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EC number: - | CAS number: -
- 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://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-01-23 to 2015-02-05
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2010
- Deviations:
- yes
- Remarks:
- Measurement of the cell proliferation by cell counting instead of radioactive labeling. In addition, measurements of ear swelling and ear weights were done to discriminate the irritating potential from the sensitizing potential of the test substance.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2008
- Principles of method if other than guideline:
- Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modifications are authorized in the OECD TG 429 and the Note of
Guidance SWP/ 2145/00 of the CPMP (2001). Information on validation of IMDS and scientific justification is given in: Ehling G et al., Toxicology 212, 60-68
and 69-79 (2005). - GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Test material form:
- other: liquid
- Details on test material:
- Reaction mass of 2,2,4-trimethylhexane-1,6-diylbis{[3-(triethoxysilyl)propyl]carbamate} and 2,4,4-trimethylhexane-1,6-diylbis{[3-(triethoxysilyl)propyl]carbamate} manufactured by Evonik Degussa GmbH. Batch No. IPES-Addukt 7W of 2014-06-23, purity: 95.05.%.
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS:
- Species: Mice (non-pregnant, nulliparous, healthy)
- Starin: NMRI / Crl:NMRI
- Source: Charles River Laboratories Germany GmbH, 97633 Sulzfeld, Germany
- Sex: female
- Age: 62 days
- Weight at study initiation: 20 - 34 g
- Housing: single
- Diet: ad libitum, ssniff R/M-H V 1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 5 days
- Controls: 6 female mice, treated with vehicle
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3 °C
- Humidity (%): 55 % +/- 15 %
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle
- Air exchange: 12 to 18 times per hour
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- Two concentrations of test item (25% and 50% (w/w), dissolved in acetone/olive oil (3+1, v/v)) (w/w) or the undiluted test item (100%) were tested in
six female NMRI mice per group and compared to a vehicle control group. - No. of animals per dose:
- 6 female mice
- Details on study design:
- PREPARATION OF TEST ITEM
- The test item was suspended in acetone /olive oil (3+1, v/v) (25%, 50%) or used as supplied.
RANGE FINDING TESTS:
- 3 animals/test item to examine irritating potential and handling/application to select the appropriate concentrations. Two concentrations of 25 and 50% of test item in acetone/olive oil (3+1, v/v) and the undiluted test item were examined. Doses were selected according to OECD guideline from
the concentration series 100%, 50%, 25%, 10%, 5%, 2.5%, 1%, 0.5% etc
TREATMENT PREPARATION AND ADMINISTRATION:
- Three concentrations of 25, 50 and 100% of test item in acetone /olive oil (3+1, v/v) were examined..
- Vehicle test item: acetone /olive oil (3+1, v/v)
- Vehicle positive control: acetone /olive oil (3+1, v/v)
- Positive control: 25 µL of a 20% solution of a-hexyl cinnamic aldehyde
- Weight of each animal, clinical observations and ear swelling measurements at the helical edge of both ears using an Oditest micrometer are
recorded
- Open application of 25 µl
- vehicle alone
- test item in 3 concentrations
- positive control onto the dorsal part of both ears of the animals.
This treatment was repeated on three consecutive days (d1, d2 and d3).
24 h after last application (day 4), ear swelling measurements are carried out at the helical edge of both ears using an Oditest micrometer
Immediatly after measurement animals were sacrificed under ether anaesthesia.
The appropriate organs were then removed.
Lymphatic organs (the auricular lymph nodes) were then stored on ice in PBS /0.5% BSA.
Investigations:
- ear swelling
- ear weight (Punch biopsies of 8 mm of the apical area)
- weight of lymph nodes
- cell counts in lymph nodes
- stimulation index is calculated by dividing the absolute number of weight or cell counts of the substance treated lymph nodes by the vehicle treated ones.
Animals were observed once daily for clinical signs of local systemic irritation at the application site or of systemic toxity. Body weight were recorded on day 1 and day 4. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The so-called stimulation (or LLN-) index to establish the sensitising potential is calculated by dividing the average absolute lymph node weight or
lymph node cell counts per group of the test item treated lymph nodes by the vehicle treated ones. Thus, in case of no stimulating effect the index
for the lymph node cell count is always below 1.4 (cut-off value). An index above 1.4 is considered positive (sensitising properties).
For lymph node weight a significance at p ≤ 0.01 is considered positive, however, an increase in lymph node weight is an indication for possible
irritating properties not sensitising properties.
In addition, the average ear weights per group and the average ear thickness per group will be compared to the vehicle control group as an indication for possible irritating properties.
Results and discussion
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- Group 1, negative control; Lymph node cell count
- Remarks on result:
- other: detailed results see below
- Key result
- Parameter:
- SI
- Value:
- 1.107
- Test group / Remarks:
- Group 2, 25%; Lymph node cell count
- Remarks on result:
- other: detailed results see below
- Key result
- Parameter:
- SI
- Value:
- 1.162
- Test group / Remarks:
- Group 4, 100%; Lymph node cell count
- Remarks on result:
- other: detailed results see below
- Key result
- Parameter:
- SI
- Value:
- 1.061
- Test group / Remarks:
- Group 3, 50%; Lymph node cell count
- Remarks on result:
- other: detailed results see below
- Parameter:
- SI
- Value:
- 1.58
- Test group / Remarks:
- Group 5, positive control; Lymph node cell count
- Remarks on result:
- other: detailed results see below
Any other information on results incl. tables
Main study results: Stimulation indices (SI):
Parameter |
Group 1, negative control |
Group 2, 25% |
Group 3, 50% |
Group 4, 100% |
Group 5, positive control |
Lymph node cell count |
1.000 |
1.107 |
1.061 |
1.162 |
1.580 |
Lymph node weight |
1.000 |
1.086 |
1.103 |
1.121 |
1.483 |
Ear weight |
1.000 |
0.995 |
1.015 |
0.970 |
1.147 |
Ear thickness, TD4 |
1.000 |
1.057 |
1.053 |
1.062 |
1.247 |
____ significantly different from control at p ≤ 0.01
Applicant's summary and conclusion
- Conclusions:
- Under the present test conditions, the test item at concentrations of 25% or 50% (w/w) in acetone/olive oil (3+1, v/v) or the undiluted test item did
not reveal any sensitising properties in the local lymph node assay. - Executive summary:
The purpose of this study was to determine the sensitising potential of the test item in the modified local lymph node assay in mice.
The study was performed according to OECD 429, however not employing the use of radioactive labelling to measure cell proliferation, as the radioactive method proposed by the OECD guideline led to problems in various EU laboratories: such as (i) practical difficulties/complexity of the test, in particular the radiochemical steps, which sometimes resulted in loss of specimen/activity; this in turn led to variability in the results and to a poor reproducibility and (ii) radiation protection issues. However, the OECD guideline allows other endpoints for assessment of proliferation in form oflymph node cell counts and lymph node weightsif justification and appropriate scientific support exist showing the validity of this method.
The alternative method used for the study employing thelymph node weightandlymph nodecell count to assessproliferationhas been established by an European interlaboratory validation exercise, as described in the two publications by Ehling et al. 2005a and 2005b.This method has the advantage of (i) more simplistic experimental work, (ii) less variability, (iii) better reproducibility, (iv) faster results, (v) reduced costs.
In addition, the acute inflammatory skin reaction is measured by ear weight determination of circular biopsies of the ears and ear thickness measurements on test day 1 and test day 4 to identify skin irritation properties of the test item. It is important to determine if a positive test result is due to the skin irritation potential of the test item or due to its sensitising properties.
Stimulation indices were calculated for the lymph node cell count, lymph node weight, ear weight and ear thickness by dividing the average values per group of the test item treated animals by the vehicle treated ones.
Values above 1.4 (lymph node cell count to identify sensitisation) or 1.1 (ear weight to identify irritation) are considered positive (these values were fixed empirically during the interlaboratory validation of this method (Ehling et al. 2005a and 2005b)).
Two concentrations of test item (25% and 50% (w/w), dissolved in acetone/olive oil (3+1, v/v))(w/w) or the undiluted test item (100%) were tested in six female NMRI mice per group and compared to a vehicle control group.
In addition, a positive control group(20% solution v/v ofa-hexyl cinnamic aldehyde inacetone/olive oil (3+1, v/v))was employed.
Stimulation indices (SI):
Parameter
Group 1, negative control
Group 2,
25%
Group 3, 50%
Group 4, 100%
Group 5,
positive control
Lymph node cell count
1.000
1.107
1.061
1.162
1.580
Lymph node weight
1.000
1.086
1.103
1.121
1.483
Ear weight
1.000
0.995
1.015
0.970
1.147
Ear thickness, TD4
1.000
1.057
1.053
1.062
1.247
____ significantly different from control at p ≤ 0.01
Treatment with test item at concentrations of 25%, 50% or 100% did not reveal any statistical significantly increased values for the lymph node cell count. The stimulation indices of the lymph node cell count did not exceed the threshold level of 1.4. In addition, no increase in the lymph node weight was observed. Hence, the test item is classified as not sensitising.
The threshold level for the ear weight of 1.1 was not exceeded and no increase of ear thickness was observed, i.e. no irritating properties were noted.
The positive control group caused the expected increases in lymph node cell countand lymph node weight (statistically significant at
p ≤ 0.01). Therefore, the study can be regarded as valid.
No signs of local or systemic intolerance were recorded. The animal body weight was not affected by the treatment.
In conclusion, under the present test conditions, the test item at concentrations of 25% or 50% (w/w) in acetone/olive oil (3+1, v/v) or the undiluted test item did not reveal any sensitising properties in the local lymph node assay
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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