Aluminium triisopropanolate

Endpoint summary

Description of key information

Upon contact with water or moisture (e.g. within mucous membranes) aluminium triisopropanolate hydrolyses immediately to isopropanol and aluminium 3+ cations (as hydroxide and oxyhydroxide). Hence, toxicity is determined by the toxicity of these two species.

Basketter (1999) investigated the allergenic potential of a.o. aluminium chloride hexahydrate (5, 10 and 25% in petrolatum) in the Local Lymph Node Assay (LLNA). Groups of 4 CBA/Ca mice (7 to 12 weeks of age) were treated with 25 μL of substance or with an equal volume of the vehicle alone, on the dorsum of both ears. The mice were treated once daily for 3 days. Two days later, the mice were injected with 250 μL of phosphate buffered saline (PBS) with 20 μCi of tritiated thymidine (2 Ci mmol-l). The mice were killed 5 hours later and a single-cell suspension of lymph node cells was prepared by mechanical disaggregation. Aluminium chloride hexahydrate did not induce a lymph node proliferation response compared to concurrent vehicle-treated controls, and therefore the response was judged as negative. The results of this study add to the weight of evidence for a low sensitisation potential of aluminium 3+ cations.

A group of 20 guinea pigs was treated with undiluted Isopropyl alcohol for a period of 6 hours weekly for 3 induction exposures (Doyle 1980). The test animals and control animals were challenged with undiluted Isopropyl alcohol. No skin reactions were observed in the test and control animals therefore, it was concluded that Isopropyl alcohol is not a sensitizer.

No experience in literature could be identified indicative of respiratory properties of isopropanol or aluminium hydroxide or oxide. A non-guideline study investigating respiratory sensitization by aluminium oxide turned out negative (Ichinose 2008).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

:

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

not specified

Details on test animals and environmental conditions:

Species and strain: mouse, 4 CBA/Ca
Source: Harlan Olac, Bicester, UK.
Justification of species and strain: Mouse is the preferred animal for this test (OECD TG#429)
Sex: not stated
Body weight range at the beginning of the study: not stated
Age at testing: 7 to 12 weeks
No further details mentioned

Vehicle:

other: petrolatum

Concentration:

5.0%, 10.0%, and 25.0%

No. of animals per dose:

4

Details on study design:

Two days after the last exposure, the mice were injected with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine (from Amersham International, Amersham, UK). Five hours later, the mice were killed, draining lymph nodes excised and a single-cell suspension of the pooled lymph node samples was prepared.

The lymph node cell suspension was washed in excess PBS, precipitated with 5% trichloroacetic acid (TCA) at 4 ºC for 18 hours. After resuspension in TCA, β-scintillation counting was used to measure tritium incorporation.

The method used to kill the animals was not reported.

Observations:
Proliferation of cells in the lymph nodes.

- A positive result was defined as a threefold or greater proliferation than in the concurrent vehicle treated controls.

Positive control substance(s):

other: positive results were seen for metal salts of gold, beryllium, cobalt, mercury, platinum and tin that were tested in parallel

Statistics:

NA

Positive control results:

positive responses were noted

Key result

Parameter:

SI

Value:

>= 0.7 - <= 0.8

Test group / Remarks:

5% 0.8; 10% 0.8; 25% 0.7

Parameter:

EC3

Remarks on result:

not determinable

Remarks:

all values SI values < 3

Parameter:

SI

Value:

0.8

Test group / Remarks:

5%

Parameter:

SI

Value:

0.8

Test group / Remarks:

10%

Parameter:

SI

Value:

0.7

Test group / Remarks:

25%

The results for aluminium chloride hexahydrate were negative. There was no information on the irritancy of the tested concentration from a pre-test

Interpretation of results:

GHS criteria not met

Conclusions:

Aluminium chloride hexahydrate did not show sensitizing potential under the conditions used in this assay.

Executive summary:

Basketter et al. (1999) investigated the allergenic potential of 13 metal salts including aluminium chloride hexahydrate (99% purity) in the Local Lymph Node Assay (LLNA). Groups of 4 CBA/Ca mice (7 to 12 weeks of age) were treated with 25 μL of substance or with an equal volume of the vehicle alone, on the dorsum of both ears. The mice were treated once daily for 3 days. Two days later, the mice were injected with 250 μL of phosphate buffered saline (PBS) with 20 μCi of tritiated thymidine (2 Ci mmol^-l). The mice were killed 5 hours later and a single-cell suspension of lymph node cells was prepared by mechanical disaggregation. A substance was considered a skin sensitizer the proliferation in the lymph nodes of treated mice was 3-fold or greater than that in the concurrent vehicle-treated controls. Aluminium chloride hexahydrate administered in petrolatum (vehicle) at test concentrations of 5.0%, 10.0% and 25.0% did not induce a lymph node proliferation response compared to concurrent vehicle-treated controls, and therefore the response was judged as negative. The results of this study add to the weight of evidence for a low sensitisation potential of aluminium 3+ cations.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1980-08-08 to 1980-09-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD Guideline 406 (Skin Sensitisation)

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Acclimation perios is 4 days instead of 5 days.Pre and post study body weight not mentioned in the report

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The information from a Buehler study performed in 1980 is available and considered to be sufficienly reliable

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Murphy Breeding Laboratories
- Age at study initiation: Not available
- Weight at study initiation: Not available
- Housing: housed singly in wire mesh cages
- Diet (e.g. ad libitum): Purina Laboratory Guinea Pig chow , ad libitum
- Water (e.g. ad libitum): animals were maintained on medicated water containing 4% of sulfaethoxypyridazine for four days and after that they were
furnished with non-medicated water, ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not available
- Humidity (%): Not available
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): 12 hour light /12 hour dark cycle


IN-LIFE DATES: From: 1980-08-08 To: 1980-09-06

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

One group of 20 test animals was treated with 0.4ml of 100% Isopropyl alcohol for a period of 6 hours weekly for 3 induction exposure.
Test group and 10 control animals were challenged with 100% Isopropyl alcohol.

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

One group of 20 test animals was treated with 0.4ml of 100% Isopropyl alcohol for a period of 6 hours weekly for 3 induction exposure.
Test group and 10 control animals were challenged with 100% Isopropyl alcohol.

No. of animals per dose:

20 animals in the test substance group and 10 animals in the vehicle control were treated with 100% Isopropyl alcohol

Details on study design:

RANGE FINDING TESTS: Four animals were exposed for 6 hours period to various concentrations of the test substance
Concentration: 100%, 50%, 25%, 10% v/v solution in distilled water
Exposure period: 24 hours
Grading: the patch site were scored for irritation four to five hours later after washing



MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 induction exposure
- Exposure period: 6 hours
- Test groups: 0.4 ml of undiluted test substance
- Control group: none
- Site: upper left quadrant of the backs of the test animals
- Frequency of applications: once a week for 3 weeks
- Duration: 6 hours webril patches under occlusion
- Concentrations: 0.4 ml of undiluted test substance


B. CHALLENGE EXPOSURE
- No. of exposures: one 6 hour exposure
- Day(s) of challenge: two weeks after second induction
- Exposure period: 6 hours under occlusion
- Test groups: 0.4 ml of undiluted test substance
- Control group: 0.4 ml of undiluted test substance
- Site: lower left quedrant of the back of the test animals
- Concentrations: 0.4 ml of undiluted test substance
- Evaluation (hr after challenge): 24 and 48 hours after challenge exposure

OTHER: None

Challenge controls:

10 animals treated with 100% Isopropyl alcohol

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100% Isopropyl alcohol

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no animals with positive responses

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100% Isopropyl alcohol

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no animals with positive responses

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% Isopropyl alcohol

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no animals with positive responses

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100% Isopropyl alcohol

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no animals with positive responses

Reading:

1st reading

Group:

positive control

Remarks on result:

not determinable because of methodological limitations

Interpretation of results:

GHS criteria not met

Conclusions:

Isopropyl alcohol did not induce sensitization in the guinea pig model.

Executive summary:

One group of 20 test animals was treated with undiluted Isopropyl alcohol for a period of 6 hours weekly for 3 induction exposures. The test animals and control animals were challenged with undiluted Isopropyl alcohol. No skin reactions were observed in the test and control animals therefore, it was concluded that Isopropyl alcohol is not a sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Aluminium tri-isopropylate hydrolyses upon contact with moisture or water immediately to form aluminium hydroxides and 2-propanol. The same effect would be expected upon contact with skin and thus the skin sensitization effects upon skin contact can be assessed by a weight of evidence approach based on results from 2-propanol and aluminium chloride. As neither 2-propanol nor aluminium chloride (representative for effects of AL3+ species) lead to skin sensitizing effects and the hydrolysis of aluminium tri-isopropylate does not significantly effects the pH (8.5 upon hydrolysis) it can be stated that aluminium tri-isopropylate is not expected to be sensitizing to skin.

For explanation for using surrogate data in a weight of evidence approach see also the justification in section 13

Respiratory sensitisation

Link to relevant study records

Reference

Endpoint:

respiratory sensitisation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

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

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).

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).

Levels of monocyte chemotactic protein (MCP)-3:
Measured using an ELISA kit from Bender Medsystems (Burlingame CA)

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:

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.

Ovoalbumina (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.

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 Al₂O₃ in 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-gand 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 Al₂O₃ does not produce allergic inflammatory effects in the lungs of mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Aluminium tri-isopropylate hydrolyses upon contact with moisture or water immediately to form aluminium hydroxides and 2-propanol. The same effect would be expected upon contact with the respiratory system and thus the respiratory sensitization effects upon inhalation can be assessed by a weight of evidence approach based on results from 2-propanol and aluminium hydroxide respectively aluminium oxide. As no valid test systems for respiratory sensitization are available classification is based mainly on human experience in use. Neither for 2-propanol nor aluminium hydroxide or aluminium oxide information about respiratory sensitization could be found in literature, although these substances are widely in use throughout industry and amongst professionals and consumers. A non-guideline study performed on aluminium oxide investigated effects on the immune system following respiratory exposure to aluminium oxide but could not detect any immuno reaction upon repeat exposure. This supports the experience in use not expecting respiratory sensitization by aluminium compounds.

For explanation for using surrogate data in a weight of evidence approach see also the justification in section 13

Justification for classification or non-classification

Based on the information provided on data on isopropanol and aluminium chloride were negative for skin sensitization. Al2O3 was not found to induce respiratory sensitization. Therefore, aluminium triisopropylate is not classified for skin or respiratory sensitization according to CLP (Regulation EC No 1272/2008)