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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 612-179-8 | CAS number: 61597-98-6
- 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:
- key study
- Study period:
- from 2012-10-08 to 2013-
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: study performed according to scientific principles
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- The stability of Frescolat® ML was investigated and the potential generation of Menthol was monitored. Therefore the test item Frescolat® ML was incubated with cryopreserved hepatocytes from humans, samples were taken after defined time points (0, 15, 60, 120 and 240 min) and the content of test item and potential metabolite was determined.
- GLP compliance:
- no
Test material
- Reference substance name:
- Menthyl lactate (Frescolat®)
- IUPAC Name:
- Menthyl lactate (Frescolat®)
- Reference substance name:
- Methyl lactate
- EC Number:
- 208-930-0
- EC Name:
- Methyl lactate
- Cas Number:
- 547-64-8
- IUPAC Name:
- methyl 2-hydroxypropanoate
- Reference substance name:
- Propanoic acid, 2-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2S)-
- EC Number:
- 612-179-8
- Cas Number:
- 61597-98-6
- Molecular formula:
- C13H24O3
- IUPAC Name:
- Propanoic acid, 2-hydroxy-, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester, (2S)-
- Details on test material:
- - Name of test material (as cited in study report): Frescolat®ML
- Storage condition of test material: Room temperature
Constituent 1
Constituent 2
Constituent 3
- Radiolabelling:
- no
Administration / exposure
- Positive control reference chemical:
- 1.0 µM naloxone (high metabolism) and 1.0 µM piroxicam (low metabolism) were added to the hepatocytes (0.5x10^6 cells/mL) to control the metabolic activity. Samples were taken after 0, 5, 15, 60, 120 and 240 min.
- Details on study design:
- At first stock solutions of the established concentrations of Frescolat®ML were prepared in TBME. The stock solutions were further diluted in Krebs-Henseleit (KH) buffer and applied to reaction vials. Afterwards the cryopreserved hepatocytes of humans were removed from the nitrogen tank and were thawed using Krebs-Henseleit buffer. After centrifugation the cells were resuspended in KH buffer to the final concentration of 1.0x10^6 cells/mL. The cryopreserved hepatocytes were applied to the test item or control solutions in the reaction vials leading to 0.5x10^6 cells/mL. 3 replicates were prepared for each concentration and the corresponding time points. The solutions within the vials were agitated at low speed. The vials were incubated at 37°C/5 % CO2 for a total incubation time of 4 hours. After the indicated time points (0, 15, 60, 120 and 240 min (T1 – T5)) the respective samples were stopped with 1.3 mL TBME. Samples were stored at -80°C immediately.
- Details on dosing and sampling:
- Two concentrations of the test item were used in the study (20 µM and 100 µM). 3 replicates were performed.
Results and discussion
Main ADME results
- Type:
- metabolism
- Results:
- The metabolized percentage of Frescolat®ML after 240 minutes was 97.4 % and 99.6 % when 20 and 100 µM of Frescolat®ML, respectively, were applied to the hepatocytes.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The measured amount of Menthol was between 16 and 27 µg/mL when 20 µM Frescolat® ML was applied. The range was 16-37 µg/mL when 100 µM Frescolat® ML was applied. The amount of Menthol detected was similar throughout the incubation time from 0 to 240 minutes. Therefore there is no correlation between metabolized Frescolat® ML and emerging Menthol. The amount of Menthol detected without hepatocytes was less than 0.5 µg/mL.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): other: Frescolat®ML was significantly metabolized by hepatocytes of humans
Frescolat®ML was significantly metabolized by hepatocytes of humans, i.e. from 97.4 to 99.6 % within 240 min. - Executive summary:
The liver is the prime organ in the metabolism of many xenobiotics and human hepatocytes are recognized as a suitable test system for the generation of human metabolites in vitro. The aim of the present study is to determine the metabolic activity of human hepatocytes towards the test item Frescolat®ML. Therefore the test item Frescolat®ML was incubated with cryopreserved hepatocytes from humans, samples were taken after defined time points (0, 15, 60, 120 and 240 min) and the content of test item and potential metabolite Menthol was determined. The test item Frescolat®ML was significantly metabolized by human hepatocytes in comparison to the buffer control without hepatocytes. The percentage of Frescolat®ML remaining after 240 minutes was between 0.4 % and 2.6 %. The measured amount of Menthol was between 16 and 37 µg/mL. The amount of Menthol detected was similar during the incubation time from 0 to 240 minutes. Therefore there is no correlation between metabolized Frescolat®ML and emerging Menthol.
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.