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EC number: 266-719-9 | CAS number: 67564-91-4
Toxicological information
Dermal absorption
Currently viewing:
Administrative data
- Endpoint:
- dermal absorption in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Aug. - Dec. 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 417
- Version / remarks:
- 04.04.1984
- Deviations:
- yes
- Remarks:
- - initial age and body weight of test animals not specified, no justification for the selected sex provided
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine
- EC Number:
- 266-719-9
- EC Name:
- cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine
- Cas Number:
- 67564-91-4
- Molecular formula:
- C20H33NO
- IUPAC Name:
- (2R,6S)-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. Karl Thomae, Biberach a.d. Riss, Germany
- Age at study initiation: not specified
- Weight at study initiation: not specified
- Housing: single
- Diet: Kliba lab diet for rat—mouse-hamster "A" GLP 343 either pelletized (e.g. during acclimatization) or granulated (e.g. in metabolism cages), ad libitum
- Water: tap water, ad libitum
- Acclimation period: yes, duration not specified
- Health status: The health status of the animals was checked prior to and during the experiment at least once daily at work days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified
- Fasting period: not specified
IN-LIFE DATES: not specified
Administration / exposure
- Type of coverage:
- other: gauze cover
- Vehicle:
- other: Cyclohexanone
- Duration of exposure:
- single application for 8 h
- Doses:
- 0.04, 0.4, 1.2 mg/cm² (nominal doses)
- No. of animals per group:
- 4 animals/dose and duration
- Control animals:
- no
- Details on study design:
- DOSE PREPARATION
- Method for preparation of dose suspensions: Stock solutions were prepared for the labelled material in toluene. Appropriate aliquots of the toluene solution were taken and the organic solvent was evaporated to dryness at 32° C under vacuum. In order to achieve the required specific activity and the planned dose unlabelled material and cyclohexanone were added to the remaining material. Prior to administration the solution was stirred in order to produce a homogeneous solution.
- Method of storage: not specified
APPLICATION OF DOSE: A silicon ring was glued to the skin, the test solution (about 10 µL/cm² cyclohexanone solution) was administered. Finally the treated area was protected by a gauze cover.
VEHICLE
- Justification for use and choice of vehicle (if other than water): not specified
- Amount(s) applied (volume or weight with unit): not specified
- Concentration (if solution): not specified
- Lot/batch no. (if required): not specified
- Purity: not specified
TEST SITE
- Preparation of test site: 24 h prior to dosing the back shoulders of the rats were clipped free of hair and the area (about 10 cm²) was washed with acetone.
- Area of exposure: back shoulders
- % coverage: not specified
- Type of cover / wrap if used: gauze cover
- Time intervals for shavings or clipplings: once
SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: not specified
REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: 8 h after application
- Washing procedures and type of cleansing agent: After 8 hours the protective
device was removed and the exposed skin was washed with a mild soap solution.
- Time after start of exposure: 8 h
SAMPLE COLLECTION
- Collection of blood: yes
- Collection of urine and faeces: yes
- Collection of expired air: no
- Terminal procedure: At the end of the various collection periods (8, 24 and 72 h) the animals were sacrificed.
- Analysis of organs: skin (treated and non-treated areas), carcass
SAMPLE PREPARATION
- Storage procedure: not specified
- Preparation details: Aliquots of liquid samples (plasma, urine, cage wash) were mixed with scintillation cocktail (Hionic Fluor, Packard) and analyzed for radioactivity without any additional treatment. Faeces were suspended in distilled water. The carcass was homogenized with distilled water using a WARING Blendor. Aliquots of these suspensions were dried by lyophilization in a freeze dryer (LYOVAC GT 3). Aliquots of the remaining powder and of the homogenate of the other tissues or aliquots of the skin were solubilized in SOLUENE (Packard). In order to bleach these samples isopropanol and H2O2-solution were added and left for 24 hours at room temperature. After addition of scintillation cocktail the samples were counted in a liquid scintillation counter (LSC)(Wallac type 1409; Wallac Rack-beta 1219).
ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
- Liquid scintillation counting results (cpm) converted to dpm as follows: not specified
- Validation of analytical procedure: not specified
- Limits of detection and quantification: not specified
Results and discussion
- Signs and symptoms of toxicity:
- not specified
- Dermal irritation:
- not specified
- Absorption in different matrices:
- - Protective cover: 18.3 - 35.6 % (8 h); 22 - 32.5 % (24 h); 13.3 - 26.3 % (72 h)
- Skin wash: 33.6 - 46.8 % (8 h); 43.4 - 53.5 % (24 h); 45.3 - 53.8 % (72 h)
- Skin test site: 29 - 34 % (8 h); 9.7 - 23 % (24 h); 2.3 - 13.6 % (72 h)
- Skin, untreated site: 1.7 - 5.4 % (8 h); 0.77 - 4.37 % (24 h); 0.25 - 0.75 % (72)
- Bloodcells: 0.02 - 0.04 % (8 h); 0.02 - 0.05 % (24 h); 0.01 - 0.03 % (72)
- Plasma: 0.03 % (8 h); 0.03 - 0.04 % (24 h); 0.01 - 0.06 % (72)
- Carcass: 4 % (8 h); 4.6 - 5.3 % (24 h); 2.2 - 6.5 % (72)
- Urine: 0.23 - 0.37 % (8 h); 1.3 - 2.2 % (24 h); 5 % (72)
- Cage wash: 0.03 - 0.06 % (8 h); 0.14 - 0.25 % (24 h); 0.03 - 1 % (72)
- Faeces: 0.03 - 0.09 % (8 h); 0.7 - 1.3 % (24 h); 3.2 - 4.4 % (72) - Total recovery:
- - Total recovery: 102.91 - 109.35 % (8 h); 93.02 - 107.19 % (24 h); 78.65 - 101.9 % (72 h)
- Recovery of applied dose acceptable: not specified
- Results adjusted for incomplete recovery of the applied dose: not specified
- Limit of detection (LOD): not specified
- Quantification of values below LOD or LOQ: not specified
Percutaneous absorptionopen allclose all
- Time point:
- 72 h
- Dose:
- 0.04 mg/cm²
- Parameter:
- percentage
- Absorption:
- 12.1 %
- Time point:
- 8 h
- Dose:
- 0.04 mg/cm²
- Parameter:
- percentage
- Absorption:
- 10 %
- Time point:
- 72 h
- Dose:
- 0.4 mg/cm²
- Parameter:
- percentage
- Absorption:
- 12.5 %
- Time point:
- 8 h
- Dose:
- 0.4 mg/cm²
- Parameter:
- percentage
- Absorption:
- 7.6 %
- Time point:
- 72 h
- Dose:
- 1.2 mg/cm²
- Parameter:
- percentage
- Absorption:
- 16.7 %
- Time point:
- 8 h
- Dose:
- 1.2 mg/cm²
- Parameter:
- percentage
- Absorption:
- 6 %
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.
