Aluminium sodium dioxide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no studies available on the skin sensitising potential of sodium aluminate.

In accordance with Column 2, Section 8.3., of Annex VII to the REACh Regulation (EC No. 1907/2006), in vivo testing does not need to be conducted if the available information indicates that the substance should be classified for skin sensitisation or corrosivity; or the substance is a strong acid (pH < 2.0) or base (pH > 11.5). Sodium aluminate is a strong base (pH > 11.5) and is therefore considered as corrosive to the skin and mucous membranes.

Available information on the skin sensitising potential of other aluminium compounds was, however, taken into account as supporting information, since the pathways leading to toxic outcomes are likely to be dominated by the chemistry and biochemistry of the aluminium ion (Al³⁺) (Krewski et al., 2007; ATSDR, 2008).

The dermal skin sensitising potential of aluminium hydroxide was studied in a Guinea Pig Maximization Test according to OECD Guideline 406 and in compliance with GLP (LAB Research Ltd., 2010). The study was performed on 15 Dunkin-Hartley guinea pigs divided into a negative control group of 10 animals and a test group of 5 animals. The test comprised two induction (intradermal and epicutaneous) and one challenge phases.

Based on a preliminary dose range finding study, 1% (w/v) aluminium hydroxide in 1% methylcellulose (vehicle) was used for intradermal induction, consisting of three injections to both left and right flanks: an injection with 0.10 mL of Freund's Complete Adjuvant mixed with physiological saline (1:1 v/v); an injection with 0.10 mL of the test item in 1% methylcellulose at the selected concentration; and an injection with 0.10 mL of test material at the appropriate concentration in a 1:1 (v/v) mixture of Freund's Adjuvant and physiological saline. Animals in the control group received three similar injections to each side with the omission of the test material.

For the epicutaneous induction phase one week later, 100% (w/v) aluminium hydroxide was used. 0.5 mL of the test material suspension was applied for 48 h under occlusive conditions. Control animals were treated similarly with 0.5 mL of the vehicle.

Two weeks after the last induction exposure, two concentrations were used for the occlusive epicutaneous challenge exposure: 0.5 mL of a 75% (w/v) aluminium hydroxide suspension was applied to the left flank of the animals and 0.5 mL of 37.5% (w/v) suspension was applied to the right flank for 24 h under occlusive conditions. After patch removal, residual test item was removed with a swab and observations were made at 24 and 48 hours. 

No irritation effects were observed during the dose-range finding study or the induction exposures. No positive responses were observed in the treated group with either the 75% (w/v) or 37.5% (w/v) formulations. Likewise, no positive responses were observed on challenge exposure in the control animals. Thus, the incidence rate was 0% and the net score 0.00. Therefore, it was concluded that under the conditions of this test, aluminium hydroxide had no detectable sensitisation potential.

A positive control test was also performed using undiluted hexyl cinnamic aldehyde for induction and at 12.5% (w/w) in ethanol/diethylphthalate 1:1 (w/w) for challenge, under experimental conditions similar to those described above. Evidence of delayed contact hypersensitivity was seen in 6 out of 10 animals (60%).

In a publication by Gad et al. (1986), the process of development and validation of the Mouse Ear Swelling Test (MEST) was described. 72 substances, including aluminium chloride, were tested for their skin sensitising potential. In the induction stage (days 0-3), at least 10 mice were used for topical application of 100 µl of the test substance (10% aluminium chloride in 70% ethanol) to abdominal skin prepared by intradermal injection of Freund's Complete Adjuvant on day 0 and tape stripping on all four days. The control group (at least 5 animals) was treated in the same way with the vehicle. On day 10, both the test and control groups were challenged by topical application of 20 µl of the test substance to one ear and topical application of 20 µl of vehicle to the contralateral ear. The ear thickness of test and control ears was measured 24 and 48 h post-application. The authors reported 0% sensitised mice and an ear swelling of 103%. The results were compared with data previously published by Magnusson and Kligman (1969), who had reported no sensitising potential for aluminium chloride.

There are no further data available on immunological/lymphoreticular effects in animals after dermal exposure to various forms of aluminium (ATSDR, 2008; Krewski et al., 2007).

Human data

There is no clear evidence for a skin sensitising potential of aluminium and aluminium compounds in humans. The information available is limited to reports on several children and one adult who had previous injections of vaccines or allergens in an aluminium-based vehicle and showed hypersensitivity to aluminium chloride in a patch test (Böhler-Sommeregger and Lindemayr 1986; Veien et al. 1986). Dermal hypersensitivity to aluminium appears to be rare in humans (ATSDR, 2008).

Migrated from Short description of key information:
Sodium aluminate is corrosive to the skin and mucous membranes. Sodium aluminate as well as aluminium and aluminium compounds are not considered skin sensitisers.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Donoghue et al. (2010) studied occupational asthma among employees in Al pre-bake smelters of Australia and New Zealand from 1991 to 2006 and examined relations between asthma in highly exposed workers and potroom air contaminants. The authors collected asthma incidence each year by a survey of seven Al smelters beginning in 1991 using diagnostic criteria developed in 1990 by the AAC’s Health Panel. Regular medical surveillance, including respiratory questionnaires and spirometry, was conducted at all smelters with intervals from 3 months to 2 years between examinations depending upon job type and duration of employment. No information was available on ages of the workers, gender, range of length of employment, etc. Asthma cases were identified by surveillance following development of symptoms or a few of the cases were diagnosed by a family physician. Pre-placement criteria and assessment of individual suitability for jobs with exposure to potroom dust, fumes, and gases were introduced before the study period; these criteria evolved over the course of the study period and these criteria were not uniform at all smelters. These parameters included a history of asthma beyond childhood, reduced FER and evidence of reversible airway obstruction. In some smelters, assessment of non-specific bronchial hyper-responsiveness using methacholine challenge was performed. Incidence rates for occupational asthma were calculated for each smelter and for all smelters combined and the data were presented for each year of the study. All cases of occupational asthma identified in smelter employees regardless of job category were divided by the number of smelter employees regardless of job category and the incidence rates were expressed as the number of cases per 1,000 employees per year. These annual surveys also obtained data on the work areas in which asthma cases were reported, but due to limited data on employees in each work area, incidence rates by work area were not calculated. Employees who worked ‘‘in close proximity to pot fume or bath material for several hours a week as part of their normal job” (e.g., potrooms, potroom services, rodding, potlining, cryolite recovery, scrubbing, and alumina) were defined as the highly “bath exposed” workers. Exposure data were based on personal sampling of inhalable particulate, respirable particulate, particulate fluoride, gaseous hydrogen fluoride, total fluoride for potroom employees charged with anode changing as it was the most consistent job across all of the smelters. Exposure data were collected from the breathing zone of potroom employees (the numbers of employees were not provided) under the supervision of qualified occupational hygienists for each year (1996–2006), but the study design was such that use of personal respiratory protection was not taken into account.

The statistical significance of changes in exposure concentrations (mg/m³) of the inhalable particulate, respirable particulate, particulate fluoride, gaseous hydrogen fluoride, total fluoride across all aluminium smelters during the study period was assessed by regression P-values and Spearman’s correlation coefficients were calculated for correlations between the incidence rate and each exposure variable. There were 329 incident cases of occupational asthma identified between1991–2006 and the highest incidence rate of occupational asthma occurred in 1992 (9.46/1,000 per year) and this declined to 0.36/1,000 per year in 2006. This decline amounted to a 96.2% reduction in the incidence of the disease. Of the 329 incident cases of occupational asthma, 180 cases (55%) occurred in potroom production employees and at least 243 of those cases (74%) occurred in employees who were assigned duties in the ‘‘bath exposed’’ areas. The mean proportion of employees who were ‘‘bath exposed’’ over the period 1991–2006 was 50% (2,916/5,827) (no other details provided). The median values of the geometric mean exposure concentrations of the inhalable particulates, respirable particulates, particulate fluoride, gaseous hydrogen fluoride, total fluoride across all seven of the Australian and New Zealand smelters show that the median values of the geometric mean exposure concentrations (mg/m³) of airborne contaminants in the breathing zone declined over the study period. Statistically significant correlations were observed between the reductions in the incidence of asthma and reductions in total respirable particulate, total F, particulate F and gaseous HF. The correlation coefficient was greatest for total F (rs = 0.497).

The Donoghue et al. (2010) results demonstrate reductions in occupational asthma among employees of seven New Zealand and Australian Al smelters from 9.46 per 1000 employees per year in 1991 to 0.36 per 1000 employees per year in 2006. Moreover, this reduction was correlated with reductions in the geometric mean of total fluoride in the breathing zone among employees undertaking anode changing (rs = 0.497, p < 0.001).

Strengths of the Donoghue et al. (2010) study design include: consistent diagnostic criteria were applied throughout the study period, prospective collection of asthma incidence and collection of personal samples for the highly exposed workers. However, the study has a number of limitations including: data on cases of occupational asthma come from different sources (including onsite medical centres and family physicians and it is not clear whether family physicians applied the same criteria to diagnose occupational asthma); the proportion of cases diagnosed by family physicians is not reported; missing data on numbers of asthma cases and/or numbers of employees for some years; the pre-placement criteria were different at different smelters and “evolved during the study period”; the pre-placement criteria “were introduced for the assessment of applicants for roles involving significant exposure to potroom dust, fumes, and gases” but the incidence rates of occupational asthma were calculated for all employees regardless of job category; there was no description of date(s) when pre-placement examinations were introduced in smelters and the possible impact of worker reassignment, migration out or replacement of the “bath-exposed” workers on the incidence rate was not discussed; lack of data on potential confounding factors (employee turnover rates, age, tobacco consumption), incomplete inhalation exposure characterization including Al metal/oxides and SO2. Although it is not clearly stated whether the mean Al exposures for anode changers represent full-time shift measurements or whether it represents the highest short-term or transient peak exposures to dust and gas, the values likely represent 8-hour time-weighted averages (the usual way in which occupational exposures of this type are measured). There may be concern regarding correlations between exposure among the most highly exposed employees and the overall rate of occupational asthma given that no data on the asthma rates among the highly exposed workers were presented. Major limitation is the absence of a well-defined study population and individual data on exposures, health outcome and potential confounders.

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

Reference:

Ichinose et al. (2008). Effects of Asian Sand Dust, Arizona Sand Dust, Amorphous Silica and Aluminium Oxide on Allergic Inflammation in the Murine Lung. Inhal Toxicol 2008; 20: 685-694.

Migrated from Short description of key information:
Based on information from aluminium oxide (read-across), sodium aluminate is not considered a respiratory sensitiser.

Justification for classification or non-classification

Based on read-across from aluminium and other aluminium compounds as structural analogues, the available data on the skin and respiratory sensitising potential of sodium aluminate is conclusive but not sufficient for classification according to DSD (67/548/EEC) and CLP (1272/2008/EC).