Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 204-420-7 | CAS number: 120-72-9
- 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:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- data is from peer reviewed journals
Data source
Reference
- Reference Type:
- publication
- Title:
- Metabolism of the test chemical in rat
- Author:
- King et.al
- Year:
- 1 966
- Bibliographic source:
- Biochem. J. (1966)
Materials and methods
- Objective of study:
- excretion
- metabolism
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- To study the metabolic fate of the test chemical in rats
- GLP compliance:
- not specified
Test material
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Animal Supplies (London) Ltd.]
- Age at study initiation:
- Weight at study initiation: weight about 200g.
- Housing:
- Diet (e.g. ad libitum): maintained on 25g./day of Diet 41B (Joseph Rank Ltd.)
- Water (e.g. ad libitum): free access to water
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: [14C]Indole and unlabelled indole were administered orally as solutions in arachis oil (5%, w/v).
DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food: - Duration and frequency of treatment / exposure:
- 3 days
Doses / concentrations
- Remarks:
- 64- 80 mg/kg
- No. of animals per sex per dose / concentration:
- number not specified
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: no data available
- Rationale for animal assignment (if not random): - Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
: Rats given [14C]indole were placed in a plastic metabolism chamber through which a current of air was drawn. The outgoing air was passed through two wash-bottles in series containing acetone at - 30° to trap volatile organic compounds and then through two wash-bottles containing 4N-NaOH to remove respiratory CO2.
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, blood, plasma, serum or other tissues, cage washes, bile : urine and faeces
- Time and frequency of sampling: Urine and faeces were collected daily. After 3 days the animals were killed and e radioactivity of the tissues was determined.
- Other:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, tissues, cage washes, bile : urine and faeces, bile
- Time and frequency of sampling: Urine and faeces were collected daily. After 3 days the animals were killed and e radioactivity of the tissues was determined.
- From how many animals: (samples pooled or not) : All the test animals
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC) :The urine was examined for metabolites qualitatively by chromatography
and radioautography, and quantitatively by reverse isotope dilution.
- Limits of detection and quantification:
- Other: Polythene cannulae were fitted into the common bile duct of rats and the animals were then allowed to recover from the operation for 24hr. They were then dosed orally with [14C]- indole and bile was collected for 48hr. into a tube kept at - 10° to minimize any possible action of biliary enzymes on conjugates. The total radioactivity of the bile was estimated and that of any metabolite present by reverse isotope dilution.
Results and discussion
Main ADME results
- Type:
- excretion
- Results:
- 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- >80% of the radiolabel in the urine within 48 h.
Toxicokinetic parameters
- Test no.:
- #1
- Toxicokinetic parameters:
- other: 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The chromatograms and radioautographs of the urine from rats dosed with indole revealed the presence of several metabolites, but most of the radioactivity was accounted for by six metabolites, namely indoxyl sulphate, indoxyl glucuronide, N-formylanthranilic acid, 5-hydroxyoxindole sulphate, 5-hydroxyoxindole glucuronide and an unidentified metabolite.Bile samples were collected at 48 hshowed that 0.56, 0.80, and 0.82% of the radiolabel was present as 5-hydroxyindole, 3-hydroxyindole sulfate, and total 3-hydroxyindole metabolites, respectively
Any other information on results incl. tables
When fed to rats, the 14C of [14C]indole (dose 70-80mg/kg) was fairly rapidly excreted, and in 2 days an average of 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air. Radioactivity was excreted in the urine as indoxyl sulphate (50% of the dose), indoxyl glucuronide (11%), oxindole (1.4%), isatin (5.8%), 5-hydroxyoxindole conjugates (3-1%), N-formylanthranilic acid (0.5%) and unchanged indole (0.07%). The faeces contain indoxyl sulphate (0.4% of the dose) and indole (0.2%), but the major metabolites have not been identified. When fed to rats with biliary cannulae an average of5.6% of a dose of [14C]indole (20-60 mg/kg) was excreted in the bile in 2 days. Radioactivity was present as indoxyl sulphate (0.8% dose) and 5-hydroxyoxindole conjugates (0-6%).Rats further metabolize indoxyl into N-formylanthranilic acid and anthranilic acid, and oxindole into 5-hydroxyoxindole.
Applicant's summary and conclusion
- Conclusions:
- When fed to rats, the 14C of [14C]indole (dose 70-80mg/kg) was fairly rapidly excreted, and in 2 days an average of 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air. Radioactivity was excreted in the urine as indoxyl sulphate (50% of the dose), indoxyl glucuronide (11%), oxindole (1.4%), isatin (5.8%), 5-hydroxyoxindole conjugates (3-1%), N-formylanthranilic acid (0.5%) and unchanged indole (0.07%). The faeces contain indoxyl sulphate (0.4% of the dose) and indole (0.2%), but the major metabolites have not been identified. When fed to rats with biliary cannulae an average of5.6% of a dose of [14C]indole (20-60 mg/kg) was excreted in the bile in 2 days. Radioactivity was present as indoxyl sulphate (0.8% dose) and 5-hydroxyoxindole conjugates (0-6%).Rats further metabolize indoxyl into N-formylanthranilic acid and anthranilic acid, and oxindole into 5-hydroxyoxindole.
- Executive summary:
A study was conducted to determine the metabolic fate of the test chemical in rats. Female Wistar rats were used for the study. [14C]Indole and unlabelled indole were administered orally as solutions in arachis oil (5%, w/v). Rats given [14C]indole were placed in a plastic metabolism chamber through which a current of air was drawn. The outgoing air was passed through two wash-bottles in series containing acetone at - 30° to trap volatile organic compounds and then through two wash-bottles containing 4N-NaOH to remove respiratory CO2. Urine and faeces were collected daily. After 3 days the animals were killed and e radioactivity of the tissues was determined. The urine was examined for metabolites qualitatively by chromatography and radioautography, and quantitatively by reverse isotope dilution. Polythene cannulae were fitted into the common bile duct of rats and the animals were then allowed to recover from the operation for 24hr. They were then dosed orally with [14C]- indole and bile was collected for 48hr. into a tube kept at - 10° to minimize any possible action of biliary enzymes on conjugates. The total radioactivity of the bile was estimated and that of any metabolite present by reverse isotope dilution.Radioactive materials were counted as samples of infinite thickness with highsensitivity low-background counting equipment (Panax Equipment Ltd.) incorporating the MX 157 anti-coincidence Geiger Counter assembly (Mullard Ltd.). Urine and bile were counted as such, tissues and faeces as homogenates in water, and the14CO2in the expired air as Bal4CO3. Samples were counted for periods of time sufficient to record at least 103counts net and to obtain a standard error of the mean less than 2%. When fed to rats, the 14C of [14C]indole (dose 70-80mg/kg) was fairly rapidly excreted, and in 2 days an average of 81% appears in the urine, 11% in the faeces and 2.4% as carbon dioxide in the expired air. Radioactivity was excreted in the urine as indoxyl sulphate (50% of the dose), indoxyl glucuronide (11%), oxindole (1.4%), isatin (5.8%), 5-hydroxyoxindole conjugates (3-1%), N-formylanthranilic acid (0.5%) and unchanged indole (0.07%). The faeces contain indoxyl sulphate (0.4% of the dose) and indole (0.2%), but the major metabolites have not been identified. When fed to rats with biliary cannulae an average of5.6% of a dose of [14C]indole (20-60 mg/kg) was excreted in the bile in 2 days. Radioactivity was present as indoxyl sulphate (0.8% dose) and 5-hydroxyoxindole conjugates (0-6%).Rats further metabolize indoxyl into N-formylanthranilic acid and anthranilic acid, and oxindole into 5-hydroxyoxindole.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.