Human Health Effects:

Toxicity Summary:

IDENTIFICATION: Aluminum is a silvery-white, ductile and malleable metal. It is released to the environment both by natural processes and from anthropogenic sources. It is highly concentrated in soil-derived dusts from such activities as mining and agriculture, and in particulate matter from coal combustion. Aluminum occurs ubiquitously in the environment in the form of silicates, oxides and hydroxides, combined with other elements such as sodium and fluorine and as complexes with organic matter. It is not found as a free metal because of its reactivity. Aluminum metal has a wide variety of uses, including structural materials in construction, automobiles and aircraft, and the production of metal alloys. Aluminum compounds and materials also have a wide variety of uses, including production of glass, ceramics, rubber, wood preservatives, pharmaceuticals and waterproofing textiles. Natural aluminum minerals, especially bentonite and zeolite, are used in water purification, sugar refining, brewing and paper industries. HUMAN EXPOSURE: Non-occupational human exposure to aluminum in the environment is primarily through ingestion of food and water. No acute pathogenic effects in the general population have been described after exposure to aluminum. Although it has been hypothesized that aluminum is a risk factor for Alzheimer's disease, present epidemiological evidence does not support a causal association between Alzheimer's disease and aluminum in drinking-water. Neurological syndromes including impairment of cognitive function, motor dysfunction and peripheral neuropathy have been reported in limited studies of workers exposed to aluminum fume. Iatrogenic exposure in patients with chronic renal failure, exposed to aluminum-containing dialysis fluids and pharmaceutical products, may cause encephalopathy, vitamin-D-resistant osteomalacia and microcytic anemia. Premature infants may develop increased tissue loading of aluminum, particularly in bone, when exposed to iatrogenic sources of aluminum. Although human exposure to aluminum is widespread, in only a few cases has hypersensitivity been reported following exposure to some aluminum compounds after dermal application or parenteral administration. There is insufficient information to allow for classification of the cancer risk from human exposures to aluminum and its compounds. Aluminum and its compounds appear to be poorly absorbed in humans. The mechanism of gastrointestinal absorption of aluminum has not yet been fully elucidated. The highest levels of aluminum may be found in the lungs, where it may be present as inhaled insoluble particles. The urine is the most important route of aluminum excretion. ANIMAL STUDIES: The acute toxicity of metallic aluminum and aluminum compounds is low. In short-term studies using rats, mice or dogs to various aluminum compounds in the diet or drinking-water, only minimal effects were observed at the highest administered doses. Adequate inhalation studies were not identified. Following intratracheal administration of aluminum oxide, particle-associated fibrosis was observed. No overt fetotoxicity was noted, nore were general reproductive parameters noted after gavage treatment of rats. There is no indication that aluminum is carcinogenic. It can form complexes with DNA and cross-link chromosomal proteins and DNA, but it has not been shown to be mutagenic in bacteria or induce mutation or transformation in mammalian cells in vitro. Chromosomal aberrations have been observed in bone marrow cells of exposed mice and rats. There is considerable evidence that aluminum is neurotoxic in experimental animals, although there is considerable variation among species. In susceptible species, toxicity following parenteral administration is characterized by progressive neurological impairment, resulting in death with status epilepticus. Osteomalacia, as it presents in man, is observed consistently in larger species (e.g. dogs and pigs) exposed to aluminum; a similar condition is observed in rodents. Absorption via the gastrointestinal tract is usually less than one percent. Aluminum is distributed in most organs within the body with accumulation occurring mainly in bone at high dose levels. To a limited extent, aluminum passes the blood-brain barrier and is also distributed to the fetus. Aluminum is eliminated effectively by urine.
[World Health Organization/International Programme on Chemical Safety. Environmental Health Criteria 194. Aluminium. pp. 1-13 (1997)]**PEER REVIEWED**

Human Toxicity Excerpts:

ACROANESTHESIA ... NUMBNESS OF FINGERS, IS REPORTED FROM COTTON MILLS IN OPERATIONS WHERE THERE IS LONG CONTACT WITH ALUMINUM IN WET BOBBIN WINDING.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 24]**PEER REVIEWED**

FOUND PNEUMOTHORAX AT NECROPSY ON A MAN WHO HAD BEEN EXPOSED TO PURE ALUMINUM DUST ... LUNG SHOWED INDURATION AND DESTRUCTION OF PARENCHYMA ... COLLAGEN DEPOSITION AND HYALINE CHANGE WERE FOUND IN LUNGS OF 5 CO-WORKERS ... /ALUMINUM DUST/
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 10]**PEER REVIEWED**

CHRONIC LUNG DISEASE IN JAPAN ... MAN 32 WHO DIED AFTER HAVING BEEN EXPOSED FOR 3.5 YR TO METALLIC ALUMINUM DUST. MAIN NECROPSY FINDINGS WERE CHRONIC INTERSTITIAL PNEUMONIA WITH SEVERE CAVITATION IN RIGHT UPPER LOBE & NUMEROUS SMALL CAVITIES IN REST OF BOTH LUNGS. /METALLIC ALUMINUM DUST/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1497]**PEER REVIEWED**

CLINICAL PICTURE /FROM INHALATION OF ALUMINUM DUST/ CONSISTS OF DYSPNEA, COUGH, PNEUMOTHORAX, & VARIABLE SPUTUM PRODUCTION, WITH FATAL OUTCOME NOT UNCOMMON. CHEST FILM & HISTOPATHOLOGY ARE ... NODULAR INTERSTITIAL FIBROSIS. /ALUMINUM DUST/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1498]**PEER REVIEWED**

ALUMINUM FIBROSIS OF LUNG WITH ENCEPHALOPATHY WAS REPORTED. ... PRESENTING SYMPTOMS WERE REFERABLE TO CNS, & DEATH RESULTED FROM BRONCHOPNEUMONIA FOLLOWING PROGRESSIVE ENCEPHALOPATHY ASSOC WITH EPILEPTIFORM SEIZURES, ALTHOUGH RADIOGRAPHIC EXAM OF CHEST OF 53 OTHER FACTORY WORKERS & CLINICAL EXAM OF 23 OF THEM REVEALED NO DEFINITE CASES OF ALUMINUM FIBROSIS. ALUMINUM CONTENT OF BRAIN AND LUNG WAS ABOUT 20 TIMES NORMAL ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1498]**PEER REVIEWED**

INHALATION OF FINE PARTICLES OF ALUMINUM METAL DUST IN FACTORIES CAUSED ... PROGRESSIVE ENCEPHALOPATHY ... FOLLOWED BY DEMENTIA & CONVULSIONS; THE BRAIN SHOWED A UNIQUE CELLULAR CHANGE, NEUROFIBRILLARY DEGENERATION. /METALLIC ALUMINUM DUST/
[Venugopal, B. and T.D. Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978. 111]**PEER REVIEWED**

A cross-sectional study was performed to clarify a possible role of atopy in the occurrence of acute bronchoconstrictive impairment observed in workers in a plant for the electrolytic extraction of aluminum. At the time of examination, mean hydrogen fluoride exposure was 0.56 mg/cu m, mean particulate fluoride exposure was 0.15 mg/cu m, and mean sulfur dioxide concentration was 3.38 mg/cu m. No information on duration of exposure or employment is provided. Of 227 workers examined (mean age 37, 43% current smokers) the percentage of those with a history of atopy and positive skin tests for common allergens was within the expected range. Six had a positive patch test with 2% sodium fluoride among 7 workers with paroxysmal wheezing and dyspnea, of whom 3 were light smokers, 3 had positive skin tests with common allergens but only 1 had an increased IgE value. The same worker also had a positive patch test with 2% sodium fluoride. Two had symptoms defined as chronic bronchitis. FEV's, with 2 exceptions, measured at the beginning of the workshift were within normal limits. In 5 of the 7 workers, nonspecific bronchoprovocative tests with histamine or metacholine indicated objectively the presence of bronchial hyperreactivity.
[Saric M et al; Am J Ind Med 9: 239-42 (1986)]**PEER REVIEWED**

Aluminum is not generally regarded as an industrial poison. Inhalation of finely divided aluminum powder has been reported as a cause of pulmonary fibrosis. May be implicated in Alzheimers disease.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 174]**PEER REVIEWED**

MAJOR HEALTH PROBLEM IN ALUMINUM REDUCTION PLANTS IS NO LONGER FLUOROSIS, BUT POSSIBLE EFFECTS TO COAL TAR PITCH VOLATILES & THEIR ASSOC POLYCYCLIC AROMATIC HYDROCARBONS ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1500]**PEER REVIEWED**

THE MAIN HEALTH HAZARD IN PRIMARY ALUMINUM PRODUCTION IS FLUORIDE EXPOSURE, NOT EXPOSURE TO ALUMINUM OR ALUMINUM OXIDE. BOTH GASEOUS & PARTICULATE FLUORIDES ARE FOUND IN THE WORKING ATMOSPHERE AS WELL AS IN THE EMISSIONS.
[Friberg, L., G.R. Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. New York: Elsevier North Holland, 1979. 281]**PEER REVIEWED**

Pulmonary aluminosis is a disease first seen in Germany between 1938 and 1945 which then reappeared in the United Kingdom between 1952 and 1959. All cases were associated with exposure to a submicron-sized aluminum pyrotechnic flake which was lubricated with a non-polar aliphatic oil. Ordinarily, stearic acid, which chemically combines with aluminum to form aluminum stearate, was used as a lubricant to retard surface oxidation during milling of such flake. This new aliphatic lubricant, which simply physically coated the flakes to prevent elemental aluminum oxidation, could be easily washed off of such flakes. In the intracellular milieu, removal of such surface oil permits exposure of oxygen to elemental aluminum; this results in a vigorous exothermic reaction and the potential for tissue damage. It appears that cases occurred only where this oily lubricant was used to manufacture near submicron-sized pyrotechnic flake (ie, United Kingdom, Germany, Sweden), but never where similar flakes have been manufactured for almost a century using polar lubricants.
[Dinman BD; J Occup Med 29 (11): 869-76 (1987)]**PEER REVIEWED**

THERE IS SOME EVIDENCE THAT @ INTAKE LEVELS CONSIDERABLY HIGHER THAN NORMAL THERE IS TENDENCY FOR BODY TO BECOME DEPLETED OF /PHOSPHORUS/, OWING TO BINDING OF DIETARY PHOSPHATE BY ALUMINUM IN DIGESTIVE TRACT.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 6]**PEER REVIEWED**

LOCALLY IN SOLN ... /ALUM IS/ RARELY IRRITATING BUT THE DRY POWDER MAY CAUSE MARKED INFLAMMATION OR CORROSION OF THE SKIN & MUCOUS MEMBRANES. WHEN INGESTED AS CONCN SOLN OR AS SOLID ... THERE IS GI IRRITATION OR CORROSION, WITH NAUSEA, VOMITING, ABDOMINAL PAIN & DIARRHEA.
[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 169]**PEER REVIEWED**

Nineteen young male workers exposed occupationally from 1975-1977 to inhaled particles of aluminum fluoride or sulfate at two plants, developed nocturnal wheezing and breathlessness with reversible airways obstruction after an average of 4 mo employment. At standardized methacholine provocation tests, 17 of 19 workers with normal spirometry showed airway hyperreactivity with a fall of FEV1 forced expiratory volume in 1 sec of greater than or equal to 15% after 0.1% methacholine. Fifteen initially asthmatic workers were followed for 2-5 yr with methacholine provocation tests. Mean TD (threshold dose) 15% FEV1 in 11 workers did not change significantly after an average of 41 mo of nonexposure. Six workers continuously exposed for 48 mo also failed to change normal airway reactivity. /Aluminum salts/
[Simonsson BG et al; Eur J Respir Dis 66 (2): 105-118 (1985)]**PEER REVIEWED**

Nuclear and chromatin fractions were prepared from the cerebral cortex of 34 human and 37 animal brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Compared to age-matched controls, aluminum content expressed per gram of DNA was significantly increased in nuclear and heterochromatin fractions in pre-senile Alzheimer's disease. In contrast, nuclear preparations from brains of patients who had died with dialysis encephalopathy contained less aluminum than controls, although whole tissue concn were elevated ten to fifteen times above the control concn. Direct injection of aluminum into the cerebrospinal fluid of cats resulted in a progressive encephalopathy with neurofibrillary degeneration and increased intranuclear aluminum content. It is speculated that in Alzheimer's disease, the normal blood-brain and cytoplasmic barriers for this neurotoxic metal are defective, permitting aluminum to gain access to DNA-containing constituents of the nuclei.
[Crapper DR et al; Acta Neuropath (Berl) 50 (1): 19-24 (1980)]**PEER REVIEWED**

Though the etiology of the dialysis dementia has not been conclusively established, there is ample evidence to implicate aluminum as the causative agent for this fatal syndrome. ... Dialysis dementia is a severe syndrome characterized by progressive neurological impairment, speech disorders, dysarthria, dyspraxia, dysphasia, aphemia, amnesia, mutism, facial grimacing and myoclonus. Of sixty dialysis dementia cases recently reviewed, 87% exhibited disturbances in communication, 66% in cognition and 93% in movement. The onset is usually insidious, with the first symptoms occurring after a mean of 37 mo from the beginning of the dialysis treatment. Hesitant, stuttering, misarticulated and non-fluent speech, difficulty in concentration, diurnal drowsiness, reduction of attention span, poor memory, dysgraphia and twitching of limbs are usually the earliest signs. Patients exhibit a very characteristic electroencephalogram demonstrating paroxysmal slowing, diffuse rhythmical bursts, with diphasic or triphasic spiked waves in the high-voltage delta frequency range in the initial early stages and only pronounced generalized delta and theta activity late in the course of the dialysis dementia. Reports exist on possible epileptogenic activity arising in the middle diencephalon and a few indicate localized cortical atrophy. Low protein content in the frontal grey matter may indicate that dialysis encephalopathy is accompanied by defects in the blood-brain barrier. Episodic apnea was also related to the EEG abnormality with intermittent respiratory arrest occurring simultaneously with paroxysmal slowing. ... The actual pathogenesis is complicated, since the symptoms are developed in some patients and not in other equally exposed patients. This can be attributed to the rate of exposure or peak free aluminum concn as well as other factors, such as parathyroid hormone, that affects aluminum absorption and/or distribution, and the impairment of some functions of the central nervous system.
[Sideman S, Manor D; Nephron 31: 1-10 (1982)]**PEER REVIEWED**

On occasion workers chronically exposed to aluminum-containing dusts or fumes have developed severe pulmonary reactions including fibrosis, emphysema and pneumothorax. A much rarer encephalopathy has also been described. The factors which predispose to lung damage are not well characterized. ... /Aluminum (dust or fumes)/
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-128]**PEER REVIEWED**

Fluorosis. Inhalation of fluoride poses a potential hazard in workers in primary aluminium production, but the majority of workers are clinically unaffected. Clinical fluorosis, which is rare, commences with stiffness in the lower back followed by pain and then limitation of rotation of the trunk. Later, the spine becomes rigid and stiff, with restriction of chest movement and of the large joints, particularly the hip, that is accompanied by osteosclerosis. /Aluminum fluorides/
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. 34(53) 1984]**PEER REVIEWED**

May cause minor irritation to lungs & eyes.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997. ,p. 49-17]**QC REVIEWED**

The high levels of aluminum found in the brain tissue of uremic patients who died are thought to be the cause of dialysis encephalopathy. Aluminum in the water supply and in phosphate binding gels is the likely source. Aluminum toxicity also is manifested by abnormal accumulation in bone. Osteomalacia is rare when aluminum-free dialysate is used and oral aluminum ingestion is minimized.
[American Medical Association, Department of Drugs. Drug Evaluations. 6th ed. Chicago, Ill: American Medical Association, 1986. 890]**PEER REVIEWED**

Certain dusts produce primarily interstitial fibrotic disease (eg, acute berylliosis, aluminosis, asbestosis) rather than the focal nodular lesions seen in simple pneumoconiosis. Fibrotic lesions appear out of proportion to the presence of dust-laden macrophages. /Aluminum dust/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 861]**PEER REVIEWED**

The metal itself is a health risk when it occurs as a fine powder, usually called stamped aluminum powder. Exposure to such aluminum powder at high concentrations may give rise to fibrosis of the lung, that is, aluminosis.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 1]**PEER REVIEWED**

Use of aluminum saucepans, aluminum-lined cooking utensils and containers may increase the content of aluminum in food. This is particularly true when acidic foodstuffs are stored in aluminum utensils. Rhubarb cooked in an aluminum saucepan contained 25 mg per normal portion compared to 0.1 mg aluminum per portion in rhubarb cooked in a stainless steel saucepan. Normally, the addition of aluminum to the diet from cooking utensils is minimal and has been assumed to have no toxicological significance. Taking antacids which contain aluminum increases daily intake by 0.2-3 g, ie, approximately 100 times the normal intake from food-stuffs. Daily doses of several grams of aluminum are not unusual in individuals using antacids.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 6]**PEER REVIEWED**

Hazardous exposures are confined to the production of aluminum and the making of aluminum abrasives; dusts and fumes in the reduction plants consist of alumina dust and fume, cryolite, ... the fluorides of aluminum, coal tar pitch volatiles consisting of 14 identified polycyclic aromatic hydrocarbons, carbon monoxide, and sulfur dioxide. ... The production of aluminum abrasives, however, in which bauxite, iron, coke, and silica are fused at 2000 deg C, poses the threat of Shaver's disease, an often fatal and rapidly progressive interstitial fibrosis of the lung, unless exposures are properly controlled. Present-day control measures have almost removed the threat. /Aluminum fluorides/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1494]**PEER REVIEWED**

Fumes from an aluminum soldering flux have been reported to result in a delayed type of asthma resembling pollen-sensitivity asthma, rather than the infiltrative type seen in farmer's lung. Delayed and prolonged bronchoconstriction was investigated by serial spirometry, peak flow rates, and body plethysmography after the inhalation of small amounts of flux fumes. Because similar responses were obtained after inhalation of (aminoethyl) ethanolamine, one of the major flux constituents, it was presumed to be the active allergic agent. If the inert-gas, tungsten-ore process is used in aluminum welding the asthma problem is eliminated, but this process can lead to upper respiratory symptoms (chest tightness and wheezing from edema) unless ozone exposures are kept below 0.2 ppm.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1499]**PEER REVIEWED**

Recently reported adverse effects of aluminum in humans have resulted from inhalation or ingestion of aluminum in concentrations many times greater than the amounts present in normal circumstances. Following large oral doses of aluminum, toxic syndromes involve gastrointestinal tract irritation and eventually, interference with phosphate absorption, which results in rickets. Industrial exposure to high concentrations of aluminum-containing airborne dusts has resulted in a number of cases of occupational pneumoconiosis. Most of these exposures were chronic, and other substances were involved in nearly all instances. For example, an asthma-like disease has been reported in workers engaged in the production of aluminum from its oxide. This condition may result from the hydrogen fluoride that evolves from the use of fluorine-bearing materials in the production of metallic aluminum. Silicosis, aluminosis, aluminum lung, and bauxite pneumoconiosis are the result of pulmonary fibrotic reactions to silical and aluminum-containing compounds, which have been observed in the lung tissue in humans. Pardoxically, aluminum powder has been used in the prevention and therapy of silicosis. The rationale is that small amounts of metallic aluminum inhibit the solubility of siliceous materials in the lungs or diminish their fibrogenic properties. There is no unequivocable evidence that the procedure is clinically effective.
[National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981. 159]**PEER REVIEWED**

Variable degrees of bony fluorosis have been seen. The first stage of this condition consists simply of an increase in bone density, particularly marked in the vertebral bodies and pelvis.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 133]**PEER REVIEWED**

A report from Italy indicated that aluminum production workers may also suffer from pneumoconiosis. Chest X-ray examination of 119 potroom workers and a similarly sized control group revealed tht the exposed group included significantly more cases of suspected and definite pneumoconiosis (30%) than the control group (15%). Small inorganic fibrous particles have been discovered in the potrooms of the Norwegian aluminum industry. The health significance of this finding is as yet unknown.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 14]**PEER REVIEWED**

Asthma, chronic pulmonary disease and skin lesions occur in potroom workers. Fluorosis has occurred in workers in the aluminum production industry.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. 34(58)1984]**PEER REVIEWED**

The available epidemiological studies provide limited evidence that ... exposures ... are carcinogenic to humans, giving rise to cancer of the lung and bladder. A possible causative agent is pitch fume. There is inadequate evidence that occupational exposures in the aluminum production industry result in haematolymphopoietic and pancreatic cancer. There is sufficient evidence that samples of particulate polynuclear organic matter from one aluminum production plant were carcinogenic to experimental animals. However, because of the incomplete characterization of the samples tested, no evaluation of the carcinogenicity to experimental animals of complex mixtures that occur in the aluminum production industry could be made. A number of individual polynuclear aromatic compounds for which there is sufficient evidence of carcinogenicity in experimental animals have been measured at high levels in air samples taken from certain areas in aluminium production plants. Taken together, the available evidence indicates that certain exposures in the aluminum production industry are probably carcinogenic to humans.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. 34 V59 (1984)]**PEER REVIEWED**

In chronic renal failure, aluminum overload may influence parathyroid function. In a study of possible aluminum-induced parathyroid abnormalities, parathyroid glands from nine parathyroidectomized patients on hemodialysis were examined by light and electron microscopy and by X-ray microanalysis. Aluminum overload was assessed by the presence of stainable aluminum (aluminum surface, 233% + or - 11% of total surface) in bone biopsy specimens. The mean plasma aluminum concentration was 7.7 + or - 1.9 umol/l. All patients but one had elevated plasma concentrations of immunoreactive parathyroid hormone as well as osteitis fibrosa. The aluminum concentrations in bone and parathyroid gland from these patients were significantly higher than those in tissue from patients on hemodialysis without stainable bone aluminum. Abundant aluminum deposits were present in parathyroid chief cell cytoplasm in lipoid bodies, lipofuscin granules, and mitochondria. These cells exhibited features of active hormonal synthesis and contained numerous secretory granules. The data show that in the parathyroid glands of these aluminum-intoxicated patients the presence of aluminum deposits neither induced cellular damage or cheif cell necrosis nor interfered with the production of parathyroid hormone.
[Cournot-Witmer G, Plachot J-J; Ultrastruct Pathol 14 (3): 211-220 (1990)]**PEER REVIEWED**

... Serum aluminum concentrations /were measured/ in 104 hemodialysis patients from 3 centers in Hong Kong. It was found that the 52 patients dialyzed in unit A had much higher mean aluminum levels (100 ug/l) than those from the other two units (61 and 39 ug/l respectively). In unit A, where water treatment by reverse osmosis had been introduced only recently, 30.8% of patients had fractures/Looser zones, 46.2% had rugger-jersey spine and 28.8% had skeletal erosions. When these patients were divided into two groups according to whether their serum aluminum concentration was below or above 100 ug/l, the latter patients had significantly lower alkaline phosphatase, serum phosphate, and higher total prescribed dose of aluminum hydroxide. It was concluded that both dialysate aluminum and oral aluminum intake seemed to have contributed to the high incidence of osteomalacic fractures among Unit A patients. In eight of these patients serum aluminum increased by more than 150 ug/l after four weeks of receiving 1.5 g desferrioxamine twice weekly. Serial X-rays showed that the mean time after dialysis for the appearance of fractures/Looser zones was 72 months. Three patients developed fractures/Looser zones after successful renal transplantation; and it was postulated that the prompt excretion of aluminum permitted increased osteoclastic activity, resulting in fractures in these patients.
[Chan MK et al; Int J Artif Organs 13 (3): 162-8 (1990)]**PEER REVIEWED**

Application ofmolecular biological techniques and sensitive elemental analysis have produced new evidence implicating aluminum as an important factor in down regulation of neuronal protein metabolism. Aluminum in Alzheimer's disease may act by electrostatically crosslinking proteins, particularly the methionine containing histone H1 degree, and DNA. The consequence of such crosslinking is reduced transcription of at least one neuron specific gene, the low molecular weight component of neurofilaments. In the superior temporal gyrus in Alzheimer's disease down regulation of this gene occurs in approximately 86% of surviving neurons and, therefore, aluminum must be considered as having active role in the pathogenesis. Epidemiological studies are reviewed that independently support the hypothesis that environmental aluminum is a significant risk factor. Preliminary evidence also suggests that a disorder in phosphorylation may be an important initiating factor. /Aluminum/
[McLachlan DR et al; Can J Neurol Sci 16 (4 Suppl): 490-7 (1989)]**PEER REVIEWED**

Bone abnormalities may complicate parenteral nutrition therapy given to patients. Bone disease, manifested by reduced bone formation and demineralization in adults, and poor mineralization in infants, is associated with bone aluminum accumulation at the mineralizing surface. Aluminum was first shown to contaminate casein hydrolysate, the parenteral nutrition protein source. Substitution of amino acid solutions, low in aluminum, reduced bone aluminum and improved bone formation in adults. Alumium also accumulates ten-fold in the bones of premature infants receiving chronic parenteral nutrition. Present sources of in paranteral nutrition are calcium and phosphate salts, albumin, and heparin. Although increased bone aluminum in infants is not proven to cause disease, use of deferoxamine in one infant produced hypocalcemia. This suggested that chelation of bone aluminum by deferoxamine increased bone calcium uptake. Thus aluminum in bone may impair bone calcium uptake and may contribute to the pathogenesis of parenteral nutrition related bone disease in infants. Another complication of parenteral nutrition therapy in infants is cholestatic liver disease, manifested by reduced bile flow, and, occasionally, gallstones. Aluminum has been found to accumulate in the livers of these infants, and there is experimental evidence that aluminum can reduce bile flow both in rats and in piglets. Aluminum contamination of parenteral nutrition solutions puts infants at increased risk for complications of parenteral nutrition therapy; amounts of aluminum in parenteral nutrition solutions should therefore be minimized.
[Klein GL; J Parenter Sci Technol 43 (3): 120-4 (1989)]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

May cause minor irritation to lungs & eyes.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997. ,p. 49-17]**QC REVIEWED**

Drug Warnings:

The most frequent adverse effect of aluminum antacids is constipation. Decreased bowel motility, dehydration, or fluid restriction may predispose patients to intestinal obstruction. Hemorrhoids and fissures, or fecal impaction may occur. In patients with chronic renal failure, hyperaluminemia may occur and aluminum may accumulate in bones, lungs, and nerve tissue. Aluminum accumulation in the CNS may be the cause of dialysis dementia which sometimes occurs in chronic renal failure patients receiving long-term aluminum antacid therapy for hyperphosphatemia. Aluminum intoxication with severe osteomalacia and extensive aluminum deposition at the junction between calcified and noncalcified bone has been reported in several young children who were receiving large dosages of aluminum hydroxide for the management of hyperphosphatemia associated with azotemia; the children were not undergoing hemodialysis during aluminum hydroxide therapy. /Aluminum/
[McEvoy, G.K. (ed.). AHFS Drug Information 90. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1990 (Plus Supplements 1990). 1619]**PEER REVIEWED**

Aluminum salts may cause phosphorus depletion which is generally negligible. However, with prolonged administration or large doses, hypophosphatemia may occur, especially in patients with inadequate dietary intake of phosphorus; hypercalciuria secondary to bone resorption and increased intestinal absorption of calcium results. This phosphorus depletion syndrome is characterized by anorexia, malaise, and muscle weakness, and prolonged aluminum antacid therapy may cause urinary calculi, osteomalacia, and osteoporosis. A low-phosphorus diet, diarrhea, excessive phosphorus losses from malabsorption, and restoration of renal function after a kidney transplant increase the likelihood of the syndrome. Serum phosphate concentrations should be monitored at monthly or bimonthly intervals in patients on maintenance hemodialysis who are receiving chronic aluminum antacid therapy. /Aluminum salts/
[McEvoy, G.K. (ed.). AHFS Drug Information 90. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1990 (Plus Supplements 1990). 1620]**PEER REVIEWED**

Aluminum cmpd /in antacids/ cause constipation. /Aluminum cmpd/
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 981]**PEER REVIEWED**

Medical Surveillance:

Employment and periodic physical examinations should give special consideration to the skin, eyes and lungs. Lung function should be followed.
[ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1982. 62]**PEER REVIEWED**

Probable Routes of Human Exposure:

INTAKE OF ALUMINUM IS CHIEFLY BY MOUTH, FROM FOODS AND BEVERAGES, ALSO BY LUNGS, FROM THE ATMOSPHERIC DUST CONTENT. IT IS PRESENT IN NATURAL DIET, IN AMT VARYING FROM VERY LOW IN ANIMAL PRODUCTS TO RELATIVELY HIGH IN PLANTS.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 5]**PEER REVIEWED**

/INHALATION OF/ COARSER VARIETY OF ALUMINUM DUST PRODUCED FROM MOLTEN METAL ... . /ALUMINUM DUST/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1497]**PEER REVIEWED**

WORKERS EXPOSED TO ... DUST OF ALUMINUM METAL IN PRODUCTION OF EXPLOSIVES & FIREWORKS. /ALUMINUM METAL/
[Friberg, L., G.R. Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. New York: Elsevier North Holland, 1979. 280]**PEER REVIEWED**

In workers in bauxite mines, foundries, and factories. In more than 1000 exposed workers given X-ray examinations of the chest, pulmonary changes were found in 3.5 percent of those exposed to bauxite dust, & in 4.9 percent exposed to cryolite dust in foundries and in factory workers exposed to alumina. /Alumina/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1499]**PEER REVIEWED**

Chronic fluorosis generally develops after prolonged (10-20 years) exposure to industrial dusts, insecticides, or water where fluorides exceed 3 to 4 ppm. This is especially true in workers involved in the production of aluminum, steel, or glass.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 533]**PEER REVIEWED**

In children living in the vicinity of poorly controlled aluminum smelters, variable degrees of mottling of permanent teeth have been reported if exposure occurred during the developmental phase of permanent teeth growth.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 133]**PEER REVIEWED**

Electrolytic production of aluminum can lead to a substantial exposure to fluorides and carcinogenic tar oils, including polyaromatic hydrocarbons.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 1]**PEER REVIEWED**

Primary aluminum production plants are located in about 40 countries. The two main methods used for aluminum production are Soderberg and prebake, which encompass a number of processes and job categories. Substantial exposures to airborne polynuclear aromatic compounds have been measured in certain occupational settings in this industry. Exposures have been higher in potrooms of plants using the Soderberg process than in those using the prebake process; some workers may have exposed to both process. Exposures to fluorides and a variety of other contaminants also occur in potrooms.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. 34(57)1984]**PEER REVIEWED**

In aluminum reduction plants ... from exposure to coal tar pitch volatiles and their associated polycyclic aromatic hydrocarbons ... Among coke oven workers, implicating coal tar pitch volatiles, a mutual exposure in aluminum reduction plants ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1500]**PEER REVIEWED**

Body Burden:

Aluminum content of normal human brain ranged from 0.1-3.9 ug/g dry weight. In a study of 208 samples taken from 7 patients, ... a mean aluminum content of 1.9 + or - 0.07 ug/g dry weight of gray matter /was found/ to be abnormal. In a study of 585 areas sampled from the brain tissue of 10 patients with Alzheimer's disease they found 28% had an aluminum concn > 4 ug/g. The range of the 585 samples was 0.4-107 ug/g.
[Crapper DR et al; Brain 99: 67 (1976)]**PEER REVIEWED**

Average Daily Intake:

The daily ingestion of aluminum by humans was estimated to be 30-50 mg.
[Bjorksten JA; Comp Therapy 8: 73-6 (1982)]**PEER REVIEWED**

Antidote and Emergency Treatment:

DIAGNOSIS: WHEN HISTORY IS UNATTAINABLE, DIAGNOSIS DEPENDS ON THE DEMONSTRATION OF LARGE AMT OF ALUMINUM IN VOMITUS, STOMACH CONTENTS OR FECES.
[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 169]**PEER REVIEWED**

Deferoxamine has been used to treat dialysis encephalopathy and osteomalacia with symptomatic relief reported. The use of deferoxamine for aluminum-toxic dialysis patients has been suggested for serum levels of aluminum between 100 and 200 ug/ml. Deferoxamine also has been used to diagnose aluminum-related osteodystrophy. After a deferoxamine infusion of 40 mg/kg over 2 hr, an increment in plasma aluminum concentration of 200 ug/l identified 35 of 37 patients with biopsy-proven aluminum-related osteodystrophy (sensitivity, 94%; specificity, 50%). Calcium disodium ethylenediaminetetraacetic acid does not appear as effective as deferoxamine in chelating aluminum. Especially in dialysis patients, aluminum-containing medications should be reduced.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1011]**PEER REVIEWED**

Animal Toxicity Studies:

Toxicity Summary:

IDENTIFICATION: Aluminum is a silvery-white, ductile and malleable metal. It is released to the environment both by natural processes and from anthropogenic sources. It is highly concentrated in soil-derived dusts from such activities as mining and agriculture, and in particulate matter from coal combustion. Aluminum occurs ubiquitously in the environment in the form of silicates, oxides and hydroxides, combined with other elements such as sodium and fluorine and as complexes with organic matter. It is not found as a free metal because of its reactivity. Aluminum metal has a wide variety of uses, including structural materials in construction, automobiles and aircraft, and the production of metal alloys. Aluminum compounds and materials also have a wide variety of uses, including production of glass, ceramics, rubber, wood preservatives, pharmaceuticals and waterproofing textiles. Natural aluminum minerals, especially bentonite and zeolite, are used in water purification, sugar refining, brewing and paper industries. HUMAN EXPOSURE: Non-occupational human exposure to aluminum in the environment is primarily through ingestion of food and water. No acute pathogenic effects in the general population have been described after exposure to aluminum. Although it has been hypothesized that aluminum is a risk factor for Alzheimer's disease, present epidemiological evidence does not support a causal association between Alzheimer's disease and aluminum in drinking-water. Neurological syndromes including impairment of cognitive function, motor dysfunction and peripheral neuropathy have been reported in limited studies of workers exposed to aluminum fume. Iatrogenic exposure in patients with chronic renal failure, exposed to aluminum-containing dialysis fluids and pharmaceutical products, may cause encephalopathy, vitamin-D-resistant osteomalacia and microcytic anemia. Premature infants may develop increased tissue loading of aluminum, particularly in bone, when exposed to iatrogenic sources of aluminum. Although human exposure to aluminum is widespread, in only a few cases has hypersensitivity been reported following exposure to some aluminum compounds after dermal application or parenteral administration. There is insufficient information to allow for classification of the cancer risk from human exposures to aluminum and its compounds. Aluminum and its compounds appear to be poorly absorbed in humans. The mechanism of gastrointestinal absorption of aluminum has not yet been fully elucidated. The highest levels of aluminum may be found in the lungs, where it may be present as inhaled insoluble particles. The urine is the most important route of aluminum excretion. ANIMAL STUDIES: The acute toxicity of metallic aluminum and aluminum compounds is low. In short-term studies using rats, mice or dogs to various aluminum compounds in the diet or drinking-water, only minimal effects were observed at the highest administered doses. Adequate inhalation studies were not identified. Following intratracheal administration of aluminum oxide, particle-associated fibrosis was observed. No overt fetotoxicity was noted, nore were general reproductive parameters noted after gavage treatment of rats. There is no indication that aluminum is carcinogenic. It can form complexes with DNA and cross-link chromosomal proteins and DNA, but it has not been shown to be mutagenic in bacteria or induce mutation or transformation in mammalian cells in vitro. Chromosomal aberrations have been observed in bone marrow cells of exposed mice and rats. There is considerable evidence that aluminum is neurotoxic in experimental animals, although there is considerable variation among species. In susceptible species, toxicity following parenteral administration is characterized by progressive neurological impairment, resulting in death with status epilepticus. Osteomalacia, as it presents in man, is observed consistently in larger species (e.g. dogs and pigs) exposed to aluminum; a similar condition is observed in rodents. Absorption via the gastrointestinal tract is usually less than one percent. Aluminum is distributed in most organs within the body with accumulation occurring mainly in bone at high dose levels. To a limited extent, aluminum passes the blood-brain barrier and is also distributed to the fetus. Aluminum is eliminated effectively by urine.
[World Health Organization/International Programme on Chemical Safety. Environmental Health Criteria 194. Aluminium. pp. 1-13 (1997)]**PEER REVIEWED**

Non-Human Toxicity Excerpts:

... INHALATION OR INTRATRACHEAL INJECTION ... OF ALUMINUM DUST CAUSED RESPIRATORY INFECTIONS ... (RATS AND RABBITS) /SHOWED/ WIDESPREAD INTERSTITIAL FIBROSIS, WITH HYALINOSIS, EMPHYSEMA AND HEMORRHAGES ... FROM WHICH OFTEN ARISE BULLOUS EMPHYSEMA, BRONCHOPNEUMONIA & HEMORRHAGIC PNEUMONIA. THESE CHANGES WERE NOT LIMITED TO THE PULMONARY PARENCHYMA BUT WERE PRESENT TO SOME DEGREE IN THE WALLS OF THE BLOOD VESSELS AND IN THE KIDNEYS, AND SOME FIBROUS THICKENING OF INTERSTITIAL TISSUE IN THE SPLEEN, LIVER AND MENINGES. /ALUMINUM DUST/
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 8]**PEER REVIEWED**

IN ANIMALS ... INGESTION OF ALUMINUM IN DIET IN /PROPORTION/ OF ... ABOUT 1400 PPM LOWERED LEVEL OF INORG PHOSPHORUS IN BLOOD AND BONES ... CHICKENS DEVELOPED SEVERE RICKETS.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 6]**PEER REVIEWED**

ALUMINUM FILINGS & SPLINTERS EMBEDDED INTO THE SKIN DO NOT INDUCE A HYPERSENSITIVE STATE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1499]**PEER REVIEWED**

... IT WAS CONCLUDED THAT "THERE WAS EXPERIMENTAL EVIDENCE THAT IN ANIMALS INHALATION OF ALUMINUM DUST AGGRAVATED PULMONARY TUBERCULOSIS."
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 10]**PEER REVIEWED**

VERY FINE ALUMINUM POWDERS ... WERE NOT FIBROGENIC IN RATS, GUINEA PIGS, & HAMSTERS WHEN INHALED; ALVEOLAR PROTEINOSIS WAS CONSISTENT FINDING, CONDITION NOT REPORTED IN FATAL CLINICAL CASES OF ALUMINOSIS. FOCAL PULMONARY FIBROSIS SEEN IN RATS ARISES FROM ARTIFACTUAL INTRATRACHEAL INJECTION OF ... 100 MG/RAT.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1499]**PEER REVIEWED**

SC IMPLANTED ... ALUMINUM FOIL INDUCED SARCOMAS IN 8 OUT OF 18 RATS; PARTICULATE SMOOTH SURFACE APPEARED TO CONTRIBUTE TO THE CARCINOGENIC ACTIVITY. FOLLOWING INHALATION, DUST OF ALUMINUM ... IN RATS, INITIAL REPONSE TO ... DEPOSIT WAS PROLIFERATION OF MACROPHAGES WITHIN ALVEOLAR SPACES, RESULTING IN LIPOID PNEUMONIA; PROLONGED EXPOSURE CAUSED FOCAL DEPOSITS OF HYALINE MATERIAL IN ALVEOLAR WALLS.
[Venugopal, B. and T.D. Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978. 111]**PEER REVIEWED**

In a 16 wk greenhouse study, forest soil samples representing three soil series were used as growth media: Captina (Fragiudult, MO), Lexington (Paleudalf, MS) and Becket (Fragiorthod, NY). Soil from two horizons from each series was separately amended in 4 treatments for a wide range of soil aluminum availability: control, limed calcium hydroxide, acidified (hydrogen chloride), acidified with supplemental calcium added (+ hydrogen chloride and calcium sulfate. . Treatments significantly (p< 0.05) altered soil pH (range 3.65 to 5.48), base saturation, and 0.01 M strontium chloride-extractable aluminum (range 0.6-37.2 mg/kg). Fifteen dormant, 1 yr old, bare-root northern red oak (Quercus rubra) seedlings were distributed to each soil horizon-treatment cell (6 horizons by 4 treatments by 15 seedlings = 360 seedlings); one seedling from each of 15 size classes was assigned to each cell. Compared to controls, both acidification treatments resulted in significant reductions in fine root and foliar biomass production and in fine root branching in all horizons, except the highly organic Bhs of the Fragiorthod. In the remaining five horizons, fine root branching and biomass production were highly and negatively correlated (R squared= 0.70 and 0.50, respectively) with 0.01 M strontium chloride-extractable aluminum. Although fine root tissue concn of aluminum correlated highly with 0.01 M strontium chloride -extractable aluminum levels, root tissue aluminum predicted root branching and biomass only moderately well (R squared= 0.30 and 0.21, respectively). Fine root branching was more sensitive to treatment effects than either root biomass production or root elongation.
[Joslin JD, Wolfe MH; Soil Sci Soc Am J 53 (1): 274-81 (1989)]**PEER REVIEWED**

The effect of aluminum (3+) on superoxide dismutase in vitro was studied, since in uremia there is excessive superoxide production and frequently an elevated serum A1(3+) level. Thus, the protective role of superoxide dismutase is particularly important. Al(+3) in concentrations similar to those found in the serum of uremic patients inhibits superoxide dismutase activity. The degree of inhibition is directly proportionl to the Al(3+) level. The combination of excessive oxygen free radical production with an increased Al(3+) level may contribute to a variety of complications, including aluminum dementia or initiation and promotion of carcinogenic process, which are known to be more common in uremic patients.
[Shainkin-Kestenbaum R et al; Clin Sci (Lond) 77 (5): 463-6 (1989)]**PEER REVIEWED**

Animal studies show that aluminum particles, in particular stamped aluminum powder, may cause fibrosis of the lung whereas particles of aluminum compounds appear to be less reactive. /Aluminum powder/
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 12]**PEER REVIEWED**

Severe aluminum intoxication following parenteral or oral administration of aluminum hydroxide, chloride, or sulfate to rats is characterized by lethargy, anorexia, or death. Other /studies/ ... have found that intratracheal instillation of aluminum salts or metallic aluminum powder has produced pulmonary fibroses. Injected intraperitoneally, aluminum compounds produce fibrotic peritonitis. /Aluminum cmpd/
[National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981. 163]**PEER REVIEWED**

Aluminum salts are much more toxic intravenously than by mouth to animals. The mechanism of this presumable systemic effect of aluminum is not known. /Aluminum salts/
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-128]**PEER REVIEWED**

Because aluminum is only sparingly absorbed from the gut, LD50 values for aluminum ingestion are unavailable, since death occurs from intestinal blockage due to precipitated aluminum species rather than systemic aluminum toxicity.
[Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988. 60]**PEER REVIEWED**

Chronic, oral administration of aluminum to rats increases the in vivo concentration of cyclic AMP and the phosphorylation of microtubule-associated protein-2 (MAP-2) and the 200 kd neurofilament subunit. In the present study, the effect of this treatment on endogenous protein phosphorylation in soluble and particulate fractions prepared from cerebral cortices was examined. Chronic aluminum treatment significantly elevated the basal and cyclic AMP-dependent phosphorylation of 11-12 endogenous proteins in the soluble fraction prepared from cerebral cortices. Endogenous protein phosphorylation in the soluble fraction occurring in the presence of calcium (+2) alone or calcium (+2) phorbol 12-myristate 13-acetate and phosphatidylserine was not significantly altered by aluminum treatment. In the particulate fraction the phosphorylatin of several proteins was significantly decreased by aluminum administration; however the phosphorylation of the majority of protein sustrates remained unaltered. Aluminum treatment did not alter the activities of cyclic AMP-dependent protein kinase or protein tyrosine kinase in the soluble and particulate fractions. The activity of calcium (+2) /phospholipid-dependent protein kinase (proteinkinase C) was increased in the particulate fraction of aluminum-fed rats. These results clearly demonstrate that specific effects on protein kinase activities results fromin vivo aluminum administration.
[Johnson GVW et al; Neuroiol Aging 11 (3): 209-16 (1990)]**PEER REVIEWED**

Aluminum compounds have been evaluated as non-mutagenic by most standard methods of mutagenic assays. /Aluminum cmpd/
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 20]**PEER REVIEWED**

Absorption, Distribution & Excretion:

It was calculated that a dialysate aluminum concn of 0.2-1.0 mg/l (a concn readily found in many water supplies) would result in the direct transfer of aluminum into the blood of 3-16 mg for each dialysis treatment or 42-211 mg/mo.
[Rosas VV et al; Arch Intern Med 138: 1375 (1978)]**PEER REVIEWED**

A given oral dose of aluminum results in significantly higher serum and tissue levels of the metal in nephrectomized rats than in intact controls in spite of the fact that only minimal amounts of aluminum are normally excreted in the urine.
[Berlyne GM et al; Lancet 1: 564 (1972)]**PEER REVIEWED**

It was found that 70-90% of total aluminum bound to plasma proteins (60-70% to a high molecular weight protein and 10-20% to albumin while only 10-30% was unbound). This high affinity of aluminum for plasma proteins strongly suggests high levels of binding of aluminum to a variety of tissue proteins.
[Elliott HL et al; Lancet 2: 1255 (1978)]**PEER REVIEWED**

It was shown that the uptake of aluminum into the blood during renal dialysis was due to the extensive binding of aluminum to plasma proteins leaving very little aluminum in the non-bound state in plasma. Thus, the plasma proteins served as a trap for accumulating the metal. It was shown that the component of plasma protein that binds aluminum is saturable. Consistent with this ... is the fact that, during dialysis with aluminum-containing dialysate, plasma aluminum levels reach a plateau.
[Kaehny WD et al; Kidney Int 12: 361-5 (1977)]**PEER REVIEWED**

Renal clearance of aluminum has been shown to be approximately 5-10% of that of urea or creatinine clearance. This is entirely consistent with the marked protein binding of aluminum in plasma, thus leaving only a small fraction of the total aluminum available for filtration in the kidney.
[Berlyn GM et al; Lancet 2: 494-6 (1970)]**PEER REVIEWED**

That the kidney is responsible for the elimination of a major portion of absorbed aluminum is reflected in the fact that, in dogs undergoing renal dialysis ligation of the ureter (resulting in cessation of urinary output) causes a greater increase in plasma aluminum concn than in intact dogs undergoing comparable dialysis.
[Kovalchik MT et al; J Lab Clin Med 92: 712 (1978)]**PEER REVIEWED**

The 200-300 mg of aluminum/kg tissue weight is most likely due to local deposition of particulate aluminum from the air following inhalation and not due to a specific predilection of lung tissue for aluminum. Aluminum has been reported in both non-urban and urban air with the latter containing as much as 10 ug/cu m.
[Norseth T; Aluminum in Handbook on the Toxicology of Metals Chapter 15 (1979)]**PEER REVIEWED**

The aluminum content of gray matter of brain (essentially the inner cellular mass of the brain) was not significantly different than that in the white matter (the outer myelinated fibers of the brain).
[Alfry AC et al; NEJM 294: 184 (1976)]**PEER REVIEWED**

SINCE LITTLE ALUMINUM IS ABSORBED, IT IS EXCRETED IN THE FECES, MUCH OF IT IN THE FORM OF ALUMINUM PHOSPHATE. THERE IS NO INCR IN THE AMT OF ALUMINUM IN TISSUES, EXCEPT IN BONE (ANIMAL EXPERIMENTS).
[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 169]**PEER REVIEWED**

AMT OF ALUMINUM IN TISSUES, ORGANS, BLOOD & URINE IS SMALL. ADULT HUMAN BODY MAY CONTAIN 50-150 MG ... AFTER INGESTION OF LARGE AMT VERY LITTLE APPEARS IN URINE ... BETWEEN 50 & 100 MG DAILY FOR ABOUT 70 DAYS.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 5]**PEER REVIEWED**

Cations that form insoluble phosphates interfere with the absorption of phosphorus. For example, high intakes of aluminum decrease absorption of phosphorus (as phosphate) by forming insoluble aluminum phosphate and increasing the excretory loss of phosphorus.
[National Research Council. Drinking Water and Health. Volume 3. Washington, DC: National Academy Press, 1980. 278]**PEER REVIEWED**

Absorption of inhaled aluminum compounds has not been studied in detail; one reason for this is probably the fact that no stable radioactive isotope of aluminum is available. Workers exposed to aluminum in connection with the production of raw aluminum, aluminum sulfate, corundum or welding of aluminum have elevated levels of aluminum in urine. This is evidence of pulmonary absorption. ... Measured the total urinary elimination of aluminum in three volunteers exposed to respirable aluminum fume from welding. The urinary excretion was 0.1-0.3% of the estimated inhaled amount. In experimental animals exposed to aluminum oxide as well as in humans occupationally exposed to aluminum particles, inhaled or deposited particles of aluminum may be retained in the lungs over long periods of time. /Aluminum cmpd/
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 7]**PEER REVIEWED**

Studies ... strongly suggest that aluminum in the gastrointestinal tract and its subsequent distribution in tissue can be influenced by increasing the concentration of parathyroid hormone. They fed male rats aluminum as 0.1% of their diet for 25 days. The ready absorption of aluminum from the gastrointestinal tract of these normal rats was enhanced by injections of parathyroid hormone (17 U twice weekly). There was also increased deposition of the metal in the kidney, muscle, bone, and the gray matter of the brain, but not in the liver or in the white matter of the brain. Thus, the parathyroid hormone exerted a specific effect on the absorption and distribution of aluminum. In 1977, ... a positive correlation between increased serum parathyroid hormone and serum aluminum levels in dialysis patients ... had been reported.
[National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981. 157]**PEER REVIEWED**

Trace determination of aluminum was carried out in blood samples from 11 patients with chronic renal failure undergoing periodical hemodialysis treatment. Analysis for aluminum was made by graphite furnace atomic absorption spectrometry in samples taken at the beginning and end of dialysis, and of dialysate from the inflow (pre) and outflow (post) lines of dialyzers. Healthy individuals, without history of renal disease, were used as controls. The aluminum concn in pre- and post-dialysis whole blood was 58 + or - 9 ug/l and 139 + or - 19 ug/l, respectively. The aluminum concn in pre- and post-dialysate was 235 + or - 39 ug/l and 129 + or - 10 ug/l, respectively. Blood aluminum concn of control subjects did not show significant differences when compared with data reported by other authors. Aluminum was transferred to the patients' blood during the dialysis treatments, because of the high metal content in the tap water used to prepare the dialysates. /Aluminum/
[Navarro JA et al; Trace Elem Med 6 (2): 70-4 (1989)]**PEER REVIEWED**

ALUMINUM IN LUNGS IS PROBABLY RESULT OF LOCAL DEPOSITION FROM INHALED AIR.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 8]**PEER REVIEWED**

ALUMINUM SALTS ARE ABSORBED IN ... SMALL AMT FROM THE DIGESTIVE TRACT. /ALUMINUM SALTS/
[Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 169]**PEER REVIEWED**

In dogs undergoing renal dialysis ligation of the ureter (resulting in cessation of urinary output), there is a greater increase in plasma aluminum concn than in intact dogs undergoing comparable dialysis. This indicates that the kidney is responsible for the elimination of a major portion of absorbed aluminum. /Aluminum/
[Kovalchik MT et al; J Lab Clin Med 92: 712 (1978)]**PEER REVIEWED**

Biological Half-Life:

The mean plasma half-life of aluminum after iv admin in dogs is approx 4.5 hr.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 1009]**PEER REVIEWED**

The shorter half-life for the urinary elimination of aluminum was about 8 hr.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 10]**PEER REVIEWED**

Mechanism of Action:

Excessive dietary aluminum has been proposed to be a factor contributing to several neurological disorders in humans. Six 8-week-old female Swiss Webster mice were fed for 10 wk purified diets containing 100 (control), 500 or 1000 ug aluminum/g diet. Brain and liver lipid peroxidation was determined by evaluating the production of 2-thiobarbituric acid reactive substances in brain and liver homogenates in the presence or absence of 50 uM ferrous iron. 2-Thiobarbituric acid reactive substances production in the absence of iron in brain homogenates from mice fed the 1000 ug/g diet was higher (30%) than that in the 100 ug/g control group (3.1 vs 2.4 nmol 2-thiobarbituric acid reactive substances/mg protein). The addition of ferrous iron increased 2-thiobarbituric acid reactive substances production in brain homogenates from all 3 dietary groups. The iron induced 2-thiobarbituric acid reactive substances production was 26% higher in the 1000 ug/g brain homogenates than in the 100 ug/g group (4.9 vs 3.9 nmol 2-thiobarbituric acid reactive subtances/mg protein). Brain 2-thiobarbituric acid reactive substances production in the presence and absence of iron was similar between the 100 and 500 ug/g aluminum groups. 2-Thiobarbituric acid reactive substances production in liver homogenates measured either with or without iron was similar for the 3 groups. These results show that, in mice, dietary aluminum intoxication leads to increased brain 2-thiobarbituric acid reactive substance production, suggesting that enhanced lipid peroxidation may be one possible mechnism underlying the neurological damage associated with increased tissue aluminum.
[Fraga CG et al; Toxicol Lett 51 (2): 213-9 (1990)]**PEER REVIEWED**

Interactions:

Groups of 120 Atlantic salmon fry (Salmo salar, 1 g mass) were kept in through-flow tanks of water (pH 5) containing various concn of aluminum and silicic acid. The aluminum concn in all but the control tank (0.85 umol aluminum/l) were 6-7 umol/l, at acutely toxic levels. Silicon levels were 0.66 umol/l (control), 93.06, 24.89, 5.46, and 0.60 umol/l, corresponding to silicon:aluminum ratios of 13.0, 3.7, 0.9, and 0.1. Exchangeable aluminum, ie, aluminum retained on Amberlite, was 6.00, 5.00, 4.11, and 1.52 umol/l in test tanks, respectively. Fish were exposed for 96 hr, and the proportion of dead fish was recorded at 12-hr intervals. The whole experiment was run three times; data are from all runs combined. At a silicon:aluminum ratio of 13, acute toxicity of aluminum was eliminated and gill structures of the fish were normal. Percent survival versus time was higher for the higher silicon:aluminum ratio groups. Accumulation of aluminum by fish fell sharply as the exchangeable aluminum increased. Aluminum and silicon levels in fish were 0.44 and 0.01 (control), 0.40 and 0.54 (silicon:aluminum ratio of 13), 2.04 and 0.35 (silicon:aluminum ratio of 3.7), 2.49 and 0.33 (silicon :aluminum ratio of 0.9), 2.38 and 0.08 (silicon:aluminum ratio of 0.1) umol per g dry mass, respectively.
[Birchall JD et al; Nature 338 (6211): 146-8 (1989)]**PEER REVIEWED**

To elucidate the interaction between aluminum and certain essential trace metals, an experiment was performed on rats fed diets with suboptimal or optimal levels of zinc or copper. Half of each group of animals were fed the same diet but with 1000 ppm aluminum added. Changes were noted after 120 days. Severe testicular damage was seen in rats fed either the low zinc or the low copper diet. The lesions included a wide range of spermatogenic cell degeneration and tubular atropy. When aluminum was added to the diet, the testicular destruction of zinc deficient rats was significantly reduced. This indicated that the presence of aluminum in the diet protected the testis against the damage caused by zinc deficiency. Pituitary glands were examined. Hypertrophy of basophils was more pronounced in rats fed the suboptimal zinc or copper diet. When aluminum was added to their diet, the changes were reversed. The mechanisms by which aluminum protects male gonadal functions against zinc deficiency are discussed. This study is the first to demonstrate the preventive effect of aluminum against testicular damage caused by zinc deficiency.
[Liu JY, Stemmer KL; Biomed Environ Sci 3 (1): 1-10 (1990)]**PEER REVIEWED**

Adult, male New Zealand rabbits (three per group) were administered drinking water containing aluminum chloride (0, 100, or 500 mg aluminum/liter) together with citrate (0.11 M) ascorbate (0.11 M), or no added ligand and libitum for 12 weeks. They were fed ad libitum regular rabbit chow analyzed to contain 297 mg aluminum/kg. Treatment had no effect upon food and water intake or weight gain during the experimental period. No effect of aluminum was observed on tissue levels of the essential metals zinc, copper, and iron, or on hemoglobin and hematocrit values. Aluminum levels were fund to increase in a dose-dependent manner in stomach and intestinal mucosa, kidney, bone, urine, and fece. There was only a slight accumulation in liver, and no accumulation in brain (cerebral cortex or hippocampus). Although plasma aluminum was directly related to aluminum intake, whole blood aluminum bore no relation to aluminum dose. Citrate had no efefct on aluminum accumulation in the stomach or intestine, but significantly enhanced plasma and bone aluminum levels. Ascorbate did not enhance aluminum accumulation in any tissue studied and even prevented accumulation in bone. Both citrate and ascorbate enhanced excretion of aluminum. Ascorbate therapy may be of potential clinical use to enhance aluminum excretion.
[Fulton B, Jeffery EH; Fundam Appl Toxicol 14 (4): 788-96 (1990)]**PEER REVIEWED**

Therapeutic Uses:

Medicinally, aluminum and its salts are used in antacids, antidiarrheals, and protective dermatological pastes. It is also found in cosmetics and deodorants. /Aluminum and its salts/
[National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981. 156]**PEER REVIEWED**

Aluminum foil has been used as a dressing for burns. /Aluminum/
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982. 926]**PEER REVIEWED**

Aluminum powder has been used for dusting the skin around an ileostomy, caecostomy, or colostomy to prevent irritation due to proteolytic or irritant discharges. The skin is dried and freed from grease and repeated applications of the powder made until a thick film adheres. Alternatively, Compound Aluminum Paste may be employed; the paste is applied thickly round the fistula or sinus in order to prevent the discharge from coming in contact with the skin. Aluminum powder has been used as a dressing for burns, /topical/ ulcers, and indolent wounds. /Aluminum powder/
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982. 926]**PEER REVIEWED**

Drug Warnings:

The most frequent adverse effect of aluminum antacids is constipation. Decreased bowel motility, dehydration, or fluid restriction may predispose patients to intestinal obstruction. Hemorrhoids and fissures, or fecal impaction may occur. In patients with chronic renal failure, hyperaluminemia may occur and aluminum may accumulate in bones, lungs, and nerve tissue. Aluminum accumulation in the CNS may be the cause of dialysis dementia which sometimes occurs in chronic renal failure patients receiving long-term aluminum antacid therapy for hyperphosphatemia. Aluminum intoxication with severe osteomalacia and extensive aluminum deposition at the junction between calcified and noncalcified bone has been reported in several young children who were receiving large dosages of aluminum hydroxide for the management of hyperphosphatemia associated with azotemia; the children were not undergoing hemodialysis during aluminum hydroxide therapy. /Aluminum/
[McEvoy, G.K. (ed.). AHFS Drug Information 90. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1990 (Plus Supplements 1990). 1619]**PEER REVIEWED**

Aluminum salts may cause phosphorus depletion which is generally negligible. However, with prolonged administration or large doses, hypophosphatemia may occur, especially in patients with inadequate dietary intake of phosphorus; hypercalciuria secondary to bone resorption and increased intestinal absorption of calcium results. This phosphorus depletion syndrome is characterized by anorexia, malaise, and muscle weakness, and prolonged aluminum antacid therapy may cause urinary calculi, osteomalacia, and osteoporosis. A low-phosphorus diet, diarrhea, excessive phosphorus losses from malabsorption, and restoration of renal function after a kidney transplant increase the likelihood of the syndrome. Serum phosphate concentrations should be monitored at monthly or bimonthly intervals in patients on maintenance hemodialysis who are receiving chronic aluminum antacid therapy. /Aluminum salts/
[McEvoy, G.K. (ed.). AHFS Drug Information 90. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1990 (Plus Supplements 1990). 1620]**PEER REVIEWED**

Aluminum cmpd /in antacids/ cause constipation. /Aluminum cmpd/
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 981]**PEER REVIEWED**

Interactions:

Groups of 120 Atlantic salmon fry (Salmo salar, 1 g mass) were kept in through-flow tanks of water (pH 5) containing various concn of aluminum and silicic acid. The aluminum concn in all but the control tank (0.85 umol aluminum/l) were 6-7 umol/l, at acutely toxic levels. Silicon levels were 0.66 umol/l (control), 93.06, 24.89, 5.46, and 0.60 umol/l, corresponding to silicon:aluminum ratios of 13.0, 3.7, 0.9, and 0.1. Exchangeable aluminum, ie, aluminum retained on Amberlite, was 6.00, 5.00, 4.11, and 1.52 umol/l in test tanks, respectively. Fish were exposed for 96 hr, and the proportion of dead fish was recorded at 12-hr intervals. The whole experiment was run three times; data are from all runs combined. At a silicon:aluminum ratio of 13, acute toxicity of aluminum was eliminated and gill structures of the fish were normal. Percent survival versus time was higher for the higher silicon:aluminum ratio groups. Accumulation of aluminum by fish fell sharply as the exchangeable aluminum increased. Aluminum and silicon levels in fish were 0.44 and 0.01 (control), 0.40 and 0.54 (silicon:aluminum ratio of 13), 2.04 and 0.35 (silicon:aluminum ratio of 3.7), 2.49 and 0.33 (silicon :aluminum ratio of 0.9), 2.38 and 0.08 (silicon:aluminum ratio of 0.1) umol per g dry mass, respectively.
[Birchall JD et al; Nature 338 (6211): 146-8 (1989)]**PEER REVIEWED**

To elucidate the interaction between aluminum and certain essential trace metals, an experiment was performed on rats fed diets with suboptimal or optimal levels of zinc or copper. Half of each group of animals were fed the same diet but with 1000 ppm aluminum added. Changes were noted after 120 days. Severe testicular damage was seen in rats fed either the low zinc or the low copper diet. The lesions included a wide range of spermatogenic cell degeneration and tubular atropy. When aluminum was added to the diet, the testicular destruction of zinc deficient rats was significantly reduced. This indicated that the presence of aluminum in the diet protected the testis against the damage caused by zinc deficiency. Pituitary glands were examined. Hypertrophy of basophils was more pronounced in rats fed the suboptimal zinc or copper diet. When aluminum was added to their diet, the changes were reversed. The mechanisms by which aluminum protects male gonadal functions against zinc deficiency are discussed. This study is the first to demonstrate the preventive effect of aluminum against testicular damage caused by zinc deficiency.
[Liu JY, Stemmer KL; Biomed Environ Sci 3 (1): 1-10 (1990)]**PEER REVIEWED**

Adult, male New Zealand rabbits (three per group) were administered drinking water containing aluminum chloride (0, 100, or 500 mg aluminum/liter) together with citrate (0.11 M) ascorbate (0.11 M), or no added ligand and libitum for 12 weeks. They were fed ad libitum regular rabbit chow analyzed to contain 297 mg aluminum/kg. Treatment had no effect upon food and water intake or weight gain during the experimental period. No effect of aluminum was observed on tissue levels of the essential metals zinc, copper, and iron, or on hemoglobin and hematocrit values. Aluminum levels were fund to increase in a dose-dependent manner in stomach and intestinal mucosa, kidney, bone, urine, and fece. There was only a slight accumulation in liver, and no accumulation in brain (cerebral cortex or hippocampus). Although plasma aluminum was directly related to aluminum intake, whole blood aluminum bore no relation to aluminum dose. Citrate had no efefct on aluminum accumulation in the stomach or intestine, but significantly enhanced plasma and bone aluminum levels. Ascorbate did not enhance aluminum accumulation in any tissue studied and even prevented accumulation in bone. Both citrate and ascorbate enhanced excretion of aluminum. Ascorbate therapy may be of potential clinical use to enhance aluminum excretion.
[Fulton B, Jeffery EH; Fundam Appl Toxicol 14 (4): 788-96 (1990)]**PEER REVIEWED**

Drug Idiosyncrasies:

Contact allergy to aluminum has been reported in a few cases. This type of allergy must be regarded very rare, considering the common exposure to the metal itself & the use of aluminum chloride hexahydrate in deodorants. /Aluminum chloride hexahydrate/
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 19]**PEER REVIEWED**

Environmental Fate & Exposure:

Probable Routes of Human Exposure:

INTAKE OF ALUMINUM IS CHIEFLY BY MOUTH, FROM FOODS AND BEVERAGES, ALSO BY LUNGS, FROM THE ATMOSPHERIC DUST CONTENT. IT IS PRESENT IN NATURAL DIET, IN AMT VARYING FROM VERY LOW IN ANIMAL PRODUCTS TO RELATIVELY HIGH IN PLANTS.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 5]**PEER REVIEWED**

/INHALATION OF/ COARSER VARIETY OF ALUMINUM DUST PRODUCED FROM MOLTEN METAL ... . /ALUMINUM DUST/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1497]**PEER REVIEWED**

WORKERS EXPOSED TO ... DUST OF ALUMINUM METAL IN PRODUCTION OF EXPLOSIVES & FIREWORKS. /ALUMINUM METAL/
[Friberg, L., G.R. Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. New York: Elsevier North Holland, 1979. 280]**PEER REVIEWED**

In workers in bauxite mines, foundries, and factories. In more than 1000 exposed workers given X-ray examinations of the chest, pulmonary changes were found in 3.5 percent of those exposed to bauxite dust, & in 4.9 percent exposed to cryolite dust in foundries and in factory workers exposed to alumina. /Alumina/
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1499]**PEER REVIEWED**

Chronic fluorosis generally develops after prolonged (10-20 years) exposure to industrial dusts, insecticides, or water where fluorides exceed 3 to 4 ppm. This is especially true in workers involved in the production of aluminum, steel, or glass.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 533]**PEER REVIEWED**

In children living in the vicinity of poorly controlled aluminum smelters, variable degrees of mottling of permanent teeth have been reported if exposure occurred during the developmental phase of permanent teeth growth.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 133]**PEER REVIEWED**

Electrolytic production of aluminum can lead to a substantial exposure to fluorides and carcinogenic tar oils, including polyaromatic hydrocarbons.
[Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986. 1]**PEER REVIEWED**

Primary aluminum production plants are located in about 40 countries. The two main methods used for aluminum production are Soderberg and prebake, which encompass a number of processes and job categories. Substantial exposures to airborne polynuclear aromatic compounds have been measured in certain occupational settings in this industry. Exposures have been higher in potrooms of plants using the Soderberg process than in those using the prebake process; some workers may have exposed to both process. Exposures to fluorides and a variety of other contaminants also occur in potrooms.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work).p. 34(57)1984]**PEER REVIEWED**

In aluminum reduction plants ... from exposure to coal tar pitch volatiles and their associated polycyclic aromatic hydrocarbons ... Among coke oven workers, implicating coal tar pitch volatiles, a mutual exposure in aluminum reduction plants ... .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 1500]**PEER REVIEWED**

Body Burden:

Aluminum content of normal human brain ranged from 0.1-3.9 ug/g dry weight. In a study of 208 samples taken from 7 patients, ... a mean aluminum content of 1.9 + or - 0.07 ug/g dry weight of gray matter /was found/ to be abnormal. In a study of 585 areas sampled from the brain tissue of 10 patients with Alzheimer's disease they found 28% had an aluminum concn > 4 ug/g. The range of the 585 samples was 0.4-107 ug/g.
[Crapper DR et al; Brain 99: 67 (1976)]**PEER REVIEWED**

Average Daily Intake:

The daily ingestion of aluminum by humans was estimated to be 30-50 mg.
[Bjorksten JA; Comp Therapy 8: 73-6 (1982)]**PEER REVIEWED**

Natural Pollution Sources:

WIDELY DISTRIBUTED IN EARTH'S CRUST IN COMBINATION WITH OXYGEN, FLUORINE, SILICON AND OTHER CONSTITUENTS. ITS MOST IMPORTANT SOURCES FROM THE INDUSTRIAL POINT OF VIEW ARE BAUXITE, CRYOLITE, ALUMINUM , CORUNDUM AND THE KAOLIN MINERALS.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 3]**PEER REVIEWED**

DOES NOT OCCUR FREE IN NATURE.
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 43]**PEER REVIEWED**

2 ug/l of aluminum occurs in a dissolved state in seawater. The species in solution is Al(OH)4-1.
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. 16(81) 279]**PEER REVIEWED**

Artificial Pollution Sources:

Deposited on boiler tubes due to corrosion effects /in processing of coal/.
[KIRK-OTHMER ENCYC CHEM TECH 3RD ED 1978-PRESENT V6 p.256]**PEER REVIEWED**

Environmental Fate:

TERRESTRIAL FATE: Air-dried, <2 mm fractions of 3 soil samples from The Netherlands and 1 from New Hampshire, were taken from the surface and sub-surface horizons of two podzols (Haplorthods) and of a recent driftsand (Udipsamment). Duplicate samples of each emulsion soil horizon were leached ... with aqueous hydrogen chloride (pH 3.0). ... Charge balances of the leachates indicate that dissolved aluminum is present mainly as aquo-aluminum(+3). Only in leachates of podzol Bhs horizons is a significant fraction (20-30%) of dissolved aluminum organically complexed. Dissolved aluminum concn are significantly correlated with the organic (Na4P2O7-extractable) aluminum content of the soil sample. Mobility of aluminum in the Hubbard Brook soils is significantly lower than in the Dutch soils, because of higher soil-solution pH values. /Aluminum cmpd/
[Mulder J et al; Nature 337 (6204): 247-9 (1989)]**PEER REVIEWED**

Albic and spodic soil horizons were sampled from old growth eastern white pine/mixed northern hardwoods. Adirondacks, and an ochric soil horizon was sampled from the Appalachian plateau of NY State. 21 Three-horizon forest floor and 21 forest floor/mineral soil (field moist equivalent of 12.0 oven-dry albic, spodic, or ochric mineral soil) columns were leached in triplicate with either 10 uM nitric acid (pH 5), 5 uM sulfuric acid (pH 5), 100 uM nitric acid (pH 4), 50 uM sulfuric acid (pH 4), 1000 uM nitric acid (pH 3), 500 uM sulfuric acid (pH 3), or distilled, deionized water ((pH 5.7) control treatment). Nitric acid leached more aluminum than did sulfuric acid from forest floor/spodic soil columns. Increasing the nitric acid concn from pH 3-5 increased total aluminum concn in leachates from 0.70 to 0.85 mM, while increasing sulfuric acid had no effect. Addition of pH 3 sulfuric acid to forest floor/spodic columns raised leachate pH relative to pH 3 nitric acid and controls, and resulted in the lowest aluminum concn of all treatments in the first 3 of 4 sequential leachings. /Aluminum/
[James BR, Riha SJ; Soil Sci Soc Am J 53 (1): 259-64 (1989)]**PEER REVIEWED**

Albic and spodic soil horizons were sampled from old growth eastern white pine/mixed northern hardwoods sites in the Adirondacks, and an ochric soil horizon was sampled from the Appalachian Plateau of NY State. 9 Three-horizon forest floor (FF), 9 mineral soil (field moist equivalent of 12.0 oven-dry albic, spodic, or ochric mineral soil) and 9 forest floor/mineral soil columns were leached with 60 ml of (a) 10 mM ammonium nitrate (control), (b) 1.0 mM nitric acid in 10 mM ammonium nitrate (pH 3), and (c) 1.0 mM ammonium nitrate (pH 3) at the rate of 10 ml/h. The above procedure was repeated on each mineral soil without a forest floor, except leaching soln were 0.5 mM calcium nitrate or calcium sulfate, each in 10 mM ammonium nitrate. Adding 2 and 0.5 cmol sub c (H+)/kg to forest floor and mineral soils, respectively, simulated snowmelt additions. Total aluminum concn in leachates from forest floor/albic or forest floor/ochric columns were greater than the sum of concn in leachates from the forest floor and mineral horizon when leached separately. This positive synergistic behavior of the forest floor-mineral horizon sequences was also observed in the forest floor-spodic horizon sequence when leached with control soln, but the synergism was negative for both labile and non-labile aluminum when leached with the acids. Sulfuric acid leached less aluminum from the spodic horizon than did nitric acid, regardless of the presence of a forest floor, but nitric acid, sulfuric acid , and control soln leached similar concn of aluminum from the albic and ochric horizons. The forest floor effects on the mineral soil leachates were attributed to effects of calcium, sulfate, nitrate, and dissolved organic C leached from the forest floor to the mineral horizon since forest floor removed nearly all added H+. /Aluminum/
[James BR, Riha SJ; Soil Sci Soc Am J 53 (1): 264-9 (1989)]**PEER REVIEWED**

Environmental Water Concentrations:

The solute and particulate aluminum chemistry of a relatively unpolluted snowfall associated with a maritime airmass was measured by neutron activation analysis and inductively-coupled plasma analysis (soluble fraction) and neutron activation analysis (particulate material), to characterize background conditions for the Scottish Highlands. Aluminum concentrations were compared to those found in a polluted black snowfall with a trajectory that originated over eastern Europe and to those levels found in seasonal snowpack. The variability of the concentration of solute and the chemical composition of particulate material is reported on an intra-and inter-site basis. The solute aluminum content of Scottish snowfall in the inter-site survey was 19.2 ug/l, and in the intra-site survey 52.2 ug/l. The aluminum composition of particulate matter found within Scottish snow was 20,600 ppm in the inter-site survey, and 21,100 ppm in the intra-site survey. For the black snow, the solute aluminum content was 84 + or - 3 ug/l, and the aluminum composition of particulate matter was 52,300 ppm. The mean concentration of aluminum in seasonal snowpack was 27,200 ppm. /Aluminum solute & particulate/
[Landsberger S et al; Atmos Environ 23 (2): 395-401 (1989)]**PEER REVIEWED**

Sediment/Soil Concentrations:

CONCN ... AS HIGH AS 150-600 G/KG HAVE BEEN REPORTED IN SOIL.
[Friberg, L., G.R. Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. New York: Elsevier North Holland, 1979. 277]**PEER REVIEWED**

Concn in soils vary ... solubility ... determined by pH.
[National Research Council. Drinking Water & Health, Volume 4. Washington, DC: National Academy Press, 1981. 156]**PEER REVIEWED**

Comparison was made between the chemical composition of soil solutions from spruce plantation soil in Denmark isolated by means of a suction method using porcelain cups and by centrifugation. The soil solutions were isolated from 3 depths of field plots, where the soil (Typic Haplohumod) had been subjected to various pretreatments. The cups were made of mullite (aluminum oxide. silicon oxide/aluminum oxide Silicon oxide and corundum (aluminum oxide) as shown by X-ray diffraction analysis.
[Raulund-Rasmussen K; J Soil Sci 40 (1): 95-101 (1989)]**PEER REVIEWED**

Atmospheric Concentrations:

CONTENT IN URBAN AIR IS REPORTED UP TO ABOUT 10 UG/CU M; IN NONURBAN AREAS VALUES LOWER THAN 0.5 UG/CU M ... .
[Friberg, L., G.R. Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. New York: Elsevier North Holland, 1979. 277]**PEER REVIEWED**

Food Survey Values:

IT IS PRESENT IN NATURAL DIET, IN AMT VARYING FROM VERY LOW IN ANIMAL PRODUCTS TO RELATIVELY HIGH IN PLANTS.
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 5]**PEER REVIEWED**

Environmental Standards & Regulations:

Federal Drinking Water Guidelines:

EPA 50-200 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)]**QC REVIEWED**

State Drinking Water Standards:

(CA) CALIFORNIA 1000 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)]**QC REVIEWED**

State Drinking Water Guidelines:

(AZ) ARIZONA 73 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)]**QC REVIEWED**

(CA) CALIFORNIA 200 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)]**QC REVIEWED**

(ME) MAINE 1430 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)]**QC REVIEWED**

FDA Requirements:

Aluminum is an indirect food additive for use only as a component of adhesives.
[21 CFR 175.105 (4/1/91)]**PEER REVIEWED**

Aluminum powder shall conform to the following specifications: fineness, 100% shall pass through a 200-mesh screen and 95% shall pass through a 325-mesh screen; mercury, not more than 1 ppm; arsenic, not more than 3 ppm; lead, not more than 20 ppm; and aluminum, not less than 99% ... Aluminum powder is safe for use in externally applied drugs ... in amt consistent with good manufacturing practice. ... Certification of this color additive is not necessary for the protection of the public health and therefore batches thereof are exempt from the certification pursuant to section 706(c) of the /Federal Food, Drug, and Cosmetic Act (as ammended)/. /Aluminum powder/
[21 CFR 73.1645 (4/1/91)]**PEER REVIEWED**

Aluminum powder may be safely used in coloring externally applied cosmetics ... in amt consistent with good manufacturing practice. ... Certification of this color additive is not necessary for the protection of the public health, and therefore batches thereof are exempt from the certification pursuant to section 706(c) of the /Federal Food, Drug and Cosmetic Act (as amended/. /Aluminum powder/
[21 CFR 73.2645 (4/1/91)]**PEER REVIEWED**

Chemical/Physical Properties:

Molecular Formula:

Al
**PEER REVIEWED**

Molecular Weight:

26.98
**PEER REVIEWED**

Color/Form:

TIN-WHITE, MALLEABLE, DUCTILE METAL, WITH SOMEWHAT BLUISH TINT
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 48]**PEER REVIEWED**

SILVER WHITE DUCTILE METAL, CUBIC
[Weast, R.C. (ed.) Handbook of Chemistry and Physics. 69th ed. Boca Raton, FL: CRC Press Inc., 1988-1989.,p. B-68]**PEER REVIEWED**

CRYSTALLINE SOLID
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 43]**PEER REVIEWED**

Silvery-white, malleable, ductile ... metal.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 12]**QC REVIEWED**

Odor:

... Odorless ...
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 12]**QC REVIEWED**

Boiling Point:

2327 DEG C
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 48]**PEER REVIEWED**

Melting Point:

660 DEG C
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 48]**PEER REVIEWED**

Density/Specific Gravity:

2.70
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 48]**PEER REVIEWED**

Solubilities:

SOL IN ALKALIES, HYDROCHLORIC ACID, SULFURIC ACID; INSOL IN CONCN NITRIC ACID, HOT ACETIC ACID; INSOL IN COLD & HOT WATER
[Weast, R.C. (ed.) Handbook of Chemistry and Physics. 69th ed. Boca Raton, FL: CRC Press Inc., 1988-1989.,p. B-68]**PEER REVIEWED**

Vapor Pressure:

1 MM HG @ 1284 DEG C
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 174]**PEER REVIEWED**

Other Chemical/Physical Properties:

DOES NOT VAPORIZE EVEN @ HIGH TEMP; CAPABLE OF TAKING BRILLIANT POLISH WHICH IS RETAINED IN DRY AIR; REDUCES THE CATIONS OF MANY HEAVY METALS TO THE METALLIC STATE ... IN MOIST AIR, OXIDE FILM FORMS WHICH PROTECTS METAL FROM CORROSION; ... NATURALLY OCCURRING ISOTOPE: (27)ALUMINUM; IN ADDN, 6 RADIOACTIVE ISOTOPES & 1 ISOMER ARE KNOWN
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 48]**PEER REVIEWED**

GOOD CONDUCTOR OF HEAT & ELECTRICITY
[Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969. 3]**PEER REVIEWED**

TENSILE STRENGTH (ANNEALED) 6800 PSI, COLD ROLLED 16,000 PSI; RAPIDLY OXIDIZED BY WATER @ 180 DEG C
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 43]**PEER REVIEWED**