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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 443-860-6 | CAS number: 302776-68-7
- 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:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - Guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Deviations:
- no
- GLP compliance:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 443-860-6
- EC Name:
- -
- Cas Number:
- 302776-68-7
- Molecular formula:
- C24 H31 N O4
- IUPAC Name:
- hexyl 2-[4-(diethylamino)-2-hydroxybenzoyl]benzoate
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- human
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Abdominal skin samples from three human female donors, which were excised during a cosmetic surgery.
- Age at study initiation: 32, 34, 36 years old
- Weight at study initiation: BMI of 21.5, 24.1, 23.9
Administration / exposure
- Type of coverage:
- other: It is an in vitro study and thus, the coverage that was made was done by covering the Franz diffusion cells with parafilm during the 24 hours exposure period in order to avoid any changes in the test substance formulation.
- Vehicle:
- other: As vehicle, a formulation of a cream with 10% active ingredient containing non-labelled TS was added to the radioactive test substance, but before toluene was evaporated.
- Duration of exposure:
- 24-hours exposure
- Doses:
- 18 mg ± 5 % of the test formulation (approximately 10 mg per cm2 of the skin) were applied by a weighing procedure of the diffusion cell to the diffusion skin area (and homogenously spread over the skin surface using a spatula and cotton swab). A calculated / theoretical test substance contents in µg which were applied are as follows:
Mean dose applied (on three skin specimen) to donor 311-01-0108: 1826.69 µg
Mean dose applied to donor 312-01-0108: 1754.63 µg
Mean dose applied to donor 313-01-0208: 1809.93 µg
The mean applied dose which was used for all skin specimens of all donors was 1801.31 µg. - No. of animals per group:
- Human skin from three different donors was divided in a way that skin of each donor had triplicate or four fold skin specimens. The skin specimen was then internally encoded.
- Control animals:
- no
- Remarks:
- For the quality control of the human skin the permeability of Caffeine (10 mg/L in KRB at pH 7.4) was carried out on skin samples of the same donors.
- Details on study design:
- DOSE PREPARATION
- Method for preparation of dose suspensions:
As vehicle for the radio-labelled test substance a cream with 10% Hexyl 2-(1-(diethylaminohydroxyphenyl)methanoyl)benzoate was used. The radio-labelled test substance was added to reach a final concentration of approximately 3.7 kBq/mg. The test formulation was prepared one day before the start of the experiment and stored over the night at 4 °C.
115 μL of the radioactive test substance were placed in an open beaker in order to evaporate the solvent (toluene) in the sample. 3 g of formulation were added to the residual and both have been homogenized using Ultraturrax for 3-5 minutes. The test formulation was mixed again at least for 2 hours prior to the start of the in vitro experiment. Two aliquots of the test formulation (approximately 100 mg) before and after the in vitro permeability study were stored in the refrigerator and sent on dry ice to the sponsor for the radio-HPLC analysis.
18 mg ± 5 % of the test formulation (approximately 10 mg per cm2 of the skin) were applied by a weighting procedure of the diffusion cell to the diffusion skin area (and homogenously spread over the skin surface using a spatula and cotton swab).
VEHICLE
See above (dose preparation).
REMOVAL OF TEST SUBSTANCE
At the end of the permeation experiments (24 hours exposure), the skin specimens were washed twice with a surfactant solution (Texapon N 70 diluted with water 1:140 (v/v, %), applied volume of the surfactant solution: 250 μL).
ANALYSIS
Samples were analyzed by the Liquid Scintillation counting - Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: From a hospital where 3 female donors agreed to donate skin samples for research, excised during their cosmetic surgery.
- Ethical approval if human skin: No data. It was written that the hospital had the prior consent of the patients that the tissue could be used for scientific research.
- Type of skin: Skin from the abdomen
- Preparative technique: The excised skin from the surgery was cooled to 4 °C and its surface was dried before being transported. Care was taken to ensure that the subcutaneous fatty tissue does not get into contact with the surface of the skin. Once in the laboratory, the skin was separated from the subcutaneous fatty layer and then an encrypted identification number issued by Across Barriers was assigned to each skin specimen.
- Thickness of skin (in mm): The skin was dermatomized to approximately 0.5 mm
- Membrane integrity check: The skin samples that were used were found to be intact by using the OECD marker substance - caffeine.
- Storage conditions and justification of the anatomical site and preparative technique:
After the subcutaneous fatty layer was removed (within two hours after reception of the abdominal skin), the residual full-thickness skin was stored at -20 °C. According to the OECD Guideline, storage of skin at -20 °C for a period of up to twelve months does not alter its permeability.
The skin was used immediately after thawing. Repeated freeze-thaw cycles were avoided.
PRINCIPLES OF ASSAY
- Diffusion cell: Cylindrical glass Franz cell
- Acceptor fluid: For the test substance- KRB (Krebs Ringer buffer) at pH 7.4 supplemented with 1 % BSA (bovine serum albumine). For the permeability assay of caffeine (carried out on skin samples of the same donors) the acceptor medium that was used was the KRB medium supplemented with 0.05% NaN3.
- The stirring speed and the temperature were set at 400 rotations per minute and 32 °C ± 2 °C, respectively. At each sampling point the stirring speed and temperature were documented.
- Sampling times: The permeation study was performed over a period of 24 hours. After 0, 2, 4, 6, 8, 20, 22 and 24 hours and after 0, 1, 2, 4, 6, 8, 22 and 24 hours in the first and second experiment, respectively. One sample with a volume of 300 μL was taken from the acceptor compartments and analyzed for the test substance content by LSC. The sampled amount was replaced with a fresh medium preheated to the temperature of 32 °C.
Results and discussion
- Signs and symptoms of toxicity:
- not examined
- Dermal irritation:
- not examined
- Absorption in different matrices:
- - Receptor fluid (in vitro test system): 0.02 +/- 0.01% of radio-labelled test substance.
- Skin preparation (in vitro test system): The mean recovery of the test substance found in the "remaining skin" (extraction of rest of the skin after tape stripping) amounts to 0.11 ±0.05 %.
Stratum corneum (in vitro test system): The mean recovery in the two first tape strips (first pool) was 1.54 ± 1.12 % over all performed experiments. In the further 18 tape strips a mean recovery of 0.41 ± 0.30 % was determined.
- Other: In the skin wash procedure after the in vitro experiment the mean range was 96.95% to 103.73% - Total recovery:
- - Total recovery:
The calculated mean total recovery rate for each of the three different skin donors used was between 98.85 % and 105.10 % of the dose applied. The overall mean of total recovery rate for the three different skin donors analyzed was 101.08 ± 10.06 %.
Percutaneous absorption
- Dose:
- 1801.31 µg
- Parameter:
- percentage
- Absorption:
- 0.5 %
- Remarks on result:
- other: 24 hours
- Remarks:
- According to the SCCNFP/0750/03 opinion the requested value should be calculated from the measurments of the test substance in the "receptor fluid" (0.02%), the "remaining skin" (0.11%) and in addition the second pool of the tape stripping (0.41%).
Any other information on results incl. tables
No remarks
Applicant's summary and conclusion
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.