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Diss Factsheets
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EC number: 203-379-2 | CAS number: 106-26-3
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Dermal absorption
Administrative data
- Endpoint:
- dermal absorption in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: study meets basic scientific principles with the following restrictions: documentation limited; low animal numbers
Data source
Reference
- Reference Type:
- publication
- Title:
- The influence of limonene on induced delayed hypersensitivity to citral in Guinea Pigs. II. Label distribution in the skin of 14C-labelled citral
- Author:
- Barbier P, Benezra C
- Year:
- 1 983
- Bibliographic source:
- Acta Dermatovener (Stockholm) 63, 93-96
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Distribution of 14C in different layers of skin and in urine and faeces investigated by liquid scintillation counting
- GLP compliance:
- no
Test material
- Reference substance name:
- Citral
- EC Number:
- 226-394-6
- EC Name:
- Citral
- Cas Number:
- 5392-40-5
- IUPAC Name:
- 3,7-dimethylocta-2,6-dienal
- Reference substance name:
- (Z)-3,7-dimethylocta-2,6-dienal
- EC Number:
- 203-379-2
- EC Name:
- (Z)-3,7-dimethylocta-2,6-dienal
- Cas Number:
- 106-26-3
- Molecular formula:
- C10H16O
- IUPAC Name:
- (2Z)-3,7-dimethylocta-2,6-dienal
- Details on test material:
- - Name of test material (as cited in study report): citral and [1,2-14C]-citral
- Analytical purity: not specified
- Specific activity (if radiolabelling): 83 µCi/mg
- Locations of the label (if radiolabelling): C1 and C2
Constituent 1
Constituent 2
- Radiolabelling:
- yes
- Remarks:
- [1,2-14C]-citral
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Versault, Luisetaines, France
- Weight at study initiation: 300-350 g
PRETREATMENT: as the study was designed to investigate the role of dermal absorption in elicitation of hypersensitivity, groups of guinea pigs were used that had been subjected to different induction procedures by applying the Freund Complete Adjuvant (FCA)Test:
Group A - citral treatment: 0.5 mL citral was dissolved in 4.75 mL FCA and then emulsioned with 4.75 mL saline, using a syringe. Each animal received intradermally 5 injections of 0.1 mL each, on alternate days.
Group B - FCA-treated control: 4.75 mL FCA was emulsioned with 4.75 mL saline, using a syringe. Each animal received intradermally 5 injections of 0.1 mL each, on alternate days.
Group C - untreated control: no pretreatment procedure
All groups: This induction procedure was followed by a 2-week rest, before elicitation (see below) was performed.
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- ethanol
- Duration of exposure:
- single
- Doses:
- - Nominal doses: 1.88 mg/animal, ca. 63 µg/cm2 skin area
- Dose volume: 188 µl of a 0.5% solution per area, 2 areas in total
- Rationale for dose selection: no data - No. of animals per group:
- 1
- Details on study design:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): ethanol due to solubility
- Amount(s) applied (volume or weight with unit): 2 x 188 µL per animal
- Concentration (if solution): 0.5%
TEST SITE
- Preparation of test site: shaving
- Area of exposure: circular 15 cm2 area on each flank
SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: no
SAMPLE COLLECTION
- Collection of urine and faeces: during 16 hr via a metabolism cage
- Terminal procedure: 16 hr p.a.
- Analysis of organs: skin
SAMPLE PREPARATION
- Storage procedure:
- Preparation details:
Step 1: Unresorbed citral: Skin was collected and wiped with a cotton swab containing methanol to remove unresorbed citral. Citral was extracted with toluene.
Step 2: Total skin: The skin was stretched on a board in such a way as to cover its initial area. The 15 cm2 marked area was punched with drills. Radioactivity was recovered from the punched skin areas and the used drills by extraction with soluene (60 °C for 4 hrs).
Step 3: Preparation of stratum corneum: The skin was stripped with a cellulose tape (15 strips) until the wet layer appeared. The tapes were extracted with toluene and radioactivity was measured.
Step 4: Stripped skin: radioactivity was extracted from the skin depleted from the stratum corneum in step 3
Step 5: Soluble skin before dialysis: remaining skin was cut into small pieces (area < 1 cm2) dipped in liquid nitrogen and blended. The preparation was stirred with phosphate buffer in cold room (5 °C) for 40 hrs. Then the buffer was centrifuged and filtered and radioactivity in the buffer was measured.
Step 6: Insoluble skin protein extracts: insoluble portion from step 5 homogenized with a spatula, aliquots were dissolved in soluene and heated for 4 hrs at 60 °C.
Step 7: Dialysate: the filtered buffer from step 5 was placed in dialysis bags (10,000 daltons exclusion) and dialyzed against deionized water. 14C in the dialysate was counted.
Step 8: Precipitate formed during dialysis in the dialysate, probably corresponding to some protein denaturation
Step 9: Unfiltered dialysate: the content of the dialysis bag from step 7 was counted.
Urine: direct measurement by dissolution in aquasol.
Faeces: After grounding dissolution in soluene and left at 60 °C for a few hrs. Aliquots of solution dissolved in mixture of aquasol/soluene.
ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
Results and discussion
- Signs and symptoms of toxicity:
- not examined
- Dermal irritation:
- not examined
- Absorption in different matrices:
- See table
- Total recovery:
- Total recovery from urine and feces, total skin and unresorbed citral at the skin surface: 42.1-47.7%
Any other information on results incl. tables
The total recovery of radioactivity from the excreta urine and feces, from total skin and from unresorbed citral at the skin surface was 42.1% in a guinea pig without pre-treatment (C) and 47.7% in a guinea pig that had been subjected to an induction treatment with citral (A). Amounts evaporated from the site of application, excreted via exhalation of 14CO2, or deposited in body tissues were not recorded in this study. The amounts absorbed into the skin within 16 hrs p.a. were 23.9% (C) and 27.5% (A). The amount of 14C in the stratum corneum was comparable in all groups (10.0-12.2 %). There was a greater variation in the penetration to deeper skin layers between the single animals (6.4-10.5%). However, the 14C-recovery after stripping the stratum corneum from the deeper skin layers was incomplete compared to 14C-acitivity in total skin. Additionally, the values were recorded from single animals only, so that the values may represent individual variation.
Table: Label distribution (% of initial deposit) of14C-citral in sensitized guinea pigs and controls
Test group (1 animal/group) |
A |
B |
C |
|
Sensitization: induction treatment |
citral |
FCA-treated control |
Untreated control |
|
Elicitation |
0.5% citral |
0.5% citral |
0.5% citral |
|
Excreta |
||||
Feces |
0.3 |
0.1 |
0.4 |
|
Urine |
11.6 |
14.1 |
11.7 |
|
Skin samples |
Skin sample preparation step |
|||
Unresorbed citral (cotton swab) |
1 |
8.3 |
7.1 |
6.1 |
Total skin |
2 |
27.5 |
17.1 |
23.9 |
Stratum corneum |
3 |
12.2 |
10.0 |
10.8 |
Stripped skin |
4 |
10.5 |
7.2 |
6.4 |
Soluble skin before dialysis |
5 |
5.1 |
3.3 |
3.5 |
Insoluble skin |
6 |
5.3 |
3.2 |
2.5 |
Dialysate |
7 |
4.6 |
3.0 |
2.4 |
Precipitate |
8 |
0.1 |
0.2 |
0.4 |
Unfiltered dialysate |
9 |
0.6 |
0.8 |
0.6 |
Ratio soluble to insoluble proteins |
10.2 |
20 |
19.3 |
|
Total 14C recovered |
47.7 |
38.4 |
42.1 |
FCA: Freund's complete adjuvant
Ratio soluble to insoluble proteins =100x [Step 9]/[Step9] + [Step6]
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.
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