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EC number: 233-135-0 | CAS number: 10043-01-3
- 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
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Respiratory sensitisation
Administrative data
- Endpoint:
- respiratory sensitisation: in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given
Data source
Reference
- Reference Type:
- publication
- Title:
- Effects of Asian Sand Dust, Arizona Sand Dust, Amorphous Silica and Aluminium Oxide on Allergic Inflammation in the Murine Lung.
- Author:
- Ichinose et al.
- Year:
- 2 008
- Bibliographic source:
- Inhal Toxicol 2008; 20: 685-694.
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Examination of the absolute and relative numbers of different cell types and specific biochemical parameters in fluid obtained from bronchoalveolar lavage of animal lungs (BALF) following either intratracheal or inhalation exposure to a substance can provide information on the nature of the reaction of the tissue, i.e the mechanism of action. This information is useful to support and interpret histopathological observations and/or external observations of respiratory symptoms or changes in lung function. In this study, histopathology and BALF analyses were done in the the presence and absence of ovalbumin, a known inducer of eosinophilic inflammation, in order to provide further information on the nature of the mechanism of action (allergenic versus non-specific irritative).
- GLP compliance:
- no
Test material
- Reference substance name:
- Aluminium oxide
- EC Number:
- 215-691-6
- EC Name:
- Aluminium oxide
- Cas Number:
- 1344-28-1
- IUPAC Name:
- 1344-28-1
- Test material form:
- solid: compact
- Details on test material:
- - Name of test material (as cited in study report):aluminium oxide
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan, Inc. (Kanagawa, Japan)
- Age at study initiation: 5 weeks at arrival; 6 weeks at testing
- Weight at study initiation: 307-315 g
- Housing: Plastic cages placed in a “conventional” room. Bedding with soft wood chips not otherwise specified.
- Diet: commercial diet CE-2 obtained from CLEA Japan Inc., Tokyo, Japan.
- Water: ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 °C
- Humidity (%): 55-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): Artificial light 12 hours daily from 6 a.m. to 6 p.m.
Justification of species and strain: ICR mice were chosen based on the results of an earlier study (Ichinose T et al., 2003; Toxicol Appl Pharmacol 187: 29-37) that showed that this species is “moderately” responsive to airway inflammation on exposure to OVA by intratracheal instillation (IT).
Test system
- Route of induction exposure:
- other: Intratracheal instillation
- Route of challenge exposure:
- other: not applicable
- Vehicle:
- other: Normal saline
- Concentration:
- Negative vehicle control (saline),
OVA alone,
Asian SD alone,
Arizona SD alone,
SiO2 alone,
Al2O3 alone,
Asian SD + OVA,
Arizona SD + OVA,
SiO2 + OVA,
Al2O3 + OVA.
Concentration: 0.1 mg per mouse
Deposition efficiencies were calculated using a tidal volume of 0.15 mL/mouse and a breathing rate of 200 breaths per minute. 0.1 mg/mouse was reported to be 111 times the weekly amount of particulate matter that would be deposited in the alveoli assuming 3% deposition (based on the ICRP model at 5.5 micron particle size) at an exposure level of 0.1 mg/m3. - No. of animals per dose:
- 16 animals/group
- 8 animals used for pathology and 8 animals for BALF analyses. - Details on study design:
- Preparation of Test Solution:
In the absence of OVA, 5 mg of particulate was suspended in 2.5 or 5 mL of vehicle and sonicated for 5 minutes while being cooled (temperature not specified)
For the combined OVA and particulate exposure, the OVA (100µg) was dissolved in 10 mL or 5 mL of saline vehicle. 2.5 mL of the OVA solution was then mixed with 2.5 mL of the particle suspension.
Administration of Test Solution:
Volume: 0.1 mL
Method: The suspension was intratracheally administered under anaesthesia (4% halothane, Takeda Chemical, Osaka, Japan) using a polyethylene tube.
The animals were dosed 4 times in total. The interval between doses was 2 weeks.
Further Study details:
The animals were killed by exsanguination one day after the last intratracheal instillation when anaesthetised using an i.p. injection of pentobarbital. At this time, the animals were approximately 12 weeks of age.
Observations:
Pathology of Lung Tissue:
Pathologic examinations were done on the lung tissue from 8 out of 16 mice/group. The lungs were fixed with 10% neutral phosphate-buffered formalin, stained with haematoxylin and eosin (H&E) to assess infiltration of eosinophils and lymphocytes and also, to assess proliferation of goblet cells, periodic acid-shiff (PAS). The evaluation was done by two pathologists independently.
Bronchoalveolar fluid (BALF) analyses:
Cell counts:
The BALF of the remaining 8 mice was evaluated for cell counts. Slides were prepared using a Cytopsin (Sakura Co., Ltd., Tokyo, Japan) and were stained with Diff-Quik. 300 cells were counted.
Levels of cytokines:
The cytokines interleukin-5 (IL-5), IL-12, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), macrophage inflammatory protein-1alpha (MIP-1α), IL-13, and eotaxin were measured using ELISA.
Levels of lactate dehydrogenase (LDH):
Measured using a lactate dehydrogenase C II-Test Wako from Wako Chemicals Ltd. (Osaka, Japan).
Antigen (OVA)-specific and total IgE and IgG1 antibodies:
The antibodies were measured using commercial ELISA kits.
Statistical Analyses:
Group differences were assessed using ANOVA and the Fisher’s projected least significant differences (P/SD) test. - Challenge controls:
- Not applicable.
- Positive control substance(s):
- none
- Negative control substance(s):
- not specified
Results and discussion
- Results:
- Pathology of Lung Tissue:
Al2O3:
The animals treated with aluminium oxide did not show a significantly increased proliferation of goblet cells or infiltration of lymphocytes when compared with the saline control.
OVA + Al2O3:
Lymphocyte infiltration was higher in the OVA+Al2O3 group compared with the control (p<0.001), and also when compared with OVA alone (p<0.01) and with Al2O3 alone (p<0.001).
Eosinophil infiltration was higher in the OVA+Al2O3 group compared with the control (p<0.01) and also OVA+Al2O3 compared with Al2O3 alone (p<0.01).
Goblet cell proliferation was higher in the OVA+Al2O3 group compared with the control (p<0.001), OVA+Al2O3 compared with OVA alone (p<0.05) and also when compared with Al2O3 alone (p<0.001).
Among the groups exposed to the particulates alone, the greatest changes were observed in the SiO2-treated group. Among the groups treated with OVA+particulates, the greatest changes were observed in the OVA+SiO2 group followed by the OVA+Arizona SD group, the OVA+Asian SD group and last the OVA+Al2O3 group.
Bronchoalveolar Lavage Fluid (BALF):
Cell counts
Total cells:
Among the groups exposed to particulates alone, only the SiO2-treated group had levels significantly greater than the control.
In the combined exposure groups, OVA+Asian SD, OVA+Arizona SD, and OVA+SiO2 had levels greater than the control (p<0.001). Total cells in the OVA + Al2O3 group were also significantly greater than the control but not to the same extent (p<0.05). No groups had cell counts greater than that observed in the group with OVA alone. The highest numbers were observed in the OVA+SiO2 group.
Macrophages:
Among the groups exposed to particulates alone, only Arizona SD and SiO2 caused significant increases in macrophages compared with the control (p<0.01 and p<0.001, respectively).
Among the combined exposure groups, OVA + Asian SD, OVA + Arizona SD, and OVA + SiO2 showed levels greater than the control. Numbers of macrophages in the OVA + Al2O3 group were greater than the control but not to the same extent (p<0.01). Only OVA+Arizona SD and OVA+SiO2 had greater numbers of macrophages than the OVA alone group (p<0.05 and p<0.001, respectively).
Eosinophils:
Particulates alone:
No effects observed.
Combined exposures:
OVA+Al2O3Numbers of eosinophils in the OVA+Asian SD (p<0.05), the OVA+Arizona SD (p<0.001) and the OVA+SiO2 (p<0.001) were greater than in the controls. None showed levels greater than OVA alone.
Neutrophils:
Particulates alone:
The SiO2 group was significantly greater than the controls (p<0.001)
Combined exposures:
OVA+Al2O3
Lymphocytes:
Levels in the Arizona SD group were significantly greater than the controls (p<0.01).
OVA+Asian SD (p<0.05) and OVA+Arizona SD (p<0.001) were significantly greater than the OVA only group.
Cytokines
IL-5
Significant elevations were observed for OVA+Arizona SD and OVA+SiO2 compared to the control and compared to OVA alone.
IL-6
A significant elevation was observed for OVA+SiO2 compared to OVA alone.
IL-12
The SiO2 group had significantly higher levels than the control (p<0.001). The OVA+SiO2 group had significantly higher levels than the control (p<0.001), the OVA alone group (p<0.001), and the SiO2 alone group (p<0.001). Levels in the OVA+Arizona SD group were marginally significantly greater than the control group (p<0.05).
IL-13
The OVA+SiO2 group had significantly higher levels than the control (p<0.001), OVA alone (p<0.001), and SiO2 alone groups.
IFN-γ
Asian SD alone (p<0.01), Arizona SD alone (p<0.01), SiO2 alone (p<0.01) and Al2O3 alone (p<0.05) had significantly higher levels than the control.
TNF-α
The Asian SD group (p<0.01), the SiO2 group (p<0.01) and the Al2O3 group (p<0.05) had significantly higher levels than the control. In the combined exposures, OVA+Asian SD and OVA+Arizona SD had higher levels than the controls. None of the particulate-treated groups had levels significantly higher than the OVA alone group.
Levels of lactate dehydrogenase (LDH):
Control: 8.48±1.38 IU/L
Asian SD: 5.56±0.26 IU/L
Arizona SD: 8.19±1.05 IU/L
SiO2: 9.99±0.75 IU/L
Al2O3: 6.17±0.77 IU/L
OVA: 5.09±0.67 IU/L
OVA+Asian SD: 5.98±0.65 IU/L
OVA+Arizona SD: 7.35±1.11 IU/L
OVA+SiO2: 31.18±8.97 IU/L
OVA+Al2O3: 6.37±0.42 IU/L
For the chemokine eotaxin, significant elevations were observed only in the OVA+SiO2 group. KC (keratinocyte chemoattractant) was significantly elevated relative to the control in the Arizona SD (p<0.01) and SiO2 (p<0.001) groups. In the combined exposure groups, the OVA+Arizona SD and OVA+SiO2 groups were significantly elevated relative to both the controls and the OVA alone groups. Levels of monocyte chemotactic protein-3 (MCP-3) in the OVA+Arizona SD and OVA+SiO2 groups were also significantly elevated relative to the control and the OVA alone group. Macrophage inflammatory protein-1α was significantly elevated in the Arizona SD and SiO2 groups relative to the controls and in the OVA+SiO2 group relative to the OVA alone group. OVA+Asian SD, OVA+Arizona SD and OVA+SiO2 had levels significantly greater than the control.
Antigen (OVA)-specific and total IgE and IgG1 antibodies:
Serum levels of OVA specific IgG1 antibodies were significantly elevated relative to levels in the OVA group alone in animals treated with OVA+Arizona SD and OVA+SiO2 (p<0.001). No OVA-specific IgE antibodies were detected. Levels of total IgE in serum in the particulate-treated groups did not differ significantly from levels in the group treated with OVA alone. - Positive control results:
- Not applicable.
- Negative control results:
- Not applicable.
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Conclusions:
- When co-administered with OVA, all the tested materials showed an increase in eosinophils on H&E stained slides (OVA+SiO2>OVA+Arizona SD>OVA+Asian SD>OVA+Al2O3). Considering the results for Al2O3, specifically, in BALF, Al2O3 alone did not lead to significant increases in total cells, macrophages, eosinophils, neutrophils or lymphocytes. When Al2O3 was administered with OVA, small but statistically significant increases in total cells (p<0.05), macrophages (p<0.01) and lymphocytes (p<0.05) were observed relative to the control but not relative to the OVA alone group. Significant (p<0.05) increases in IFN-γ and TNF-α relative to the saline control were observed in BALF of Al2O3 treated animals. IL-5, IL-6, IL-12 and IL-13 did not show significant increases in the Al2O3-treated animals. In exposures combined with OVA, the only significantly elevated cytokine was IFN-γ.
Overall, the results from the study showed that allergic inflammatory effects of atmospheric dusts are likely due to SiO2. Al2O3 was the least inflammatory material tested and led to only weak effects on the mouse lung. - Executive summary:
Ichinose et al. (2008) studied allergic inflammation after intratracheal instillation of Asian sand dust,sand dust, amorphous silica and Al2O3in 6-week old male ICR mice. Four instillations were performed at 2-week intervals. There were ten groups of animals (n=16 in each). One of these groups received Al2O3(particle size 1 ~ 5 µm), a dose of 0.1 mg suspended in saline. The control group received saline only (0.1 mL). The animals were killed one day after the last instillation. Eight out of 16 animals in each group were used for pathologic examination. The lung samples were stained with haematoxylin and eosin to evaluate the degree of infiltration of eosinophils or lymphocytes in the airways, and with periodic acid-shiff to evaluate the degree of proliferation of goblet cells in the bronchial epithelium. The other 8 mice were used for examination of free cell counts (total and differential), determination of levels of lactate dehydrogenase (LDH), cytokines (Interleukins – IL-5, IL-6, IL-12, IL-13, interferon-IFN- g and tumor necrosis factor- TNF- a ) and chemokines in bronchoalveolar lavage fluids (BALF), and also total IgE in serum using enzyme-linked immunosorbent assays (ELISA). In the group of mice exposed to Al2O3, the levels of eosinophil and lymphocyte infiltration in the submucosa and proliferation of goblet cells in the airways, the level of LDH, chemokines and interleukins, number of cells in BALF and the level of IgE in serum were not significantly different from those in the control mice. The results suggest that intratracheal administration of Al2O3does not produce allergic inflammatory effects in the lungs of mice.
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