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EC number: 207-889-6 | CAS number: 499-75-2
- 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 vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
Data source
Reference
- Reference Type:
- publication
- Title:
- Identification of CYP isoforms involved in the metabolism of thymol and carvacrol in human liver microsomes (HLMs)
- Author:
- Dong, Fang, Zhu, Ge, Cao, Li, Hu, Yang, Liu.
- Year:
- 2 012
- Bibliographic source:
- Pharmazie 67: 1002–1006 (2012)
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- The aim of the study was to investigate the role of cytochrome P450s (CYPs) in the metabolism of thymol and carvacrol. After incubation with human liver microsomes (HLMs) in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. A combination of chemical inhibition studies and assays with recombinant CYP isoforms was used to investigate what aret the predominant drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol.
- GLP compliance:
- no
Test material
- Reference substance name:
- Carvacrol
- EC Number:
- 207-889-6
- EC Name:
- Carvacrol
- Cas Number:
- 499-75-2
- Molecular formula:
- C10H14O
- IUPAC Name:
- 2-methyl-5-(propan-2-yl)phenol
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source of test material: Carvacrol; Aladdin Corp. (Shanghai, China)
- Purity: 99%
- Source of test material: Thymol; Aladdin Corp. (Shanghai, China0
- Purity: 99% - Radiolabelling:
- no
Results and discussion
Main ADME results
- Type:
- metabolism
- Results:
- CYP2A6 was demonstrated to be the major drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol.
Metabolite characterisation studies
- Metabolites identified:
- no
- Details on metabolites:
- After incubation with HLMs in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. These metabolies were not identified.
Any other information on results incl. tables
Detection of thymol and carvacrol metabolites in HLM
After incubation of thymol with HLMs and NADPH-generating system, a new peak was eluted at 14.5 min (M) for thymol (Fig. 2A). This new peak was not detected in the negative controls without NADPH, without substrate, and without microsomes. For the metabolism of carvacrol, two new peaks were eluted at 14.7 min (M-1) and 15.3 min (M-2) (Fig. 2B). These two new peaks were not detected in the negative controls without NADPH, without substrate, and without microsomes.
Kinetic study
Under the experimental conditions used, the metabolism of thymol in HLMs obeyed typical Michaelis-Menten kinetics, as evidenced by Eadie-Hofstee plots (Fig. 3A). The kinetic parameters (apparent Vmax and Km) were calculated to be 0.58±0.02 nmol/min/mg pro and 19.8±2.2µM. The metabolism of carvacrol in HLMs obeyed the typical Michaelis-Menten kinetics, as evidenced by Eadie-Hofstee plots (Fig. 3B and Fig. 3C).The kinetic parameters (Km and Vmax) were 9.8µM and 0.78 nmol/min/mg pro for M-1, and 9.3 µM and 0.37 nmol/min/mg pro for M-2.
Chemical inhibition study
The effect of various chemical inhibitors on the metabolism of thymol was investigated in pooled HLMs (Fig. 4A). ABT, the broad CYP inhibitor, strongly inhibited the formation of thymol metabolite, suggesting that CYPs were the major drug-metabolizing enzymes involved in the metabolism of thymol. Among the selective inhibitors of nine CYP iso- forms, 8-methoxypsolaren (the selective inhibitor of CYP2A6) almost completely inhibited the formation of thymol metabolite. As shown in Fig. 4B, ABT, the broad CYP inhibitor, strongly inhibited the formation of carvacrol metabolites (M-1, M-2), suggesting that CYPs were the major drug metabolizing enzymes involved in the metabolism of carvacrol. 8-methoxypsolaren (the selective inhibitor of CYP2A6) almost completely inhibited the formation of M-1 and M-2.
Assay with human recombinant CYP isoforms
Nine recombinant CYP isoforms were employed to identify the CYP isoforms involved in the metabolism of thymol and carvacrol. The results (Fig. 5A) showed that CYP1A2, CYP2A6 and CYP2B6 could catalyze the formation of thymol metabolite. The levels of involvement of other CYP isoforms in the metabolism of thymol were negligible. For the metabolism of carvacrol, the results (Fig. 5B) showed that CYP1A2, and CYP2A6 could catalyze the formation of M-1, and CYP1A2, CYP2A6 and CYP2B6 could catalyze the formation of M-2. The levels of involvement of other CYP isoforms in the metabolism of carvacrol were negligible.
Applicant's summary and conclusion
- Conclusions:
- After incubation with human liver microsomes (HLMs) in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. These metabolites were not identified. A combination of chemical inhibition studies and assays with recombinant CYP isoforms demonstrated that CYP2A6 was the predominant drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol.
- Executive summary:
In an vitro enzyme assay (Dong et al., 2012), the role of cytochrome P450s (CYPs) in the metabolism of thymol and carvacrol was investigated.
After incubation with human liver microsomes (HLMs) in the presence of NADPH, a new metabolite and two metabolites were detected for thymol and carvacrol, respectively. These metabolites were not identified. A combination of chemical inhibition studies and assays with recombinant CYP isoforms demonstrated that CYP2A6 was the predominant drug-metabolizing enzyme involved in the metabolism of thymol and carvacrol.
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