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EC number: 237-301-3 | CAS number: 13732-62-2
- 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:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable publication which meets basic scientific principles.
Data source
Reference
- Reference Type:
- publication
- Title:
- Excretion and Distribution of Morpholine Salts in Rats.
- Author:
- Tanaka A, Tokieda T, Nambaru S, Osawa M & Yamaha T
- Year:
- 1 978
- Bibliographic source:
- J. Food Hygienic Soc. 19: 329-334.
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Elimination, distribution and metabolism of Morpholine salts in rats were investigated by means of chemical analysis and/or radioassay . Gas-liquid chromatography was used for chemical analysis of Morpholine in the rat urine and faeces. The analytical results of the excreta accorded with those made by the tracer technique.
- GLP compliance:
- no
Test material
- Reference substance name:
- Morpholine
- EC Number:
- 203-815-1
- EC Name:
- Morpholine
- Cas Number:
- 110-91-8
- Molecular formula:
- C4H9NO
- IUPAC Name:
- morpholine
- Details on test material:
- Morpholine (purity >99 %), Morpholine-hydrochloride und -palmitate
Labelled Morpholine was diluted with nonradioactive Morpholine to the specific activity of 10200 dpm/mg.
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: young adult (based on body weight)
- Weight at study initiation: 200 to 350 g
- Metabolism cages: yes
- Diet: standard diet (CE-2, Japan CLEA, Tokyo, Japan), ad libitum (fasted overnight in the case of peroral administration)
- Water: ad libitum
Administration / exposure
- Route of administration:
- other: oral and intravenous
- Vehicle:
- not specified
- Details on exposure:
- Please refer to "Doses / concentrations"
- Duration and frequency of treatment / exposure:
- single treatment
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Radioassay
14C-Morpholine: 200 mg/kg bw (oral); 150 mg/kg bw (intravenous injection)
14C-Morpholine palmitate: 400 mg/kg bw (oral)
Chemical Assay
Morpholine-HCI: 500 mg/kg bw (oral); 250 mg/kg bw (intravenous injection)
- No. of animals per sex per dose / concentration:
- 3 animals
- Control animals:
- not specified
- Positive control reference chemical:
- Not indicated
- Details on study design:
- A rationale for dose selection was not provided.
- Details on dosing and sampling:
- Elimination study:
Rats were given an oral dose of 200 mg/kg bw of 14C-Morpholine or were treated intravenously at 150 mg/kg bw. 14C-Morpholine palmitate was administered by gavage at 400 mg/kg bw. Morpholine-HCl was dosed as a 5% aqueous solution, and palmitate as a dimethyl sulfoxide solution. Urine and faeces were collected every 24 hours. A water wash of the cages at the end of the experiment was combined with the final day urine. Dose levels of Morpholine-HCI were 500 mg/kg bw for oral administration and 250 mg/kg bw for intravenous injection.
Distribution study:
After dosing wih 14C-Morpholine HCl, the animals were killed at 2, 6 and 12 hour intervals. Organs and tissues were removed, dried in air, powdered and weighed. Portions of the samples were oxidized to carbon dioxide for measuring radioactivity in a scintillator. Only the intestine was solubilized in a 0.5 N sodium hydroxide solution under gentle reflux and an aliquot of the solution was mixed with a dioxane scintillator for counting. The organ-affinity was compared with regard to the level of radioactivity content in terms of RSA (relative specific activity).
Metabolic studies:
The collected urine was extracted with ether or isopropyl ether, and an aliquot of the concentrate was spotted onto thin-layer films, and subsequently developed with several solvents to detect urinary metabolites. - Statistics:
- Mean values and standard deviations were calculated.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- The distribution of 14C-labeled Morpholine following oral administration (200 mg/kg bw) or i.v. injection (150 mg/kg bw) to 3 animals per group was investigated. The highest level was found in the muscles and intestines.
- Details on excretion:
- The analytical method by GLC was sufficient to determine free Morpholine in biological fluids. Morpholine salts were rapidly excreted by rats after peroral or intravenous administration. The urinary excretion accounted for most of the dose and a small fraction was found in the faeces. The elimination patterns were essentially similar for Morpholine-HCl and –palmitate. Morpholine was excreted almost unchanged in the rat urine. Ninety percent of the original dose was found in the urine after 3 days and 0.08 to 0.14 % was found in the faeces.
Metabolite characterisation studies
- Metabolites identified:
- no
- Details on metabolites:
- Thin-layer chromatography of concentrated urine revealed only the existence of 14C-Morpholine which indicated the same Rf values as those of the authentic sample in some solvents. It became clear that Morpholine was mainly excreted unchanged in the urine.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Morpholine exhibited a very low bioaccumulation potential. Morpholine appeared to be an inert substance in the body. - Executive summary:
In this toxicokinetic study provided by Tanaka et al. (1977), elimination, distribution and metabolism of Morpholine salts in rats were investigated by means of chemical analysis and/or radioassay. Gas-liquid chromatography was used for chemical analysis of Morpholine in the rat urine and faeces. The distribution of 14C-labeled Morpholine via oral administration (200 mg/kg bw) or i.v. injection (150 mg/kg bw) to 3 male animals per group was investigated. The analytical results of the excreta accorded with those made by the tracer technique. When rats were given Morpholine-HCl or -palmitate, about 90% of the dose was excreted in the urine over a period of 3 days and the remaining in the faeces (0.08 to 0.14 %). Morpholine was largely excreted unchanged in the urine: Ninety percent of the original dose was found in the urine after 3 days. The lowest affinity was found for adipose regardless of routes of administration. The elimination of Morpholine from organs, tissues and blood was generally rapid and specific organ-affinity was not observed in other organs except the intestine. The highest level was found in the muscle and intestine.
This toxicokinetic study in the rat is as classified acceptable.
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