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EC number: 253-775-4 | CAS number: 38083-17-9
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1980-09-22 (report date)
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study was conducted neither as per any regulatory guideline nor GLP regulation.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 980
- Report date:
- 1980
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- Concentrations of crinipan (climbazole) and of its metabolite (BAY g 5919) in blood plasma of beagle dogs treated orally with BAY e 6975 were determined on days 1, 47 and 92 of a sub-chronic toxicity study. The daily dose was 5, 10 and 20 mg/kg, respectively.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Climbazole
- EC Number:
- 253-775-4
- EC Name:
- Climbazole
- Cas Number:
- 38083-17-9
- Molecular formula:
- C15H17ClN2O2
- IUPAC Name:
- 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- dog
- Strain:
- Beagle
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 12 male and 12 female beagle hounds with a mean body weight of 9.5 kg (range: 7.7 to 11.4 kg) were included in this study.
Administration / exposure
- Route of administration:
- oral: capsule
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- The substance was administered in gelatine capsules and the control group received empty gelatine capsules.
- Duration and frequency of treatment / exposure:
- The test animals were weighed weekly; the daily single doses were adjusted for 7 d to the body weight as last determined. The administration took place over a period of 13 weeks, once daily, on all seven days of the-week, about 1 h before the daily feeding. After administration the animals were observed for another 10 min in order to readminister capsules that may have been vomited up or spat out.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Daily dose were 5, 10 and 20 mg/kg
- No. of animals per sex per dose / concentration:
- 3 animals per sex per group i.e. 6 animals per group
- Control animals:
- yes
- Positive control reference chemical:
- not applicable
- Details on study design:
- Concentrations of crinipan (BAY e 6975) and of its metabolite (BAY g 5919) in blood plasma samples were determined using thin-layer densitometric method.
- Details on dosing and sampling:
- Blood sampling for the determination of the concentrations of the active substance in plasma was carried out at 4 and 24 h post-administration, on test days 1, 47 and 92. On the 47th test day also blood was taken in addition before the administration (= 24 h after the 46th dose).
- Statistics:
- Concentrations of crinipan and metabolite were calculated using the calibration curves based on the serum standards of the same plate.
Results and discussion
- Preliminary studies:
- In almost all 24 h samples of the three days of investigation, as well as in the plasma of the additionally taken blood samples before administration on the 47th test day (= 24 h after the 46th dose) the concentrations of the unchanged substance and metabolite were below the determination limit of 10 ng/ml.
The concentrations of BAY e 6975 in the plasma 4 h after administration were on average on the three days of investigation:
in the 5 mg group between 17, 36, and 34 ng/mL, respectively
in the 10 mg group between 47, 94, and 97 ng/mL, respectively
in the 20 mg group between 357, 234 and 167 ng/mL, respectively
and thus show that the high dose also results in a higher concentration of the active substance: in the plasma. The concentrations of BAY e 6975 in the plasma were very low, however, compared to the dose administered. The mean equipartition concentrations P [P= Concentration in plasma (mg/L) / Dose (mg/kg)] at the time 4 h after administration were between 0.008 and 0.018; even assuming a plasma level maximum 2 h after administration with twice as high concentration values, this means that in the dog more than 95% of the administered dose was metabolized in the first pass metabolism, whereby among other substances, BAY g 5919 was formed. The 4 h plasma levels of metabolite BAY g 5919 were on average 2 to 5 times higher than those of the unchanged substance.
Main ADME results
- Type:
- metabolism
- Results:
- In the dog more than 95% of the administered dose was metabolized in the first pass metabolism (main metabolite was a secondary alcohol).
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- no data
- Details on distribution in tissues:
- no data
- Details on excretion:
- no data
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Metabolite BAY g 5919 (secondary alcohol)
Any other information on results incl. tables
not applicable
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): other: In the dog more than 95% of the administered dose was metabolized in the first pass metabolism, whereby among other substances BAY g 5919 was formed
Crinipan plasma levels in dogs treated orally with 5, 10, 20 mg/kg/day for 90 days were low compared with the dose administered, indicating a pronounced first pass metabolism (>95% of parent compound was metabolised). Concentrations of the metabolite (a secondary alcohol) exceeded those of the parent drug by a factor of 2 to 5. 24 h after substance administration, concentrations of both parent compound and metabolite were less than 10 ng/mL (detection limit). - Executive summary:
Concentrations of crinipan (BAY e 6975) and of its metabolite (BAY g 5919) in blood plasma of beagle dogs treated orally with crinipan were determined on days 1, 47 and 92 of a sub-chronic toxicity study. The daily dose was 5, 10 and 20 mg/kg, respectively were administer to 3 male and 3 female dogs per group with a mean body weight of 9.5 kg (range: 7.7 to 11.4 kg). Concentrations of crinipan and BAY g 5919 were determined using thin-layer densitometric method. Crinipan plasma levels in all three dosage group 4 h after application, were low compared with the dose administered, indicating a pronounced first pass metabolism. Concentrations of the BAY g 5919 (secondary alcohol) however exceeded those of the crinipan by a factor of 2 to 5. After 24 h of drug administration, concentrations of both crinipan and metabolite were less than 10 ng/mL (determination limit).
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