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EC number: 201-696-0 | CAS number: 86-74-8
- 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:
- other: Acceptable, well-documented publication which meets basic scientific principles
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- The Metabolism of Carbazole in Rats and Rabbits
- Author:
- Johns SR and Wright SE
- Year:
- 1 964
- Bibliographic source:
- J Med Chem 7 (2), 158-161
- Reference Type:
- publication
- Title:
- Metabolism of Carbazole
- Author:
- Johns SR and Wright SE
- Year:
- 1 962
- Bibliographic source:
- Experientia 18, 416-417
Materials and methods
- Objective of study:
- excretion
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Isolation and identification of metabolites of carbazole in the urine of rats and rabbit after i.p. injection or oral administration using non labeled and C14-radiolabeled carbazole
- GLP compliance:
- no
Test material
- Reference substance name:
- Carbazole
- EC Number:
- 201-696-0
- EC Name:
- Carbazole
- Cas Number:
- 86-74-8
- Molecular formula:
- C12H9N
- IUPAC Name:
- 9H-carbazole
- Details on test material:
- - Name of test material (as cited in study report): carbazole
C14-radiolabeled carbazole was synthezised in a three step synthesis starting from C14-aniline.
- Analytical purity: no data
- Specific activity (if radiolabelling): 6.0 x 10E5 d.p.m./mg
- Locations of the label (if radiolabelling): C-atom in one benzene-nucleus
- no further information on test substance
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- other: rats and rabbit
- Strain:
- not specified
- Sex:
- not specified
Administration / exposure
- Route of administration:
- other: rats: intraperitoneal injection; rabbit: oral, gavage
- Vehicle:
- other: rats: propylene glycol; rabbit: acacia suspension
- Duration and frequency of treatment / exposure:
- single dose exposure
Doses / concentrations
- Remarks:
- Doses / Concentrations:
rats: 4 mg/kg; rabbit: 1 g; rats (radiolabeled test compound): 4.13 x 10E5 d.p.m./rat
- No. of animals per sex per dose / concentration:
- rats: no data; rabbit: 1; rats (radiolabeled test compound): total of 6 animals in 3 groups (2 animals per group)
- Control animals:
- no
- Details on dosing and sampling:
- METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine
- Time and frequency of sampling: rats: for 3 days; rabbit: daily for 3 days, rats (radiolabeled test compound): daily for 3 days for each of the 3 groups
- From how many animals: rats: no data; rabbit: 1 animal; rats (radiolabeled test compound): 6 animals
- Method type(s) for identification: co-chromatography with authentic samples on paper and thin-layer chromatography, liquid scintillation counting
TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): 0.5 N hydrochloric acid, ß-glucuronidase
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on excretion:
- 65% of the radioactivity, administered as C14-carbazole to rats (4.13 x 10E5 d.p.m./rat), was excreted in urine within 3 days (day 1: 61%; day 2: 3.5%; day 3: 0.5%; mean for six rats).
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- In the urine of rabbit and rats, the glucuronide of 3-hydroxycarbazole was identified as major metabolite of carbazole.
Any other information on results incl. tables
Rabbit
After oral application of 1 g of carbazole, a two-fold increase in glucuronide content was observed in urine during the first day returning to normal after 3 days. Isolation of glucuronides from urine resulted in a gum which was methylated and acetylated to form the tri-O-acetylglucuronide methyl ester. From the reaction mixture, three products were isolated by chromatography over neutral alumina: 3-methoxycarbazole as byproduct of the processing of urine, a tri-O-acetyl methyl ester of a hydroxycarbazole glucuronide as major metabolite, and a small amount of a third product, also a tri-O-acetyl methyl ester of a glucuronide with a symmetrically disubstituted carbazole structure conjugated as indicated by IR spectra.
After hydrolysis of the hydroxycarbazole glucuronide using ß-glucuronidase, the resulting phenolic product was identified as 3-hydroxycarbazole by comparative paper and thin-layer chromatography with an authentic reference sample.
Rat
In the urine of rats treated i.p. with a single carbazole dose of 4 mg/kg, a major metabolite was isolated and purified by paper chromatography using several solvent systems. After hydrolysis of the purified product with 0.5 N hydrochloric acid, the phenolic product showed the same chromatographic characteristics as the hydrolysis product from rabbit urine. Identification was accomplished by chromatographic comparison with an authentic sample and the identity proven to be 3-hydroxycarbazole.
After i.p. injection of radiolabeled carbazole into rats, the three-day urine contained 65% of radioactivity (mean of 6 rats). Acid hydrolysis resulted in an ether-extractable fraction which could be further separated by paper chromatography. Distribution of radioactivity in different fractions of urine was as follows.
Initial dose |
100 % (2.48 x 10E6 d.p.m.) |
|||
|
Urine acid hydrolysis |
65 % (1.61 x 10E6 d.p.m.) |
||
|
ether extract paper chromatography |
55 % (1.36 x 10E6 d.p.m.) |
||
|
moving band radioactivity (isolated 3-hydroxycarbazole) |
33 % (0.82 x 10E6 d.p.m.) |
||
starting line radioactivity (at least 2 more metabolites) |
20 % (0.50 x 10E6 d.p.m.) |
|||
aqueous phase |
10 % (0.25 x 10E6 d.p.m.) |
Elution of the moving band radioactivity with methanol yielded 3-hydroxycarbazole (33%) as demonstrated by co-chromatography with an authentic sample. Re-chromatography of the starting-line radioactivity with a more polar solvent revealed at least two more phenolic products with unknown structure (possibly di- and polyhydroxylated carbazoles).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
In experiments using rats and rabbit, the glucuronide of 3-hydroxycarbazole was demonstrated to be the major metabolite.
After administration of C14-labeled carbazole to rats, 65% of the radioactivity administered was found in the 3 d urine. After acid hydrolysis of the urine, 55% of the total radioactive dose distributed into an ether extract of the urine. After further purification, 33% of the dose were isolated from the ether extract as 3-hydroxycarbazole. Another 10% of total radioactivity in the ether extract could be attributed to at least two more phenolic carbazole derivatives more polar than 3-hydroxcarbazole (possibly di- and polyhydroxylated carbazoles).
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