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Diss Factsheets
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EC number: 604-139-3 | CAS number: 139481-69-9
- 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
Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Justification for type of information:
- The read-across of data from chemical source (candesartan) to chemical target (CAN5) is based on the following hypothesis:
- chemical source and chemical target have the same organic functional groups (according to the profile “Organic functional groups nested” of QSAR Toolbox)
- chemical source and chemical target have a very close structure similarity, as calculated by QSAR Toolbox
- chemical source and chemical target have the same general mechanistic profile, as calculated by QSAR Toolbox
- chemical source and chemical target have the same end point-specific mechanistic profile, as calculated by QSAR Toolbox
- chemical source and chemical target have similar partition coefficient n-octanol/water - Principles of method if other than guideline:
- Read-across of data from chemical source (candesartan) to chemical target (CAN5)
- GLP compliance:
- not specified
- Key result
- Dose descriptor:
- other:
- Remarks:
- no specified
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: - fetal toxicity (decreased renal function, oligohydramnios, skull ossification retardation) - neonatal toxicity (renal failure, hypotension, hyperkalemia)
- Conclusions:
- No data are available for substance target (CAN 5). Read-across with Candesartan is performed for this hazard. The adverse fetal effects appear to reflect a pharmacologic response of the fetus to Candesartan during the second half of gestation rather than abnormal embryogenesis. There is a substantial risk of oligohydramnios and fetal distress or death in hypertensive women treated with Candesartan in the latter part of the pregnancy; therefore, the use of the drug during these trimesters is contraindicated.
Rats are not a good model for this human teratogen although fetal death and decreased weight occur after treatment on days 15-20.
Candesartan did not impair fertility in male or female rats. Overall, considering all these data, the substance should be classified for this hazard class into category 2. - Executive summary:
The substance should be classified as Repr 2; H361d.
A series of 20 pregnancies with oligohydramnios.
Data source
Reference
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2016
Materials and methods
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- Candesartan is an angiotensin-II receptor blocker used in the treatment of hypertension. Angiotensin converting enzyme (ACE) inhibitors have been associated with fetal abnormalities including oliguria, skull defects, and death after second or third trimester exposure, and the product labels for angiotensin-II receptor blockers carry a warning that assumes these agents are capable of the same effects. Case reports of oliguria, perinatal renal failure, neonatal kidney dysfunction, developmental delay, and death associated with use of candesartan during the 2nd and 3rd trimester support this assumption, as do case reports with other agents of this class (losartan, valsartan, or telmisartan). The U.S. Food and Drug Administration's Pregnancy Category is the Category D that states “There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
- GLP compliance:
- no
Test material
- Reference substance name:
- 2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid
- EC Number:
- 604-138-8
- Cas Number:
- 139481-59-7
- Molecular formula:
- C24H20N6O3
- IUPAC Name:
- 2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- No specified
Administration / exposure
- Route of administration:
- other: Oral administration
- Details on exposure:
- Candesartan exposure during the pregnancy.
- Details on analytical verification of doses or concentrations:
- No specified
- Duration of treatment / exposure:
- No specified
- Frequency of treatment:
- No specified
- Duration of test:
- No specified
Doses / concentrations
- Remarks:
- No specified
Results and discussion
Effect levels
- Key result
- Dose descriptor:
- other:
- Remarks:
- No specified
- Based on:
- not specified
- Sex:
- not specified
- Basis for effect level:
- other: fetal toxicity (decreased renal function, oligohydramnios, skull ossification retardation) - neonatal toxicity (renal failure, hypotension, hyperkalemia)
- Remarks on result:
- other:
- Remarks:
- Observation in Human
Observed effects
A series of 20 pregnancies with oligohydramnios.
Applicant's summary and conclusion
- Conclusions:
- No data are available for the substance target (CAN 5). Read-across with Candesartan is performed for this hazard. The adverse fetal effects appear to reflect a pharmacologic response of the fetus to Candesartan during the second half of gestation rather than abnormal embryogenesis. There is a substantial risk of oligohydramnios and fetal distress or death in hypertensive women treated with Candesartan in the latter part of the pregnancy; therefore, the use of the drug during these trimesters is contraindicated.
Rats are not a good model for this human teratogen although fetal death and decreased weight occur after treatment on days 15-20. Candesartan did not impair fertility in male or female rats. Overall, considering all these data, CAN 5 should be classified for this hazard class into category 2.
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.
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