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EC number: 927-344-2 | CAS number: -
- 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
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented study report which meets basic scientific principles.
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented study report which meets basic scientific principles.
- Reason / purpose for cross-reference:
- read-across source
- Objective of study:
- metabolism
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- GLP compliance:
- not specified
- Radiolabelling:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Fourteen Fischer-344 male rats weighing 307+/-10g. Feed (Purina Rat Chow, Ralston Purina Co., St. Louis, MO) and water were provided ad libitum.
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Duration and frequency of treatment / exposure:
- 2 weeks
- Remarks:
- Doses / Concentrations:
0.8 g/kg - No. of animals per sex per dose / concentration:
- 8 treated, 6 control
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Fourteen Fischer-344 male rats weighing 307±10 g were randomly divided into 2 groups (8 treated, 6 control). Doses (0.8 g/kg) of t-butylcyclohexane or water (0.8 g/kg) were administered by gavage on an every other day regimen for 2 weeks. Feed (Purina Rat Chow, Ralston Purina Co., St. Louis, MO) and water were provided ad libitum and animals were weighed daily. Following the 14-day exposure period, the rats were sacrificed by halothane.
- Details on dosing and sampling:
- During the first 48 h of the initial dosing period, the rats were placed in metabolism cages and the urine was collected. A 5.0 ml aliquot of each urine sample was adjusted to a pH of 4.0, and 0.2 ml glucuronidase/sulfatase was added. The sample was shaken for 16 h at 37°C, then cooled to room temperature and filtered through a diatomaceous earth column using methylene chloride as the eluent. The methylene chloride extracts of the hydrolyzed rat urine were analyzed on a gas-liquid chromatograph (GC) equipped with a flame ionization detector. A 25 m x 0.2 mm ID carbowax 20 M fused silica column was used with injection port and detector temperatures of 200 and 250°C, respectively. The oven temperature was programmed to rise from 60 to 170° C at a rate of 5°C/mm and helium was used as the carrier gas. Additional metabolite identification was accomplished using a Hewlett-Packard 5985 gas chromatography/mass spectrometer (GS/MS) system. The GC was equipped with a 15 m x 0.2 mm ID DX-4 capillary column and the injection port temperature and the oven temperature were the same as reported above. Helium was the carrier gas. The MS was a quadrupole instrument operated in the electron impact mode with a voltage of 70 eV and an ion source temperature of 200°C.
The relative abundance of the urinary metabolites was found by preparing a standard solution utilizing a weighed amount of each pure compound and dodecane as an internal standard and then comparing the integrated areas of the GC curve with the areas of the CC urinary metabolite curve containing added dodecane. - Metabolites identified:
- yes
- Details on metabolites:
- The majority of the oxidative metabolism of t-butylcyclohexane occurred on the cyclohexane structure. Of the 2 products which were the result of metabolic oxidation of the t-butyl side chain, 2-methyl-2-cyclohexylpropanoic acid was formed in greater abundance. The formation of the other alkyl side chain, metabolite 2-methyl-2-cyclohexyl-1,3-propanediol can be envisioned as 2 separate monooxidation steps involving the t-butyl group. Each of the branched chain products could hypothetically originate from a common precursor: 2-methyl-2-cyclohexylpropanol. The GC showed no trace of this propanol precursor, suggesting that, if formed, it was rapidly metabolized.
The metabolic oxidation of the cyclohexane ring of t-butylcyclohexane preferentially occurred at the 4-position. The bulkiness of the t-butyl group apparently inhibited monooxidation at the 2- and 3-positions. Both cis- and trans-4-t-butyl- cyclohexanol are formed with the latter being the overall principle metabolic product. The remaining minor metabolites identified were the result of dioxidation on the cyclohexane ring at the 3-position. The least formed cyclohexanediol was the isomer in which all the ring substituents exist in the equatorial position of the cyclohexane chair conformation of 2- hydroxy-4-t-butylcyclohexanol. 2-Hydroxy-4-t-butylcyclohexanol has the t-butyl and the OH at C1 groups in the equatorial position, while the OH at C2 is in the axial position. The most abundant cyclohexanediol, 2-hydroxy-4-t-butylcyclohexanol, has the OH at C2 and the t-butyl groups in the equatorial positions while the OH at C1 is in the axial position. If one envisions that the starting materials for the cyclohexanediols were the corresponding 4-t-butylcyclohexanols, the small amount of cis-4-t-butylcyclohexanol found may be due to its facile conversion into the 2 most abundant t-butyl-1,2-cyclohexanediols isolated. The large amount of trans-4-t-butylcyclohexadiol found may be a reflection of its easier conjugation with glucuronic acid relative to cis-4-t-butylcyclohexanol. The difficulty in glucuronidation of the cis-4-t-butylcyclohexanol could then, conceivably, result in further hydroxylation to facilitate urinary excretion by creating more polar metabolites (diols). - Conclusions:
- Interpretation of results:
The major metabolites of t-butylcyclohexane were found to be: trans-4-t-butylcyclohexanol, 2c-hydroxy-4t-t-butylcyclohexanol, 2-methyl-2-cyclohexylpropanoic acid, 2c-hydroxy-4c-t-butylcyclohexanol, 2-methyl-2-cyclohexyl-1,3-propanediol, 2t-hydroxy-4t-t-butylcyclohexanol, and cis -4-t-butylcyclohexanol. - Executive summary:
The major metabolites of t-butylcyclohexane were found to be: trans-4-t-butylcyclohexanol, 2c-hydroxy-4t-t-butylcyclohexanol, 2-methyl-2-cyclohexylpropanoic acid, 2c-hydroxy-4c-t-butylcyclohexanol, 2-methyl-2-cyclohexyl-1,3-propanediol, 2t-hydroxy-4t-t-butylcyclohexanol, and cis -4-t-butylcyclohexanol.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 987
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- GLP compliance:
- not specified
Test material
- Details on test material:
- t-butylcyclohexane
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Fourteen Fischer-344 male rats weighing 307+/-10g. Feed (Purina Rat Chow, Ralston Purina Co., St. Louis, MO) and water were provided ad libitum.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Duration and frequency of treatment / exposure:
- 2 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.8 g/kg
- No. of animals per sex per dose / concentration:
- 8 treated, 6 control
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Fourteen Fischer-344 male rats weighing 307±10 g were randomly divided into 2 groups (8 treated, 6 control). Doses (0.8 g/kg) of t-butylcyclohexane or water (0.8 g/kg) were administered by gavage on an every other day regimen for 2 weeks. Feed (Purina Rat Chow, Ralston Purina Co., St. Louis, MO) and water were provided ad libitum and animals were weighed daily. Following the 14-day exposure period, the rats were sacrificed by halothane.
- Details on dosing and sampling:
- During the first 48 h of the initial dosing period, the rats were placed in metabolism cages and the urine was collected. A 5.0 ml aliquot of each urine sample was adjusted to a pH of 4.0, and 0.2 ml glucuronidase/sulfatase was added. The sample was shaken for 16 h at 37°C, then cooled to room temperature and filtered through a diatomaceous earth column using methylene chloride as the eluent. The methylene chloride extracts of the hydrolyzed rat urine were analyzed on a gas-liquid chromatograph (GC) equipped with a flame ionization detector. A 25 m x 0.2 mm ID carbowax 20 M fused silica column was used with injection port and detector temperatures of 200 and 250°C, respectively. The oven temperature was programmed to rise from 60 to 170° C at a rate of 5°C/mm and helium was used as the carrier gas. Additional metabolite identification was accomplished using a Hewlett-Packard 5985 gas chromatography/mass spectrometer (GS/MS) system. The GC was equipped with a 15 m x 0.2 mm ID DX-4 capillary column and the injection port temperature and the oven temperature were the same as reported above. Helium was the carrier gas. The MS was a quadrupole instrument operated in the electron impact mode with a voltage of 70 eV and an ion source temperature of 200°C.
The relative abundance of the urinary metabolites was found by preparing a standard solution utilizing a weighed amount of each pure compound and dodecane as an internal standard and then comparing the integrated areas of the GC curve with the areas of the CC urinary metabolite curve containing added dodecane.
Results and discussion
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The majority of the oxidative metabolism of t-butylcyclohexane occurred on the cyclohexane structure. Of the 2 products which were the result of metabolic oxidation of the t-butyl side chain, 2-methyl-2-cyclohexylpropanoic acid was formed in greater abundance. The formation of the other alkyl side chain, metabolite 2-methyl-2-cyclohexyl-1,3-propanediol can be envisioned as 2 separate monooxidation steps involving the t-butyl group. Each of the branched chain products could hypothetically originate from a common precursor: 2-methyl-2-cyclohexylpropanol. The GC showed no trace of this propanol precursor, suggesting that, if formed, it was rapidly metabolized.
The metabolic oxidation of the cyclohexane ring of t-butylcyclohexane preferentially occurred at the 4-position. The bulkiness of the t-butyl group apparently inhibited monooxidation at the 2- and 3-positions. Both cis- and trans-4-t-butyl- cyclohexanol are formed with the latter being the overall principle metabolic product. The remaining minor metabolites identified were the result of dioxidation on the cyclohexane ring at the 3-position. The least formed cyclohexanediol was the isomer in which all the ring substituents exist in the equatorial position of the cyclohexane chair conformation of 2- hydroxy-4-t-butylcyclohexanol. 2-Hydroxy-4-t-butylcyclohexanol has the t-butyl and the OH at C1 groups in the equatorial position, while the OH at C2 is in the axial position. The most abundant cyclohexanediol, 2-hydroxy-4-t-butylcyclohexanol, has the OH at C2 and the t-butyl groups in the equatorial positions while the OH at C1 is in the axial position. If one envisions that the starting materials for the cyclohexanediols were the corresponding 4-t-butylcyclohexanols, the small amount of cis-4-t-butylcyclohexanol found may be due to its facile conversion into the 2 most abundant t-butyl-1,2-cyclohexanediols isolated. The large amount of trans-4-t-butylcyclohexadiol found may be a reflection of its easier conjugation with glucuronic acid relative to cis-4-t-butylcyclohexanol. The difficulty in glucuronidation of the cis-4-t-butylcyclohexanol could then, conceivably, result in further hydroxylation to facilitate urinary excretion by creating more polar metabolites (diols).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results:
The major metabolites of t-butylcyclohexane were found to be: trans-4-t-butylcyclohexanol, 2c-hydroxy-4t-t-butylcyclohexanol, 2-methyl-2-cyclohexylpropanoic acid, 2c-hydroxy-4c-t-butylcyclohexanol, 2-methyl-2-cyclohexyl-1,3-propanediol, 2t-hydroxy-4t-t-butylcyclohexanol, and cis -4-t-butylcyclohexanol. - Executive summary:
The major metabolites of t-butylcyclohexane were found to be: trans-4-t-butylcyclohexanol, 2c-hydroxy-4t-t-butylcyclohexanol, 2-methyl-2-cyclohexylpropanoic acid, 2c-hydroxy-4c-t-butylcyclohexanol, 2-methyl-2-cyclohexyl-1,3-propanediol, 2t-hydroxy-4t-t-butylcyclohexanol, and cis -4-t-butylcyclohexanol.
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.
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