Boehmite (Al(OH)O)

Endpoint summary

Description of key information

Based on read-across: 
Skin irritation
-LAB Research Ltd., Study 09/164-006N (OECD TG# 404) [Al(OH)3 powder, Klimisch=1], test substance is not a skin irritant
-Lansdown (1973), [Al(OH)3 suspension, Klimisch=2] no guideline study, test substance is not a skin irritant
Eye irritation 
 -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

There are no studies available, which investigate the skin and eye irritant properties of Bohmite. Thus, information available on supporting substances was taken into account by read-across following a structural analogue approach as well. Aluminium compounds were considered for this approach, since the pathways leading to toxic outcomes are dominated by the chemistry and biochemistry of the aluminium ion (Al³⁺) (Krewski et al.,2007).

Skin irritation

An animal study of aluminium hydroxide conducted in accordance with OECD TG #404 (Lab Research Ltd., 2009) provides key evidence for the absence of acute dermal irritation effects on exposure to this substance. Supporting evidence is available from an earlier animal study of aluminium hydroxide powder conducted in accordance with OECD TG 404 “Acute Dermal Irritation/Corrosion” (1989) aluminium hydroxide (Aluminium hydroxide, IUCLID, 2000). A full report of this study is not available for review. A negative result from a non-guideline animal study that applied aluminium hydroxide solution (10%) (Lansdown, 1973) daily for five consecutive days also contributes to the weight of evidence for a lack of irritative or corrosive effects according to Regulation (EC) No. 1272/2008.

 

Eye irritation

The negative results from the LAB Research Ltd. Study (2009) on aluminium hydroxide support a lack of irritant properties of aluminium hydroxide on acute eye exposure. This study is a key in the weight of evidence assessment. The negative results of the key study are supported by an animal study conducted according to OECD TG 405 “Acute Eye Irritation/Corrosion” (1989) (Aluminium hydroxide, IUCLID, 2000). The studies showing negative results for skin irritation also contribute to the weight of evidence. Overall, the weight of evidence suggests a lack of chemical irritant properties for aluminium hydroxide dust on acute eye exposure.

 

Respiratory irritation

Human Studies

Results from two studies that examined cross-shift lung effects among aluminium reduction workers (Chan-Yeunget 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; Krewskiet al., 2007; Sorgdrageret 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; Schalleret al., 2007). Results from three studies that examined cross-shift lung effects among aluminium-exposed welders (Kilburnet al., 1989; Fishwicket al., 2004; Gubeet 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 (Beachet al.,2001; Fritschiet al.2001/2003; Townsendet 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 Al₂O₃to Fischer 344 rats by intratracheal instillation (ITI). Responses to crystalline silica and TiO₂were also examined and compared with a saline control. At 50 mg/kg bw, both Al₂O₃and TiO₂exhibited 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. Tornlinget 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

Based on the read-across from aluminium and other aluminium compounds as structural analogues, the available data on skin, eye and respiratory irritation for Boehmite are conclusive but not sufficient for classification according to DSD (67/548/EEC) or CLP (1272/2008/EC)classification criteria