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Diss Factsheets
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EC number: 232-087-8 | CAS number: 7785-70-8
- 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
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Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vitro / ex vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 2006
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Recent well described and well conducted study.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 006
Materials and methods
- Principles of method if other than guideline:
- Skin absorption and elimination kinetics were studied using human skin from the region of thorax of 40-50-years old Caucasian women, mounted on flow-through Teflon diffusion cells. 500 mg alpha-pinene was applied and after 1 to 4-h exposure, the content in the stratum corneum layers (separated by a tape-stripping method) and in the epidermis/dermis was determined using GC. Similarly, the elimination kinetics in the skin were analysed during 4 h following 1 h absorption.
- GLP compliance:
- no
Test material
- Reference substance name:
- Pin-2(3)-ene
- EC Number:
- 201-291-9
- EC Name:
- Pin-2(3)-ene
- Cas Number:
- 80-56-8
- Molecular formula:
- C10H16
- IUPAC Name:
- 2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
- Details on test material:
- - Name of test material (as cited in study report): alpha-pinene, (-)-alpha-pinene
- Analytical purity: > 99%
- Source: Fluka, Buchs, Switzerland
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- human
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Human cadaver skin was obtained from the region of thorax of 40-50-years old Caucasian women. The subjects did not have skin diseases. Before the experiment, the skin was stored frozen at -20 °C.
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 1, 2 or 4 h
- Doses:
- 500 mg on 0.65 cm²
- No. of animals per group:
- 4 for each time point
- Control animals:
- no
- Details on study design:
- No data
- Details on in vitro test system (if applicable):
- Diffusion cell: flow-through Teflon diffusion cell (Crown Glass, USA)
The diffusion area of the skin was 0.65 cm². The donor compartment was occluded with Parafilm (Sigma-Aldrich, Steinheim, Germany), and the system was maintained at temperature 37 ± 0.5 °C. An isotonic pH 7.3 phosphate buffer, 10 mL, preserved with 0.005% sodium azide (Fluka, Buchs, Switzerland) was recirculated beneath the skin with a constant rate 10 mL/h. The two-phase acceptor fluid protected against evaporation was used and sink conditions were ensured for all steps of the study. It was obtained by addition of 5 mL of methylene chloride to the vial served as reservoir of the buffer. The skin was only in contact with the aqueous phase. The experiment was terminated by removing terpenes from the skin surface and very short rinsing with methanol. The stratum corneum layers were separated by a tapestripping method, using 21 fragments of an adhesive
tape (3M Medica Pharma, St. Paul, USA). Collected samples were divided into three fractions (SC I-III). Each fraction, as well as the remaining viable epidermis with dermis (ED) was extracted with methanol (HPLC-grade, P.O.Ch., Gliwice, Poland).
In the elimination studies, the terpenes were applied only for 1 h and next, after removing terpenes from the donor chamber as described above, the skin was left in the chambers for 1, 2, 3 or 4 h. The acceptor medium was replaced by a fresh portion and its circulation was maintained. After the specified time, the skin was rinsed, removed and separated as described above. The terpenes in the extracts were analysed by GC with the detection limit 0.5 mg/mL.
Results and discussion
- Signs and symptoms of toxicity:
- not specified
- Dermal irritation:
- not specified
- Absorption in different matrices:
- The dermal penetration of pure terpenes was studied during 4 h. The terpenes were present on the skin in infinite doses and the system was protected against evaporation. During that time no terpenes were detected in the acceptor fluid but extensive accumulation in the skin tissue occurred (see table 1).
Analysis of stratum corneum (SC) collected with an adhesive tape and merged into three groups demonstrates cumulation of terpenes in the outer (SC I), middle (SC II) and inner (SC III) layers. The results demonstrate rapid penetration of terpenes not only to the SC I layers but also to viable epidermis and dermis. The distance-dependent decreasing gradient of concentration for all terpenes is observed, although the concentrations were not normalized in respect of the collected SC mass. A steady-state concentration of terpenes in the SC can be assumed as soon as after 1 h. Maximum concentration in the SC was achieved as soon as after 1 h and did not further increase in the course of the study.
All studied terpenes are absorbed in high amounts in the viable epidermis with dermis (ED), however penetration into this layers is time-dependent process, constantly increasing during 4 h. - Total recovery:
- No data
- Conversion factor human vs. animal skin:
- None
Any other information on results incl. tables
Table 1: Absorption of alpha-pinene (mg/cm2) into human skin layers (mean ± S.D., n = 4)
Skin layer |
1-h exposure |
2-h exposure |
4-h exposure |
SC I |
4.3 ± 0.8 |
3.4 ± 0.4 |
7.7 ± 4.3 |
SC II |
4.0 ± 0.5 |
3.2 ± 0.6 |
6.5 ± 4.1 |
SC III |
3.0 ± 0.4 |
3.4 ± 0.8 |
6.0 ± 4.0 |
SC total |
11.3 ± 4.7 |
10.0 ± 2.1 |
18.2 ± 12.1 |
ED |
66.4 ± 16.8 |
147.2 ± 25.9 |
313.7 ± 38.3 |
Skin total |
77.7 ± 14.5 |
157.2 ± 25.8 |
331.9 ± 34.7 |
Table 2: Elimination of alpha-pinene (mg/cm2) from human skin layers following 1 h absorption (t = 0) (mean ± S.D., n = 4)
|
Time after 1-h exposure |
||||
Skin layer |
0 |
1 |
2 |
3 |
4 |
SC I |
4.3 ± 0.8 |
3.2 ± 1.9 |
2.0 ± 1.8 |
0.7 ± 0.6 |
0.6 ± 0.7 |
SC II |
4.0 ± 0.5 |
0.9 ± 1.0 |
0 |
0 |
0 |
SC III |
3.0 ± 0.4 |
0.2 ± 0.2 |
0 |
0 |
0 |
SC total |
11.3 ± 4.7 |
4.3 ± 3.0 |
2.0 ± 1.8 |
0.7 ± 0.6 |
0.6 ± 0.7 |
ED |
66.4 ± 16.8 |
45.7 ± 13.0 |
35.9 ± 8.2 |
37.3 ± 3.6 |
33.9 ± 5.7 |
Skin total |
77.7 ± 14.5 |
50.0 ± 10.1 |
37.9 ± 6.8 |
38.0 ± 3.3 |
34.5 ± 5.1 |
Applicant's summary and conclusion
- Conclusions:
- Alpha pinene absorption into the different skin layers is rapid (steady-state concentrations in the skin obtained after 1-h exposure) but do not permeate through the skin to the acceptor medium due to large accumulation into the skin tissue.
- Executive summary:
Skin absorption and elimination kinetics were studied using human skin from the region of thorax of 40-50-years old Caucasian women, mounted on flow-through Teflon diffusion cells. Alpha pinene (500 mg) was applied onto the human skin (0.65 cm²), and after 1 to 4-h exposure, the content in the stratum corneum layers (separated by a tape-stripping method) and in the epidermis/dermis was determined using GC. Similarly, the elimination kinetics in the skin were analysed during 4 h following 1 h absorption. Quadruplicates were used for each time point.
The results demonstrate rapid penetration of terpenes not only to the first stratum corneum layers but also to viable epidermis and dermis (steady-state concentrations assumed to be obtained at 1-h exposure). However, alpha pinene did not permeate across the skin to the acceptor medium due to large cumulation in the skin tissue. Two mechanisms of elimination process of terpenes from the SC are suggested: evaporation and slightly progressive penetration from inner layer into dermis.
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