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EC number: 841-499-2 | CAS number: 1340593-59-0
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics, other
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Objective of study:
- toxicokinetics
- Qualifier:
- no guideline required
- GLP compliance:
- not specified
- Radiolabelling:
- yes
- Type:
- other: absorption, distribution
- Results:
- Test item was absorbed and widely distributed into tissues
- Type:
- excretion
- Results:
- Test item was mainly excreted in the feces and bile; recovery of radioactivity in urine was low.
- Type:
- metabolism
- Results:
- Test item was not significantly metabolised when incubated in vitro with mouse, rat, dog, or human hepatocytes. Only 1 metabolite was detected.
- Details on absorption:
- Test item was absorbed widely into tissues
- Details on distribution in tissues:
- Test item was absorbed and widely distributed into tissues. In most tissues test item concentrations were higher than blood.
- Details on excretion:
- While in most tissues test item concentrations were higher than blood, test item elimination from tissues was similar to blood. Low levels of radioactivity remained in hair/fur and adrenal gland cortex at 2866 hours post-dose. The test item was mainly excreted in the feces and bile; recovery of radioactivity in urine was low.
- Metabolites identified:
- yes
- Details on metabolites:
- The test item was not significantly metabolised when incubated in vitro with mouse, rat, dog, or human hepatocytes. Only 1 possible metabolite consistent with hydroxylation and glucuronidation of the test item was detected in dog hepatocytes. No additional metabolites were detected in any of the 4 species. Furthermore, results from a metabolite screen in human plasma samples demonstrated that the sum of metabolites formed was much less than 1% of the parent concentration, thereby supporting the lack of significant metabolism in human.
- Conclusions:
- The test item was reported to be absorbed and widely distributed into tissues. It was mainly excreted in the feces and bile; recovery of radioactivity in urine was low. It was also reported to be not significantly metabolised when incubated in vitro with mouse, rat, dog, or human hepatocytes. Furthermore, only one metabolite was detected in dogs hepatocytes.
- Executive summary:
(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl]propan-2-ol was reported to be absorbed and widely distributed into tissues.While in most tissues test item concentrations were higher than blood, test item elimination from tissues was similar to blood. Low levels of radioactivity remained in hair/fur and adrenal gland cortex at 2866 hours post-dose. It was mainly excreted in the feces and bile; recovery of radioactivity in urine was low. It was also reported to be not significantly metabolised when incubated in vitro with mouse, rat, dog, or human hepatocytes. Furthermore, only one metabolite consistent with hydroxylation and glucuronidation of the test item was detected in dogs hepatocytes. No additional metabolites were detected in any of the 4 species. Results from a metabolite screen in human plasma samples demonstrated that the sum of metabolites formed was much less than 1% of the parent concentration, thereby supporting the lack of significant metabolism in human.
Reference
In the single-dose and repeat-dose toxicity studies conducted in rats and dogs reported in the review document with the test item administered orally, blood was collected for TK analysis:
Study design |
|
Dose |
Cmax (ng/mL) |
AUC (h•ng/mL) |
Single-dose toxicity study in female dogs (tested doses: 30, 100, 300, or 1,000 mg/kg). |
|
1000 mg/kg |
13000 |
AUClast : 2680000 |
7-day repeated-dose toxicity study in rats (tested doses: 0, 30, 100 or 300 mg/kg/day). |
Day 7 |
30 mg/kg/day |
80100 for males 77200 for females |
AUC(2-24): 1530000 for males AUC(2-24): 1520000 for females |
28-day repeated-dose toxicity study in rats (tested doses: 0, 5, 25, 60 or 120 mg/kg/day). |
Day 28 |
5 mg/kg/day |
9163 for males 12833 for females |
AUC(0-24): 181520 for males AUC (0-24): 233340 for females |
14-day repeated-dose toxicity study in rats (tested doses: 0, 1, 3, 5 mg/kg/day) |
Day 14 |
3 mg/kg/day |
5320 (both sexes) |
AUC(0-24):111 148 (both sexes) |
26-week repeated-dose toxicity study in rats (tested doses: 0, 0.15, 0.5, 1.5, or 5 mg/kg/day) |
Week 26 |
0.5 mg/kg/day |
667 |
AUCτ: 14500 |
7-day repeated-dose toxicity study in dogs (tested doses: 0, 10, 30, 100 or 300 mg/kg/day). |
Day 7 |
30 mg/kg/day |
104000 for males 43100 for females |
AUC (0-24):2240000 for males AUC (0-24):944000 for females |
28-day repeated-dose toxicity study in dogs (tested doses: 0, 10, 30 or 100 mg/kg/day). |
Day 28 |
10 mg/kg/day |
21100 for males 25900 for females |
AUC (0-24): 473467 for males AUC (0-24): 547933 for females |
39-week repeated-dose toxicity study in rats (tested doses: 0, 0.75, 2.5, 7.5, or 20 mg/kg/day) |
Week 39 |
17 mg/kg/day |
74700 (both sexes) |
AUC(0-24): 1680000 (both sexes) |
Description of key information
(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl]propan-2-ol was reported to be absorbed and widely distributed into tissues.While in most tissues test item concentrations were higher than blood, test item elimination from tissues was similar to blood. Low levels of radioactivity remained in hair/fur and adrenal gland cortex at 2866 hours post-dose. It was mainly excreted in the feces and bile; recovery of radioactivity in urine was low. It was also reported to be not significantly metabolised when incubated in vitro with mouse, rat, dog, or human hepatocytes. Furthermore, only one metabolite consistent with hydroxylation and glucuronidation of the test item was detected in dogs hepatocytes. No additional metabolites were detected in any of the 4 species. Results from a metabolite screen in human plasma samples demonstrated that the sum of metabolites formed was much less than 1% of the parent concentration, thereby supporting the lack of significant metabolism in human.
Key value for chemical safety assessment
Additional information
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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