Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 242-285-6 | CAS number: 18406-41-2
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-05-16 until 2018-07-03
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
- Reference Type:
- other: Amendment to the study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- Individual Method, 22 July 2010
- Deviations:
- yes
- Remarks:
- Pre-dose clinical observation on Day 3 (Main Test) were not recorded. This deviation was considered to have not affected the integrity or validity of the study.
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 3,3,6,6-tetramethoxy-2,7-dioxa-3,6-disilaoctane
- EC Number:
- 242-285-6
- EC Name:
- 3,3,6,6-tetramethoxy-2,7-dioxa-3,6-disilaoctane
- Cas Number:
- 18406-41-2
- Molecular formula:
- C8H22O6Si2
- IUPAC Name:
- 3,3,6,6-tetramethoxy-2,7-dioxa-3,6-disilaoctane
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Batch No.of test material: 611220160318
- Storage stability: 31 December 2018
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: approx. 4 °C in the dark
- Stability and homogenity under test conditions: Due to the short-term nature of the study no analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. This exception is considered not to affect the integrity or validity of the study.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: preparation of a solution in acetone/olive oil 4:1 (v/v)
- Final dilution of the stock liquid: acetone/olive oil 4:1 (v/v)
FORM AS APPLIED IN THE TEST: solution in acetone/olive oil
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- CBA/CaOlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Horst, The Netherlands
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 15 to 23 g
- Housing: suspended, in solid floor polypropylene cages equipped with enrichements
- Diet: ad libitum, 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK
- Water: ad libitum, tap water
- Acclimation period: at least 5 days
- Indication of any skin lesions: no clinical observations on day 1
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (LLNA)
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Remarks:
- 50%, 0.5 mL test item + 0.5 mL vehicle
- Concentration:
- preliminary screening test: 50, 10, 2, 1 or 0.5% v/v in acetone/olive oil 4:1 (v/v)
main test: 1%, 0.5% or 0.25% v/v in acetone/olive oil 4:1 (v/v) - No. of animals per dose:
- preliminary screening test: 1 (4 mice in total)
main test: 5 - Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: given criteria: suitable for dosing if formulation is a solution or fine homogenous suspension which can be administered via a micropipette
- Irritation/Sensibilisation:
- 10% v/v: face and head was markedly swollen in the animal treated
- 1% or 0.5% v/v: no signs of visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness
- Systemic toxicity:
- 50%, 10% or 2% v/v: annimals had to be humanely killed, pre-dose on Days 1, 2 or 3, due to the occurrence of clinical signs of toxicity that were considered to approach the moderate severity limit set forth in the UK Home Office Project Licence
- 50%, 10% or 2% v/v: signs were prostration, decreased respiratory rate, labored respiration, ptosis, hunched posture, lethargy, tip toe gait and vocalization
- 1% or 0.5% v/v: no signs of systemic toxicity
- all animals showed body weight loss
Further details of the pre-screen test including results for irritation and ear thickness measurement are shown in table 1, 2 and 3.
MAIN STUDY :
- Criteria used to consider a positive response:
- proliferation response of lymph node cells expressed: (number of radioactive disintegrations / minute / animal) AND Stimulation Index = (3HTdR incorporation into lymph node cells of test nodes / recorded for the control nodes)
- test item regarded as a sensitizer: at least one concentration of the test item results in a threefold or greater increase in 3HTdR incorporation compared to control values (unless excessive irritation may have affected the result)
- "non-sensitizer": test item failing to produce a threefold or greater increase in 3HTdR incorporation
- EC3 value also calculated: concentration of test item expected to cause a 3 fold increase in 3HTdR incorporation
- EC3 = c + [[(3-d)/(b-d)] x (a-c)]
a = lowest concentration giving stimulation index >3
b = actual stimulation index caused by ‘a’
c = highest concentration failing to produce a stimulation index of 3
d = actual stimulation index caused by ‘c’
TREATMENT PREPARATION:
- test item was applied to the test system within 2 hours of being formulated (freshly prepared as a solution in acetone/olive oil 4:1 (v/v))
It is assumed that the formulation was stable for this duration.
- formulations of a representative 1 mL of each prepared concentration and 1 mL of vehicle were taken daily and stored frozen in pre-labelled containers for possible future dose formulation analysis
TREATMENT ADMINISTRATION:
- mice treated by daily application of 25 μL of the appropriate concentration of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3)
- test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette
- further group of five mice received the vehicle alone
- 5 days following the first topical application of the test item or vehicle (Day 6) all mice were injected via the tail vein with 0.25 mL (250 μL) of phosphate buffered saline (PBS) containing 3H-methyl thymidine (3HTdR: 80 μCi/mL, specific activity 2.0 Ci/mmoL, ARC UK Ltd) giving a total of 20 μCi to each mouse - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- - group mean values for disintegrations per minute, ear weight increase, lymph node weight and cell count and standard deviations
- data assessed for suitability by analysis of normality and homogeneity of variance
- normally distributed data with homogeneity of variances: parametric one way analysis of variance (ANOVA) and Dunnett’s multiple comparison procedure were used to determine statistical significance
- other data were assessed by non-parametric Kruskal-Wallis Rank Sum and Mann-Whitney U test procedures
Probability values (p):
P<0.001: ***
P<0.01: **
P<0.05: *
P>0.05: (not significant)
Results and discussion
- Positive control results:
- The result of the current positive control study is given in table 4.
Table 5 depicts the historical control data of the positive control.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 0.87
- Test group / Remarks:
- 0.25 % v/v in acetone/olive oil 4:1
- Parameter:
- SI
- Value:
- 1.55
- Test group / Remarks:
- 0.5 % v/v in acetone/olive oil 4:1
- Parameter:
- SI
- Value:
- 4.68
- Test group / Remarks:
- 1 % v/v in acetone/olive oil 4:1
- Remarks on result:
- other: false positive (see further details in chapter 'overall remarks')
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
Lymph node weight and weight changes are given in table 8. The mean weight change for group 2 was noticeably different to the control group.
The lymph node cell count is given in table 9. All group mean cell counts for the test groups showed a significant increase when compared to the control group.
DETAILS ON STIMULATION INDEX CALCULATION
Details on radioactive disintegrations per minute per animal and the stimulation index are given in table 6.
CLINICAL OBSERVATIONS:
There were no deaths or any signs of systemic toxicity noted in the test or control animals during the test.
BODY WEIGHTS
Body weight change of the test animals between Day 1 and Day 6 was comparable to that observed in the corresponding control group animals over the same period.
Details are given in table 10.
EAR WEIGHT AS INDICATOR OF IRRITATION POTENTIAL
Results of the ear weight measurement are given in table 7.
The mean increase in ear weight for group 4 was significantly different to the control group and was indicative of excessive irritation as it exceeded the cut-off value mentioned in the OECD guideline.
Any other information on results incl. tables
Table 4: Results of the current positive control study for LLNA
Concentration (% v/v) in acetone/olive oil 4:1 |
Stimulation Index |
Result |
25 |
5.54 |
Positive |
Table 5: Summary of historical positive control data for the LLNA
Study Number |
Start Date |
Finish Date |
Test Item |
Concentration |
Vehicle |
Stimulation Indexa |
Classificationb |
WR55NG |
09/06/17 |
15/06/17 |
α-Hexylcinnamaldehyde,tech., 85% |
25% v/v |
dimethyl sulphoxide |
8.47 |
Positive |
CT74KC |
09/06/17 |
15/06/17 |
α-Hexylcinnamaldehyde,tech., 85% |
15% v/v |
ethanol/distilled water 7:3 |
10.60 |
Positive |
BQ66KP |
30/06/17 |
06/07/17 |
α-Hexylcinnamaldehyde,tech., 85% |
15% v/v |
butanone |
4.28 |
Positive |
PB44SR |
30/06/17 |
06/07/17 |
α-Hexylcinnamaldehyde,tech., 85% |
15% v/v |
acetone |
3.98 |
Positive |
CP04BC |
29/11/17 |
05/12/17 |
Phenylacetaldehyde (>90%) |
5% v/v |
propylene glycol |
8.44 |
Positive |
GL18PB |
29/11/17 |
05/12/17 |
α-Hexylcinnamaldehyde,tech., 85% |
25% v/v |
dimethyl formamide |
7.28 |
Positive |
TH50YP |
30/11/17 |
06/12/17 |
α-Hexylcinnamaldehyde,tech., 85% |
25% v/v |
acetone/olive oil 4:1 |
5.54 |
Positive |
XQ67PF |
30/11/17 |
06/12/17 |
α-Hexylcinnamaldehyde,tech., 85% |
25% v/v |
1% pluronic L92 in distilled water |
6.48 |
Positive |
MV86JM |
09/05/18 |
15/05/18 |
α-Hexylcinnamaldehyde,tech., 85% |
15% v/v |
ethanol/distilled water 7:3 |
5.96 |
Positive |
JR21XK |
09/05/18 |
15/05/18 |
Phenylacetaldehyde > 90% |
5% v/v |
cottonseed oil |
4.46 |
Positive |
TY92VS |
10/05/18 |
16/05/18 |
α-Hexylcinnamaldehyde,tech., 85% |
25% v/v |
dimethyl sulfoxide |
4.37 |
Positive |
VV05BT |
11/05/18 |
17/05/18 |
α-Hexylcinnamaldehyde,tech., 85% |
15% v/v |
butanone |
3.78 |
Positive |
a = Ratio of test to control lymphocyte proliferation, b = Stimulation index greater than 3.0 indicates a positive result, na = Not applicable
Table 6: Results of the individual disintegrations per minute and calculated SI
Concentration (% v/v) in acetone/olive oil 4:1 |
Animal Number |
dpm/ Animala |
Mean dpm/Animal (Standard Deviation) |
Stimulation Indexb |
Result |
Vehicle |
1-1 |
1376.64 |
2323.90 (±908.65) |
na |
na |
1-2 |
2723.91 |
||||
1-3 |
3696.24 |
||||
1-4 |
1807.51 |
||||
1-5 |
2015.20 |
||||
0.25 |
2-1 |
1890.31 |
2017.00 (±274.48) |
0.87 |
Negative |
2-2 |
2111.87 |
||||
2-3 |
1776.91 |
||||
2-4 |
2454.37 |
||||
2-5 |
1851.56 |
||||
0.5 |
3-1 |
4051.49 |
3611.31 (±1429.99) |
1.55 |
Negative |
3-2 |
5891.71 |
||||
3-3 |
2960.87 |
||||
3-4 |
2244.77 |
||||
3-5 |
2907.73 |
||||
1 |
4-1 |
9039.12 |
10880.05** (±1506.18) |
4.68 |
Positive + |
4-2 |
9690.86 |
||||
4-3 |
11245.61 |
||||
4-4 |
11670.32 |
||||
4-5 |
12754.34 |
+ False positive (see discussion and conclusion)
dpm = Disintegrations per minute
a = Total number of lymph nodes per animal is 2
b = Stimulation Index of 3.0 or greater indicates a positive result
na = Not applicable
** = Significantly different from control group p<0.01
Table 7: Results of the measurement of ear weight and mean ear weight change
Concentration(% v/v) in acetone/olive oil 4:1 |
Animal Number |
Ear Weight (g)^ |
Mean Ear Weight (g) |
Overall Mean Ear Weight Change (compared to control group) |
Vehicle |
1-1 |
0.0378 |
0.0412 |
na |
1-2 |
0.0495 |
|||
1-3 |
0.0462 |
|||
1-4 |
0.0337 |
|||
1-5 |
0.0389 |
|||
0.25 |
2-1 |
0.0503 |
0.0480 |
16.49% |
2-2 |
0.0409 |
|||
2-3 |
0.0609 |
|||
2-4 |
0.0435 |
|||
2-5 |
0.0442 |
|||
0.5 |
3-1 |
0.0527 |
0.0461 |
11.98% |
3-2 |
0.0402 |
|||
3-3 |
0.0485 |
|||
3-4 |
0.0474 |
|||
3-5 |
0.0415 |
|||
1 |
4-1 |
0.0551 |
0.0548* |
32.95% |
4-2 |
0.0426 |
|||
4-3 |
0.0692 |
|||
4-4 |
0.0548 |
|||
4-5 |
0.0521 |
^ = Combined weight of two biopsy punches, one per ear
na = Not applicable
* = Significantly different from control group p<0.05
Table 8: Results of the lymph node weight measurement and the change compared to controls
Concentration(% v/v) in acetone/olive oil 4:1 |
Animal Number |
Lymph Nodes Weight (g) |
Mean Lymph Node Weight (g) |
Overall Mean Lymph Node Weight Change (compared to control group) |
Vehicle |
1-1 |
0.0245 |
0.1120 |
Na |
1-2 |
0.1996 |
|||
1-3 |
0.0690 |
|||
1-4 |
0.2384 |
|||
1-5 |
0.0668 |
|||
0.25 |
2-1 |
0.1783 |
0.1518 |
35.54% |
2-2 |
0.0234 |
|||
2-3 |
0.2224 |
|||
2-4 |
0.0880 |
|||
2-5 |
0.2467 |
|||
0.5 |
3-1 |
0.1184 |
0.1086 |
-3.04% |
3-2 |
0.0821 |
|||
3-3 |
0.1246 |
|||
3-4 |
0.0199 |
|||
3-5 |
0.1978 |
|||
1 |
4-1 |
0.0156 |
0.1027 |
-8.31% |
4-2 |
0.0350 |
|||
4-3 |
0.2187 |
|||
4-4 |
0.2303 |
|||
4-5 |
0.0137 |
Na = Not applicable
Table 9: Results of the lymph node cell count
Concentration (% v/v) in acetone/olive oil 4:1 |
Animal Number |
Cell Count A (X 105 cells/mL) |
Cell Count B (X 105 cells/mL) |
Mean Cell Count (X 105 cells/mL) |
Group Mean Cell |
% Change |
Vehicle |
1-1 |
5.7 |
6.9 |
6.3 |
5.4 |
Na |
1-2 |
4.5 |
4.2 |
4.4 |
|||
1-3 |
5.1 |
5.7 |
5.4 |
|||
1-4 |
5.3 |
4.9 |
5.1 |
|||
1-5 |
6.7 |
4.9 |
5.8 |
|||
0.25 |
2-1 |
6.7 |
6.1 |
6.4 |
6.34* |
17.4 |
2-2 |
6.4 |
6.7 |
6.6 |
|||
2-3 |
7.0 |
6.0 |
6.5 |
|||
2-4 |
6.0 |
6.8 |
6.4 |
|||
2-5 |
6.4 |
5.2 |
5.8 |
|||
0.5 |
3-1 |
6.8 |
6.6 |
6.7 |
9.04** |
58.5 |
3-2 |
7.9 |
8.1 |
8.0 |
|||
3-3 |
11.4 |
9.8 |
10.6 |
|||
3-4 |
10.1 |
10.9 |
10.5 |
|||
3-5 |
9.2 |
9.6 |
9.4 |
|||
1 |
4-1 |
10.9 |
10.1 |
10.5 |
12.9** |
138.9 |
4-2 |
10.8 |
12.4 |
11.6 |
|||
4-3 |
16.3 |
14.2 |
15.3 |
|||
4-4 |
14.3 |
15.7 |
15.0 |
|||
4-5 |
11.4 |
12.8 |
12.1 |
* = Significantly different from control group p<0.05
** = Significantly different from control group p<0.01
Table 10: Results of the body weight measurements and body weight change
Concentration (% v/v) in acetone/olive oil 4:1 |
Animal Number |
Body Weight (g) |
Body Weight Change (g) |
|
Day 1 |
Day 6 |
|||
Vehicle |
1-1 |
19.6 |
19.6 |
0.0 |
1-2 |
18.2 |
18.1 |
-0.1 |
|
1-3 |
19.3 |
18.4 |
-0.9 |
|
1-4 |
18.6 |
18.8 |
0.2 |
|
1-5 |
16.2 |
16.4 |
0.2 |
|
0.25 |
2-1 |
20.7 |
20.1 |
-0.6 |
2-2 |
19.2 |
19.6 |
0.4 |
|
2-3 |
20.3 |
20.0 |
-0.3 |
|
2-4 |
19.8 |
19.9 |
0.1 |
|
2-5 |
21.8 |
23.0 |
1.2 |
|
0.5 |
3-1 |
20.2 |
19.5 |
-0.7 |
3-2 |
18.5 |
18.6 |
0.1 |
|
3-3 |
17.8 |
17.8 |
0.0 |
|
3-4 |
18.1 |
18.0 |
-0.1 |
|
3-5 |
19.4 |
19.0 |
-0.4 |
|
1 |
4-1 |
19.0 |
18.7 |
-0.3 |
4-2 |
19.2 |
19.4 |
0.2 |
|
4-3 |
21.1 |
19.9 |
-1.2 |
|
4-4 |
20.7 |
21.2 |
0.5 |
|
4-5 |
18.3 |
18.8 |
0.5 |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item was considered unlikely to be a skin sensitizer under the conditions of the test.
The mean ear weight increase in the 1% dose group reflected that the test item was excessively irritant (increase of 32.95%) at this concentration, so the cut-off of 25% mentioned in the OECD guideline was exceeded. Therefore it is likely a false positive result for sensitization was obtained. The lower doses caused clearly negative stimulation indices (lower than a 3-fold increase, indices of 0.87 and 1.55 respectively).
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.