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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 231-403-1 | CAS number: 7534-94-3
- 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
- Study period:
- 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Three male rats per compound were intravenously administered IBOMA at target concentration 8.0 mg/kg (36 µmol/kg), using Intralipid 20% as the dose vehicle. After dose administration, blood samples (~200 μL) were collected at 5, 10, 30, 60, and 180 minutes into individual pre-weighed glass vials containing ethyl acetate (600 μL) acidified with 10% trifluoroacetic acid (TFA). After vortexing and subsequent centrifugation, the blood extracts underwent quantitative analysis for IBOMA by gas chromatography tandem mass spectrometry (GC/MS-MS).
- GLP compliance:
- no
Test material
- Reference substance name:
- Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methacrylate
- EC Number:
- 231-403-1
- EC Name:
- Exo-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methacrylate
- Cas Number:
- 7534-94-3
- Molecular formula:
- C14H22O2
- IUPAC Name:
- 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methacrylate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- TEST MATERIAL:
- Name of test material: Isoborny methacrylate - Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Fischer 344/DuCrj
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (Kingston, New York)
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 183-196 g
- Housing: singly in glass Roth-type metabolism cages
- Diet (e.g. ad libitum): LabDiet Certified Rodent Diet #5002 (PMI Nutrition International, St. Louis, Missouri) in pelleted form, ad libitum
- Water (e.g. ad libitum): Municipal water, ad libitum
- Acclimation period: 7d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C with a range of 20°C-26°C
- Humidity (%): 50% with a range of 30-70%
- Photoperiod (hrs dark / hrs light): 12-hour light/dark (on at 6:00 a.m. and off at 6:00 p.m.)
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- other: Intralipid 20%
- Details on exposure:
- Appropriate amounts of the test substance were added to sterile pharmaceutical grade Intralipid 20% using aseptic technique to obtain the appropriate concentration. The amount of dose solution administered was targeted at 2.5 mL/kg bw and injected over ~1minute to correspond to an injection rate of ~0.5 mL/min. The dose was stored at ambient temperature (19-25°C) and used within 24 hours of preparation.
- Duration and frequency of treatment / exposure:
- single iv treatment
Doses / concentrations
- Dose / conc.:
- 8 mg/kg bw/day (nominal)
- Remarks:
- corresponds to 36 µmol/kg
- No. of animals per sex per dose / concentration:
- 3 males
- Control animals:
- yes, concurrent vehicle
- other: another isobornyl ester (isobornyl acetate, IBOAC) was tested for its toxikokinetic properties for comparison reasons (rad-across background)
- Positive control reference chemical:
- no
- Details on study design:
- - Dose selection rationale: previous studies of this type have used similar equimolar ratios
- Details on dosing and sampling:
- TOXICOKINETIC / PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: blood
- Time and frequency of sampling: 5, 10, 30, 60 and 180 minutes post-dosing - Statistics:
- Descriptive statistics were used, i.e., mean ± standard deviation, where applicable. All descriptive statistic calculations were conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington) spreadsheets in full precision mode (15 digits of accuracy). Pharmacokinetic parameters that were calculated for blood used the pharmacokinetic computer modeling program PK Plus (v. 9.6, Simulation Plus, Inc., Lancaster, California, United States of America).
Results and discussion
- Preliminary studies:
- The solubility of both IBOAC and IBOA was tested up to 10 mg/mL in saline and Intralipid 20%. Both test materials were insoluble at this concentration in saline but were soluble in Intralipid 20%; thus they were prepared using the latter vehicle .
Toxicokinetic / pharmacokinetic studies
Toxicokinetic parametersopen allclose all
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- half-life 1st: 1.27 min-1
- Remarks:
- relevant for the vast majority of applied test substance
- Key result
- Test no.:
- #1
- Toxicokinetic parameters:
- other: <1.0% of the corresponding administered dose remains in the blood 10 minutes post-intravenous administration
- Test no.:
- #1
- Toxicokinetic parameters:
- AUC: 397 µg-min/g
Metabolite characterisation studies
- Metabolites identified:
- not measured
Any other information on results incl. tables
The resulting blood time course showed that the substance was quickly hydrolyzed with less than 1.0% of the corresponding administered dose remaining in the blood 10 minutes post-intravenous administration and around 0.1% remaining 180 minutes post-intravenous administration. Further pharmacokinetic analysis of the blood concentrations of the substance showed that both compounds were biphasic (alpha [α] and beta [β] phases; i.e. a two-compartment model) in which there is a dominant initial distribution and hydrolysis step (i.e. t½α) with a subsequent phase of further hydrolysis and elimination (i.e. t½β). The initial distribution and hydrolysis step had an average calculated t½αvalue of 1.27 min-1and accounts for metabolic fate of the vast majority of applied test substance quantities. The secondary hydrolysis and elimination phase (t½β) had an average value of 61.1 min-. The cause of the beta-phase associated with the minor portion of the test substance's kinetics is currently unclear and may be of limited relevance to normal physiology. The average area under the curve (AUC0-t) value was 397 µg-min/g, respectively.
Applicant's summary and conclusion
- Conclusions:
- Overall, the analysis of the blood pharmacokinetics indicated that the parent test material is rapidly removed from blood circulation (i.e. blood compartment)in vivo in a very similar manner. Hence, these data support a pharmacokinetics-based Read-Across for IBOAC and IBOMA.
- Executive summary:
This non-GLP pharmacokinetic study of isobornyl acetate (IBOAC) and isobornyl methacrylate (IBOMA) in rats via intravenous administration evaluated the hydrolysis and pharmacokinetic characteristics as measured by the rate of parent (IBOAC or IBOMA) disappearance. The purpose of this study was to evaluate whether these data can be used in a pharmacokinetics-based Read-Across approach similar to several other well-studied (meth)acrylates.
Three male rats per compound were intravenously administered either IBOAC or IBOMA at target concentrations 7.0 mg/kg (36 µmol/kg) or 8.0 mg/kg (36 µmol/kg), respectively, using Intralipid 20% as the dose vehicle. After dose administration, blood samples (~200 μL) were collected at 5, 10, 30, 60, and 180 minutes into individual pre-weighed glass vials containing ethyl acetate (600 μL) acidified with 10% trifluoroacetic acid (TFA). After vortexing and subsequent centrifugation, the blood extracts underwent quantitative analysis for either IBOAC or IBOMA by gas chromatography tandem mass spectrometry (GC/MS-MS).
The resulting blood time course showed that both substances were quickly hydrolyzed with less than 1.0% of the corresponding administered dose remaining in the blood 10 minutes post-intravenous administration and around 0.1% remaining 180 minutes post-intravenous administration. Further pharmacokinetic analysis of the blood concentrations of both IBOAC and IBOMA showed that both compounds were biphasic (alpha [α] and beta [β] phases; i.e. a two-compartment model) in which there is a dominant initial distribution and hydrolysis step (i.e. t½α) with a subsequent phase of further hydrolysis and elimination (i.e. t½β). The initial distribution and hydrolysis step had average calculated t½αvalues of 0.866 and 1.27 min-1for IBOAC and IBOMA, respectively, and accounts for metabolic fate of the vast majority of applied test substance quantities. The secondary hydrolysis and elimination phase (t½β) had average values of 55.1 and 61.1 min-1for IBOAC and IBOMA, respectively. The cause of the beta-phase associated with the minor portion of IBOAC and IBOMA kinetics is currently unclear and may be of limited relevance to normal physiology. The average area under the curve (AUC0-t) values for IBOAC and IBOMA were 363 and 397 µg-min/g, respectively.
NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.
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.