Aluminum exposure

We do not know if aluminum will affect reproduction in people. Aluminum does not appear to affect reproduction in animals. Aluminum has not been shown to cause cancer in animals. To learn more about the health effects of aluminum exposure, see Chapter 2. 

In general, these occupational exposure studies poorly characterize aluminum exposure. Some of the studies reported aluminum air concentrations for a single time period (Dick et al. 1997 Sim et al. 1997 Sjogren et al. 1996 White et al. 1992), but did not have earlier monitoring data when aluminum exposures were higher. The lack of adequate exposure monitoring data and the different types of aluminum exposure makes it difficult to compare these studies and draw conclusions regarding the neurotoxic potential of inhaled aluminum in workers. 

Respiratory Effects. No studies were located regarding respiratory effects of various forms of aluminum following intermediate- or chronic-duration oral exposure in humans. Acute-duration oral exposure to aluminum phosphide has been shown to cause pulmonary edema in persons following accidental or volitional ingestion (Chopra et al. 1986 Khosla et al. 1988). The toxicity was probably due to the formation of highly toxic phosphine gas rather than to aluminum exposure. 

A large number of epidemiology and case-control studies have examined the potential association between oral aluminum exposure and Alzheimer s disease. A number of these studies have been criticized for flawed patient selection, poor comparability of exposed and control groups, poor exposure assessment, poor assessment of health outcomes, and weak statistical correlations (Nieboer et al. 1995 Schupf et al. 1989). Studies conducted by Martyn et al. (1989), McLachlan et al. (1996), and Michel et al. (1990) have found an association between oral exposure to aluminum and an increased risk of Alzheimer s disease. In a survey study conducted by Martyn et al. (1989), the incidence of Alzheimer s disease in individuals under the age of 70 was estimated from computerized tomographic (CT) records. The 1,203 subjects lived in 88 county districts within England and Wales. Data on aluminum concentrations in the municipal water over a 10-year period were obtained from water authorities and water companies. The subjects were classified as having probable Alzheimer s disease, possible Alzheimer s disease, other causes of dementia, or epilepsy. The relative risks of Alzheimer s disease were elevated in the subjects living in districts with aluminum water concentrations of >0.01 mg/L. However, the relative risk exceeded unity only in the subjects with aluminum water concentrations of >0.11 mg/L (relative risk of 1.5, 95% confidence interval of 1.1-2.2). 

Subtle neurological effects have also been observed in workers chronically exposed to aluminum dust or fumes. These effects include impaired performance on neurobehavioral tests, increased reporting of subjective neurological symptoms, and altered EEGs (Bast-Peetersen et al. 1994 Hanninen et al. 1994 Hosovski et al. 1990 Rifat et al. 1990 Sjogren et al. 1996 White et al. 1992). Poor characterization of aluminum exposure precludes using these studies to develop an inhalation MRL for aluminum. 

Hematological Effects. Hematological effects have not been observed in humans or animals with normal renal function. However, microcytic, hypochromatic anemia has been observed in individuals with impaired renal function. The anemia is unresponsive to iron therapy. The severity of the anemia correlates with plasma and erythrocyte aluminum levels and can be reversed by terminating aluminum exposure and chelation therapy with DFO. 

Several animal studies have examined potential age-related differences in the distribution, neurotoxicity, skeletal toxicity, and interactions of aluminum. However, conflicting results have been found and the database is not adequate to assess whether these differences are due to the animal species tested, the aluminum compound used, or the route of exposure. Additionally, there are no studies on the influence of immature renal function on aluminum retention in the body and no studies on the long-term effects of aluminum exposure on skeletal maturation or neurotoxicity. Multiple species studies examining a wide range of effects in immature, mature, and older animals would be useful in assessing the children s susceptibility to the toxicity of aluminum. 

Numerous mechanistic studies of aluminum neurotoxicity have been performed, but the main sites of action have not been discerned as discussed in Section 2.4.2 and by Strong et al. (1996). Additional studies could help identify a single unifying mechanism that can explain and reconcile the wide variety of pathological, neurochemical, and behavioral effects of aluminum induced by oral exposure and in various model systems (e.g., intracerebral and intracistemal administration), but these kinds of studies are unlikely to better characterize neurotoxicity NOAELs and LOAELs relevant to MRL assessment. The relationship between aluminum exposure and neurotoxicity is an active area of research. 

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Cherroret G, Capolaghi B, Hutin MF, et al. 1995. Effects of postnatal aluminum exposure on biological parameters in the rat plasma. Toxicol Lett 78 119-125. 

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Golub MS, Gershwin ME, Donald JM, et al. 1987. Maternal and developmental toxicity of chronic aluminum exposure in mice. Fundam Appl Toxicol 8 346-357. 

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