Canadian perspectives on aluminum Jay C. Van Oostdam*, Harry Zwanenburg and John R. Harrison Department of National Health and Welfare, Rm 241, Environmental Health Centre, Tunney's Pasture, Ottawa, Ontario, Canada, K1A OL2
Introduction Aluminum, as aluminum silicate, is the third most common element in the Earth's crust and a widespread constituent of the environment. It has also been widely used in consumer products. Subsequently, human exposure to A1 occurs through a number of different media such as air, water, food, and through the use of pharmaceuticals and other products containing aluminum. Recent attention has been focussed on the possible adverse health effects of aluminum (A1) due to the tentative links that have been made between this metal and Alzheimer's Disease (AD) (Crapper McLachlan, 1986). Graves (1987), Heyman (1984), and Vogt (1986) have examined this relationship from an epidemiological perspective and their results have contributed to the controversy around this association. In epidemiological studies of the effects of an environmental contaminant such as A1, the accuracy of the exposure estimate is an essential aspect. This paper will focus on preliminary estimates of human exposure to A1 in Canada, and on the usefulness of the multi-media approach, which can be selectively applied to epidemiological studies designed to investigate the relationship between human disease and environmental contamination. The second aspect of this paper will focus on the bioavailability/speciation of A1 and how this impacts on the exposure estimate.
Multi-media Exposure Assessment The purpose of a multi-media approach to human exposure assessment is, first, to identify the major sources of exposure (media); and second, to quantify the relative contributions of each media. Estimates of aluminum exposure in adults from different media are outlined in Table 1. Water The 1987-88 data for A1 levels in drinking water in the province of Ontario are used in this report. The data on drinking water indicate a maximum daily intake of 2.3 mg and 0.8 mg aluminum per adult (for untreated and treated drinking water, respectively) (OME, 1988). Treated water does not appear to be a major source of A1, even though alum (aluminum sulphate) is widely used in Canadian water treatment plants for water clarification. On average, * To whom correspondence should be addressed.
the A1 content in treated water is slightly higher than that in untreated drinking water (OME, 1988), and the higher range in untreated water is due to a few extreme values. In Canada, there are few data on levels of AI in non-municipal drinking water; however, the levels in untreated drinking water (Table 1) may be representative of these non-municipal sources (lakes, rivers, wells). The potential impact of transported acidic air pollution on water quality and aggressiveness of water in plumbing systems is being evaluated. Food Two recent assessments of adult dietary intake of A1 indicate that daily intake through food is 6 mg in the United Kingdom (MAFF, 1985) and 9 to 14 mg in the United States (Pennington, 1988). The 9 to 14 mg/day intake of AI from food is probably a reasonably accurate assessment of Canadian intake due to the widespread exchange of food products in North America. There is, however, a wide range (0.007 to 69.5 mg/100g) of A1 in various food types (Pennington, 1988) suggesting that individuals with unusual dietary habits may have different levels of A1 intake. Another contribution of A1 in food may arise from the leaching of A1 from containers and utensils. Lione (1985) showed that the storage or cooking of acidic food in aluminum containers may increase the AI content of the food by several mg per serving. Hence, the use of aluminum cookware may make a significant contribution to the total daily exposure. Other researchers have concluded that, on a population basis, aluminum utensils and containers do not contribute significantlyto total intake (Jaworski, 1986; Pennington, 1988). Consumer products Some personal care products, such as anti-perspirants, contain aluminum compounds. Daily exposures are likely to be in the mg per adult per day range. However, uptake of A1 from this source has not been demonstrated (Ganrot, 1986; Jones and Bennet, 1985). Air Exposure to ambient air does not significantly contribute to A1 exposure as the maximum daily intake is only 4.2 lxg (OME, 1984). However, occupational exposure may be significant. Pharmaceuticals Based on a recommended dose, Lione (1985) has stated that the range of AI exposure from anti-acids and buffered aspirin is 120- 7,200 mg/day. For people who use these
72
Canadian perspectives on aluminum Table 1 Estimates of daily aluminum exposure in Canadian adults.
Medium
Drinking water Untreated Treated (OME, 1988) Food Diet survey Aluminum containers, utensilsf Consumer products Anti-perspirants Air Ambient (OME,1984) Occupational (Stokinger, 1981; ACGIH, 1987) Pharmaceuticals Anti-acids Buffered acetylsalicylic acid (Lione, 1985) Soil (Kramer, 1986) Total Intake
Concentration range
Daily exposure range
0.004- 1.5 mg/L 0.004 - 0.5 mg/L
0.006 - 2.3 mg a 0.006 - 0.8 mg a
0.007 - 69.5 mg/lO0 gb
47 - 109 mg/g g 0.01 - 0.54 gg/m 3 1.0 - 2.0 mg/m3
? ? 10 mg/100 mg ?
9 - 14mg b ?
? 0.08 - 4.2 gge 3.5 7.0 mg d
1 20 - 7,200 mg 2 00 - 1,000 mg 2 mge ?
a b e d in
Intake of drinking water is 1.5 L/day (NHW, 1983). Pennington, 1988. Intake of air is 23 m3/day (ICRP, 1975) and 35% particle retention in the lungs (Jones and Bennet, 1985). Concentration of A1 in the workplace is assumed to be 10-20% of TLV (ACGIH, 1987), 10 m 3 would be inhaled 8 hours (Stockinger, 1981), and 35% particle retention in the lungs (Jones and Bennet, 1985). Consumption of 20 mg soil/day, estimated. (NAS, 1980). f Depends on the acidity of food products and storage time in vessel. g Varies with product (e.g. 15-35% aluminum chlorohydrate).
products, this exposure would be high, relative to levels obtained through other media.
Soil Concenlxations of A1 in soil depend on geological factors, soil acidity, and proximity to pollution sources. Exposure in adults is dependent on the amount of airborne soil and the degree to which vegetables and fruits are washed prior to consumption. Intakes can be significant.
Comments This paper presents preliminary exposure estimates which indicate that a broad range of highly variable media can contribute to the total AI intake by Canadian adults. Several epidemiological studies have attempted to relate AI exposure from a single medium to AD or age-related dementia. For example, Vogt (1986), utilizing an ecological approach, has attempted to show an association between levels of A1 in ambient water and the prevalence of age-related dementia in southern Norway. In the United States, a case-control study of the relationship between consumption of anti-acids (containing AI) and AD showed no significant association (Heyman, 1984). Another
case-control study indicated an association between the use of A1 containing anti-perspirants and AD (Graves et al., 1987). A multi-media approach to exposure assessment would indicate which of these studies addressed the major media of exposure. Higher levels of individual exposure to AI are possible due to such factors as unusual diets, occupational exposure to polluted air, consumption of AI containing pharmaceuticals, drinking water with high concentration of AI, or use of some consumer products. Epidemiological studies would have a greater likelihood of establishing cause-effect relationships if they focussed on the individual's exposure to AI since the intake of this metal is extremely variable. Interpretation of individual and aggregate exposure data should be approached with caution due to the number of highly variable factors that contribute to total intake.
Bioavailability and Aluminum Speciation A multi-media exposure assessment utilizes exposure or intake data to estimate uptake. However, it is critical that there is understanding of the type of A1 compounds/species
J. C. Van Oostdam, H. Zwanenburg & J. R. Harrison
present in the different media, and how this affects uptake. For example, the Al-species occurring in surface water are: free ionic species (A13§ simple mononuclear species (Al(OI-1))2+), polynuclear species (A1203), and organically bound species (Na3AI(C6H402)3) (Kramer, 1986). Uptake of aluminum is dependent on the concentration of Al in the different media and on the bioavailability/absorption of AI through the epithelium of the lung, the skin, or the gastro-intestinal tract. In this paper, bioavailability is considered, for the sake of simplicity, to be identical to absorption; it is dependent on the chemical form(s) or species of AI. Aluminium uptake is reflected in concentrations of Al in the blood and tissues of the body. Some researchers indicate that absorption of Al is dependent on the concentration of AI and the type of Al compounds, both of which vary in the different media (Greger and Baier, 1983; Jones and Bennet, 1985; Ganrot, 1986; Kaehny et al., 1977). This implies different absorption/bioavailability from the various media. The product of the exposure and the bioavailability/absorption provides estimates of uptake for each medium; furthermore, a summation of the products allows an assessment of total daily uptake. Careful comparison of the actual uptake of Al from the various media will determine which are the major contributing media. Data on bioavailability and absorption of AI, important determinants of uptake, are limited. These data are essential elements of multi-media assessments that estimate uptake. They are also essential for estimation of target tissue concentrations. The relative toxicity of the Al species must also be considered, although it is beyond the scope of this paper. Research in these areas is warranted. Etiology - Diagnosis
Although the focus of this paper is primarily on the need for a multi-media approach to exposure assessment for use in research on the adverse health effects of A1, it is necessary to address the relationship between Al and AD. Controversy about the relationship between this metal and neurological disease exists (McDermott, 1977), i.e. some consider A1 to be a secondary feature and not the primary event in the development of AD (Davies, 1986). A number of other factors have been linked to AD, which may indicate a multi-factorial etiology. Of those patients with dementia 50% to 60% have AD. A definitive diagnosis of AD requires histopathologic confirmation on tissue from the patient's brain. Although clinical accuracy can be close to 90% (Katzman, 1986), researchers have found that, at autopsy, 20% of AD patients had other conditions. This indicates that clinical diagnosis criteria need to be refined and death certificate data may have limited value for diseases characterized by dementia (McKhann, 1984). Canadian Initiatives
The Department of National Health and Welfare has undertaken four initiatives which incorporate, in varying degrees, work directed to address public health concerns on AI. First, a detailed assessment of the importance of Al speciation on toxicity has started. Second, the development
73
of a Canadian Drinking Water Guideline for A1 is under consideration. Third, a feasibility study is planned to determine what type of monitoring should be conducted to ascertain the impact of acidification on drinking water quality. A preliminary study has shown that more than 300,000 Canadians obtain their drinking water from these wells, cisterns, or lakes. These sources are potentially at risk due to leaching of materials from the environment or leaching of materials from the plumbing systems. And fourth, a research program is being developed to investigate the incidence, prevalence, etiology, and modifiable risk factors of AD; this program will also address the health care and social service needs of AD patients and their caregivers. It is anticipated that AI will be considered a~ one of the potential risk factors to study. Summary
The multi-media approach to aluminum exposure will allow a more informed decision on the inclusion or exclusion of various exposure media in future epidemiological studies. Knowledge of the types of A1 (speciation) and their respective bioavailability will enable interpretation of the importance of specific media. References ACGIH 1987. Threshold Limit Values and Biological Exposure Indices. American Conference of Governmental Industrial Hygienists, Cincinatti, U.S.A. Crapper MeLaehlan, D.R. 1986. Aluminum and Alzheimer's disease. Neurobiol. of Aging, 7, 525-532. Davies, I. 1986. Aluminum, neurotoxlcology, and dementia. Rev. Environ. Hlth., VI(1-4), 251-296. Ganrot, P.O. 1986. Metabolism and possible health effects of aluminum. Envir. Health Perspect., 65, 363-441. Graves, A.B., White, E., KoepseU, T., and Reifler, B. 1987. A case-control study of Alzheimer's disease. Am. J. EpMemiol., 126(4), 754 (abstract). Greger, J.L. and Baler, M.J. 1983. Excretion and retention of low or moderate levels of aluminum by human subjects. Food Chem. Toxicol., 21(4), 473-477. Havas, M. 1986. Aluminum chemistry of inland waters. In: M. Havas and J.F. 1aworski (eds.), Aluminum in the Canadian Environment. National Research Council, Ottawa, Canada. Heyman, A., Wilkinson, W.E., Stefford, LA., Helms, MJ., Sigman, A.H. and Weinberg, T. 1984. Alzheimer's disease: a study of epidemiological aspects. Annals Neurol., 15, 335-341. ICRP 1975. Report of Task Group on Reference Man. International Commission on Radiation Protection, Publication 23. Pergamon Press, Oxford, UK. Jaworski, J.F. 1986. Aluminum in the human diet. In: M. Havas and J.F. Jaworski (eds.), Aluminum in the Canadian Environment. National Research Council, Ottawa, Canada. Jones, K.C. and Bennet, B.G. 1985. Summary Exposure Assessment for Aluminum. Exposure Commitment Assessment of Environmental Pollutants, Vol. 4, Report No. 33. Monitoring and Assessment Research Centre. London, UK. Kaehny, W.D., Hegg, A.P. and Alfrey, A.C. 1977. Gastrointestinal absorption of aluminum from aluminmn--containing antacids. New England J. Meal., 269, 1389-1390. Katzman, R. 1986. Alzheimer's disease. New England d. Med., 314(15), 964-973. Kramer, I.IL 1986. Aluminum geochemistry. In: M. Havas and LF. Jaworski (eds.), Aluminum in the Canadian Environment. National Research Council, Ottawa, Canada. Lione, A. 1985. The reduction of aluminum intake in patients with
74
Canadian perspectives on aluminum
Alzheimer's disease. J. Envir. Pathol., Toxicol., Oncol., 6(1), 21-32. MAFF 1985. Survey of Aluminum, Antimony, Chromium, Cobalt, Indium, Nickel, Thallium, and Tin in FooeL Food Surveillance Paper No.15. British Ministry of Agriculture, Fisheries, and Food, London, UK. McDermott, LR, Smith, A.I., Iqbal, K. and Wisniewski, H.M. 1979. Brain aluminum in aging and Alzheimer's disease. Neurology 29, 809-814. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E.M. 1984. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on A]zheimer's Disease. Neurology, 34, 939-944. NAS. 1980. Lead in the Human Environment. National Academy of Sciences, Washington, D.C. NHW. 1981. Tapwater Consumption in Ca _~_da Environmental
Health Directorate. National Health and Welfare 82-EHD-80, Ottawa, Canada. OME. 1984. Cumulative Ambient Air ConcentrationsListings. August 31, 1981 - January 4, 1983. Ontario Ministry of the Environment. Toronto, Canada. OME. 1988. WaterSurveillance Program. Selected Results 19871988. Drinking Water Section. Ontario Ministry of the Environment. Toronto, Canada. Pennington, J.A.T. 1988. Aluminum content of foods and diets. Food Add. Contain., 5(2), 161-232. Stokinger, H.E. 1981. The metals - aluminum. In: G.D. Clayton and F.E. Clayton (r Party's Industrial Hygiene and Toxicology, 3rd Edn. John Wiley and Sons, Toronto, Canada. Vogt, T. 1986. Water Quality and Health. A Study of a Possible Relationship between Aluminum in Drinking Waterand Age Related Dementia. Statisk Sentral Byra, Oslo, Kongsvinger, Norway (Norwegian).
Introduction Aluminum, as aluminum silicate, is the third most common element in the Earth's crust and a widespread constituent of the environment. It has also been widely used in consumer products. Subsequently, human exposure to A1 occurs through a number of different media such as air, water, food, and through the use of pharmaceuticals and other products containing aluminum. Recent attention has been focussed on the possible adverse health effects of aluminum (A1) due to the tentative links that have been made between this metal and Alzheimer's Disease (AD) (Crapper McLachlan, 1986). Graves (1987), Heyman (1984), and Vogt (1986) have examined this relationship from an epidemiological perspective and their results have contributed to the controversy around this association. In epidemiological studies of the effects of an environmental contaminant such as A1, the accuracy of the exposure estimate is an essential aspect. This paper will focus on preliminary estimates of human exposure to A1 in Canada, and on the usefulness of the multi-media approach, which can be selectively applied to epidemiological studies designed to investigate the relationship between human disease and environmental contamination. The second aspect of this paper will focus on the bioavailability/speciation of A1 and how this impacts on the exposure estimate.
Multi-media Exposure Assessment The purpose of a multi-media approach to human exposure assessment is, first, to identify the major sources of exposure (media); and second, to quantify the relative contributions of each media. Estimates of aluminum exposure in adults from different media are outlined in Table 1. Water The 1987-88 data for A1 levels in drinking water in the province of Ontario are used in this report. The data on drinking water indicate a maximum daily intake of 2.3 mg and 0.8 mg aluminum per adult (for untreated and treated drinking water, respectively) (OME, 1988). Treated water does not appear to be a major source of A1, even though alum (aluminum sulphate) is widely used in Canadian water treatment plants for water clarification. On average, * To whom correspondence should be addressed.
the A1 content in treated water is slightly higher than that in untreated drinking water (OME, 1988), and the higher range in untreated water is due to a few extreme values. In Canada, there are few data on levels of AI in non-municipal drinking water; however, the levels in untreated drinking water (Table 1) may be representative of these non-municipal sources (lakes, rivers, wells). The potential impact of transported acidic air pollution on water quality and aggressiveness of water in plumbing systems is being evaluated. Food Two recent assessments of adult dietary intake of A1 indicate that daily intake through food is 6 mg in the United Kingdom (MAFF, 1985) and 9 to 14 mg in the United States (Pennington, 1988). The 9 to 14 mg/day intake of AI from food is probably a reasonably accurate assessment of Canadian intake due to the widespread exchange of food products in North America. There is, however, a wide range (0.007 to 69.5 mg/100g) of A1 in various food types (Pennington, 1988) suggesting that individuals with unusual dietary habits may have different levels of A1 intake. Another contribution of A1 in food may arise from the leaching of A1 from containers and utensils. Lione (1985) showed that the storage or cooking of acidic food in aluminum containers may increase the AI content of the food by several mg per serving. Hence, the use of aluminum cookware may make a significant contribution to the total daily exposure. Other researchers have concluded that, on a population basis, aluminum utensils and containers do not contribute significantlyto total intake (Jaworski, 1986; Pennington, 1988). Consumer products Some personal care products, such as anti-perspirants, contain aluminum compounds. Daily exposures are likely to be in the mg per adult per day range. However, uptake of A1 from this source has not been demonstrated (Ganrot, 1986; Jones and Bennet, 1985). Air Exposure to ambient air does not significantly contribute to A1 exposure as the maximum daily intake is only 4.2 lxg (OME, 1984). However, occupational exposure may be significant. Pharmaceuticals Based on a recommended dose, Lione (1985) has stated that the range of AI exposure from anti-acids and buffered aspirin is 120- 7,200 mg/day. For people who use these
72
Canadian perspectives on aluminum Table 1 Estimates of daily aluminum exposure in Canadian adults.
Medium
Drinking water Untreated Treated (OME, 1988) Food Diet survey Aluminum containers, utensilsf Consumer products Anti-perspirants Air Ambient (OME,1984) Occupational (Stokinger, 1981; ACGIH, 1987) Pharmaceuticals Anti-acids Buffered acetylsalicylic acid (Lione, 1985) Soil (Kramer, 1986) Total Intake
Concentration range
Daily exposure range
0.004- 1.5 mg/L 0.004 - 0.5 mg/L
0.006 - 2.3 mg a 0.006 - 0.8 mg a
0.007 - 69.5 mg/lO0 gb
47 - 109 mg/g g 0.01 - 0.54 gg/m 3 1.0 - 2.0 mg/m3
? ? 10 mg/100 mg ?
9 - 14mg b ?
? 0.08 - 4.2 gge 3.5 7.0 mg d
1 20 - 7,200 mg 2 00 - 1,000 mg 2 mge ?
a b e d in
Intake of drinking water is 1.5 L/day (NHW, 1983). Pennington, 1988. Intake of air is 23 m3/day (ICRP, 1975) and 35% particle retention in the lungs (Jones and Bennet, 1985). Concentration of A1 in the workplace is assumed to be 10-20% of TLV (ACGIH, 1987), 10 m 3 would be inhaled 8 hours (Stockinger, 1981), and 35% particle retention in the lungs (Jones and Bennet, 1985). Consumption of 20 mg soil/day, estimated. (NAS, 1980). f Depends on the acidity of food products and storage time in vessel. g Varies with product (e.g. 15-35% aluminum chlorohydrate).
products, this exposure would be high, relative to levels obtained through other media.
Soil Concenlxations of A1 in soil depend on geological factors, soil acidity, and proximity to pollution sources. Exposure in adults is dependent on the amount of airborne soil and the degree to which vegetables and fruits are washed prior to consumption. Intakes can be significant.
Comments This paper presents preliminary exposure estimates which indicate that a broad range of highly variable media can contribute to the total AI intake by Canadian adults. Several epidemiological studies have attempted to relate AI exposure from a single medium to AD or age-related dementia. For example, Vogt (1986), utilizing an ecological approach, has attempted to show an association between levels of A1 in ambient water and the prevalence of age-related dementia in southern Norway. In the United States, a case-control study of the relationship between consumption of anti-acids (containing AI) and AD showed no significant association (Heyman, 1984). Another
case-control study indicated an association between the use of A1 containing anti-perspirants and AD (Graves et al., 1987). A multi-media approach to exposure assessment would indicate which of these studies addressed the major media of exposure. Higher levels of individual exposure to AI are possible due to such factors as unusual diets, occupational exposure to polluted air, consumption of AI containing pharmaceuticals, drinking water with high concentration of AI, or use of some consumer products. Epidemiological studies would have a greater likelihood of establishing cause-effect relationships if they focussed on the individual's exposure to AI since the intake of this metal is extremely variable. Interpretation of individual and aggregate exposure data should be approached with caution due to the number of highly variable factors that contribute to total intake.
Bioavailability and Aluminum Speciation A multi-media exposure assessment utilizes exposure or intake data to estimate uptake. However, it is critical that there is understanding of the type of A1 compounds/species
J. C. Van Oostdam, H. Zwanenburg & J. R. Harrison
present in the different media, and how this affects uptake. For example, the Al-species occurring in surface water are: free ionic species (A13§ simple mononuclear species (Al(OI-1))2+), polynuclear species (A1203), and organically bound species (Na3AI(C6H402)3) (Kramer, 1986). Uptake of aluminum is dependent on the concentration of Al in the different media and on the bioavailability/absorption of AI through the epithelium of the lung, the skin, or the gastro-intestinal tract. In this paper, bioavailability is considered, for the sake of simplicity, to be identical to absorption; it is dependent on the chemical form(s) or species of AI. Aluminium uptake is reflected in concentrations of Al in the blood and tissues of the body. Some researchers indicate that absorption of Al is dependent on the concentration of AI and the type of Al compounds, both of which vary in the different media (Greger and Baier, 1983; Jones and Bennet, 1985; Ganrot, 1986; Kaehny et al., 1977). This implies different absorption/bioavailability from the various media. The product of the exposure and the bioavailability/absorption provides estimates of uptake for each medium; furthermore, a summation of the products allows an assessment of total daily uptake. Careful comparison of the actual uptake of Al from the various media will determine which are the major contributing media. Data on bioavailability and absorption of AI, important determinants of uptake, are limited. These data are essential elements of multi-media assessments that estimate uptake. They are also essential for estimation of target tissue concentrations. The relative toxicity of the Al species must also be considered, although it is beyond the scope of this paper. Research in these areas is warranted. Etiology - Diagnosis
Although the focus of this paper is primarily on the need for a multi-media approach to exposure assessment for use in research on the adverse health effects of A1, it is necessary to address the relationship between Al and AD. Controversy about the relationship between this metal and neurological disease exists (McDermott, 1977), i.e. some consider A1 to be a secondary feature and not the primary event in the development of AD (Davies, 1986). A number of other factors have been linked to AD, which may indicate a multi-factorial etiology. Of those patients with dementia 50% to 60% have AD. A definitive diagnosis of AD requires histopathologic confirmation on tissue from the patient's brain. Although clinical accuracy can be close to 90% (Katzman, 1986), researchers have found that, at autopsy, 20% of AD patients had other conditions. This indicates that clinical diagnosis criteria need to be refined and death certificate data may have limited value for diseases characterized by dementia (McKhann, 1984). Canadian Initiatives
The Department of National Health and Welfare has undertaken four initiatives which incorporate, in varying degrees, work directed to address public health concerns on AI. First, a detailed assessment of the importance of Al speciation on toxicity has started. Second, the development
73
of a Canadian Drinking Water Guideline for A1 is under consideration. Third, a feasibility study is planned to determine what type of monitoring should be conducted to ascertain the impact of acidification on drinking water quality. A preliminary study has shown that more than 300,000 Canadians obtain their drinking water from these wells, cisterns, or lakes. These sources are potentially at risk due to leaching of materials from the environment or leaching of materials from the plumbing systems. And fourth, a research program is being developed to investigate the incidence, prevalence, etiology, and modifiable risk factors of AD; this program will also address the health care and social service needs of AD patients and their caregivers. It is anticipated that AI will be considered a~ one of the potential risk factors to study. Summary
The multi-media approach to aluminum exposure will allow a more informed decision on the inclusion or exclusion of various exposure media in future epidemiological studies. Knowledge of the types of A1 (speciation) and their respective bioavailability will enable interpretation of the importance of specific media. References ACGIH 1987. Threshold Limit Values and Biological Exposure Indices. American Conference of Governmental Industrial Hygienists, Cincinatti, U.S.A. Crapper MeLaehlan, D.R. 1986. Aluminum and Alzheimer's disease. Neurobiol. of Aging, 7, 525-532. Davies, I. 1986. Aluminum, neurotoxlcology, and dementia. Rev. Environ. Hlth., VI(1-4), 251-296. Ganrot, P.O. 1986. Metabolism and possible health effects of aluminum. Envir. Health Perspect., 65, 363-441. Graves, A.B., White, E., KoepseU, T., and Reifler, B. 1987. A case-control study of Alzheimer's disease. Am. J. EpMemiol., 126(4), 754 (abstract). Greger, J.L. and Baler, M.J. 1983. Excretion and retention of low or moderate levels of aluminum by human subjects. Food Chem. Toxicol., 21(4), 473-477. Havas, M. 1986. Aluminum chemistry of inland waters. In: M. Havas and J.F. 1aworski (eds.), Aluminum in the Canadian Environment. National Research Council, Ottawa, Canada. Heyman, A., Wilkinson, W.E., Stefford, LA., Helms, MJ., Sigman, A.H. and Weinberg, T. 1984. Alzheimer's disease: a study of epidemiological aspects. Annals Neurol., 15, 335-341. ICRP 1975. Report of Task Group on Reference Man. International Commission on Radiation Protection, Publication 23. Pergamon Press, Oxford, UK. Jaworski, J.F. 1986. Aluminum in the human diet. In: M. Havas and J.F. Jaworski (eds.), Aluminum in the Canadian Environment. National Research Council, Ottawa, Canada. Jones, K.C. and Bennet, B.G. 1985. Summary Exposure Assessment for Aluminum. Exposure Commitment Assessment of Environmental Pollutants, Vol. 4, Report No. 33. Monitoring and Assessment Research Centre. London, UK. Kaehny, W.D., Hegg, A.P. and Alfrey, A.C. 1977. Gastrointestinal absorption of aluminum from aluminmn--containing antacids. New England J. Meal., 269, 1389-1390. Katzman, R. 1986. Alzheimer's disease. New England d. Med., 314(15), 964-973. Kramer, I.IL 1986. Aluminum geochemistry. In: M. Havas and LF. Jaworski (eds.), Aluminum in the Canadian Environment. National Research Council, Ottawa, Canada. Lione, A. 1985. The reduction of aluminum intake in patients with
74
Canadian perspectives on aluminum
Alzheimer's disease. J. Envir. Pathol., Toxicol., Oncol., 6(1), 21-32. MAFF 1985. Survey of Aluminum, Antimony, Chromium, Cobalt, Indium, Nickel, Thallium, and Tin in FooeL Food Surveillance Paper No.15. British Ministry of Agriculture, Fisheries, and Food, London, UK. McDermott, LR, Smith, A.I., Iqbal, K. and Wisniewski, H.M. 1979. Brain aluminum in aging and Alzheimer's disease. Neurology 29, 809-814. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E.M. 1984. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on A]zheimer's Disease. Neurology, 34, 939-944. NAS. 1980. Lead in the Human Environment. National Academy of Sciences, Washington, D.C. NHW. 1981. Tapwater Consumption in Ca _~_da Environmental
Health Directorate. National Health and Welfare 82-EHD-80, Ottawa, Canada. OME. 1984. Cumulative Ambient Air ConcentrationsListings. August 31, 1981 - January 4, 1983. Ontario Ministry of the Environment. Toronto, Canada. OME. 1988. WaterSurveillance Program. Selected Results 19871988. Drinking Water Section. Ontario Ministry of the Environment. Toronto, Canada. Pennington, J.A.T. 1988. Aluminum content of foods and diets. Food Add. Contain., 5(2), 161-232. Stokinger, H.E. 1981. The metals - aluminum. In: G.D. Clayton and F.E. Clayton (r Party's Industrial Hygiene and Toxicology, 3rd Edn. John Wiley and Sons, Toronto, Canada. Vogt, T. 1986. Water Quality and Health. A Study of a Possible Relationship between Aluminum in Drinking Waterand Age Related Dementia. Statisk Sentral Byra, Oslo, Kongsvinger, Norway (Norwegian).
