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EC number: 240-212-2 | CAS number: 16068-37-4
- 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://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 19/12/1996 - 17/08/1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- GLP compliance:
- yes
Test material
- Reference substance name:
- 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane
- EC Number:
- 240-212-2
- EC Name:
- 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane
- Cas Number:
- 16068-37-4
- Molecular formula:
- C14H34O6Si2
- IUPAC Name:
- 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: ca. 6 weeks
- Weight at study initiation: males 196 g, females 146 g (average)
- Fasting period before study: 16 hours before exposure and sacrifice
- Housing: stainless steel, wire mesh cages
- Diet: ad libitum, except during exposure
- Water: ad libitum, except during exposure
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 44-75
- Air changes (per hr): 10 - 10.4
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Remarks on MMAD:
- MMAD / GSD: Particle size distribution measurements to detect aerosol formation were made using TSI Aerodynamic Particle Sizer.
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Method of holding animals in test chamber: 5 male and 5 female rats, individually, in suspended stainless steel inhalation caging units
- Source and rate of air: syringe pump equipped with a plastic syringe delivered the test material via tubing onto the glass helix of a counter current volatalization chamber.
- System of generating particulates/aerosols: Not applicable
- Temperature, humidity, pressure in air chamber: Were recorded every 30 minutes using a temperature/humidity gauge. The chambers were operated dynamically under slight negative pressure. The chamber size and airflow rates were considered adequate to maintain the animal loading factor below 5% and an oxygen content at least 19%.
- Air flow rate: 218-227 Lpm
- Air change rate: 4.4 - 4.6 min
- Method of particle size determination: TSI Aerodynamic Particle Sizer
- Treatment of exhaust air: Coarse filter, HEPA filter, charcoal filter and in incinerator.
TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Exposure levels were determined by gas chromatography.
- Duration of treatment / exposure:
- 6 hours per day
- Frequency of treatment:
- Once daily, 5 days per week, for 4 weeks.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.12 ppm
- Remarks:
- target
- Dose / conc.:
- 0.36 ppm
- Remarks:
- target
- Dose / conc.:
- 1.2 ppm
- Remarks:
- target
- Dose / conc.:
- 0.186 ppm (analytical)
- Dose / conc.:
- 0.567 ppm (analytical)
- Dose / conc.:
- 1.4 ppm (analytical)
- No. of animals per sex per dose:
- Five
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: Not given
- Rationale for animal assignment (if not random): random
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once per exposure
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice pre-test, and weekly thereafter.
BODY WEIGHT: Yes
- Time schedule for examinations: twice pre-test, weekly thereafter, pre- and post-fasting before sacrifice.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, once pre-test, weekly thereafter
HAEMATOLOGY: Yes
- Time schedule for collection of blood: just prior to sacrifice
- Anaesthetic used for blood collection: Yes (Co2/02)
- Animals fasted: Yes
- How many animals: total of 40 animals
- Parameters checked: hemoglobin concentration, hematocrit, erythrocyte count, platelet count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, total leukocyte counts, differential leukocyte count, absolut lymphocytes, absolute segmented neutrophils, reticulocyte count, erythrocyte morphology.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: just prior to sacrifice
- Animals fasted: Yes
- How many animals: total of 40 animals
- Parameters checked: aspartame amino transferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatinine, fasting glucose, total protein, albumin, globulin, albumin, total bilirubin, sodium, potassium, chloride, calcium, inorganic phosphorus, gamma-glutamyl transferase.
URINALYSIS: Yes
- Time schedule for collection of urine: test day 30
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked: appearance, specific gravity, protein, glucose, pH, ketones, occult blood (semi-quantitatively), bilirubin, urobilinogen. Protein results of 100 mg/dL or greater were verified using a three percent sulfosalicylic acid test. POsitiv bilirubin results were confirmed via lctotest reagent tablets. Microscopic examination of sediment was performed on urine samples via light microscopy. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 1)
HISTOPATHOLOGY: Yes (see table 1)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
All animals survived the duration of the study. No adverse effects were seen in clinical observations.
BODY WEIGHT AND WEIGHT GAIN
No effects.
FOOD CONSUMPTION
No effects.
HAEMATOLOGY
Increased haemoglobin values and/or erythrocyte counts at all exposure levels.
CLINICAL CHEMISTRY
Increased total serum protein in 1.40 ppm exposed male animals.
URINALYSIS
No treatment related effects.
ORGAN WEIGHTS
No effects.
GROSS PATHOLOGY
There were no exposure related macroscopic findings
HISTOPATHOLOGY: NON-NEOPLASTIC
Adverse effects were seen in microscopic histopathological examinations at all exposure levels, including degenerative changes in the nasoturbinal mucosa and metaplasia/hyperplasia of laryngeal tissues.
OLFACTORY MUCOSA
Degeneration/atrophy (moderate to severe) of olfactory epithelium was seen in all males and females from all the exposure groups. In both sexes, there was a dose dependent increase in severity. The degenerative changes were characterised by epithelial disorganization, cytoplasmic disruption and fragmentation and/or exfoliation. In the affected areas, the basement membrane appeared to remain intact. The following changes were associated with olfactory degeneration: edema, dilated glands, focal ulcers, subacute (chronic active)/chronic inflammation and fusion involving nasoturbinates and the nasal septum.
RESPIRATORY MUCOSA
Goblet cell hypertrophy/hyperplasia (minimal to moderately severe) in the anterior portion of the nose was seen in all rats from all groups. In both sexes there was a dose related increase in severity. Hyperplasia of the respiratory epithelium (minimal to moderate) was seen at the anterior part of the nose in both sexes at the higher doses. The following changes were also seen: focal ulcers, subacute (chronic active/chronic) inflammation, scattered foci of squamous metaplasia. The incidence and severity of the findings was greatest at high dose.
NASAL LUMEN
Inflammatory cell debris was seen in nasal lumen of all rats from the exposure groups, with little difference in severity between groups.
LARYNX
Squamous/squamoid metaplasia/hyperplasia (minimum to slight) of the pseudostratified columnar epithelium in the sections with the ventral seromucous gland was evident in rats from groups 0.36 and 1.2 ppm. Hyperplasia (minimal to slight) of the stratified squamous epithelium normally lining portions of the larynx was seen in a number of rats from high dose . Some evidence of hyperkeratosis also present.
NASOPHARYNX
Eosinophilic material (minimal to slight) was seen in a number of rats, mainly at high dose.
A NOAEL could not be determined due to histopathology effects in the nasoturbinal tissues, larynx, and nasopharynx.
Effect levels
- Key result
- Dose descriptor:
- LOAEC
- Effect level:
- 0.186 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 2. Findings in the olfactory nasal mucosa
|
|
MALE |
FEMALE |
||||||
Group |
|
I |
II |
II |
IV |
I |
II |
III |
IV |
Target Exposure |
|
0.0 |
0.12 |
0.36 |
1.2 |
0 |
0.12 |
0.36 |
1.2 |
Number Examined |
|
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
|||||||||
Epithelium –Degeneration/ Atrophy |
Total |
1 |
5 |
5 |
5 |
0 |
5 |
5 |
5 |
Slight |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Moderate |
0 |
3 |
0 |
0 |
0 |
5 |
0 |
0 |
|
Moderately |
0 |
2 |
3 |
0 |
0 |
0 |
4 |
3 |
|
Severe |
|
|
|
|
|
|
|
|
|
severe |
0 |
0 |
2 |
5 |
0 |
0 |
1 |
2 |
|
|
|||||||||
Re-epithelized with Cuboidal/Columnar Epithelium (non-ciliated and/or ciliated) |
total |
0 |
5 |
5 |
5 |
0 |
3 |
5 |
5 |
Slight |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
|
Moderate |
0 |
4 |
4 |
3 |
0 |
3 |
3 |
2 |
|
Moderately |
0 |
0 |
1 |
2 |
0 |
0 |
2 |
2 |
|
severe |
|
|
|
|
|
|
|
|
|
|
|||||||||
Oedema |
Total |
0 |
5 |
5 |
5 |
0 |
5 |
5 |
5 |
Minimal |
0 |
1 |
0 |
0 |
0 |
1 |
0 |
0 |
|
Slight |
0 |
2 |
0 |
0 |
0 |
3 |
1 |
0 |
|
Moderate |
0 |
2 |
4 |
4 |
0 |
1 |
3 |
5 |
|
Moderately |
0 |
0 |
1 |
1 |
0 |
0 |
1 |
0 |
|
Severe |
|
|
|
|
|
|
|
|
|
|
|||||||||
Glands-dilated |
Total |
0 |
4 |
5 |
5 |
0 |
4 |
5 |
5 |
Minimal |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Slight |
0 |
3 |
0 |
0 |
0 |
4 |
0 |
0 |
|
Moderate |
0 |
0 |
5 |
5 |
0 |
0 |
4 |
4 |
|
Moderately |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
1 |
|
Severe |
|
|
|
|
|
|
|
|
Table 3. Findings in the respiratory nasal mucosa
|
|
MALE |
FEMALE |
||||||
Group |
|
I |
II |
II |
IV |
I |
II |
III |
IV |
Target Exposure |
|
0.0 |
0.12 |
0.36 |
1.2 |
0 |
0.12 |
0.36 |
1.2 |
Number Examined |
|
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
|||||||||
Goblet Cell Hypertrophy/Hyperplasia |
Total |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Minimal |
4 |
0 |
0 |
0 |
5 |
4 |
0 |
0 |
|
Slight |
0 |
1 |
1 |
0 |
0 |
1 |
2 |
0 |
|
Moderate |
1 |
4 |
3 |
1 |
0 |
0 |
1 |
2 |
|
Moderately |
0 |
0 |
1 |
4 |
0 |
0 |
2 |
3 |
|
severe |
|
|
|
|
|
|
|
|
|
|
|||||||||
Epithelium - Hyperplasia |
total |
0 |
3 |
3 |
5 |
0 |
0 |
2 |
5 |
Minimal |
0 |
2 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Slight |
0 |
1 |
2 |
1 |
0 |
0 |
1 |
2 |
|
Moderate |
0 |
0 |
0 |
4 |
0 |
0 |
1 |
3 |
|
|
|||||||||
Erosions/Ulcers |
Total |
0 |
1 |
0 |
1 |
0 |
0 |
0 |
3 |
Minimal |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Slight |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
2 |
|
Moderate |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
|
|
|||||||||
Subacute (chronic active/chronic inflammation |
Total |
1 |
2 |
1 |
5 |
0 |
0 |
2 |
3 |
Minimal |
|
|
|
|
|
|
|
|
|
Slight |
1 |
2 |
1 |
0 |
0 |
0 |
1 |
0 |
|
Moderate |
0 |
0 |
0 |
5 |
0 |
0 |
1 |
3 |
|
|
|||||||||
Squamous/Squamoid Metaplasia |
Total |
1 |
2 |
2 |
3 |
0 |
0 |
0 |
2 |
slight |
1 |
2 |
2 |
3 |
0 |
0 |
0 |
2 |
Table 4. Findings in the larynx mucosa
|
|
MALE |
FEMALE |
||||||
Group |
|
I |
II |
II |
IV |
I |
II |
III |
IV |
Target Exposure |
|
0.0 |
0.12 |
0.36 |
1.2 |
0 |
0.12 |
0.36 |
1.2 |
Number Examined |
|
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
|||||||||
Squamous/Squamoid Metaplasia/Hyperplasia |
Total |
0 |
0 |
4 |
5 |
0 |
0 |
3 |
4 |
Minimal |
0 |
0 |
0 |
1 |
0 |
0 |
3 |
2 |
|
Slight |
0 |
0 |
4 |
4 |
0 |
0 |
0 |
2 |
|
|
|||||||||
Stratified Squamous Epithelium (Normal) - Hyperplasia |
Total |
0 |
0 |
1 |
5 |
0 |
0 |
0 |
2 |
Minimal |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
2 |
|
Slight |
0 |
0 |
1 |
4 |
0 |
0 |
0 |
0 |
|
|
|||||||||
Stratified Squamous Epithelium (Normal)- Hyperkeratosis |
Total |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
Minimal |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
Table 5. Findings in the nasopharynx
|
|
MALE |
FEMALE |
||||||
Group |
|
I |
II |
II |
IV |
I |
II |
III |
IV |
Target Exposure |
|
0.0 |
0.12 |
0.36 |
1.2 |
0 |
0.12 |
0.36 |
1.2 |
Number Examined |
|
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
|||||||||
Eosinophilic Material (lumen) |
Total |
0 |
1 |
2 |
3 |
0 |
1 |
1 |
2 |
Minimal |
0 |
1 |
2 |
1 |
0 |
1 |
1 |
2 |
|
Slight |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
|
|
|||||||||
Goblet Cell Hypertrophy/Hyperplasia |
Total |
0 |
0 |
1 |
2 |
0 |
0 |
0 |
2 |
Minimal |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
2 |
|
Slight |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
Applicant's summary and conclusion
- Conclusions:
- A NOAEC could not be determined for 4,4,7,7,-tetraethoxy-3,8-dioxa-4,7-disiladecane due to clinical pathology and histopathology effects in the respiratory tract seen at all exposure levels. The LOAEC for these local effects was therefore concluded to be 0.186 ppm (equivalent to 2.7 mg/m3). There were no adverse systemic effects reported, as the effects on serum protein and haematology parameters are considered to be a secondary consequence of the local effects (study summary author opinion).
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