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EC number: 201-289-8 | CAS number: 80-54-6
- 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
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:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Version / remarks:
- adopted April 13, 2004 (“Skin Absorption: in vitro Method”)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- BASF SE Experimental Toxicology and Ecology 67056 Ludwigshafen, Germany
Test material
- Reference substance name:
- 2-(4-tert-butylbenzyl)propionaldehyde
- EC Number:
- 201-289-8
- EC Name:
- 2-(4-tert-butylbenzyl)propionaldehyde
- Cas Number:
- 80-54-6
- Molecular formula:
- C14H20O
- IUPAC Name:
- 3-(4-tert-butylphenyl)-2-methylpropanal
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 3-14C
Administration / exposure
- Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: dermatomed human skin preparations; surgically removed skin from abdomen and/or breast
- Donors: age <65 years, without scars and strechmarks.
- Preparative technique: Dermatomized human skin preparations were supplied in suitable pieces frozen. Each skin preparation was hydrated in physiological saline for about 10 minutes before mounting to the diffusion cells which are filled up with physiological saline with protease inhibitor. The prepared diffusion cells were stored overnight in a refrigerator.
- Thickness of skin (in mm): 200 – 400 μm (217 - 389 μm, 261 – 400 μm, 200 – 389 μm, 238 – 386 μm for exp. 1&2, exp. 3&4, exp. 5&6, exp.7&8, respectively),
- Membrane integrity check: only visually intact skin with a TEER (impedance value) above 1 kΩ was used. Electrical resistance (TEER) was tested with a LCR bridge.
- Storage conditions: maximum storage time of 3 days in a refrigerator or 12 months at -20°C.
PRINCIPLES OF ASSAY
- Diffusion cells: Modified Franz cells, exposed skin area: 1 cm²
- Number of cells: 8 cells/group, minimum 4 donors/group
- Exposure time: 24 h
- Receptor fluid: tap water (exp. 1, 3, 5, 7) and tap water with 0.01 % (w/w), NaN3 (exp. 2, 4, 6, 8)
- Solubility of test substance in receptor fluid: The test substance is soluble in tap water with 0.033 g/L. Taking into account the amounts of a.i. administered for the high dose (target dose: 95 μg/cm²) and for the low dose (target dose: 5 μg/cm²), the amounts of test substance penetrated through the skin during the experiments as well as the volume of receptor fluid used (flow: 2.3 mL/h; corresponds to about 55 mL over the exposure period of 24 h), no rate limiting effects on the diffusion process by saturation of the aqueous receptor fluid were present.
- Flow-through system: continuous flow of 2.3 mL/h
- Test temperature: The temperature of the water was adjusted to 36 ± 1°C to realize a surface temperature of the skin preparation of 32 ± 1°C.
- Occlusion: charcoal filter and Fixomull® Stretch adhesive fleece to fix the filters after application (semi-occlusive conditions)
- Formuations: Four test-substance preparations (dose groups) of Lysmeral that reflect commercial applications were tested:
Formulation 1 - ethanol in water 70%
Formulation 2 - Oil in water
Formulation 3 - Water in oil
Formulation 4 - Silicone in oil
- Doses: The test-substance preparations were realized with pure 14C-Lysmeral and had the following target concentrations:
Dose group 1: 1.9 % 14C-Lysmeral in formulation 1
Dose group 2: 0.1 % 14C-Lysmeral in formulation 2
Dose group 3: 0.1 % 14C-Lysmeral in formulation 3
Dose group 4: 0.1 % 14C-Lysmeral in formulation 4
An application volume corresponding to about 5 mg/cm² was administered and lead to the following target doses of 14C-Lysmeral
Dose group 1: 95.0 μg Lysmeral / cm²
Dose group 2: 5.0 μg Lysmeral / cm²
Dose group 3: 5.0 μg Lysmeral / cm²
Dose group 4: 5.0 μg Lysmeral / cm²
Taking the specific activity of 14C-Lysmeral into account, the target doses correspond to the following radioactive target doses:
Dose group 1: 1035.5 kBq / cm²
Dose group 2: 54.5 kBq / cm²
Dose group 3: 54.5 kBq / cm²
Dose group 4: 54.5 kBq / cm²
- Experiments:
Experiment 1: dose group 1 (Formulation 1) 24h sampling, 24h skin wash, terminal procedure at 24h.
Experiment 2: dose group 1 (Formulation 1) 72h sampling, 24h+72h skin wash, terminal procedure at 72h. Methanol extraction of skin preparations.
Experiment 3: dose group 2 (Formulation 2) 24h sampling, 24h skin wash, terminal procedure at 24h.
Experiment 4: dose group 2 (Formulation 2) 72h sampling, 24h+72h skin wash, terminal procedure at 72h. Methanol extraction of skin preparations.
Experiment 5: dose group 3 (Formulation 3) 24h sampling, 24h skin wash, terminal procedure at 24h.
Experiment 6: dose group 3 (Formulation 3) 72h sampling, 24h+72h skin wash, terminal procedure at 72h. Methanol extraction of skin preparations.
Experiment 7: dose group 4 (Formulation 4) 24h sampling, 24h skin wash, terminal procedure at 24h.
Experiment 8: dose group 4 (Formulation 4) 72h sampling, 24h+72h skin wash, terminal procedure at 72h. Methanol extraction of skin preparations.
Experiment 9: dose group 1 (Formulation 1); Control group
Experiment 10: dose group 2 (Formulation 2); Control group
- Controls: Controls were performed to demonstrate the extractability of the test-substance on the skin preparations without exposure time. Therefore, the test-substance preparations were applied on untreated skin preparations and were extracted immediately after application.
- Sampling:
Receptor Fluid:
Experiment 1,3,5,7: pre-dose (collection about 15 minutes), 0-1; 1-2; 2-3; 3-4; 4-5; 5-6; 6-7; 7-8, 8-10; 10-12; 12-14; 14-16; 16-18; 18-21, 21-24 hours after application.
Experiment 2,4,6,8: pre-dose (collection about 15 minutes), 0-1; 1-2; 2-3; 3-4; 4-5; 5-6; 6-7; 7-8, 8-10; 10-12; 12-14; 14-16; 16-18; 18-21, 21-24, 24-48, 48-72 hours after application.
Samples for the mass balance:
Extract of charcoal filter
Post exposure wash: skin surface was thoroughly washed twice with washing fluid (Sodium-laurylethersulfate diluted 1:140 w/w in tap water). The washing fluid, tap water, pipette tips and cotton swabs used were stored for analysis. All parts of the diffusion cell (with the exception of the stainless steel clamp) were extracted in a suitable solvent.
Tape stripping: Twenty tape strips were taken. The tapes were pooled into three samples (the first 2 tapes as sample 1, the subsequent 9 tapes as sample 2 and the last 9 samples as sample 3) for analysis.
Remaining skin:
Experiment 1,3,5,7: The remaining skin was separated into dermis and epidermis by heat separation and was analyzed separately.
Experiment 2,4,6,8,9,10: The remaining skin were extracted immediately after the stripping procedure or application (for controls). Each skin piece was placed into Eppendorf reaction vials and two beads as well 0.8 mL methanol were added and extraction and homogenization was performed in the tissue lyzer following a defined protocol. The homogenates of each skin were centrifuged for 10 minutes at 4500 rpm. The
supernatants were measured by LSC. Aliquots of the non extractable residues in the pellet were measured by LSC after addition of about 5 mL Soluene®-350 and incubation at room temperature for at least 3 days at room temperature.
- Test sample analyses: Liquid Scintillation Counting (LSC) of all study samples; prior digestion by Soluene for skin samples. High Performance liquid chromatography for radiochemical purity of stock preparation of 14C BMHCA and purity/ concentration in formulation vehicles.
Results and discussion
Percutaneous absorptionopen allclose all
- Time point:
- 24 h
- Dose:
- 1.9% in Ethanol (70%)
- Parameter:
- percentage
- Absorption:
- 7.08 %
- Remarks on result:
- other:
- Remarks:
- (Absorbed dose) + (Epidermis + Dermis * 80%) = 5.31+((1.5+0.71)*(100-20)%) = 7.08%
- Time point:
- 24 h
- Dose:
- 0.1 % in Oil-in-Water
- Parameter:
- percentage
- Absorption:
- 5.67 %
- Remarks on result:
- other:
- Remarks:
- (Absorbed dose) + (Epidermis + Dermis * 61%) = 4.77+((0.69+0.78)*(100-39)%) = 5.67%
- Time point:
- 24 h
- Dose:
- 0.1 % in Silicone-in-Water
- Parameter:
- percentage
- Absorption:
- 4.68 %
- Remarks on result:
- other:
- Remarks:
- (Absorbed dose) + (Epidermis + Dermis * 74%) = 3.5+((0.96+0.64)*(100-26)%) = 4.68%
- Time point:
- 24 h
- Dose:
- 0.1 % in Water-in-Oil
- Parameter:
- percentage
- Absorption:
- 5.83 %
- Remarks on result:
- other:
- Remarks:
- (Absorbed dose) + (Epidermis + Dermis * 68%) = 4.83+((0.74+0.73)*(100-32)%) = 5.83%
Any other information on results incl. tables
Summary of [14C]-BMHCA penetration through and into human skin after single topical application of target doses of 95.0 μg/cm² and 5.0 μg/cm² of test substance formulated in different test-substance preparations expressed as % of applied doses
% | Dose group | Exp. 1 | Exp. 2 | Exp. 3 | Exp. 4 | Exp. 5 | Exp. 6 | Exp. 7 | Exp. 8 | |||||||||
Vehicle | EtOH 70% | Silicone in water | Water in oil | Oil in water | ||||||||||||||
exposure/sampling | 24h/24h | SD | 24h/72h | SD | 24h/24h | SD | 24h/72h | SD | 24h/24h | SD | 24h/72h | SD | 24h/24h | SD | 24h/72h | SD | ||
target concentration | [mg/g] | 19,0 | 19,0 | 1,0 | 1,0 | 1,0 | 1,0 | 1,0 | 1,0 | |||||||||
target dose level of test substance | [µg/cm²] | 95,0 | 95,0 | 5,0 | 5,0 | 5,0 | 5,0 | 5,0 | 5,0 | |||||||||
mean actual nominal dose level test substance | [µg/cm²] | 91,3 | 95,8 | 4,7 | 4,2 | 4,7 | 5,0 | 4,7 | 4,6 | |||||||||
Dislodgeable dose | charcoal filter | mean % of applied dose |
55,35 | 2,37 | 56,49 | 12,93 | 55,13 | 4,15 | 62,88 | 4,48 | 32,87 | 6,61 | 28,24 | 9,99 | 35,11 | 4,41 | 23,92 | 3,10 |
membrane washing after 24 hours | mean % of applied dose |
11,60 | 3,55 | 13,20 | 4,00 | 14,45 | 6,41 | 12,28 | 1,76 | 53,85 | 8,85 | 50,37 | 13,07 | 47,75 | 5,01 | 56,23 | 5,43 | |
membrane washing after 72 hours | mean % of applied dose |
- | - | 1,80 | 1,19 | - | - | 2,78 | 0,88 | - | - | 1,21 | 0,97 | - | - | 0,82 | 0,33 | |
donor chamber washing | mean % of applied dose |
1,65 | 1,46 | 1,99 | 1,06 | 4,03 | 2,47 | 2,62 | 1,85 | 1,06 | 0,68 | 0,96 | 0,61 | 1,71 | 0,90 | 0,92 | 0,47 | |
sum | 68,60 | 3,77 | 73,48 | 12,35 | 73,61 | 5,57 | 80,55 | 4,28 | 87,77 | 4,85 | 84,86 | 14,82 | 84,58 | 4,40 | 81,89 | 5,14 | ||
Dose associated to tape strips | tape strip sample 1 (first two strips) | mean % of applied dose |
0,90 | 0,33 | 1,52 | 1,17 | 1,19 | 0,42 | 0,88 | 0,46 | 1,16 | 0,75 | 0,62 | 0,51 | 1,88 | 0,77 | 0,22 | 0,17 |
tape strip sample 2 (3-11) | mean % of applied dose |
2,40 | 1,00 | 2,42 | 0,86 | 2,60 | 1,38 | 1,16 | 0,71 | 1,84 | 1,07 | 0,94 | 0,79 | 3,11 | 1,65 | 0,32 | 0,25 | |
tape strip sample 3 (12-20) | mean % of applied dose |
1,02 | 0,85 | 0,31 | 0,24 | 0,58 | 0,27 | 0,12 | 0,16 | 0,26 | 0,13 | 0,11 | 0,17 | 0,41 | 0,17 | 0,02 | 0,03 | |
Dose associated to remaining skin | epidermal membrane | mean % of applied dose |
1,50 | 0,49 | - | - | 0,96 | 0,18 | - | - | 0,74 | 0,31 | - | - | 0,69 | 0,31 | - | - |
dermal membrane | mean % of applied dose |
0,71 | 0,28 | - | - | 0,64 | 0,23 | - | - | 0,73 | 0,35 | - | - | 0,78 | 0,17 | - | - | |
skin residue | mean % of applied dose |
- | - | 0,32 | 0,11 | - | - | 0,25 | 0,10 | - | - | 0,24 | 0,15 | - | - | 0,18 | 0,06 | |
skin extract | mean % of applied dose | - | - | 1,31 | 0,33 | - | - | 0,71 | 0,24 | - | - | 0,50 | 0,48 | - | - | 0,28 | 0,12 | |
Absorbed dose | sum receptor samples 0 - 24 h | mean % of applied dose |
1,78 | 0,65 | 2,20 | 0,82 | 1,62 | 0,72 | 2,49 | 1,56 | 3,81 | 2,85 | 5,49 | 3,76 | 3,43 | 1,68 | 3,17 | 1,49 |
receptor fluid | mean % of applied dose |
0,04 | 0,02 | 0,00 | 0,00 | 0,03 | 0,01 | 0,00 | 0,00 | 0,13 | 0,08 | 0,00 | 0,00 | 0,12 | 0,03 | 0,00 | 0,00 | |
receptor chamber washing | mean % of applied dose |
3,49 | 1,57 | 3,09 | 1,78 | 1,85 | 0,72 | 2,55 | 1,18 | 0,89 | 0,65 | 2,33 | 1,70 | 1,22 | 0,46 | 1,80 | 0,83 | |
sum | 5,31 | 2,22 | 5,29 | 2,52 | 3,50 | 1,31 | 5,04 | 2,60 | 4,83 | 3,54 | 7,82 | 5,42 | 4,77 | 2,16 | 4,97 | 2,26 | ||
Total recovery | mean % of applied dose |
80,44 | 1,83 | 84,67 | 13,80 | 83,08 | 3,28 | 88,72 | 2,97 | 97,32 | 3,91 | 91,01 | 13,82 | 96,21 | 2,98 | 87,88 | 3,44 |
Applicant's summary and conclusion
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