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EC number: 936-023-6 | CAS number: 950782-86-2
- 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 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:
- 2 008
- Report date:
- 2008
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 427 (Skin Absorption: In Vivo Method)
- Version / remarks:
- adopted in 2004
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Environmental Health and Safety Publications Series on testing and Assessment N° 28. Guidance Document for the Conduct of Skin Absorption Studies
- Version / remarks:
- adopted in 2004
- Qualifier:
- according to guideline
- Guideline:
- other: European Commission Guidance Document on Dermal Absorption- Sanco/222/2000 rev. 7
- Version / remarks:
- adopted in 2004
- GLP compliance:
- yes
Test material
- Reference substance name:
- N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine
- EC Number:
- 619-749-5
- Cas Number:
- 730979-19-8
- Molecular formula:
- C16H20FN5
- IUPAC Name:
- N-[(1R,2S)-2,6-dimethyl-2,3-dihydro-1H-inden-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine
Constituent 1
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- other: Wistar Rj: WI (IOPS HAN)
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: R. Janvier, Le Genest St Isle, France
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation: 259 - 391 g
- Housing: suspended, stainless steel and wire mesh cages
- Individual metabolism cages: yes (Jencon's metabowls Mk III or Radleys metabolism cages)
- Diet: Rodent diet A04C-10, pelleted and irradiated, (S.A.F.E. Scientific Animal Food and Engineering, Augy, France), ad libitum
- Water: filtered and softened tap water, ad libitum
- Acclimation period: at least 13 days in the room, 24 h in the metabolism cages
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 8 hours
- Doses:
- - Nominal doses: 0.05, 0.2 and 500 g/L (corresponding to 0.5, 2 and 5000 µg/cm²)
- Actual doses: 0.28-0.31 µg/cm², 1.5 - 1.8 µg/cm² and 5.67 - 6.14 mg/cm²
- Dose volume: approximately 10 µL/cm²
- Rationale for dose selection: neat product and 2 spray dilutions
Please refer to Table 1 under "Any other information on material and methods incl. tables"). - No. of animals per group:
- 4 animals per dose and termination time point
- Control animals:
- no
- Details on study design:
- DOSE PREPARATION
- Method for preparation of dose suspensions: Undiluted test substance or spray dilutions with water.
- Method of storage: at approximately -20°C in the dark
APPLICATION OF DOSE:
TEST SITE
- Preparation of test site: The test site was shaved approximately 24 hours prior to dosing. Just prior to dosing the animals were lightly anaesthetized and two plastic protective saddles were secured in place using Cyanoacrylate adhesive to define the site for application of the test substance.
- Area of exposure: dorsal skin, approximately 2 x 6 cm²
- Type of cover / wrap: a perforated plastic cover (to allow ventilation) held in place over the plastic saddle with surgical tape
SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: (cover was held in place over the plastic saddle with surgical tape
REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: cover was removed
- Washing procedures and type of cleansing agent: Cover and application site were swabbed with freshly prepared 1% v/v Tween 80 in PBS using natural sponge swabs until no more radioactivity was detected on the swabs with a Geiger monitor. Animals that were required to provide samples beyond 8 hours were then fitted with a clean cover to capture any 14C lost by desquamation and replaced in the metabolism cage
- Time after start of exposure: 8 hours
SAMPLE COLLECTION
- Collection of blood: cardiac puncture at different termination time points under anaesthasia (Isofluran)
- Collection of urine and faeces: Urine and faeces were collected separately into receivers at 0 to 8, 8 to 24 and at 24-hour intervals up to sacrifice. At the end of each collection period all debris was removed from the metabolism cage and retained. At each sampling, the cage was carefully washed with distilled water. At study termination the cage was washed with an appropriate organic solvent in addition to water.
- Terminal procedure: The rats were exsanguinated whilst under anaesthesia (Isofluran). The treated skin was swabbed following sacrifice prior to removal. The skin was then shaved (shavings retained), if necessary, prior to tape-stripping to remove the stratum corneum. This procedure involved the application of an adhesive tape (CILS, France) for 5 seconds before the tape was carefully removed against the direction of hair growth. This process was continued until a 'shiny' appearance of the epidermis was evident, indicating that the stratum corneum had been removed.
- Analysis of organs: The treated area of skin was removed and taken for analysis. Further skin samples were also taken for analysis, including the area immediately surrounding the treated skin (approx. 1 cm wide) and a control sample (untreated skin: clearly separated from the application site). The residual carcass was also retained for analysis.
SAMPLE PREPARATION
- Storage procedure: Whenever possible samples were processed as they were collected. Remaining samples were stored at approximately -20°C in the dark until required.
- Preparation details:
Urine: The urine samples were thawed to about room temperature. The weights were recorded and duplicate weighed aliquots added directly to scintillation fluid and analysed.
Cage wash and debris: The cage washings were thawed to about room temperature, and weighed. Duplicate weighed aliquots were taken for analysis. The cage debris (if appropriate) was analysed by a suitable method depending on the nature of the debris.
Faeces: The faeces samples were thawed, then weighed and homogenised in a measured weight of distilled water using a top drive homogeniser (Ultra-Turrax). Triplicate aliquots of the homogenate were combusted directly after drying on Combusto-pads.
Whole blood: The samples of blood were thawed to about room temperature. Triplicate weighed aliquots of cardiac blood were combusted directly after drying of weighed aliquots on Combusto-pads contained in Combusto-cones.
Skin swabs: according to the type of samples the following procedures were used: Swabs 8h and at termination time and surrounding swabs: The swabs of the application site were weighed and were solubilised using Soluene®. Triplicate weighed aliquots were taken for LSC analysis. Swabs X, Y and Z (last three swabs): 2 mL of Soluene and scintillation fluid were directly added to each swab for LSC analysis.
Tape strips: All tape strips were solubilised using tetrahydrofuran. Scintillation fluid was directly added to each tape strip sample for LSC analysis
Skin samples: Skin samples were solubilised separately using alcoholic potassium hydroxide, the total weight determined and duplicate weighed aliquots taken for LSC analysis.
Saddle, gauze, tapes and cover (dressing): The saddle, surgical tape and cover were soaked in an appropriate solvent (acetonitrile). The washings were weighed and duplicate weighed aliquots taken for LSC analysis.
Fur samples: The fur samples removed from the treated skin prior to tape-stripping were soaked in an appropriate solvent (acetonitrile, 2 mL). Scintillation fluid was directly added to each fur sample for LSC analysis
Carcass: The residual carcass was thawed, then weighed and solubilised in alcoholic potassium hydroxide; the total weight determined and duplicated weighed aliquots taken for LSC analysis.
ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
- Limits of detection: twice the background values for blank samples in appropriate scintillation cocktails
Results and discussion
- Signs and symptoms of toxicity:
- no effects
- Dermal irritation:
- not specified
- Absorption in different matrices:
- For detailed absorption in different matrices please refer to the result tables included under "Any other information on results incl. tables".
- Total recovery:
- - Total recovery of groups 1 to 4: 90.6 - 92.7% (500 g/L), 92.7 - 101.4% (0.2 g/L), 99.7 - 107.7% (0.05 g/L)
- Recovery of applied dose acceptable: no (groups 1 - 4, 500 g/L); yes (groups 5 and 6, 0.2 g/L); no (groups 7 and 8, 0.2 g/L); yes (groups 9 -12, 0.05 g/L)
- Results adjusted for incomplete recovery of the applied dose: yes (according to EFSA Guidance on dermal absorption, 2017)
- Limit of detection (LOD): The limit of detection was taken to be twice the background values for blank samples in appropriate scintillation cocktails.
- Quantification of values below LOD or LOQ: no
Percutaneous absorptionopen allclose all
- Time point:
- 8 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 5.268 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 8 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 20 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 24 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 3.025 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 24 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 12 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 72 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 2.403 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 72 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 17 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 168 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 2.764 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 168 h
- Dose:
- 500 g/L
- Parameter:
- percentage
- Absorption:
- 15 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 8 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 21.254 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 8 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 27 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 24 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 18.98 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 24 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 28 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 72 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 11.451 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 72 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 22 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 168 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 14.866 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 168 h
- Dose:
- 0.2 g/L
- Parameter:
- percentage
- Absorption:
- 32 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 8 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 42.659 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 8 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 48 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 24 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 28.687 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 24 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 41 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 72 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 30.208 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 72 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 38 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
- Time point:
- 168 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 23.467 %
- Remarks on result:
- other: mean potentially absorbable percentage
- Time point:
- 168 h
- Dose:
- 0.05 g/L
- Parameter:
- percentage
- Absorption:
- 29 %
- Remarks on result:
- other: mean potentially absorbable percentage, re-evaluated according to EFSA Guidance on dermal absorption (2017)
Any other information on results incl. tables
Table 2: Achieved doses
|
High dose (500 g/L nominal) |
Intermediate dose (0.2 g/L nominal) |
Low dose (0.05 g/L nominal) |
Radiochemical dose applied per animal |
537.1 to 582.1 kBq |
69.3 to 85.6 kBq |
13.2 to 15.0 kBq |
Compound dose applied per animal |
67.98 to 73.68 mg |
17.9 to 21.6 µg |
3.3 to 3.8 µg |
Compound dose applied per cm² * |
5.67 to 6.14 mg/cm² |
1.5 to 1.8 µg/cm² |
0.28 to 0.31 µg/cm² |
*The application rate of the three formulations was 10 µL/cm² and the area of application 12 cm².
Table 3: Mean distribution of radioactivity 8, 24, 72 and 168 h after a single topical application of the test material at the highest dose level (500 g/L; results expressed as % of applied dose; n=4 rats/group)
Group |
1 |
2 |
3 |
4 |
||||
Termination time |
8 h |
24 h |
72 h |
168 h |
||||
|
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
SURFACE COMPARTMENT |
||||||||
Skin swabs at 8 h |
84.516 |
3.336 |
86.305 |
1.073 |
86.440 |
2.637 |
85.807 |
1.324 |
Skin swabs at termination time |
- |
- |
0.925 |
1.081 |
0.571 |
0.519 |
0.734 |
0.280 |
Surrounding swabs |
0.169 |
0.101 |
0.006 |
0.006 |
0.009 |
0.011 |
0.000 |
0.000 |
Total % swabs |
84.685 |
3.266 |
87.236 |
1.349 |
87.019 |
2.886 |
86.541 |
1.130 |
Surface dose (Tape-strips 1 & 2) |
0.283 |
0.140 |
0.952 |
0.418 |
0.652 |
0.357 |
0.508 |
0.136 |
Fur |
- |
- |
- |
- |
- |
- |
1.421 |
0.335 |
Dressing |
0.320 |
0.059 |
0.646 |
0.589 |
0.997 |
1.365 |
1.491 |
0.570 |
Total % non absorbed |
85.287 |
3.160 |
88.834 |
0.530 |
88.669 |
3.323 |
89.961 |
1.817 |
WASHED SKIN COMPARTMENT |
||||||||
Stratum corneuma |
1.842 |
0.855 |
2.155 |
0.987 |
1.894 |
0.783 |
1.243 |
0.582 |
Treated skinb |
1.210 |
0.942 |
0.252 |
0.209 |
0.062 |
0.050 |
0.317 |
0.238 |
Surrounding skin |
0.695 |
0.352 |
0.155 |
0.090 |
0.095 |
0.082 |
0.440 |
0.235 |
Total % at dose site |
3.747 |
1.898 |
2562 |
1.208 |
2.051 |
0.878 |
2.001 |
0.428 |
SYSTEMIC COMPARTMENT |
||||||||
Urines |
0.001 |
0.002 |
0.013 |
0.003 |
0.010 |
0.003 |
0.038 |
0.012 |
Faeces |
0.019 |
0.002 |
0.070 |
0.019 |
0.101 |
0.010 |
0.202 |
0.041 |
Cage wash |
0.012 |
0.015 |
0.018 |
0.015 |
0.000 |
0.001 |
0.093 |
0.067 |
Total % excreted |
0.032 |
0.014 |
0.101 |
0.032 |
0.112 |
0.011 |
0.333 |
0.071 |
Cardiac blood |
0.000 |
0.000 |
0.003 |
0.001 |
0.002 |
0.001 |
0.002 |
0.001 |
Non treated skin |
1.020 |
0.788 |
0.111 |
0.060 |
0.076 |
0.009 |
0.246 |
0.122 |
Carcass |
0.469 |
0.233 |
0.249 |
0.032 |
0.162 |
0.009 |
0.183 |
0.029 |
Total % directly absorbed |
1.521 |
0.969 |
0.463 |
0.109 |
0.352 |
0.013 |
0. 763 |
0.218 |
Total % potentially absorbablec |
5.268 |
2.001 |
3.025 |
1.224 |
2.403 |
0.880 |
2.764 |
0.438 |
Overall Total % Recovery |
90.555 |
2.075 |
91.859 |
1.362 |
91.072 |
2.553 |
92.724 |
1.888 |
a: tape-strips excluding 1 & 2 which are considered to be non-absorbed dose
b: skin after tape stripping procedure
c: total % directly absorbed + total at dose site
SD: standard deviation
- = no sample
Table 4: Mean distribution of radioactivity 8, 24, 72 and 168 h after a single topical application of the test material at the intermediate dose level (0.2 g/L; results expressed as % of applied dose; n=4 rats/group)
Group |
1 |
2 |
3 |
4 |
||||
Termination time |
8 h |
24 h |
72 h |
168 h |
||||
|
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
SURFACE COMPARTMENT |
||||||||
Skin swabs at 8 h |
72.008 |
4.972 |
56.794 |
6.427 |
75.583 |
4.192 |
71.019 |
9.816 |
Skin swabs at termination time |
- |
- |
17.819 |
8.593 |
2.259 |
1.030 |
0.765 |
0.458 |
Surrounding swabs |
0.124 |
0.158 |
0.011 |
0.009 |
0.016 |
0.017 |
0.008 |
0.001 |
Total % swabs |
72.133 |
4.849 |
74.624 |
3.989 |
77.858 |
4.301 |
71.792 |
9.384 |
Surface dose (Tape-strips 1 & 2) |
5.420 |
2.948 |
3.949 |
1.820 |
1.248 |
0.743 |
1.357 |
1.187 |
Fur |
- |
- |
- |
- |
0.223 |
0.447 |
0.712 |
0.545 |
Dressing |
2.573 |
2.041 |
0.715 |
0.271 |
1.951 |
3.193 |
5.368 |
2.268 |
Total % non absorbed |
80.126 |
5.577 |
79.288 |
3.916 |
81.280 |
2.024 |
79.229 |
6.971 |
WASHED SKIN COMPARTMENT |
||||||||
Stratum corneuma |
13.877 |
3.301 |
10.255 |
4.339 |
2.570 |
1.093 |
2.466 |
2.389 |
Treated skinb |
3.702 |
2.688 |
0.763 |
0.439 |
0.291 |
0.100 |
0.611 |
0.583 |
Surrounding skin |
0.443 |
0.256 |
0.174 |
0.033 |
0.190 |
0.054 |
0.563 |
0.381 |
Total % at dose site |
18.023 |
3.521 |
11.192 |
4.062 |
3.052 |
1.166 |
3.640 |
3.204 |
SYSTEMIC COMPARTMENT |
||||||||
Urines |
0.074 |
0.030 |
0.664 |
0.100 |
1.319 |
0.148 |
2.457 |
1.282 |
Faeces |
0.014 |
0.029 |
1.565 |
0.383 |
3.354 |
0.892 |
5.887 |
2.511 |
Cage wash |
0.000 |
0.000 |
0.122 |
0.200 |
0.372 |
0.247 |
0.520 |
0.388 |
Total % excreted |
0.089 |
0.044 |
2.352 |
0.643 |
5.045 |
1.188 |
8.864 |
4.023 |
Cardiac blood |
0.008 |
0.016 |
0.000 |
0.000 |
0.000 |
0.000 |
0.000 |
0.000 |
Non treated skin |
0.644 |
0.108 |
0.379 |
0.044 |
0.460 |
0.083 |
0.564 |
0.109 |
Carcass |
2.491 |
0.080 |
5.058 |
2.749 |
2.894 |
0.264 |
1.797 |
0.312 |
Total % directly absorbed |
3.232 |
0.222 |
7.788 |
2.617 |
8.399 |
1.254 |
11.226 |
4.442 |
Total % potentially absorbablec |
21.254 |
3.573 |
18.980 |
5.654 |
11.451 |
2.068 |
14.866 |
7.517 |
Overall Total % Recovery |
101.380 |
3.716 |
98.267 |
2.092 |
92.701 |
1.307 |
94.094 |
0.654 |
a: tape-strips excluding 1 & 2 which are considered to be non-absorbed dose
b: skin after tape stripping procedure
c: total % directly absorbed + total at dose site
SD: standard deviation
- = no sample
Table 5: Mean distribution of radioactivity 8, 24, 72 and 168 h after a single topical application of the test material at the low dose level (0.05 g/L; results expressed as % of applied dose; n=4 rats/group)
Group |
1 |
2 |
3 |
4 |
||||
Termination time |
8 h |
24 h |
72 h |
168 h |
||||
|
Mean |
SD |
Mean |
SD |
Mean |
SD |
Mean |
SD |
SURFACE COMPARTMENT |
||||||||
Skin swabs at 8 h |
56.565 |
7.240 |
60.826 |
13.318 |
62.481 |
11.227 |
64.537 |
6.532 |
Skin swabs at termination time |
- |
- |
6.730 |
4.433 |
4.244 |
2.780 |
3.911 |
1.515 |
Surrounding swabs |
0.237 |
0.215 |
0.028 |
0.019 |
0.009 |
0.008 |
0.035 |
0.035 |
Total % swabs |
56.802 |
7.225 |
67.585 |
10.411 |
66.734 |
12.042 |
68.483 |
5.426 |
Surface dose (Tape-strips 1 & 2) |
3.713 |
1.617 |
7.749 |
7.860 |
3.012 |
1.016 |
1.149 |
0.280 |
Fur |
- |
- |
- |
- |
2.869 |
2.970 |
2.137 |
0.852 |
Dressing |
1.780 |
2.084 |
0.746 |
1.492 |
4.896 |
3.981 |
4.500 |
1.967 |
Total % non absorbed |
62.295 |
6.264 |
76.080 |
8.188 |
77.511 |
6.647 |
76.269 |
4.541 |
WASHED SKIN COMPARTMENT |
||||||||
Stratum corneuma |
21.447 |
3.650 |
10.978 |
6.837 |
7.253 |
1.700 |
3.285 |
0.328 |
Treated skinb |
7.063 |
6.602 |
2.402 |
2.553 |
0.834 |
0.218 |
0.933 |
0.491 |
Surrounding skin |
1.214 |
0.702 |
0.421 |
0.122 |
1.675 |
1.072 |
0.687 |
0.060 |
Total % at dose site |
29.725 |
5.557 |
13.801 |
9.319 |
9.761 |
2.649 |
4.904 |
0.810 |
SYSTEMIC COMPARTMENT |
||||||||
Urines |
0.214 |
0.070 |
1.497 |
0.474 |
2.646 |
0.661 |
2.589 |
0.727 |
Faeces |
0.000 |
0.000 |
2.879 |
1.147 |
5.844 |
1.681 |
6.430 |
0.882 |
Cage wash |
0.000 |
0.000 |
0.658 |
0.660 |
0.115 |
0.230 |
0.721 |
1.191 |
Total % excreted |
0.214 |
0.070 |
5.034 |
2.094 |
8.605 |
2.073 |
9.740 |
2.041 |
Cardiac blood |
0.000 |
0.000 |
0.118 |
0.125 |
0.241 |
0.062 |
0.000 |
0.000 |
Non treated skin |
2.575 |
0.283 |
1.820 |
0.177 |
3.018 |
0.620 |
2.814 |
0.276 |
Carcass |
10.146 |
2.635 |
7.913 |
0.478 |
8.583 |
1.251 |
6.010 |
1.238 |
Total % directly absorbed |
12.935 |
2.767 |
14.886 |
2.526 |
20.446 |
3.178 |
18.563 |
3.403 |
Total % potentially absorbablec |
42.659 |
3.584 |
28.687 |
7.656 |
30.208 |
4.586 |
23.467 |
3.593 |
Overall Total % Recovery |
104.955 |
4.568 |
104.767 |
2.822 |
107.718 |
2.691 |
99.737 |
4.728 |
a: tape-strips excluding 1 & 2 which are considered to be non-absorbed dose
b: skin after tape stripping procedure
c: total % directly absorbed + total at dose site
SD: standard deviation
- = no sample
Results (total potentially absorbed) were corrected for the missing material when recovery was below the set limit (mean over all animals < 95%) as well as for variability between animals according to the EFSA Guidance on dermal absorption (2017). Results are shown in the results table "Percutaneous absorption".
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