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EC number: 241-281-1 | CAS number: 17243-69-5
- 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:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Animal experimental study, published in peer reviewed literature
Data source
Reference
- Reference Type:
- publication
- Title:
- Zum Metabolismus von DL-trans-2-Dimethylamino-1-phenyl-cyclohex-3-en-trans-1-carbonsäureäthylester-hydrochlorid (Tilidin-HCl)
- Author:
- Vollmer K.O.
- Year:
- 1 977
- Bibliographic source:
- Arzneimittelforschung. 1977;27(9):1707-13.
Materials and methods
- Objective of study:
- excretion
- Principles of method if other than guideline:
- Metabolism and excretion of ethyl-DL-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride were investigated in rats using the radioactively labelled substance.
- GLP compliance:
- no
Test material
- Reference substance name:
- Ethyl trans-(±)-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate hydrochloride
- EC Number:
- 248-226-0
- EC Name:
- Ethyl trans-(±)-2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate hydrochloride
- Cas Number:
- 27107-79-5
- IUPAC Name:
- 27107-79-5
- Reference substance name:
- 3-Cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester, hydrochloride, (1R,2S)-rel-
- IUPAC Name:
- 3-Cyclohexene-1-carboxylic acid, 2-(dimethylamino)-1-phenyl-, ethyl ester, hydrochloride, (1R,2S)-rel-
- Details on test material:
- - Name of test material (as cited in study report): DL-trans-Dimethylamino-1-phenyl-cyclohex-3-en-trans-1-carbonsäureäthylester-hydrochlorid (Tilidin-HCl, Gö 1261 C)
- Purity: 98 - 99 %
Constituent 1
Constituent 2
- Radiolabelling:
- yes
- Remarks:
- 14C
Test animals
- Species:
- rat
- Strain:
- SIV 50
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Gödecke
- Weight at study initiation: 170 - 200 g
- Fasting period before study: yes
- Diet: no feed during the study
- Water: ad libitium
Administration / exposure
- Route of administration:
- other: oral gavage or intravenous
- Vehicle:
- water
- Details on exposure:
- - Animals received Tilidin-(6-14C)-HCl with an activity of 2 mCi/mMol.
- The radioactive Tilidin-HCl was diluted with normal Tilidin-HCl, to expose the test subjects to 5-10 µCi.
- Administration volume: 1 mL/100 g bw - Duration and frequency of treatment / exposure:
- Single administration
Doses / concentrations
- Remarks:
- Doses / Concentrations:
23 mg/kg
- No. of animals per sex per dose / concentration:
- - intravenous administration: 12
- oral gavage administration: 8 - Details on study design:
- Renal excretion was measured by measuring the radioactively labelled excreted substance and metabolites in urine fractions taken in different time frames. 50% of each fraction until 24 h was pooled to get a 0-24 h urine. Metabolites were evaluated using several enzym extraction methods and thin-layer chromatography.
- Details on dosing and sampling:
- PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: urine was collected in the following time frames: 0-4 h, 4-8 h, 8-12 h, 12-24 h after administration.
- Before a time frame sampling animals received 1 mL/100 g bw physiologic saline.
- 50% of every timeframe fraction of urine was pooled for a 0-24 h urine.
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: urine was collected in the following time frames: 0-4 h, 4-8 h, 8-12 h, 12-24 h after administration.
- Method type(s) for identification: Liquid scintillation counting, thin-layer chromatography and several enzym incubations (arylsulfatase, beta-glucuronidase)
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- - 47.1 and 51.0% of the substance administered was excreted via urine within one day of administration, after intravenous and oral gavage administration, respectively.
- Most of the excreted products were metabolites of the administered substance.
Toxicokinetic parametersopen allclose all
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 8 h (oral gavage administration)
- Test no.:
- #2
- Toxicokinetic parameters:
- half-life 1st: 8 h (intravenous administration)
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- - Several metabolites were observed, among which nortildin and bisnortilidin.
- 17 % of the urinary radioactivity, of animals exposed via oral gavage, could be extracted with ether at alkaline pH value as so called unpolar metabolites. Of this <0.2% corresponded to the unchanged substance, 3.7% to nortilidin and bisnortilidin (<0.1% and 2.9% of applied dose, respectively).
- Ca. 25% of the urinary radioactivity, of animals exposed intravenously, could be extracted with ether at alkaline pH value as so called unpolar metabolites. Of this 7.2% corresponded to the unchanged substance, 3.7% to nortilidin and bisnortilidin (3.4% and 2.8% of applied dose, respectively).
- The largest part of the polarized metabolites were glucuronide conjugates, this was based on the incubation of the urine with different enzymes.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): no bioaccumulation potential based on study results
- Executive summary:
Metabolism and excretion of ethyl-DL-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride were investigated in SIV-50 rats using the radioactively labelled substance. Following oral administration 51 % of the applied radioacitivity was eliminated via urine. After intravenous administration this elimination was 47.1%. The half-life of renal elimation, after both administration routes, was 8 h. The largest part of the administered substance was excreted as a metabolite. Several metabolites were identified, among which nortilidin and bisnortilidin. 17% of the urinary radioactivity could be extracted with ether at alkaline pH values as so called unpolar metabolites, after oral administration. After intravenous administration this was ca. 25%. The higher proportion of unchanged tilidine in the urine of the i.v. rat test in comparison to the i.g. test (3.4% and <0.1% resp. of applied dose) indicated a first-pass effect during absorption. The major part of the polarized metabolites consists of glucuronides.
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