Registration Dossier
Registration Dossier
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: 201-126-0 | CAS number: 78-59-1
- 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

Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2005-08-17 to 2005-12-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test procedure in accordance with national standard methods
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
- Principles of method if other than guideline:
- Percutaneous absortion and cutaneous disposition of [14C]-isophorone in vitro in human skin
(U.S. EPA final rule 40 CFR Parts 9 and 799: In vitro dermal absorption rate testing of certain chemicals of interest to the
Occupational Safety and Health Administration) - GLP compliance:
- yes
Test material
- Reference substance name:
- 3,5,5-trimethylcyclohex-2-enone
- EC Number:
- 201-126-0
- EC Name:
- 3,5,5-trimethylcyclohex-2-enone
- Cas Number:
- 78-59-1
- Molecular formula:
- C9H14O
- IUPAC Name:
- 3,5,5-trimethylcyclohex-2-enone
- Details on test material:
- 14C]-isophorone labeled in position 1.
Specific activity = 53.5 mCi/mmol, dissolved in acetonitrile at 0.3 mCi/ml
Radioactive purity >= 99 %, Lot No. 050425
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- [14C]-isophorone
Test animals
- Species:
- human
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST SYSTEM
- Skin disks from abdominal region of three human cadavers
- Two disks per donor in each of three sets = six disks/set and six disks/donor
- Two additional disks per donor for stability tests (see *** below)
- Removal of subcutaneous fat layer
- Cutting to a split thickness of 200 to 500 µm
- Barrier function test before exposure: < 0.3% penetration of tritiated water in 20 minutes
- *** Stability tests: barrier function tests at 0 and 24 hours in the presence of: 25 mg/ml unlabeled isophorone (1 disk/donor) and 5 % acetonitrile (1 disk/donor)
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- other: isopropyl myristate
- Duration of exposure:
- 10 minutes (Set 1), 1 hour (Set 2), 24 hours (Set 3)
- Doses:
- Skin disks with acceptable barrier function were dosed with 200 µl of the [14C]-isophorone dosing solution on the epidermal surface of each skin
disk. - Details on study design:
- EXPOSURE CONDITIONS
- Test substance preparation: Mixing with unlabelled isophorone in isopropyl myristate to obtain: target concentrations of 25 mg/ml and 15 µCi/ml (protocol: 25 µCi/ml), actual 10.9 and 9.88 µCi/ml
Stability of dosing solutions confirmed by HPLC/radioactive detection
- Receptor fluid: balanced salt solution containing antibiotics and 6 % polyethoxylate, pH 7.45-7.63
- Simultaneous exposure of several disks in Bronaugh flow-through diffusion cells
- Exposure area approx. 63.6 mm2 (diameter 9 mm)
- Occlusive application of 200 µm dosing solution per disk
- Skin temperature during exposure: approx. 32 °C (30.5-35.0 °C)
SAMPLING
- Collection of receptor fluid (flow rate 1.66-2.19 ml/h) in one vial per disk
Set 1: application time 10 minutes, receptor fluid collection at 10 minutes
Set 2: application time 1 hour, receptor fluid collection at 1 hour
Set 3: application time 24 hours, receptor fluid collection at 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 20, and 24 hours
- Washing of skin disks, separation into component layers stratum corneum, epidermis, and dermis
- Digestion of skin layers in 1 ml of 1 N sodium hydroxide
ANALYSIS
- Addition of liquid scintillation cocktail to all samples (surface washes, receptor fluid collections, skin layer digests, cotton
swabs used for cleaning operations)
- Placing in the dark for at least 24 hours at ambient temperature and scintillation counting. - Details on in vitro test system (if applicable):
- see "Details on study design"
Results and discussion
- Signs and symptoms of toxicity:
- not examined
- Dermal irritation:
- not examined
- Absorption in different matrices:
- SKIN INTEGRITY:
< 0.3 % penetration were observed for all skin disks used in the experiment with tritiated water.
After 24 hours of incubation with 25 mg/ml isophorone or 5 % acetonitrile, permeability of water through the skin disks had
increased (from 0.114 % to 0.273 % for acetonitrile, lower levels for isophorone) but was still below 0.3 %.
PERCUTANEOUS ABSORPTION
- Absorption rates:
10 minutes: 2.04 +- 1.74 µg/cm2 = 12.2 +- 10.4 µg/cm2/h
1 hour: 0.909 +- 0.836 µg/cm2 = 0.909 +- 0.836 µg/cm2/h
8 hours: Steady state established. Permeability constant = 5.09E-4 cm/h (+- 1.79E-4 cm/h) = moderate to fast penetrant.
- Total amount absorbed:
10 minutes: 2.04 +- 1.74 µg/cm2
1 hour: 5.14 +- 1.49 µg/cm2
24 hours: 296 +- 97.1 µg/cm2
CUTANEOUS DISPOSITION
---------------------------------------------------------------------
Incubation stratum corneum epidermis dermis
---------------------------------------------------------------------
10 minutes 0.886 +- 0.814 0.166 +- 0.161 0.457 +- 0.388 µg/cm2
1 hour 0.683 +- 0.394 0.383 +- 0.240 1.02 +- 0.971 µg/cm2
24 hours 4.16 +- 2.47 3.54 +- 1.02 7.20 +- 3.75 µg/cm2
---------------------------------------------------------------------
In general, the amount of isophorone in each skin layer increased with increasing exposure time and appeared to accumulate into dermis more than the epidermis.
- Total recovery:
- TOTAL RECOVERY (% of total applied dose)
- 10 minutes: 84.4 +- 5.70 (surface wash: 84.4 %)
- 1 hour: 82.6 +- 3.83 (surface wash: 82.6 %)
- 24 hours 78.1 +- 7.37 (surface wash: 74.3 %)
Most of the applied dose was recoved in the surface wash at the end of the incubation time. The total amount absorbed was less than 5% even after
exposure for 24 hours.
- Conversion factor human vs. animal skin:
- not reported
Any other information on results incl. tables
no further remarks
Applicant's summary and conclusion
- Conclusions:
- The amount of isophorone dosed onto the skin disks appeared to simulate an infinite dose under the experimental conditions used. This is inferred
from the observations that the total amount absorbed was less than 5% even after exposure for 24 hours and that the amount of isophorone
absorbed into the receptor fluid reached a stady state.
The short-term absorption rates for isophorone were estimated to be 12.2 +/- 10.44 µg/cm2/hour (following 10 minutes exposure) and 0.909 +/- 0.836 µg/cm2/hour (following 1 hour exposure). The permeability constant (Kp) for isophorone was estimated to be 0.000509 +/- 0.000179 cm/
hour. The Kp value obtained indicates that isophorone is a moderate to fast penetrant based on the classification by Marzulli, et al.
The total amount of isophorone absorbed was determined to be 2.04 +/- 1.74, 5.14 +/- 1.49, and 296 +/- 97.1 µg/cm2, following exposure for 10 minutes, 1 hour, and 24 hours, respectively. The amount absorbed and the amount recovered from the wash fractions accounted for 84.4 +/- 5.70,
82.6 +/- 3.83, and 78.1 +/- 7.37 % of the total applied dose following exposure for 10 minutes, 1 hour, and 24 hours, respectively. - Executive summary:
The objectives of this study were to evaluate the rate and amount of [14C]-isophorone absorbed across human skin after in vitro exposure, to calculate the permeability constant, to determine two short-term absorption rates, and to evaluate the disposition of [14C]-isophorone in the various layers (stratum corneum, epidermis, and dermis) of human skin after in vitro exposure.
Three sets of incubation were conducted for each donor in this study. Human skin samples were incubated for 10 minutes (Set 1), 1 hour (Set 2), and 24 hours (Set 3) with the epidermal surface exposed to [14C]-isophorone in a Bronaugh flow-through diffusion cell under occluded conditions. The amount of [14C]-isophorone absorbed across the skin into the rceptor fluid and the disposition of [14C]-isophorone in the various skin layers following each incubation period were determined by liquid scintillation counting. Receptor fluid was collected during the 24 -hour incubation (Set 3) at multiple time points to facilitate calculation of a rate of absorption and a steady-state permeability constant.
The amount of isophorone dosed onto the skin disks appeared to simulate an infinite dose under the experimental conditions used. This is inferred from the observations that the total amount absorbed was less than 5% even after exposure for 24 hours and that the amount of isophorone absorbed into the receptor fluid reached a stady state.
The short-term absorption rates for isophorone were estimated to be 12.2 +/- 10.44 µg/cm2/hour (following 10 minutes exposure) and 0.909 +/- 0.836 µg/cm2/hour (following 1 hour exposure). The permeability constant (Kp) for isophorone was estimated to be 0.000509 +/- 0.000179 cm/hour. The Kp value obtained indicates that isophorone is a moderate to fast penetrant based on the classification by Marzulli, et al.
The total amount of isophorone absorbed was determined to be 2.04 +/- 1.74, 5.14 +/- 1.49, and 296 +/- 97.1 µg/cm2, following exposure for 10 minutes, 1 hour, and 24 hours, respectively. The amount absorbed and the amount recovered from the wash fractions accounted for 84.4 +/- 5.70, 82.6 +/- 3.83, and 78.1 +/- 7.37 % of the total applied dose following exposure for 10 minutes, 1 hour, and 24 hours, respectively.
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.
