 20 mg/kg/day was similar to controls.
Reference
52-week study
There was an increased incidence of myelocytic leukaemia at the 90 and 270 mg/kg doses. Leukaemia was observed in the high-dose group after 28 weeks of treatment. There were significant increases in mammary tumours (adenomas, fibroadenomas and adenocarcinomas) and no significant increase of hepatocellular carcinoma, jejunal adenocarcinoma, follicular and medullary adenomas of the thyroid and adenomas of the kidney, pancreas, lung and ear duct. Cellular hypertrophy in the liver, thyroid and adrenal gland were seen after 52 weeks of dosing with potassium canrenoate. However, after 13 weeks of recovery, most of these changes were reversible.
104-week study
A dose-related incidence of myelocytic leukaemia, more frequent in males than females, was seen. Leukaemia was observed at dosages of 50 mg/kg/day and above, reaching statistical significance at 125 and 270 mg/kg/day. The first observation of leukaemia was at 32 weeks, eight were diagnosed at post-mortem examination at 52 weeks and there was a total of 30 cases by the end of two years. A statistically significant increase in the incidence of hepatic, thyroid, testicular, skin, brain, histiocytic and mammary tumours was noted. However, the tumour incidence in all organs at 20 mg/kg/day was similar to controls.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 20 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the results of two long-term studies in rats (increased incidence of myelocytic leukemia) a self classification of the substance according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is recommended as follows:
DSD: R40, Carc. Cat. 3 (Limited evidence of a carcinogenic effect)
GHS: Carc. 2 (H351: Suspected of causing cancer)
Additional information
Canrenone is a metabolite of potassium canrenoate, a drug formerly used for therapy of hypertension.
A 52-week study of potassium canrenoate in the rat was conducted. Animals were given oral doses of 30, 90 and 270 mg/kg/day. There was an increased incidence of myelocytic leukaemia at the 90 and 270 mg/kg doses. Leukaemia was observed in the high-dose group after 28 weeks of treatment. There were significant increases in mammary tumours (adenomas, fibroadenomas and adenocarcinomas) and no significant increase of hepatocellular carcinoma, jejunal adenocarcinoma, follicular and medullary adenomas of the thyroid and adenomas of the kidney, pancreas, lung and ear duct. Cellular hypertrophy in the liver, thyroid and adrenal gland were seen after 52 weeks of dosing with potassium canrenoate. However, after 13 weeks of recovery, most of these changes were reversible.
These findings prompted a two-year study of potassium canrenoate in rats. Animals were given doses of 20, 50, 125 and 270 mg/kg/day, with 50 rats of each sex per dose. A dose-related incidence of myelocytic leukaemia, more frequent in males than females, was seen. Leukaemia was observed at dosages of 50 mg/kg/day and above, reaching statistical significance at 125 and 270 mg/kg/day. The first observation of leukaemia was at 32 weeks, eight were diagnosed at post-mortem examination at 52 weeks and there was a total of 30 cases by the end of two years. A statistically significant increase in the incidence of hepatic, thyroid, testicular, skin, brain, histiocytic and mammary tumours was noted. However, the tumour incidence in all organs at 20 mg/kg/day was similar to controls.
Justification for selection of carcinogenicity via oral route endpoint:
Only one publication with 52- and 104-week studies available
Carcinogenicity: via oral route (target organ): cardiovascular / hematological: other
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.