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EC number: 224-169-7 | CAS number: 4223-03-4
- 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
- Study period:
- 1998-04-22 to 1998-04-30
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study in accordance with OECD draft guidelines (1996) and ECVAM and COLIPA guidelines
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 428 (Skin Absorption: In Vitro Method)
- Version / remarks:
- The guideline was adopted in 2004, test was conducted in accordance with OECD TG draft from 1996
- Deviations:
- no
- Principles of method if other than guideline:
- Test followed COLIPA guidelines (Cosmetic Ingredients: Guidelines for Percutaneous Penetration/Absorption, November 1995)
- GLP compliance:
- yes
Test material
- Reference substance name:
- N-(1,1,3,3-tetramethylbutyl)acrylamide
- EC Number:
- 224-169-7
- EC Name:
- N-(1,1,3,3-tetramethylbutyl)acrylamide
- Cas Number:
- 4223-03-4
- Molecular formula:
- C11H21NO
- IUPAC Name:
- N-(1,1,3,3-tetramethylbutyl)acrylamide
- Details on test material:
- - Name of test material (as cited in study report): N-tert-octylacrylamide
- Physical state: Off white, waxy solid
- Analytical purity: 99.73%
- Impurities (identity and concentrations): not reported
- Purity test date: not reported
- Lot/batch No.: KGS-1152
- Expiration date of the lot/batch: not reported, but substance was used within expiry date
- Storage condition of test material: room temperature
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- other: Human female (post mortem) and male rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Human skin: female, abdominal skin obtained post mortem
Rat skin: male rats of the Wistar-derived strain (Charles River UK, Margale, Kent, UK) aged 28 ± 2 days
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 24 hours
- Doses:
- 10 mg/cm2; total weight applied was 25.4 mg
- No. of animals per group:
- 6 tests with human skin; 6 tests with rat skin
- Control animals:
- no
- Details on in vitro test system (if applicable):
- SKIN PREPARATION
- Source of skin: human female skin was obtained post mortem
- Ethical approval if human skin: not reported
- Type of skin: human abdominal
- Preparative technique (human skin): extraneous tissue was removed from whole skin samples; skin samples were immersed in water at 60 °C for about 45 seconds and the epidermis teased off the dermis; epidermal membrane was stored frozen on aluminium foil until use
- Preparation technique (rat skin): skin was obtained from dorsal and flank regions; skin was carefully shaved avoiding damage of the skin and shaved skin was excised and subcutaneous fat removed; removed skins were soaked for 20 hours in 1.5 M sodium bromide and then rinsed in distilled water; epidermis was carefully peeled from the dermis and stored frozen on aluminium foil until use
- Thickness of skin (in mm): not reported
- Membrane integrity check: samples of epidermis were mounted in glass diffusion cells with an exposed area of 2.54 cm2; cells were placed in a water bath maintained at 32 ± 1 °C; membrane integrity was determined by measuring the electrical resistance across the membrane; membranes with < 10 kOhm (human) or < 2.5 kOhm (rat) were rejected
- Storage conditions: frozen on aluminium foil
- Justification of species, anatomical site and preparative technique: skin type, application rates and exposure conditions were related to COLIPA guidelines
PRINCIPLES OF ASSAY
- Diffusion cell: glass chamber consisting of donor chamber, receptor chamber and sampling arm (skin membrane and support grid were placed between the donor and receptor chambers)
- Receptor fluid: 50% ethanol in water
- Solubility of test substance in receptor fluid: not reported
- Static system: yes
- Test temperature: 32 ± 1 °C
- Humidity: not reported
- Occlusion: open
- Reference substance(s): di-n-butyl phthalate, dimethyl phthalate, 2-(2-butoxyethoxy) ethanol, n-butanol, benzyl alcohol, 2-phenyl ethanol, ethanol, 2-ethoxyethyl acetate, 2-methoxyethanol, methanol
Results and discussion
- Absorption in different matrices:
- - Donour chamber: washed with ethanol at the end of experiment and sample was analysed
- Skin wash: the surface of the epidermis ws rinsed with 5 mL volumes of distilled water, rinsings were combined, made up to a known volume with ethanol and analysed
- Skin test site: the epidermis was carefully removed from the receptor chamber and extracted with ethanol and the extracts were analysed
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): at recorded intervals, 0.5 mL samples of the receptor fluid were taken for analysis - Total recovery:
- - Total recovery: 90% for human skin and 90.6% for rat skin
- Recovery of applied dose acceptable: yes
- Results adjusted for incomplete recovery of the applied dose: no
- Limit of detection (LOD): not reported
- Quantification of values below LOD or LOQ: no quantification of values below LOQ
Percutaneous absorptionopen allclose all
- Dose:
- 10 mg/cm2
- Parameter:
- percentage
- Absorption:
- 0.1 %
- Remarks on result:
- other: 6 to 24 hours
- Remarks:
- Human skin
- Dose:
- 10 mg/cm2
- Parameter:
- percentage
- Absorption:
- 0.3 %
- Remarks on result:
- other: 6 to 24 hours
- Remarks:
- Rat skin
- Conversion factor human vs. animal skin:
- The ration of percutaneous absorption rates in human and rat skin was 1:2.66
Any other information on results incl. tables
Table 1: Summary of distribution and mass balance of dose
|
Percent of dose recovered |
|
Sampled material |
Human skin |
Rat skin |
Donor chamber |
4.1 |
0.6 |
Skin wash after 24 hours |
85.7 |
89.6 |
Epidermal membrane |
0.1 |
<0.2 |
Receptor fluid at 24 hours |
0.1 |
0.3 |
Total |
90.0 |
90.6 |
Table 2: Absorption of rates determined in single experiments with human and rat epidermis
Diffusion cell number |
Skin type and reference |
Absorption rate (µg/cm2/hour) |
1 |
Human, 4217 |
0.262 |
2 |
Human, 4217 |
0.347 |
5 |
Human, 4219 |
0.342 |
6 |
Human, 4219 |
0.539 |
9 |
Human, 4218 |
1.061 |
10 |
Human, 4218 |
0.581 |
Mean (n = 6) |
|
0.522 |
Standard deviation |
|
0.213 |
12 |
Rat, 3404 |
1.924 |
13 |
Rat, 3404 |
1.529 |
18 |
Rat, 3406 |
1.538 |
19 |
Rat, 3406 |
1.108 |
22 |
Rat, 3407 |
0.965 |
23 |
Rat, 3407 |
1.253 |
Mean (n = 6) |
|
1.386 |
Standard deviation |
|
0.317 |
Table 3: Absorption rates of comparative organic substances
Substance |
Absorption rate (µg/cm2/h) |
Di-n-butyl phthalate |
6.6 |
Dimethyl phthalate |
33.0 |
2-(2-Butoxyethoxy) ethanol |
35.0 |
n-butanol |
60.0 |
Benzyl alcohol |
73.0 |
2-phenyl ethanol |
260.0 |
Ethanol |
570.0 |
2-ethoxyethyl acetate |
800.0 |
2-methoxyethanol |
2820.0 |
Methanol |
8400.0* |
* Methanol causes extensive damage to the stratum corneum |
Applicant's summary and conclusion
- Conclusions:
- Dermal absorption of N-tert-octylacrylamide through human skin in vitro was found to be very slow when compared with the absorption rates of other organic materials. Further, data from the in vitro test show that the use of rat as model for dermal absorption is likely to over-estimate the absorption of the test substance in human skin.
- Executive summary:
The dermal absorption of N-tert-octylacrylamide through human and rat skin was studied under GLP in an in-vitro assay according to COLIPA guidelines (Cosmetic Ingredients: Guidelines for Percutaneous Penetration/Absorption, November 1995), which are equivalent to the principles of OECD TG 428.
For human epidermis, the amounts of subtance absorbed 6, 8 or 10 hours after application were either below or close to the limit of quantification (<5.315, 5.335 and 4.508 µg/cm2). The amount of substance absorbed after 24 hours was 9.397 µg/cm2. The mean absorption rate between 6 and 24 hours after application was 0.522 µg/cm2/hour. The mass balance gave a total mean percentage recovery of 90% of the applied dose. The greatest portion of the recovered dose was readily removed from the skin surface by mild washing (85.7% of applied dose). The epidermal membrane contained only 0.1% of the applied dose.
For rat epidermis, the mean absorption rate of substance over an exposure interval of 24 hours was 1.386 µg/cm2/hour. Steadily increasing amounts of substance were absorbed over periods of 8, 10 an 24 hours with mean amounts reaching 9.371, 12.31 and 31.878 µg/cm2, respectively. The value after 24 hours was equivalent to 0.31% of the applied dose. The mass balance gave a total mean percentage recovery of 90.6% of the applied dose, 90% of which was recovered from the skin surface by mild skin washing. The amounts recovered from the epidermal membrane were below the limit of quantification.
The recovery of applied dose of about 90% for human and rat skin is considered to be acceptable. Dermal absorption of N-tert-octylacrylamide through human and rat skin was demonstrated to be very slow. Rat skin was more permeable than human skin by a factor of 2.66.
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