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EC number: 701-039-2 | CAS number: 156324-78-6
- 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, other
- Remarks:
- hydrolysis assay
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- not specified
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
- Objective of study:
- other: hydrolysis
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- An in vitro hydrolysis test in different media with and without enzymolysis was conducted with the test item. The test media were as follows: simulated gastric juice, simulated intestinal fluid, and rat liver homogenate. In addition, the test substance was also tested in distilled water without enzymolysis. Chemical composition of the substance before and after hydrolysis test procedure was determined by extraction with addition of an internal standard substance and following GC with FID. Extraction was made by liquid-liquid extraction in a modified device described by Kutscher and Stendel with pentane/ethylether 2:1.
- GLP compliance:
- no
Test material
- Reference substance name:
- 2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol
- EC Number:
- 701-039-2
- Cas Number:
- 156324-78-6
- Molecular formula:
- C13H24O4
- IUPAC Name:
- 2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol
Constituent 1
- Radiolabelling:
- no
Test animals
- Details on test animals or test system and environmental conditions:
- Not applicable - Since this is an in vitro study there is no information on test animals.
Administration / exposure
- Route of administration:
- other: in vitro hydrolysis study in different media
- Vehicle:
- propylene glycol
- Duration and frequency of treatment / exposure:
- 4 hours
Doses / concentrationsopen allclose all
- Dose / conc.:
- 122 other: mg
- Remarks:
- hydrolysis test with simulated gastric juice or simulated intestinal fluid
- Dose / conc.:
- 20 other: mg
- Remarks:
- hydrolysis test with rat liver homogenate
- No. of animals per sex per dose / concentration:
- not applicable
- Positive control reference chemical:
- not applicable
- Details on study design:
- not specified
- Details on dosing and sampling:
- GENERAL INFORMATION ON HYDROLYSIS PROCEDURE
- hydrolysis test was conducted in different media (with and without enzymolysis): simulated gastric juice, simulated intestinal fluid, and rat liver homogenate
- hydrolysis procedure for each medium with and without enzymolysis was conducted twice.
- hydrolysis of the test item without enzymolysis was also determined in distilled water (untreated batch).
- chemical composition of the substance before and after hydrolysis test procedure has been determined by extraction with addition of an internal standard substance and following GC with FID equipped with a 60 m x 0.32 mm internal diameter DB-1 column and a 60 m x 0.32 mm i.d. WAX column.
- extraction was made by liquid-liquid extraction in a modified device described by Kutscher and Stendel with pentane/ethylether 2:1.
HYDROLYSIS WITH SIMULATED GASTRIC JUICE OR SIMULATED INTESTINAL JUICE
- test medium (simulated gastric juice): pepsin solved in buffer I (sodium chloride, hydrochlorid acid conc. and distilled water (pH = 1.1))
- hydrolysis test with simulated gastric juice: 1.22 g of a 10 % solution of the test item in the vehicle (= 122 mg test item) has been solved in test medium 3:1 and given in a flask.
- test medium (simulated intestinal fluid): pancreatin solved in buffer II (dibasic potassium phosphate, distilled water, sodium hydroxide solution (pH = 7.5))
- hydrolysis test with simulated intestinal juice: 1.22 g of a 10 % solution of the test item in the vehicle (= 122 mg test item) has been solved in test medium 4:1 and given in a flask.
The following applies to both hydrolysis tests:
- flask content has been stirred at 37 - 38 °C for four hours and kept in the refrigerator over night (16 hours).
- menthon has been added as an internal standard and distilled water.
- extraction was made by liquid-liquid extraction for 8 hours with pentane/ether (2:1).
- extract was dried with sodium sulfate and concentrated to 1 mL.
HYDROLYSIS WITH LIVER HOMOGENATE
- test medium: masculine rat liver was homogenized in Sörensen buffer solution (0.1 M; pH = 7.6) and cooled down (4 °C).
- 0.200 g of a 10 % solution of the test item in the vehicle (= 20 mg test item) was incubated with test medium (5:1) at 37 °C for 4 hours.
- then trichloroacetic acid (20 %) was added to inactivate the enzymes and the batch has been frozen until GC process.
- menthon was added as an internal standard and distilled water
- extraction was made by liquid-liquid extraction for 8 hours with pentane/ether (2:1)
- extract was dried with sodium sulfate and concentrated to 1 mL.
CONCENTRATED SUBSTANCE
- 1.29 g of a 10 % solution of the test item in the vehicle (= 129 mg test item) was solved in distilled water and extracted in the same as described above without enzymolysis. - Statistics:
- not specified
Results and discussion
- Preliminary studies:
- not applicable
Main ADME results
- Type:
- other: hydrolysis
- Results:
- The incubation with simulated gastric juice and intestinal fluid did not modify the test item, whereas the incubation with rat liver homogenate did hydrolyse the menthol from the test item almost completely (theoretical value 12.7 mg).
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- not measured
- Details on distribution in tissues:
- not measured
- Details on excretion:
- not measured
Metabolite characterisation studies
- Metabolites identified:
- not measured
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- not measured
Any other information on results incl. tables
As hydrolysis product menthol was to be expected. In the tests the final content of menthol was measured via the relation to the internal standard. Each test was done twice. The tests without enzymolysis and the test with distilled water were used for control.
|
Untreated batch (mg) |
Inactive* simulated gastric juice (pH 1) (mg) |
Active simulated gastric juice (pepsin pH 1) (mg) |
Inactive* intestinal fluid (pH 7.5) (mg) |
Active simulated intestinal fluid (pancreatin pH 7.5) (mg) |
Inactivated rat liver homogenate (pH 7.6) (mg) |
Rat liver homogenate (pH 7.6) (mg) |
Menthol |
2.0 |
2.0 |
2.2 |
3.2 |
1.4 |
0.2 |
10.7 |
2.4 |
4.1 |
1.2 |
5.3 |
1.8 |
0.2 |
11.6 |
* inactive means without enzyme addition
Applicant's summary and conclusion
- Conclusions:
- The incubation with simulated gastric juice and intestinal fluid did not modify the test item, whereas the incubation with rat liver homogenate did hydrolyse the menthol from the test item almost completely (theoretical value 12.7 mg).
- Executive summary:
An in vitro hydrolysis test in different media with and without enzymolysis was conducted with the test item. The test media were as follows: simulated gastric juice, simulated intestinal fluid, and rat liver homogenate. In addition, the test substance was also tested in distilled water without enzymolysis. Chemical composition of the substance before and after hydrolysis test procedure was determined by extraction with addition of an internal standard substance and following GC with FID. Extraction was made by liquid-liquid extraction in a modified device described by Kutscher and Stendel with pentane/ethylether 2:1.
The results showed that the incubation with simulated gastric juice and intestinal fluid did not modify the test item, whereas the incubation with rat liver homogenate did hydrolyse the menthol from the test item almost completely (theoretical value 12.7 mg).
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