Reaction mass of aluminium and aluminium oxide and calcium oxide and magnesium oxide

Endpoint summary

Description of key information

The available data suggests that aluminium oxide is unlikely to lead to skin, eye or respiratory irritative effects.
Skin irritation
- Degussa (1979a) [Al2O3, Klimisch=2], similar to OECD TG 404, test substance is not a skin irritant; 
-Degussa (1979b) [Al2O3, Klimisch=2], similar to OECD TG 404, test substance is not a skin irritant; 
-Cabot (1969a) [Al2O3, Klimisch=2], similar to OECD TG 404, test substance is not a skin irritant; 
-LAB Research Ltd., Study 09/164-006N (OECD TG# 404) [Al(OH)3 powder, Klimisch=1], test substance is not a skin irritant
Eye irritation 
-Degussa (1979a) [Al2O3, Klimisch=2], FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) Draize and Kelly (Drug Cosmet. Industr. 71 (1952) 36), test substance is not a eye irritant; 
-Degussa (1979b) [Al2O3, Klimisch=2], FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) Draize and Kelly (Drug Cosmet. Industr. 71 (1952) 36)  test substance is not a eye irritant;
-Cabot (1969a) [Al2O3, Klimisch=2], similar to OECD TG 405, test substance is not a eye irritant; 
-LAB Research Ltd., Study 09/164-006N (OECD TG# 405) [Al(OH)3 powder, Klimisch=2], test substance is not a eye irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation:

No human studies were located that examined acute dermal irritation/corrosion effects in workers exposed occupationally to aluminium oxide particulates. Animal studies conducted by Degussa (1979a,b) reported negative results for acute dermal irritation. An animal study that exposed rabbits to aluminium oxide powder in accordance with OECD TG 404 “Acute Dermal Irritation/Corrosion” (1989) provides evidence supporting the absence of dermal irritation effects of aluminium oxide (Aluminium oxide, IUCLID, 2000). A full report of this study is not available. 

A pre-guideline study conducted by Cabot (Cabot, 1969a) on Al2O3, a high purity fumed alumina formed by the chemical hydrolysis of aluminium chloride, also reported negative results and contributes to the weight of evidence. The negative results from the LAB Research Ltd. Study (2009) and Lansdown (1973) for aluminium hydroxide also contribute to the weight of evidence that irritative properties of aluminium oxide are unlikely on acute dermal exposure. Overall, the weight of evidence suggests that aluminium oxide dust or powder is unlikely to lead to irritative effects on acute dermal exposure.

 

Eye irritation:

An animal study conducted according to OECD TG #405 “Acute Eye Irritation/Corrosion” (1989) has provided data supporting the absence of irritation effects of aluminium oxide (Aluminium oxide, IUCLID, 2000). However, the full report of this study is not available. Studies by Degussa (1979a,b) on aluminium oxide and a study by Cabot (1969) on a fumed alumina, also reported negative results. The negative results from the LAB Research Ltd. Study (2009) on aluminium hydroxide also contribute to the weight of evidence for a lack of irritative properties of aluminium oxide on acute eye exposure. Overall, the weight of evidence suggests a lack of chemical irritative properties for aluminium oxide dust on acute eye exposure.

 

Respiratory irritation:

Human Studies

Results from two studies that examined cross-shift lung effects among aluminium reduction workers (Chan-Yeung et al., 1983; Kilburn and Warshaw, 1989) provide insufficient evidence for an acute, irritative, substance-specific effect from inhalation of aluminium oxide particulates in this occupational setting. 

Airborne exposures in the potroom are multiple – several of which may contribute to a pulmonary response. The evidence suggests a role for aluminium fluoride (AlF3), cryolite

(Na4AlF6), or hydrogen fluoride (HF) in the causation of observed lung effects (ATSDR, 2008; Krewski et al., 2007; Sorgdrager et al., 1995; Soyseth and Kongerud, 1992; Kongerud, 1992). Co-exposure to nickel and the extremely high, accidental exposure levels cannot be excluded as contributory to the toxic pneumonia and fibrosis found in a thermal sprayer (20% aluminium and 80% nickel metal content; Schaller et al., 2007). Results from three studies that examined cross-shift lung effects among aluminium-exposed welders (Kilburn et al., 1989; Fishwick et al., 2004; Gube et al., 2009) provide insufficient evidence for an acute, irritative, substance-specific effect from inhalation of aluminium oxide fume.

No studies were located that reported acute lung effects in workers from short-term inhalation exposure to aluminium hydroxide dust. Results from cross-sectional studies among bauxite-exposed workers are inconclusive concerning a respiratory irritative effect associated with the cumulative exposure levels encountered in the workplace (Beach et al., 2001; Fritschi et al. 2001/2003; Townsend et al., 1985, 1988). Threats to the validity of the available studies include possible selection biases due to cross-sectional designs, residual confounding by smoking, possibly irritative co-exposures, and the lack of measurements of the respirable fraction. 

 

Animal Studies

Pauluhn (2009a) observed an inflammatory response in BALF cytology and biochemistry that was mild and to some degree reversible in a subacute study in rats exposed by inhalation to agglomerated nano-sized aluminium oxyhydroxide particulates. The inflammatory response after 10 days of exposure was significant at the highest dose of 28 mg/m³ but was not detectable at 0.4 and 3 mg/m³. Lindenschmidt et al. (1990) administered single doses of 10 and 50 mg/kg bw Al2O3 to Fischer 344 rats by intratracheal instillation (ITI). Responses to crystalline silica and TiO2 were also examined and compared with a saline control. At 50 mg/kg bw, both Al2O3 and TiO2 exhibited early changes in BAL biochemistry and cells consistent with a mild inflammatory response. All values returned to baseline by 9 weeks post-treatment. For the 10 mg/kg bw level, values had returned to normal 2 weeks post-treatment. Tornling et al. (1993) compared BAL biochemistry in Sprague-Dawley rats on single intratracheal instillation of primary or secondary alumina. Only the fluoride-containing secondary alumina exhibited a reversible, short-term inflammatory response. Fibronectin was elevated in both the primary and secondary alumina-treated groups at the end of the study suggesting a role of the alumina component in the development oflonger-term effects. White et al. (1987) compared BAL biochemistry, BAL cell counts, and lung tissue biochemistry in male Fischer 344 rats exposed to virginal alumina or potroom dust in a short-term, single ITI dose study. The effects of the alumina were typical of a nuisance dust with no evidence of an acute inflammatory response. 

Summary

Overall, the current evidence for an acute irritative effect on inhalation exposure to aluminium oxide or bauxite from human studies does not support a chemical-specific irritative effect. The evidence from animal studies and in-vitro studies also does not support a chemical-specific irritative effect. Based on the available data, aluminium oxide and aluminium hydroxide dust are low cytotoxicity “nuisance dusts” with mild, respiratory irritant effects on acute exposure.

Justification for classification or non-classification

Acute Skin Irritation

Available data are adequate to conclude that there is no need to recommend Classification and Labelling (2008) requirements for skin irritation from acute exposures to aluminium oxide.

 

Acute Eye Irritation

Available data are adequate to conclude that there is no need to recommend Classification and Labelling (2008) requirements for eye irritation from acute exposures to aluminium oxide dust or powder.

 

 Acute respiratory irritation:

Overall, the current evidence for an acute irritative effect on inhalation exposure to aluminium oxide or bauxite from human studies does not support a chemical-specific irritative effect. The evidence from animal studies and in-vitro studies also does not support a chemical-specific irritative effect.

Overall, according to DSD (67/548/EEC) or CLP (1272/2008/EC)classification criteria for irritation/corrosion, no classification is required.