TOXICOLOGICAL PROFILE FOR
 

ALUMINUM
 


 


 


 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2008 
 

ALUMINUM ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
ALUMINUM iii 

UPDATE STATEMENT
 

A Toxicological Profile for Aluminum, Draft for Public Comment, was released in September 2006. This 

edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. For information regarding the update 

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine/Applied Toxicology Branch
 

1600 Clifton Road NE
 

Mailstop F-32
 

Atlanta, Georgia 30333
 
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ALUMINUM v 

FOREWORD 

This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic 

Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary. 

The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects 

information for the hazardous substance described therein. Each peer-reviewed profile identifies and 

reviews the key literature that describes a hazardous substance’s toxicologic properties. Other pertinent 

literature is also presented, but is described in less detail than the key studies. The profile is not intended 

to be an exhaustive document; however, more comprehensive sources of specialty information are 

referenced. 

The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile 

begins with a public health statement that describes, in nontechnical language, a substance’s relevant 

toxicological properties. Following the public health statement is information concerning levels of 

significant human exposure and, where known, significant health effects. The adequacy of information to 

determine a substance’s health effects is described in a health effects summary. Data needs that are of 

significance to protection of public health are identified by ATSDR and EPA. 

Each profile includes the following: 

(A) The examination, summary, and interpretation of available toxicologic information and 

epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human 

exposure for the substance and the associated acute, subacute, and chronic health effects; 

(B) A determination of whether adequate information on the health effects of each substance 

is available or in the process of development to determine levels of exposure that present a 

significant risk to human health of acute, subacute, and chronic health effects; and 

(C) Where appropriate, identification of toxicologic testing needed to identify the types or 

levels of exposure that may present significant risk of adverse health effects in humans. 

The principal audiences for the toxicological profiles are health professionals at the Federal, State, and 

local levels; interested private sector organizations and groups; and members of the public. 

This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been 

peer-reviewed. Staff of the Centers for Disease Control and Prevention and other Federal scientists have 

also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel 
 

 

ALUMINUM vi 

and was made available for public review. Final responsibility for the contents and views expressed in 

this toxicological profile resides with ATSDR. 

Howard Frumkin M.D., Dr.P.H. Julie Louise Gerberding, M.D., M.P.H. 

Director Administrator 

National Center for Environmental Health/ Agency for Toxic Substances and 

Agency for Toxic Substances and Disease Registry 

Disease Registry 

*Legislative Background 

The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization 

Act (SARA) of 1986 (Public Law 99 499) which amended the Comprehensive Environmental Response, 

Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to 

prepare toxicological profiles for hazardous substances most commonly found at facilities on the 

CERCLA National Priorities List and that pose the most significant potential threat to human health, as 

determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous 

substances was announced in the Federal Register on December 7, 2005 (70 FR 72840). For prior 

versions of the list of substances, see Federal Register notices dated April 17, 1987 (52 FR 12866); 

October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17,1990 (55 FR 42067); 

October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); February 28, 1994 (59 FR 9486); 

April 29, 1996 (61 FR 18744); November 17, 1997 (62 FR 61332); October 21, 1999(64 FR 56792); 

October 25, 2001 (66 FR 54014) and November 7, 2003 (68 FR 63098). Section 104(i)(3) of CERCLA, 

as amended, directs the Administrator of ATSDR to prepare a toxicological profile for each substance on 

the list. 
 

 

 

 

 

 

ALUMINUM vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant 

toxicologic properties in a nontechnical, question-and-answer format, and it includes a review of 

the general health effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length 

of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are 

reported in this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. Please refer to the Public Health Statement to identify general health effects observed 

following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children?
 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)?
 

Section 3.7 Children’s Susceptibility
 

Section 6.6 Exposures of Children
 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-800-CDC-INFO (800-232-4636) or 1-888-232-6348 (TTY) Fax: (770) 488-4178 

E-mail: cdcinfo@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure 

history is provided. Other case studies of interest include Reproductive and Developmental 

Hazards; Skin Lesions and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies. 
 

 

 

 

 

 

 

ALUMINUM viii 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials 

incident. Volumes I and II are planning guides to assist first responders and hospital emergency 

department personnel in planning for incidents that involve hazardous materials. Volume III— 

Medical Management Guidelines for Acute Chemical Exposures—is a guide for health care 

professionals treating patients exposed to hazardous materials. 

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

Other Agencies and Organizations 

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, 

GA 30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015. 

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and 

safety in the workplace, recommends standards to the Occupational Safety and Health 

Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains 

professionals in occupational safety and health. Contact: NIOSH, 200 Independence Avenue, 

SW, Washington, DC 20201 • Phone: 800-356-4674 or NIOSH Technical Information Branch, 

Robert A. Taft Laboratory, Mailstop C-19, 4676 Columbia Parkway, Cincinnati, OH 45226-1998 

• Phone: 800-35-NIOSH. 

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for 

biomedical research on the effects of chemical, physical, and biologic environmental agents on 

human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, 

Research Triangle Park, NC 27709 • Phone: 919-541-3212. 

Referrals 

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: 

AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 

• FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/. 

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and 

environmental medicine. Contact: ACOEM, 25 Northwest Point Boulevard, Suite 700, Elk 

Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266. 
ALUMINUM ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Sam Keith, M.S.
 

Dennis Jones, D.V.M.
 

Zemoria Rosemond, B.A.
 

ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, Georgia
 

Lisa Ingerman, Ph.D., DABT
 

Lara Chappell, Ph.D.
 

Syracuse Research Corporation, North Syracuse, New York
 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1.	 Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3.	 Data Needs Review. The Applied Toxicology Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

4.	 Green Border Review. Green Border review assures the consistency with ATSDR policy. 
ALUMINUM x 

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ALUMINUM xi 

PEER REVIEW
 

A peer review panel was assembled for aluminum. The panel consisted of the following members: 

1.	 Dr. Jerrold Abraham, Professor of Family Medicine, Upstate Medical University, Syracuse, New 

York, 

2.	 Dr. Michael Aschner, Director, Department of Pediatrics, Vanderbilt University Medical Center, 

Nashville, Tennessee, and 

3.	 Dr. Robert Yokel, Professor, Division of Pharmaceutical Sciences, University of Kentucky, 

College of Pharmacy, Lexington, Kentucky. 

These experts collectively have knowledge of aluminum's physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 
ALUMINUM xii 

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ALUMINUM xiii 

CONTENTS 

DISCLAIMER .............................................................................................................................................. ii

UPDATE STATEMENT ............................................................................................................................. iii

FOREWORD ................................................................................................................................................ v

QUICK REFERENCE FOR HEALTH CARE PROVIDERS .................................................................... vii

CONTRIBUTORS ....................................................................................................................................... ix

PEER REVIEW ........................................................................................................................................... xi

CONTENTS ............................................................................................................................................... xiii

LIST OF FIGURES .................................................................................................................................. xvii

LIST OF TABLES ..................................................................................................................................... xix

1. PUBLIC HEALTH STATEMENT .......................................................................................................... 1

1.1 WHAT IS ALUMINUM? .............................................................................................................. 2

1.2 WHAT HAPPENS TO ALUMINUM WHEN IT ENTERS THE ENVIRONMENT? ................. 3

1.3 HOW MIGHT I BE EXPOSED TO ALUMINUM? ...................................................................... 3

1.4 HOW CAN ALUMINUM ENTER AND LEAVE MY BODY? ................................................... 4

1.5 HOW CAN ALUMINUM AFFECT MY HEALTH? .................................................................... 5

1.6 HOW CAN ALUMINUM AFFECT CHILDREN? ....................................................................... 6

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ALUMINUM? ................... 6

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED 

TO ALUMINUM? ......................................................................................................................... 7

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? ................................................................................................... 7

1.10 WHERE CAN I GET MORE INFORMATION? .......................................................................... 8

2. RELEVANCE TO PUBLIC HEALTH ................................................................................................. 11

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ALUMINUM IN THE 

UNITED STATES ....................................................................................................................... 11

2.2 SUMMARY OF HEALTH EFFECTS ......................................................................................... 12

2.3 MINIMAL RISK LEVELS (MRLs) ............................................................................................ 15

3. HEALTH EFFECTS .............................................................................................................................. 27

3.1 INTRODUCTION ........................................................................................................................ 27

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................... 27

3.2.1 Inhalation Exposure .............................................................................................................. 28

3.2.1.1 Death .............................................................................................................................. 28

3.2.1.2 Systemic Effects ............................................................................................................. 29

3.2.1.3 Immunological and Lymphoreticular Effects ................................................................ 45

3.2.1.4 Neurological Effects ...................................................................................................... 45

3.2.1.5 Reproductive Effects ...................................................................................................... 47

3.2.1.6 Developmental Effects ................................................................................................... 47

3.2.1.7 Cancer ............................................................................................................................ 48

3.2.2 Oral Exposure ........................................................................................................................ 49

3.2.2.1 Death .............................................................................................................................. 66

3.2.2.2 Systemic Effects ............................................................................................................. 67

3.2.2.3 Immunological and Lymphoreticular Effects ................................................................ 75

3.2.2.4 Neurological Effects ...................................................................................................... 76

3.2.2.5 Reproductive Effects ...................................................................................................... 83

3.2.2.6 Developmental Effects ................................................................................................... 85

3.2.2.7 Cancer ............................................................................................................................ 89
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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3.2.3 Dermal Exposure...................................................................................................................90
 

3.2.3.1 Death..............................................................................................................................90
 

3.2.3.2 Systemic Effects.............................................................................................................90
 

3.2.3.3 Immunological and Lymphoreticular Effects................................................................96
 

3.2.3.4 Neurological Effects ......................................................................................................96
 

3.2.3.5 Reproductive Effects......................................................................................................97
 

3.2.3.6 Developmental Effects...................................................................................................97
 

3.2.3.7 Cancer............................................................................................................................97
 

3.3 GENOTOXICITY........................................................................................................................97
 

3.4 TOXICOKINETICS.....................................................................................................................97
 

3.4.1 Absorption.............................................................................................................................99
 

3.4.1.1 Inhalation Exposure .......................................................................................................99
 

3.4.1.2 Oral Exposure ..............................................................................................................100
 

3.4.1.3 Dermal Exposure .........................................................................................................103
 

3.4.1.4 Other Routes of Exposure............................................................................................103
 

3.4.2 Distribution .........................................................................................................................103
 

3.4.2.1 Inhalation Exposure .....................................................................................................104
 

3.4.2.2 Oral Exposure ..............................................................................................................105
 

3.4.2.3 Dermal Exposure .........................................................................................................107
 

3.4.2.4 Other Routes of Exposure............................................................................................107
 

3.4.3 Metabolism..........................................................................................................................109
 

3.4.4 Elimination and Excretion...................................................................................................110
 

3.4.4.1 Inhalation Exposure .....................................................................................................110
 

3.4.4.2 Oral Exposure ..............................................................................................................110
 

3.4.4.3 Dermal Exposure .........................................................................................................111
 

3.4.4.4 Other Routes of Exposure............................................................................................112
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models...........112
 

3.5 MECHANISMS OF ACTION ...................................................................................................115
 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................115
 

3.5.2 Mechanisms of Toxicity......................................................................................................117
 

3.5.3 Animal-to-Human Extrapolations.......................................................................................119
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS...........................119
 

3.7 CHILDREN’S SUSCEPTIBILITY............................................................................................120
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT .....................................................................124
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Aluminum .....................................125
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Aluminum .......................................125
 

3.9 INTERACTIONS WITH OTHER CHEMICALS .....................................................................126
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ............................................126
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS................................................................127
 

3.11.1 Reducing Peak Absorption Following Exposure.............................................................127
 

3.11.2 Reducing Body Burden ...................................................................................................128
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects..........................................128
 

3.12 ADEQUACY OF THE DATABASE.....................................................................................129
 

3.12.1 Existing Information on Health Effects of Aluminum ....................................................129
 

3.12.2 Identification of Data Needs............................................................................................131
 

3.12.3 Ongoing Studies ..............................................................................................................142
 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................145
 

4.1 CHEMICAL IDENTITY............................................................................................................145
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES.........................................................................145
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................157
 

5.1 PRODUCTION ..........................................................................................................................157
 

5.2 IMPORT/EXPORT ....................................................................................................................166
 

5.3 USE ............................................................................................................................................171
 

5.4 DISPOSAL.................................................................................................................................173
 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................175
 

6.1 OVERVIEW...............................................................................................................................175
 

6.2 RELEASES TO THE ENVIRONMENT...................................................................................178
 

6.2.1 Air .......................................................................................................................................183
 

6.2.2 Water...................................................................................................................................184
 

6.2.3 Soil ......................................................................................................................................185
 

6.3 ENVIRONMENTAL FATE ......................................................................................................186
 

6.3.1 Transport and Partitioning...................................................................................................186
 

6.3.2 Transformation and Degradation ........................................................................................191
 

6.3.2.1 Air................................................................................................................................191
 

6.3.2.2 Water............................................................................................................................191
 

6.3.2.3 Sediment and Soil ........................................................................................................192
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT..................................193
 

6.4.1 Air .......................................................................................................................................193
 

6.4.2 Water...................................................................................................................................194
 

6.4.3 Sediment and Soil ...............................................................................................................198
 

6.4.4 Other Environmental Media................................................................................................199
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE........................................210
 

6.6 EXPOSURES OF CHILDREN..................................................................................................214
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ..............................................219
 

6.8 ADEQUACY OF THE DATABASE ........................................................................................221
 

6.8.1 Identification of Data Needs ...............................................................................................221
 

6.8.2 Ongoing Studies..................................................................................................................226
 

7. ANALYTICAL METHODS................................................................................................................229
 

7.1 BIOLOGICAL MATERIALS....................................................................................................229
 

7.2 ENVIRONMENTAL SAMPLES ..............................................................................................236
 

7.3 ADEQUACY OF THE DATABASE ........................................................................................241
 

7.3.1 Identification of Data Needs ...............................................................................................241
 

7.3.2 Ongoing Studies..................................................................................................................243
 

8. REGULATIONS AND ADVISORIES ...............................................................................................245
 

9. REFERENCES ....................................................................................................................................251
 

10. GLOSSARY ......................................................................................................................................305
 
 

 

 

 

ALUMINUM xvi 

APPENDICES 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS .............................................................A-1
 

B. USER’S GUIDE.................................................................................................................................. B-1
 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS...................................................................... C-1
 

D. INDEX ................................................................................................................................................D-1
 
 

 

 

 

 

 

ALUMINUM xvii 

LIST OF FIGURES
 

3-1. Levels of Significant Exposure to Aluminum and Compounds - Inhalation...................................... 35
 

3-2. Levels of Significant Exposure to Aluminum and Compounds - Oral............................................... 62
 

3-3. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance....................................................................................................114
 

3-4. Existing Information on Health Effects of Aluminum .....................................................................130
 

6-1. Frequency of NPL Sites with Aluminum Contamination.................................................................176
 
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ALUMINUM xix 

LIST OF TABLES
 

3-1. Levels of Significant Exposure to Aluminum and Compounds - Inhalation...................................... 30
 

3-2. Levels of Significant Exposure to Aluminum and Compounds - Oral............................................... 51
 

3-3. Levels of Significant Exposure to Aluminum and Compounds - Dermal.......................................... 92
 

3-4. Genotoxicity of Aluminum In Vitro ...................................................................................................98
 

3-5. Ongoing Studies on Aluminum ........................................................................................................143
 

4-1. Chemical Identity of Aluminum and Compounds............................................................................146
 

4-2. Physical and Chemical Properties of Aluminum and Compounds...................................................151
 

5-1. U.S. Manufacturers of Aluminum ....................................................................................................159
 

5-2. U.S. Producers of Selected Aluminum Compounds.........................................................................160
 

5-3. Facilities that Produce, Process, or Use Aluminum (Fume or Dust)................................................167
 

5-4. Facilities that Produce, Process, or Use Aluminum Oxide (Fibrous Forms)....................................169
 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Aluminum
 

(Fume or Dust) .................................................................................................................................179
 

6-2. Releases to the Environment from Facilities that Produce, Process, or Use Aluminum
 

Oxide (Fibrous Forms).....................................................................................................................181
 

6-3. Aluminum Concentrations Detected in Drinking Water in Various Regions of the
 

United States ....................................................................................................................................196
 

6-4. Estimated Aluminum Concentrations of Selected Foods .................................................................200
 

6-5. Dietary Intakes of Aluminum in Children........................................................................................216
 

6-6. Major Sources of Aluminum in Food by Age-Sex Group................................................................217
 

6-7. Ongoing Studies on Aluminum ........................................................................................................227
 

7-1. Analytical Methods for Determining Aluminum in Biological Materials........................................230
 

7-2. Analytical Methods for Determining Aluminum in Environmental Samples..................................237
 

7-3. Ongoing Studies on Aluminum ........................................................................................................244
 

8-1. Regulations and Guidelines Applicable to Aluminum and Compounds..........................................246
 
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ALUMINUM 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about aluminum and the effects of exposure to it. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. 

These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal 

clean-up activities. Aluminum (in some form, e.g., in compounds with other elements such as oxygen, 

sulfur, or phosphorus) has been found at elevated levels in at least 596 of the 1,699 current or former NPL 

sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility 

exists that the number of sites at which aluminum is found may increase in the future as more sites are 

evaluated. This information is important because these sites may be sources of exposure and exposure to 

this substance at high levels may be harmful. 

When a substance is released either from a large area, such as an industrial plant, or from a container, 

such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You 

can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, 

eating, or drinking the substance, or by skin contact. However, it should be noted that aluminum is a very 

abundant and widely distributed element and will be found in most rocks, soils, waters, air, and foods. 

You will always have some exposure to low levels of aluminum from eating food, drinking water, and 

breathing air. 

If you are exposed to aluminum, many factors will determine whether you will be harmed. These factors 

include the dose (how much), the duration (how long), and how you come in contact with it. You must 

also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and 

state of health. 
 

 

 

ALUMINUM 2 

1. PUBLIC HEALTH STATEMENT 

1.1 WHAT IS ALUMINUM? 

Description Aluminum is the most abundant metal in the earth's crust and it is widely 

distributed. 

Aluminum is a very reactive element and is never found as the free metal in 

nature. It is found combined with other elements, most commonly with 

oxygen, silicon, and fluorine. These chemical compounds are commonly 

found in soil, minerals (e.g., sapphires, rubies, turquoise), rocks (especially 

igneous rocks), and clays. 

Aluminum as the metal is obtained from aluminum-containing minerals, 

primarily bauxite. 

Aluminum metal is light in weight and silvery-white in appearance. 

Uses 

• Aluminum 

metal 

• Aluminum 

compounds 

• Consumer 

products 

Aluminum is used to make beverage cans, pots and pans, airplanes, siding 

and roofing, and foil. 

Powdered aluminum metal is often used in explosives and fireworks. 

Aluminum compounds are used in many diverse and important industrial 

applications such as alums (aluminum sulfate) in water-treatment and 

alumina in abrasives and furnace linings. 

Aluminum is found in consumer products including: 

• antacids 

• astringents 

• buffered aspirin 

• food additives 

• antiperspirants 

• cosmetics 

For more information on the physical and chemical properties of aluminum and its production, disposal, 

and use, see Chapters 4 and 5. 
 

 

 

 

 

 

 

ALUMINUM 3 

1. PUBLIC HEALTH STATEMENT 

1.2 WHAT HAPPENS TO ALUMINUM WHEN IT ENTERS THE ENVIRONMENT? 

Sources Aluminum occurs naturally in soil, water, and air. 

High levels in the environment can be caused by the mining and processing 

of aluminum ores or the production of aluminum metal, alloys, and 

compounds. 

Small amounts of aluminum are released into the environment from coal-fired 

power plants and incinerators. 

Break down 

• Air 

• Water and 

soil 

Aluminum cannot be destroyed in the environment. It can only change its 

form or become attached or separated from particles. 

Aluminum particles in air settle to the ground or are washed out of the air by 

rain. However, very small aluminum particles can stay in the air for many 

days. 

Most aluminum-containing compounds do not dissolve to a large extent in 

water unless the water is acidic or very alkaline. 

For more information on aluminum in the environment, see Chapter 6. 

1.3 HOW MIGHT I BE EXPOSED TO ALUMINUM? 

Food—primary Unprocessed foods like fresh fruits, vegetables, and meat contain very little 

source of aluminum. 

exposure 

Aluminum compounds may be added during processing of foods, such as: 

• flour 

• baking powder 

• coloring agents 

• anticaking agents 

An average adult in the United States eats about 7–9 mg of aluminum per 

day in their food. 

Air Most people take in very little aluminum from breathing. Levels of aluminum 

in the air generally range from 0.005 to 0.18 micrograms per cubic meter 

(μg/m3

), depending on location, weather conditions, and type and level of 

industrial activity in the area. Most of the aluminum in the air is in the form of 

small suspended particles of soil (dust). 

Aluminum levels in urban and industrial areas may be higher and can range 

from 0.4 to 8.0 μg/m3 

. 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 4 

1. PUBLIC HEALTH STATEMENT 

Water and soil The concentration of aluminum in natural waters (e.g., ponds, lakes, 

streams) is generally below 0.1 milligrams per liter (mg/L). 

People generally consume little aluminum from drinking water. Water is 

sometimes treated with aluminum salts while it is processed to become 

drinking water. But even then, aluminum levels generally do not exceed 

0.1 mg/L. Several cities have reported concentrations as high as 0.4– 

1 mg/L of aluminum in their drinking water. 

Consumer People are exposed to aluminum in some cosmetics, antiperspirants, and 

Products pharmaceuticals such as antacids and buffered aspirin. 

• Antacids have 300–600 mg aluminum hydroxide (approximately 104– 

208 mg of aluminum) per tablet, capsule, or 5 milliliter (mL) liquid dose. 

Little of this form of aluminum is taken up into the bloodstream. 

• Buffered aspirin may contain 10–20 mg of aluminum per tablet 

• Vaccines may contain small amounts of aluminum compounds, no 

greater than 0.85 mg/dose. 

For more information on how you might be exposed to aluminum, see Chapter 6. 

1.4 HOW CAN ALUMINUM ENTER AND LEAVE MY BODY? 

Enter your body 

• Inhalation 

• Ingestion 

• Dermal 

contact 

A small amount of the aluminum you breathe will enter your body through 

your lungs. 

A very small amount of the aluminum in food or water will enter your body 

through the digestive tract. An extremely small amount of the aluminum 

found in antacids will be absorbed. 

A very small amount may enter through your skin when you come into 

contact with aluminum. 

Leave your body Most aluminum in food, water, and medicines leaves your body quickly in 

the feces. Much of the small amount of aluminum that does enter the 

bloodstream will quickly leave your body in the urine. 

For more information on how aluminum enters and leaves the body, see Chapter 3. 
 

 

 

 

 

 

 

ALUMINUM 5 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN ALUMINUM AFFECT MY HEALTH? 

This section looks at studies concerning potential health effects in animal and human studies. 

Workers Workers who breathe large amounts of aluminum dusts can have lung 

• Inhalation problems, such as coughing or changes that show up in chest X-rays. The 

use of breathing masks and controls on the levels of dust in factories have 

largely eliminated this problem. 

Some workers who breathe aluminum-containing dusts or aluminum fumes 

have decreased performance in some tests that measure functions of the 

nervous system. 

Humans Oral exposure to aluminum is usually not harmful. Some studies show that 

• Oral people exposed to high levels of aluminum may develop Alzheimer’s 

disease, but other studies have not found this to be true. We do not know 

for certain that aluminum causes Alzheimer’s disease. 

Some people who have kidney disease store a lot of aluminum in their 

bodies. The kidney disease causes less aluminum to be removed from the 

body in the urine. Sometimes, these people developed bone or brain 

diseases that doctors think were caused by the excess aluminum. 

Although aluminum-containing over the counter oral products are 

considered safe in healthy individuals at recommended doses, some 

adverse effects have been observed following long-term use in some 

individuals. 

Laboratory 

animals 

• Inhalation 

• Oral 

Lung effects have been observed in animals exposed to aluminum dust. 

Scientists do not know if these effects are dur to the aluminum or to the 

animals breathing in a lot of dust. 

Studies in animals show that the nervous system is a sensitive target of 

aluminum toxicity. Obvious signs of damage were not seen in animals after 

high oral doses of aluminum. However, the animals did not perform as well 

in tests that measured the strength of their grip or how much they moved 

around. 

Further information on the health effects of aluminum in humans and animals can be found in 

Chapters 2 and 3. 
 

 

 

 

 

 

 

ALUMINUM 6 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN ALUMINUM AFFECT CHILDREN? 

This section discusses potential health effects in humans from exposures during the period from 

conception to maturity at 18 years of age. 

Effects in children Brain and bone disease caused by high levels of aluminum in the body have 

been seen in children with kidney disease. Bone disease has also been 

seen in children taking some medicines containing aluminum. In these 

children, the bone damage is caused by aluminum in the stomach 

preventing the absorption of phosphate, a chemical compound required for 

healthy bones. 

Aluminum is found in breast milk, but only a small amount of this aluminum 

will enter the infant’s body through breastfeeding. Typical aluminum 

concentrations in human breast milk range from 0.0092 to 0.049 mg/L. 

Aluminum is also found in soy-based infant formula (0.46–0.93 mg/L) and 

milk-based infant formula (0.058–0.15 mg/L). 

Birth defects We do not know if aluminum will cause birth defects in people. Birth defects 

have not been seen in animals. 

Very young animals appeared weaker and less active in their cages and 

some movements appeared less coordinated when their mothers were 

exposed to large amounts of aluminum during pregnancy and while nursing. 

In addition, aluminum also affected the animal’s memory. These effects are 

similar to those that have been seen in adults. 

It does not appear that children are more sensitive than adult animals. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ALUMINUM?
 

Food You cannot avoid exposure to aluminum because it is so common and 

widespread in the environment. 

Exposure to the levels of aluminum that are naturally present in food and 

water and the forms of aluminum that are present in dirt and aluminum pots 

and pans are not considered to be harmful. 

Eating large amounts of processed food containing aluminum additives or 

frequently cooking acidic foods in aluminum pots may expose a person to 

higher levels of aluminum than a person who generally consumes 

unprocessed foods and uses pots made of other materials (e.g., stainless 

steel or glass). However, aluminum levels found in processed foods and 

foods cooked in aluminum pots are generally considered to be safe. 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 7 

1. PUBLIC HEALTH STATEMENT 

Consumer 

products 

Limiting your intake of large quantities of aluminum-containing antacids and 

buffered aspirin and using these medications only as directed is the best 

way to limit exposure to aluminum from these sources. 

As a precaution, such products should have child-proof caps or should be 

kept out of reach of children so that children will not accidentally injest them. 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO 

ALUMINUM? 

Detecting 

exposure 

All people have small amounts of aluminum in their bodies. It can be 

measured in the blood, bones, feces, or urine. 

Measuring 

exposure 

Urine and blood aluminum measurements can tell you whether you have 

been exposed to larger-than-normal amounts of aluminum, especially for 

recent amounts. 

Measuring bone aluminum can also indicate exposure to high levels of 

aluminum, but this requires a bone biopsy. 

Information about tests for detecting aluminum in the body is given in Chapters 3 and 7. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. Regulations 

can be enforced by law. The EPA, the Occupational Safety and Health Administration (OSHA), and the 

Food and Drug Administration (FDA) are some federal agencies that develop regulations for toxic 

substances. Recommendations provide valuable guidelines to protect public health, but cannot be 

enforced by law. The Agency for Toxic Substances and Disease Registry (ATSDR) and the National 

Institute for Occupational Safety and Health (NIOSH) are two federal organizations that develop 

recommendations for toxic substances. 

Regulations and recommendations can be expressed as “not-to-exceed” levels, that is, levels of a toxic 

substance in air, water, soil, or food that do not exceed a critical value that is usually based on levels that 

affect animals; they are then adjusted to levels that will help protect humans. Sometimes these not-toexceed levels differ among federal organizations because they used different exposure times (an 8-hour 

workday or a 24-hour day), different animal studies, or other factors. 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 8 

1. PUBLIC HEALTH STATEMENT 

Recommendations and regulations are also updated periodically as more information becomes available. 

For the most current information, check with the federal agency or organization that provides it. Some 

regulations and recommendations for aluminum include the following: 

Drinking water The EPA has recommended a Secondary Maximum Contaminant Level 

(SMCL) of 0.05–0.2 mg/L for aluminum in drinking water. The SMCL is not 

based on levels that will affect humans or animals. It is based on taste, 

smell, or color. 

Consumer 

products 

The FDA has determined that aluminum used as food additives and 

medicinals such as antacids are generally safe. 

FDA set a limit for bottled water of 0.2 mg/L. 

Workplace air OSHA set a legal limit of 15 mg/m3 (total dust) and 5 mg/m3 (respirable 

fraction) aluminum in dusts averaged over an 8-hour work day. 

For more information on regulations and advisories, see Chapter 8. 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department, or contact ATSDR at the address and phone number below. 

ATSDR can also tell you the location of occupational and environmental health clinics. These clinics 

specialize in recognizing, evaluating, and treating illnesses that result from exposure to hazardous 

substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You may 

request a copy of the ATSDR ToxProfilesTM CD-ROM by calling the toll-free information and technical 

assistance number at 1-800-CDC-INFO (1-800-232-4636), by e-mail at cdcinfo@cdc.gov, or by writing 

to: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology and Environmental Medicine
 

1600 Clifton Road NE
 

Mailstop F-32
 

Atlanta, GA 30333
 

Fax: 1-770-488-4178
 
 

 

 

 

 

 

 

ALUMINUM 9 

1. PUBLIC HEALTH STATEMENT 

Organizations for-profit may request copies of final Toxicological Profiles from the following: 

National Technical Information Service (NTIS) 

5285 Port Royal Road 

Springfield, VA 22161 

Phone: 1-800-553-6847 or 1-703-605-6000 

Web site: http://www.ntis.gov/ 
 

ALUMINUM 10 

1. PUBLIC HEALTH STATEMENT 

This page is intentionally blank. 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 11 

2. RELEVANCE TO PUBLIC HEALTH 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ALUMINUM IN THE 

UNITED STATES 

Aluminum is ubiquitous; the third most common element of the earth's crust. It is naturally released to 

the environment from the weathering of rocks and volcanic activity. Human activities such as mining 

also result in the release of aluminum to the environment. Aluminum levels in environmental media vary 

widely depending upon the location and sampling site. In general, background levels of aluminum in the 

atmosphere are low, typically ranging from about 0.005 to 0.18 μg/m3

. Much higher levels are routinely 

observed in urban and industrial locations. Aluminum levels in surface water is usually very low 

(<0.1 mg/L); however, in acidic waters or water high in humic or fulvic acid content, the concentration of 

soluble aluminum increases due to the increased solubility of aluminum oxide and aluminum salts. Its 

concentration in soils varies widely, ranging from about 7 to over 100 g/kg. 

In the environment, aluminum exists in only one oxidation state (+3), and does not undergo oxidationreduction reactions. It can react with other matter in the environment to form various complexes. The 

fate and transport of aluminum is largely controlled by environmental factors such as pH, salinity, and the 

presence of various species with which it may form complexes. In general, the solubility and mobility of 

aluminum in soil is greatest when the soil is rich in organic matter capable of forming aluminum-organic 

complexes and when the pH is low, such as in areas prone to acid rain or in acidic mine tailings. 

The general population is primarily exposed to aluminum through the consumption of food items, 

although minor exposures may occur through ingestion of aluminum in drinking water and inhalation of 

ambient air. Aluminum found in over-the-counter medicinals, such as antacids and buffered aspirin, is 

used as a food additive, and is found in a number of topically applied consumer products such as 

antiperspirants, and first aid antibiotic and antiseptics, diaper rash and prickly heat, insect sting and bite, 

sunscreen and suntan, and dry skin products. The concentration of aluminum in foods and beverages 

varies widely, depending upon the food product, the type of processing used, and the geographical areas 

in which food crops are grown (see Section 6.4). Based on the FDA’s 1993 Total Diet Study dietary 

exposure model and the 1987–1988 U.S. Department of Agriculture (USDA) Nationwide Food 

Consumption Survey, the authors estimated daily aluminum intakes of 0.10 mg Al/kg/day for 6– 

11-month-old infants; 0.30–0.35 mg Al/kg/day for 2–6-year-old children; 0.11 mg Al/kg/day for 10-yearold children; 0.15–0.18 mg Al/kg/day for 14–16-year-old males and females; and 0.10– 

0.12 mg Al/kg/day for adult (25–30- and 70+-year-old) males and females. Users of aluminum­
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 12 

2. RELEVANCE TO PUBLIC HEALTH 

containing medications who are healthy (i.e., have normal renal function) can ingest much larger amounts 

of aluminum than in the diet, possibly as high as 12–71 mg Al/kg/day from antacid/anti-ulcer products 

and 2–10 mg Al/kg/day from buffered analgesics when taken at recommended dosages. 

Gastrointestinal absorption of aluminum is low, generally in the range of 0.1–0.4% in humans, although 

absorption of particularly bioavailable forms such as aluminum citrate may be on the order of 0.5–5%. 

Although large bolus doses of as much as half a gram of aluminum as aluminum hydroxide throughout 

the day can be ingested during antacid therapy, absorption of aluminum hydroxide is usually ≤0.01% of

the intake amount. Bioavailability of aluminum varies depending mainly on the chemical form of the 

ingested compound (i.e., type of anion) and the concurrent exposure to dietary chelators such as citric 

acid, ascorbic acid, or lactic acid. The total body burden of aluminum in healthy human subjects is 

approximately 30–50 mg. Normal levels of aluminum in serum are approximately 1–3 μg/L. Of the total

body burden of aluminum, about one-half is in the skeleton, and about one-fourth is in the lungs. 

2.2 SUMMARY OF HEALTH EFFECTS 

There are numerous studies that have examined aluminum’s potential to induce toxic effects in humans 

exposed via inhalation, oral, or dermal exposure. Most of these findings are supported by a large number 

of studies in laboratory animals. Occupational exposure studies and animal studies suggest that the lungs 

and nervous system may be the most sensitive targets of toxicity following inhalation exposure. 

Respiratory effects, in particular impaired lung function and fibrosis, have been observed in workers 

exposed to aluminum dust or fumes; however, this has not been consistently observed across studies and 

it is possible that co-exposure to other compounds contributed to observed effects. Respiratory effects 

(granulomatous lesions) have also been observed in rats, hamsters, and guinea pigs. There is concern that 

these effects are due to dust overload rather than a direct effect of aluminum in lung tissue. Occupational 

studies in workers exposed to aluminum dust in the form of McIntyre powder, aluminum dust and fumes 

in potrooms, and aluminum fumes during welding provide suggestive evidence that there may be a 

relationship between chronic aluminum exposure and subclinical neurological effects such as impairment 

on neurobehavioral tests for psychomotor and cognitive performance and an increased incidence of 

subjective neurological symptoms. With the exception of some isolated cases, inhalation exposure has 

not been associated with overt symptoms of neurotoxicity. A common limitation of these occupational 

exposure studies is that aluminum exposure has not been well characterized. The available animal 

inhalation studies are inadequate for assessing the potential for aluminum-induced neurotoxicity because 
 

 

 

 

 

 

 

ALUMINUM 13 

2. RELEVANCE TO PUBLIC HEALTH 

the only neurological end points examined were brain weight and histology of the brain; no function tests 

were performed. 

There is limited information on aluminum toxicity following dermal exposure. Application of aluminum 

compounds to the skin, such as aluminum chloride in ethanol or alum, may cause rashes in some people. 

Skin damage has been observed in mice, rabbits, and pigs exposed to aluminum chloride or aluminum 

nitrate, but not following exposure to aluminum sulfate, aluminum hydroxide, aluminum acetate, or 

aluminum chlorhydrate. 

There is a fair amount of human data on the toxicity of aluminum following oral exposure. However, the 

preponderance of human studies are in patients with reduced renal function who accumulated aluminum 

as a result of long-term intravenous hemodialysis therapy with aluminum-contaminated dialysis fluid and, 

in many cases, concurrent administration of high oral doses of aluminum to regulate phosphate levels 

(i.e., reduce uptake of phosphate by binding it in the gut) and have limited usefulness in predicting 

toxicity in the general population because the very large aluminum exposure levels and impaired renal 

function results in aluminum accumulation. Dialysis encephalopathy syndrome (also referred to as 

dialysis dementia) can result from this accumulation of aluminum in the brain. Dialysis encephalopathy 

is a degenerative neurological syndrome, characterized by the gradual loss of motor, speech, and 

cognitive functions. Another neurological effect that has been proposed to be associated with aluminum 

exposure is Alzheimer’s disease. Although a possible association was proposed over 40 years ago, this 

association is still highly controversial and there is little consensus regarding current evidence. A number 

of studies have found weak associations between living in areas with elevated aluminum levels in 

drinking water and an increased risk (or prevalence) of Alzheimer’s disease; other studies have not found 

significant associations. In contrast, no significant associations have been found between tea 

consumption or antacid use and the risk of Alzheimer’s disease; although the levels of aluminum in tea 

and antacids are very high compared to drinking water, aluminum from these sources is poorly absorbed. 

The available data do not suggest that aluminum is a causative agent of Alzheimer’s disease; however, it 

is possible that it may play a role in the disease development. 

Aluminum is found in several ingested over-the-counter products such as antacids and buffered aspirin; 

clinical studies on health effects of aluminum medicinals in people with normal renal function have been 

identified. These aluminum-containing products are assumed to be safe in healthy individuals at 

recommended doses based on historical use. The assumed safety of aluminum is also partly due to the 

generally regarded as safe (GRAS) status of aluminum-containing food additives. However, there is 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 14 

2. RELEVANCE TO PUBLIC HEALTH 

some indication that adverse effects can result from long-term use of aluminum-containing medications in 

some healthy individuals. There are a number of case reports of skeletal changes (e.g., osteomalacia) in 

adults and children with normal kidney function due to long-term antacid use for the treatment of 

gastrointestinal disorders. These skeletal effects are secondary to hypophosphatemia and phosphate 

depletion caused by aluminum impairing phosphorus absorption by binding with dietary phosphorus. 

There is a rather extensive database on the oral toxicity of aluminum in animals. These studies clearly 

identify the nervous system as the most sensitive target of aluminum toxicity and most of the animal 

studies have focused on neurotoxicity and neurodevelopmental toxicity. Other adverse effects that have 

been observed in animals orally exposed to aluminum include impaired erythropoiesis in rats exposed to 

230 mg Al/kg/day and higher, erythrocyte damage (as evidenced by decreases in hemoglobin, hematocrit, 

and erythrocyte osmotic fragility, and altered erythrocyte morphology) in rats exposed to 

230 mg Al/kg/day and higher, increased susceptibility to infection in mouse dams exposed to 

155 mg Al/kg/day, delays in pup maturation following exposure of rats to 53 mg Al/kg/day, and 

decreases in pup body weight gain in rats and mice exposed to 103 mg Al/kg/day and higher. 

Neurodegenerative changes in the brain, manifested as intraneuronal hyperphosphorylated neurofilamentous aggregates, is a characteristic response to aluminum in certain species and nonnatural 

exposure situations generally involving direct application to brain tissue, particularly intracerebral and 

intracisternal administration and in vitro incubation in rabbits, cats, ferrets, and nonhuman primates. Oral 

studies in rats and mice have not found significant histopathological changes in the brain under typical 

exposure conditions; however, altered myelination was found in the spinal cord of mouse pups exposed to 

330 mg Al/kg/day on gestation day 1 through postnatal day 35. Overt signs of neurotoxicity are rarely 

reported at the doses tested in the available animal studies ( ≤330mg Al/kg/day for bioavailable aluminum 

compounds); rather, exposure to these doses is associated with subtle neurological effects detected with 

neurobehavioral performance tests. Significant alterations in motor function, sensory function, and 

cognitive function have been detected following exposure to adult or weanling rats and mice or following 

gestation and/or lactation exposure of rats and mice to aluminum lactate, aluminum nitrate, and aluminum 

chloride. The most consistently affected performance tests were forelimb and/or hindlimb grip strength, 

spontaneous motor activity, thermal sensitivity, and startle responsiveness. Significant impairments in 

cognitive function have been observed in some studies, although this has not been found in other studies 

even at higher doses. Adverse neurological effects have been observed in rats and mice at doses of 100– 

200 mg Al/kg/day and neurodevelopmental effects have been observed in rats and mice at doses of 103– 

330 mg Al/kg/day. 
 

 

 

 

 

ALUMINUM 15 

2. RELEVANCE TO PUBLIC HEALTH 

A number of human studies have examined the occurrence of cancer among aluminum industry workers 

and found a higher-than-expected cancer mortality rate, but this is probably due to the other potent 

carcinogens to which they are exposed, such as polycyclic aromatic hydrocarbons (PAHs) and tobacco 

smoke. Available cancer studies in animals have not found biologically relevant increases in malignant 

tumors. The International Agency for Research on Cancer (IARC) concluded that aluminum production 

was carcinogenic to humans and that pitch volatiles have fairly consistently been suggested in 

epidemiological studies as being possible causative agents. The Department of Health and Human 

Services and EPA have not evaluated the human carcinogenic potential of aluminum. 

2.3 MINIMAL RISK LEVELS (MRLs) 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for aluminum. An 

MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an 

appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are 

derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive 

health effect(s) for a specific duration within a given route of exposure. MRLs are based on 

noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for 

acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate 

methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

Inhalation MRLs 

No acute-, intermediate-, or chronic-duration inhalation MRLs were derived for aluminum. Results from 

human and animal studies suggest that the respiratory tract, particularly the lung, is a sensitive target of 

airborne aluminum toxicity; human studies also suggest that the nervous system may also be a target of 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 16 

2. RELEVANCE TO PUBLIC HEALTH 

inhaled aluminum. Interpretation of the human data is complicated by the lack of exposure assessment 

and the potential for concomitant exposure to other toxic compounds. Numerous studies have found 

impaired lung function in a variety of aluminum workers (Abbate et al. 2003; Al-Masalkhi and Walton 

1994; Bast-Pettersen et al. 1994; Bost and Newman 1993; Burge et al. 2000; Chan-Yeung et al. 1983; 

Herbert et al. 1982; Hull and Abraham 2002; Jederlinic et al. 1990; Korogiannos et al. 1998; Miller et al. 

1984b; Radon et al. 1999; Simonsson et al. 1985; Vandenplas et al. 1998). Other effects that have been 

observed include occupational asthma (Abramson et al. 1989; Burge et al. 2000; Kilburn 1998; 

Vandenplas et al. 1998) and pulmonary fibrosis (Al-Masalkhi and Walton 1994; De Vuyst et al. 1986; 

Edling 1961; Gaffuri et al. 1985; Gilks and Churg 1987; Jederlinic et al. 1990; Jephcott 1948; 

McLaughlin et al. 1962; Mitchell et al. 1961; Musk et al. 1980; Riddell 1948; Shaver 1948; Shaver and 

Riddell 1947; Ueda et al. 1958; Vallyathan et al. 1982). 

Acute-, intermediate-, and chronic-duration animal studies have also reported respiratory effects. These 

respiratory effects include increases in alveolar macrophages, granulomatous lesions in the lungs and 

peribronchial lymph nodes, and increases in lung weight (Drew et al. 1974; Klosterkotter 1960; Pigott et 

al. 1981; Steinhagen et al. 1978; Stone et al. 1979). The lung effects observed in humans and animals are 

suggestive of dust overload. Dust overload occurs when the volume of dust in the lungs markedly 

impairs pulmonary clearance mechanisms. Lung overload is not dependent on the inherent toxicity of the 

compound, and dust overloading has been shown to modify both the dosimetry and toxicological effects 

of the compound (Morrow 1988). When excessive amounts of widely considered benign dusts are 

persistently retained in the lungs, the resultant lung effects are similar to those observed following 

exposure to dusts that are highly toxic to the lungs. Because it is unclear whether the observed respiratory 

effects are related to aluminum toxicity or to dust overload, inhalation MRLs based on respiratory effects 

were not derived. 

Subtle neurological effects have also been observed in workers chronically exposed to aluminum dust or 

fumes. These effects include impaired performance on neurobehavioral tests (Akila et al. 1999; BastPettersen et al. 2000; Buchta et al. 2003, 2005; Hänninen et al. 1994; Hosovski et al. 1990; Polizzi et al. 

2001; Rifat et al. 1990; Riihimäki et al. 2000; Sjögren et al. 1990) and increased reporting of subjective 

neurological symptoms (Bast-Pettersen et al. 1994, 2000; Hänninen et al. 1994; Hosovski et al. 1990; 

Iregren et al. 2001; Rifat et al. 1990; Riihimäki et al. 2000; Sim et al. 1997; Sjögren et al. 1990, 1996; 

White et al. 1992). Neurological exams in the available animal studies (Steinhagen et al. 1978; Stone et 

al. 1979) have been limited to measurement of brain weight and/or histopathology of the brain; no 

function tests were performed. The identification of neurotoxicity as a sensitive end point in workers 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 17 

2. RELEVANCE TO PUBLIC HEALTH 

exposed to aluminum dust and fumes is well supported by a large number of animal studies reporting a 

variety of neurobehavioral alterations following oral exposure. However, the poor characterization of 

aluminum exposure in the occupational exposure studies precludes using these studies to develop an 

inhalation MRL for aluminum. 

Oral MRLs 

Data on health effects of ingested aluminum in humans are unsuitable for MRL consideration because 

studies have centered on specific patient populations (i.e., dialysis, neurodegenerative disease) and are not 

the types typically used in risk evaluation. Studies in patients with reduced renal function who 

accumulated aluminum as a result of long-term intravenous hemodialysis therapy with aluminumcontaminated dialysate and the use of aluminum-containing phosphate binding agents provide evidence 

that aluminum is an important etiologic factor in dialysis-related health disorders, particularly the 

neurological syndrome dialysis encephalopathy. The effects are manifested under unnatural exposure 

conditions in which the gastrointestinal barrier is bypassed (exposure to aluminum in dialysate fluid) and 

aluminum excretion is impaired by the poor renal function. There are case reports of skeletal changes 

(e.g., osteomalacia) consequent to long-term ingestion of antacids in healthy adults and children with 

normal kidney function (Carmichael et al. 1984; Chines and Pacifici 1990; Pivnick et al. 1995; Woodson 

1998), but these effects are attributable to an interaction between aluminum and phosphate in the gut 

(aluminum binds with phosphate in the gut resulting in decreased phosphate absorption and 

hypophosphatemia). Although the use of aluminum medicinals in people is widespread, there are a 

limited number of experimental studies that examined the potential toxicity of the aluminum in these 

medicinals in individuals with normal renal function. 

Derivation of an MRL(s) for aluminum based on animal studies is complicated by limitations in the 

database, particularly the lack of information on aluminum content in the base diet. As discussed in the 

introduction to Section 3.2.2, commercial laboratory animal feeds contain high levels of aluminum that 

can significantly contribute to total experimental exposure. Due to the likelihood of significant base 

dietary exposure to aluminum, studies with insufficient information on aluminum content in the base diet 

must be assumed to underestimate the actual aluminum intake. The magnitude of the underestimate can 

be considerable; for example, approximate feed concentrations of 250 and 350 ppm aluminum reported in 

some rat and mouse studies, respectively (Colomina et al. 1998; Domingo et al. 1993; Oteiza et al. 1993), 

are roughly equivalent to daily doses of 25 mg Al/kg/day (rats) and 68 mg Al/kg/day (mice), which 

represents a significant portion of the lethal dose for these species. Consequently, although studies with 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 18 

2. RELEVANCE TO PUBLIC HEALTH 

inadequate data on base dietary levels of aluminum provide useful information on health effects of 

aluminum, no-observed-adverse-effect levels (NOAELs) and lowest-observed-adverse-effect levels 

(LOAELs) from these studies cannot be assumed to be accurate, are not suitable for comparing with 

effect levels from studies that used diets with known amounts of aluminum, and are inappropriate for 

MRL consideration. 

The available data were considered inadequate for derivation of an acute-duration oral MRL for 

aluminum. Two studies were identified that provided sufficient information on the levels of aluminum in 

the basal diet. McCormack et al. (1979) and Domingo et al. (1989) did not find any significant alterations 

in pup viability/lethality, pup body weight, or the incidence of malformation in rats exposed to 110 mg 

Al/kg/day as aluminum chloride in the diet on gestation days 6–19 (McCormack et al. 1979) or 141 mg 

Al/kg/day as aluminum nitrate administered via gavage on gestation days 6–15 (Domingo et al. 1989). 

Neither study evaluated the potential neurotoxicity of aluminum following acute-duration exposure; 

intermediate-duration studies provide strong evidence that the nervous system (in adults and developing 

organisms) is the most sensitive target of aluminum toxicity. 

•	 An MRL of 1 mg Al/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to aluminum. 

A fair number of animal studies have examined the oral toxicity of aluminum following intermediateduration exposure. A subset of these studies that provide information on the aluminum content of the 

basal diet and involved exposure to aluminum via the diet or drinking water will be the focus of this 

discussion. With the possible exception of reproductive function, these studies have examined most 

potential end points of aluminum toxicity. Systemic toxicity studies have not consistently reported 

adverse effects in rats exposed to up to 284 mg Al/kg/day (Domingo et al. 1987b; Gomez et al. 1986; 

Konishi et al. 1996), mice exposed to doses as high as 195 mg Al/kg/day (Oteiza et al. 1989), or dogs 

exposed to doses as high as 88 mg Al/kg/day (Katz et al. 1984; Pettersen et al. 1990). An increased 

susceptibility to bacterial infections was observed in mouse dams exposed to 155 mg Al/kg/day as 

aluminum lactate in the diet on gestation day 1 through lactation day 21 (Yoshida et al. 1989). However, 

a similar aluminum dose did not result in a change in susceptibility in virgin female mice exposed to 

107 mg Al/kg/day as aluminum lactate in the diet for 6 weeks (Yoshida et al. 1989). Immunological 

alterations (decreased spleen concentrations of interleukin-2, interferon g, and tumor necrosis factor and a 

decrease in CD4+ cells) were observed in mice exposed to 200 mg Al/kg/day as aluminum lactate in the 

diet on gestation day 1 through postnatal day 180 (Golub et al. 1993). There is limited information on the 

potential for aluminum to induce reproductive effects. Although a number of studies have reported no 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 19 

2. RELEVANCE TO PUBLIC HEALTH 

alterations in the occurrence of resorption, litter size, sex ratio, or pup body weight, no studies have 

examined fertility or potential effects on sperm morphology or motility. A significant alteration in 

gestation length was observed in mice exposed to 155 or 330 mg Al/kg/day as aluminum lactate in the 

diet on gestation day 1 through lactation 21 (Donald et al. 1989); in the aluminum exposed mice, 4 of the 

17 litters were born earlier or later (days 17, 19, or 20 versus day 18 in controls) than control litters. 

However, this has not been reported in other studies in mice or rats (Colomina et al. 2005; Golub and 

Germann 2001; Golub et al. 1992a, 1995). 

The preponderance of available intermediate-duration studies has focused on the potential for aluminum 

to induce neurological and neurodevelopmental effects. Although neurotoxicity of aluminum has not 

been established in people with normal renal function, the data for dialysis encephalopathy (as well as 

some occupational studies) establish that the human nervous system is susceptible to aluminum and 

neurotoxicity is a well-documented effect of aluminum in orally-exposed in mice and rats. A wide 

variety of behavioral tests were conducted in rats and mice, in which the most consistently affected 

behaviors involve motor function. Alterations in forelimb and hindlimb grip strength have been observed 

in adult mice exposed to 195 mg Al/kg/day as aluminum lactate in the diet for 90 days (Golub et al. 

1992b), mice (6 weeks of age at study beginning) exposed to 195 mg Al/kg/day as aluminum lactate in 

the diet for 5–7 weeks (Oteiza et al. 1993), the offspring of mice exposed on gestation day 1 through 

lactation day 21 to 155 mg Al/kg/day (Donald et al. 1989; Golub et al. 1995) or 250 mg Al/kg/day (Golub 

et al. 1995) as aluminum lactate, and the offspring of rats exposed to 103 mg Al/kg/day as aluminum 

nitrate in drinking water (with added citric acid) for 15 days prior to mating and on gestation 

day 1 through lactation day 21 (Colomina et al. 2005). Decreases in spontaneous motor activity were 

observed in mice exposed to 130 mg Al/kg/day for 6 weeks (Golub et al. 1989) or 195 mg Al/kg/day for 

90 days (Golub et al. 1992b). Motor impairments have also been detected in mice in the wire suspension 

test in which offspring exposed to 130 mg Al/kg/day had a shorter latency to fall from the wire and in the 

rotorod test in which offspring exposed to 260 mg Al/kg/day had a higher number of rotations (which 

occur when the animals lost its footing, clung to the rod, and rotated with it for a full turn) (Golub and 

Germann 2001). Neurobehavioral alterations that have occurred at similar dose levels include decreased 

responsiveness to auditory or air-puff startle (Golub et al. 1992b, 1995), decreased thermal sensitivity 

(Golub et al. 1992a), increased negative geotaxis latency (Golub et al. 1992a), and increased foot splay 

(Donald et al. 1989). Additionally, one study found significant impairment in performance of the water 

maze test in offspring of mice exposed to 130 mg Al/kg/day on gestation day 1 through lactation 

day 21 (Golub and Germann 2001). Colomina et al. (2005) did not find alterations in this test in rats 

exposed to 53 mg Al/kg/day; however, this study did not run probe tests, which showed significant 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 20 

2. RELEVANCE TO PUBLIC HEALTH 

alterations in the Golub and Germann (2001) study. Other studies have utilized passive avoidance tests or 

operant training tests to evaluate potential impairment of cognitive function. However, the interpretation 

of the results of these tests is complicated by an increase in food motivation in aluminum exposed mice 

(Golub and Germann 1998). 

There is also strong evidence that gestational and/or lactational exposure can cause other developmental 

effects. Gestation and/or lactation exposure can result in significant decreases in pup body weight gain in 

rats and mice (Colomina et al. 2005; Golub and Germann 2001; Golub et al. 1992a). The decreases in 

pup body weight are often associated with decreases in maternal body weight during the lactation phase 

of the study; however, decreases in body weight have also been observed in a cross-fostering study when 

gestation-exposed pups were nursed by control mice (Golub et al. 1992a). Other studies involving 

gestation and lactation exposure to aluminum did not find changes in pup growth in mice (Donald et al. 

1989; Golub and Germann 1998; Golub et al. 1995). In rats, a delay in physical maturation, particularly 

delays in vagina opening, testes descent, and incisor eruption, has been reported at 53 mg Al/kg/day 

(Colomina et al. 2005). In the Colomina et al. (2005) study, a delay in vagina opening was observed in 

rat offspring exposed to 53 mg Al/kg/day. The number of days to vagina opening was 31.1, 40.9, and 

45.9 days in the control, 53, and 103 mg Al/kg/day groups, respectively. Delays in maturations were also 

observed for testes descent (23.9, 22.8, and 27.1 days in the control, 53, and 103 mg Al/kg/day groups, 

significant at 103 mg Al/kg/day) and incisor eruption in males (5.5, 6.1, and 5.3 days, significant at 53 mg 

Al/kg/day, but not at 103 mg Al/kg/day). Significant delays in vagina opening and testes descent were 

also observed at 103 mg Al/kg/day in the offspring of rats similarly exposed but with the addition of 

restraint stress on gestation days 6–20. The mean number of days to maturation in the control, 53, and 

103 mg Al/kg/day groups were 32.5, 40.4, and 44.9 days for vagina opening and 24.9, 23.2, and 27.7 days 

for testes descent. However, another study by Colomina et al. (1999) did not find significant delays in 

vagina opening or testes descent, but did find significant delays in pinna attachment and eye opening 

following administration of 75 mg/kg/day (15 mg Al/kg/day) aluminum chloride via intraperitoneal 

injection to mice on gestation days 6–15. Another study did not find delays in pinna attachment, eye 

opening, or incisor eruption in the offspring of rats administered via gavage 73 mg Al/kg/day as 

aluminum chloride (aluminum content of the diet was not reported) on gestation days 8–20 (Misawa and 

Shigeta 1992). Collectively, these studies provide equivocal evidence that aluminum induces delays in 

maturation. 

The Golub et al. (1989), Golub and Germann (2001), and Colomina et al. (2005) studies identified the 

lowest LOAELs for the critical effects (neurotoxicity, neurodevelopmental toxicity, and delays in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 21 

2. RELEVANCE TO PUBLIC HEALTH 

maturation) and were considered as possible principal studies. Golub et al. (1989) identified the lowest 

LOAEL for neurotoxicity. In this study in which mice were exposed to aluminum lactate in the diet for 

6 weeks, significant decreases in total activity and vertical activity (rearing) were observed at 130 mg 

Al/kg/day; no significant alterations were observed at 62 mg Al/kg/day. One limitation of this study is 

that motor activity was the only neurobehavioral test evaluated; other studies have shown that grip 

strength is one of the more sensitive end points. Golub and Germann (2001) examined a number of 

sensitive end points of neurodevelopmental toxicity in the offspring of mice exposed to aluminum lactate 

in the diet on gestation day 1 through lactation day 21, after which the pups were fed a diet containing the 

same levels of aluminum as the dams on postnatal days 21–35. The study identified a NOAEL of 26 mg 

Al/kg/day and a LOAEL of 130 mg Al/kg/day for alterations in tests of motor function (a shorter latency 

to fall off a wire) and cognitive function (impaired performance in the water maze test). This study used a 

suboptimal diet, which complicates the interpretation of the study results. The dietary levels of 

phosphorus, calcium, magnesium, iron, and zinc were lower than the National Research Council’s 

recommendation in an attempt to mimic the intakes of these nutrients by young women. The 

investigators noted that even though the intakes of several nutrients were below the recommendations, the 

diet was not deficient. The impact of the suboptimal diet on the developmental toxicity of aluminum is 

not known. The observed effects are similar to those reported in other studies, as are the adverse effect 

levels. In the Colomina et al. (2005) study, a significant decrease in forelimb grip strength was observed 

in the offspring of rats exposed to 103 mg Al/kg/day as aluminum nitrate in the drinking water (with citric 

acid added to increase aluminum absorption) for 15 days prior to mating and during gestation and 

lactation; grip strength was not adversely affected at 53 mg Al/kg/day. This study also found significant 

delays in vagina opening at 53 mg Al/kg/day. As previously noted, there are limited data to confirm or 

refute the identification of delays in maturation as a critical effect of aluminum. The delays in maturation 

may be secondary to decreases in maternal weight or food intake or decreases in pup body weight and/or 

food intake; however, these data are only reported for some time periods. The Golub et al. (1989) study 

was not selected as the principal study because the NOAEL of 62 mg Al/kg/day identified in this study is 

higher than the dose associated with delayed maturation in the Colomina et al. (2005) study. The Golub 

and Germann (2001) and Colomina et al. (2005) studies were selected as co-principal studies. A short 

description of these studies follows. 

In the Golub and Germann (2001) study, groups of pregnant Swiss Webster mice were exposed to 0, 100, 

500, or 1,000 mg Al/kg diet on gestational days 0–21 and during lactation until day 21. On postnatal day 

(PND) 21, one male and one female pup from each litter were placed on the same diet as the dam. The 

offspring were exposed until PND 35. The composition of the diet was modified from the National 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 22 

2. RELEVANCE TO PUBLIC HEALTH 

Research Council's recommendations; the investigators noted that the nutrients were reduced to 

correspond to the usual intake of these nutrients by young women. The average daily intakes of 

phosphorus, calcium, magnesium, iron, and zinc in women aged 18–24 years are 83, 56, 71, 69, and 67% 

of the recommended dietary allowance (RDA); these percents were used to modify the recommended 

dietary intake for the mice used in this study. Doses of 26, 130, and 260 mg Al/kg/day are calculated by 

averaging reported estimated doses of 10, 50, and 100 mg Al/kg/day for adults (i.e., at beginning of 

pregnancy) and 42, 210, and 420 mg Al/kg/day maximal intake during lactation. The doses at lactation 

were calculated using doses estimated in previous studies with similar exposure protocols performed by 

the same group of investigators (Golub et al. 1995). At 3 months of age, the females were tested for 

neurotoxicity using the Morris water maze. At 5 months of age, males were tested for motor activity and 

function using rotarod, grip strength, wire suspension, mesh pole descent, and beam traversal tests. No 

alterations in pregnancy weight gain or pup birth weights were observed. At PND 21, significant 

decreases in pup body weights were observed at 130 and 260 mg Al/kg/day. No information on maternal 

weight gain during lactation was reported; however, the investigators noted that the decrease in pup 

weight was not associated with reduced maternal food intake. At PND 35, the decrease in body weight 

was statistically significant at 260 mg Al/kg/day. On PND 90, female mice in the 260 mg Al/kg/day 

group weighed 15% less than controls. Decreases in heart and kidney weights were observed at 260 mg 

Al/kg/day in the females. Also, increases in absolute brain weight were observed in females at 26 mg 

Al/kg/day and relative brain weights were observed at 26 or 260 mg Al/kg/day, but not at 130 mg 

Al/kg/day. In the males, significant decreases in body weight were observed at 130 (10%) and 260 (18%) 

mg Al/kg/day at 5 months; an increase in food intake was also observed at these doses. In the Morris 

maze (tested at 3 months in females), fewer animals in the 260 mg Al/kg/day group had escape latencies 

of <60 seconds during sessions 1–3 (learning phase) and a relocation of the visible cues resulted in 

increased latencies at 130 and 260 mg Al/kg/day. Body weight did not correlate with latency to find the 

platform or with the distribution of quadrant times. The investigators concluded that controls used salient 

and/or nonsalient cues, 26 and 130 mg Al/kg/day animals used both cues, but had difficulty using only 

one cue, and 260 mg Al/kg/day animals only used the salient cues. In the males tested at 5 months, a 

significant decrease in hindlimb grip strength was observed at 260 mg Al/kg/day, an increase in the 

number of rotations on the rotorod as observed at 260 mg Al/kg/day, and a shorter latency to fall in the 

wire suspension test was observed at 130 and 260 mg Al/kg/day. The investigators noted that there were 

significant correlations between body weight and grip strength and number of rotations. When hindlimb 

grip strength was statistically adjusted for body weight, the aluminum-exposed mice were no longer 

significantly different from controls; the number of rotations was still significantly different from control 

after adjustment for body weight. 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 23 

2. RELEVANCE TO PUBLIC HEALTH 

In the Colomina et al. (2005) study, groups of female Sprague Dawley rats were exposed to 0, 50, or 

100 mg Al/kg/day aluminum nitrate nonahydrate in drinking water; citric acid (710, 355, and 

710 mg/kg/day in the control, 50, and 100 ppm groups, respectively) was added to the drinking water to 

increase aluminum absorption. The adult rats were exposed to aluminum for 15 days prior to mating and 

during gestation and lactation periods; after weaning, the pups were exposed to the same aluminum 

concentration as the mothers from PND 21 through 68. The basal diet (Panlab rodent chow) contained 

41.85 μg Al/g diet. Aluminum doses were calculated by adding the basal dietary aluminum doses

(calculated using reference values for mature Sprague-Dawley rats) to reported aluminum doses from 

water; the total aluminum doses were 3, 53, and 103 mg Al/kg/day. In addition to aluminum exposure, 

some animals in each group underwent restraint stress for 2 hours/day on gestation days 6–20; the 

restraint consisted of placing the rats in cylindrical holders. The following neurobehavioral tests were 

performed on the offspring: righting reflex (PNDs 4, 5, 6), negative geotaxis (PNDs 7, 8, 9), forelimb 

grip strength (PNDs 10–13), open field activity (PND 30), passive avoidance (PND 35), and water maze 

(only tested at 53 mg/kg/day on PND 60). The rats were killed on PND 68. No significant alterations in 

body weight, food consumption, or water consumption were observed during gestation in the dams 

exposed to aluminum. The investigators noted that decreases in water and food consumption were 

observed during the lactation period in the rats exposed to 103 mg Al/kg/day, but the data were not shown 

and maternal body weight during lactation was not mentioned. No significant alterations in the number of 

litters, number of fetuses per litter, viability index, or lactation index were observed. Additionally, no 

differences in days at pinna detachment or eye opening were observed. Age at incisor eruption was 

significantly higher in males exposed to 53 mg/kg/day, but not in males exposed to 103 mg/kg/day or in 

females. A significant delay in age at testes descent was observed at 103 mg/kg/day and vagina opening 

was delayed at 53 and 103 mg/kg/day. A decrease in forelimb grip strength was observed at 

103 mg/kg/day; no alterations in other neuromotor tests were observed. Additionally, no alterations in 

open field behavior or passive avoidance test were observed. In the water maze test, latency to find the 

hidden platform was decreased in the 53 mg/kg/day group on test day 2, but not on days 1 or 3; no 

significant alteration in time in the target quadrant was found. 

The Golub and Germann (2001) and Colomina et al. (2005) studies identify four end points that could be 

used as the point of departure for derivation of the intermediate-duration oral MRL: 

(1) latency to fall off wire in wire suspension test; adverse effect level of 130 mg Al/kg/day, no 

effect level of 26 mg Al/kg/day (Golub and Germann 2001); 
 

 

 

 

 

 

 

 

ALUMINUM 24 

2. RELEVANCE TO PUBLIC HEALTH 

(2) latency to locate the platform following cue relocation in the water maze test; adverse effect 

level of 130 mg Al/kg/day, no effect level of 26 mg Al/kg/day (Golub and Germann 2001); 

(3) decreased forelimb grip strength; adverse effect level of 103 mg Al/kg/day, no effect level of 

53 mg Al/kg/day (Colomina et al. 2005); and 

(4) delay in vagina opening; adverse effect level of 53 mg Al/kg/day, no effect level not 

identified (Colomina et al. 2005). 

Benchmark dose (BMD) modeling was considered for each of these end points. As discussed in 

Appendix A, BMD modeling was not used to identify the point of departure due to incomplete reporting 

of the data or because the models did not provide adequate fit. 

Using a NOAEL/LOAEL approach, the NOAEL of 26 mg Al/kg/day identified in the Golub and 

Germann (2001) study was selected as the point of departure for the MRL. An MRL based on this 

NOAEL should be protective for neurological effects, neurodevelopmental effects, and for delays in 

maturation. Dividing the NOAEL by an uncertainty factor of 100 (10 to account for the extrapolation 

from mice to humans and 10 for human variability) and a modifying factor of 0.3 to account for possible 

differences in the bioavailability of the aluminum lactate used in the Golub and Germann (2001) study 

and the bioavailability of aluminum from drinking water and a typical U.S. diet results in an MRL of 

1 mg Al/kg/day. No studies were identified that estimated the bioavailability of aluminum lactate 

following long-term dietary exposure; however, a bioavailability of 0.63% was estimated in rabbits 

receiving a single dose of aluminum lactate (Yokel and McNamara 1988). Yokel and McNamara (2001) 

and Powell and Thompson (1993) suggest that the bioavailability of aluminum from the typical U.S. diet 

was 0.1%; the bioavailability of aluminum from drinking water ranges from 0.07 to 0.39% (Hohl et al. 

1994; Priest et al. 1998; Stauber et al. 1999; Steinhausen et al. 2004). These data suggest that aluminum 

lactate has a higher bioavailability than aluminum compounds typically found in drinking water or the 

diet. 

•	 An MRL of 1 mg Al/kg/day has been derived for chronic-duration oral exposure (365 days or 

longer) to aluminum. 

A small number of animal studies examined the chronic toxicity of aluminum. Schroeder and Mitchener 

(1975a, 1975b) examined the systemic toxicity of aluminum following lifetime exposure of rats and mice 

to very low doses of aluminum sulfate in the drinking water. Although the levels of aluminum in the diet 

were not reported, they are assumed to be low because the animals were fed a low-metal diet in metal-free 

environmental conditions. Studies conducted by Roig et al. (2006) and Golub et al. (2000) primarily 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 25 

2. RELEVANCE TO PUBLIC HEALTH 

focused on the neurotoxicity of aluminum following lifetime exposure (gestation day 1 through 

24 months of age). In the Golub et al. (2000) study, significant decreases in forelimb and hindlimb grip 

strength, and a decrease in thermal sensitivity were observed in mice exposed to 100 mg Al/kg/day; 

negative geotaxis was significantly altered at 18 months, but not at 24 months. No effect on horizontal 

activity was observed. A 10% increase in body weight and a 20% decrease in body weight were observed 

in the males and females, respectively. In a companion study by this group, no significant cognitive 

impairments were found in the Morris water maze test; in fact, aluminum-exposed mice performed better 

than controls in the learning tasks. Roig et al. (2006) also found no significant alterations in performance 

on the Morris water maze in rats exposed to 100 mg Al/kg/day as aluminum nitrate in the drinking water 

(with added citric acid). Although significant differences were found between the two aluminum groups 

(50 and 100 mg Al/kg/day); this was primarily due to the improved performance (as compared to 

controls, no significant differences) in the 50 mg Al/kg/day group. Roig et al. (2006) also found no 

significant alterations in open field activity. 

Based on the results of these chronic-duration studies, the decreases in forelimb and hindlimb grip 

strength and the decrease in thermal sensitivity identified in the Golub et al. (2000) study were selected as 

the critical effect for derivation of a chronic-duration oral MRL for aluminum. The selection of these end 

points, and neurotoxicity in general, is well supported by the findings of a number of intermediateduration studies that indicate that this is one of the most sensitive targets of aluminum toxicity (Colomina 

et al. 2005; Donald et al. 1989; Golub and Germann 2001; Golub et al. 1992a, 1995). 

In the Golub et al. (2000) study, groups of 8 male and 10 female Swiss Webster mice were exposed to 

7 or 1,000 μg Al/g diet as aluminum lactate in a purified diet. The investigators estimated adult doses of 

<1 and 100 mg/kg/day. The mice were exposed to aluminum from conception (via feeding the dams) 

through 24 months of age. Body weight, food intake, and clinical signs were determined during the last 

6 months of the study. A neurobehavioral test battery (foot splay, temperature sensitivity, negative 

geotaxis, and grip strength), 1 hour spontaneous activity measurement, and auditory startle tests were 

conducted at 18 and 24 months. In a companion study, groups of 6–9 male and female Swiss Webster 

mice or 7 male and female C57BL/6J mice (number per sex were not reported) were exposed to 7 or 

1,000 μg Al/g diet as aluminum lactate in a purified diet (<1 and 100 mg/kg/day) from conception (via 

feeding the dams) through 24 months of age. Body weight, food intake, and clinical signs were 

determined during the last 6 months of the study. A neurobehavioral test battery (foot splay, temperature 

sensitivity, negative geotaxis, and grip strength) and Morris maze testing were performed at 22– 

23 months of age. In the principal study, no significant alterations in mortality were observed. A 
 

 

 

 

 

 

 

ALUMINUM 26 

2. RELEVANCE TO PUBLIC HEALTH 

significant decrease in body weight was observed in the female mice (approximately 20%). In the males, 

there was a significant increase in body weight (approximately 10%). No significant alterations in food 

intake were observed in either sex. However, food intake/g body weight was significantly higher in the 

aluminum-exposed mice. No significant alterations in the occurrence of clinical signs or indications of 

neurodegenerative syndromes were found. Significant increases in relative spinal cord, heart, and kidney 

weights were found. Significant alterations in negative geotaxis and tail withdrawal time in the 

temperature sensitivity test (males only) were observed at 18 months. At 24 months, significant 

alterations in forelimb and hindlimb grip strength and temperature sensitivity were found in male and 

female mice. Forelimb and hindlimb grip strengths were decreased and thermal sensitivity was 

decreased, as evidenced by an increase in tail withdrawal times. Auditory startle response tests could not 

be completed in the older mice. Similarly, vertical spontaneous movement could not be measured; no 

effect on horizontal movement was found. In the companion study, no alterations in neurobehavioral 

battery test performance were observed; the investigators note that this may be due to the small number of 

animals per group. In general, aluminum-exposed mice performed better on the water maze test than 

controls. 

A chronic-duration oral MRL was derived using the LOAEL of 100 mg Al/kg/day for decreased forelimb 

and hindlimb grip strength and decreased thermal sensitivity identified in the Golub et al. (2000) study. A 

BMD approach for deriving an MRL was not utilized because the Golub et al. (2000) study only tested 

one aluminum group. The MRL of 1 mg Al/kg/day was calculated by dividing the LOAEL of 100 mg 

Al/kg/day by an uncertainty factor of 300 (3 for use of a minimal LOAEL, 10 for extrapolation from 

animals to humans, and 10 for human variability) and a modifying factor of 0.3 to account for possible 

differences in the bioavailability of the aluminum lactate used in the Golub and Germann (2001) study 

and the bioavailability of aluminum from drinking water and a typical U.S. diet. No studies were 

identified that estimated the bioavailability of aluminum lactate following long-term dietary exposure; 

however, a bioavailability of 0.63% was estimated in rabbits receiving a single dose of aluminum lactate 

(Yokel and McNamara 1988). Yokel and McNamara (2001) and Powell and Thompson (1993) suggest 

that the bioavailability of aluminum from the typical U.S. diet was 0.1%; the bioavailability of aluminum 

from drinking water ranges from 0.07 to 0.39% (Hohl et al. 1994; Priest et al. 1998; Stauber et al. 1999; 

Steinhausen et al. 2004). These data suggest that aluminum lactate has a higher bioavailability than 

aluminum compounds typically found in drinking water or the diet. 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 27 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of aluminum. It 

contains descriptions and evaluations of toxicological studies and epidemiological investigations and 

provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. 

Once mineral-bound aluminum is recovered from ores, it forms metal compounds, complexes, or 

chelates. Examples of the different forms of aluminum include aluminum oxide, aluminum chlorhydrate, 

aluminum hydroxide, aluminum chloride, aluminum lactate, aluminum phosphate, and aluminum nitrate. 

The metal itself is also used. With the exception of aluminum phosphide, the anionic component does not 

appear to influence toxicity, although it does appear to influence bioavailability. Aluminum phosphide, 

which is used as a pesticide, is more dangerous than the other forms; however, this is because of the 

evolution of phosphine gas (a potent respiratory tract and systemic toxin) rather than to the exposure to 

aluminum. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that 

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress 

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, 

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a 
 

 

 

 

 

 

 

 

ALUMINUM 28 

3. HEALTH EFFECTS 

considerable amount of judgment may be required in establishing whether an end point should be 

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be 

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the 

Agency has established guidelines and policies that are used to classify these end points. ATSDR 

believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between 

"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is 

considered to be important because it helps the users of the profiles to identify levels of exposure at which 

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not 

the effects vary with dose and/or duration, and place into perspective the possible significance of these 

effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user's perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

No studies were located regarding death following acute- or intermediate-duration inhalation exposure to 

various forms of aluminum in humans. 

Several deaths have been reported after occupational exposure to a finely powdered metallic aluminum 

used in paints, explosives, and fireworks (Mitchell et al. 1961); it should be noted that changes in 

production technology have resulted in decreased occupational exposures to finely powdered aluminum. 

In one case, a 19-year-old male who worked in an atmosphere heavily contaminated with this powder 

developed dyspnea after 2.5 years. This symptom grew worse, and the man had to stop working 3 months 

later and died after a further 8 months. Before death, respiratory excursion was poor and chest X-rays 

showed signs of pulmonary nodular interstitial fibrosis. Of a total of 27 workers examined in this factory, 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 29 

3. HEALTH EFFECTS 

2 died and 4 others had radiological changes on chest X-rays. Total dust in the workplace air was 615– 

685 mg Al/m3

, and respirable dust was 51 mg Al/m3. Chemical analysis showed the dust to be 81% 

metallic aluminum and 17% various oxides and hydroxides of aluminum. There have also been a number 

of case reports of deaths of workers exposed to aluminum flake powder (McLaughlin et al. 1962), 

welding fumes (Hull and Abraham 2002), or smelter fumes (Gilks and Churg 1987); it is likely that the 

cause of death in these men was respiratory tract damage. 

No studies were located that evaluated death from an intermediate-duration inhalation exposure in 

animals to aluminum or its compounds. Of the experiments performed in animals, none has shown death 

from inhalation exposure to aluminum or its compounds. For example, no deaths were reported following 

an acute 4-hour exposure to up to 1,000 mg Al/m3 as aluminum oxide in groups of 12–18 male 

Fischer 344 rats (Thomson et al. 1986) or following chronic exposure to 2.18–2.45 mg Al/m3 as 

refractory alumina fiber for 86 weeks in groups of 50 male and female Wistar rats (Pigott et al. 1981). 

3.2.1.2 Systemic Effects 

No studies were located regarding gastrointestinal, dermal, or body weight effects in humans or metabolic 

effects in animals after acute-duration inhalation exposure to various forms of aluminum. 

The highest NOAEL values and all LOAEL values for inhalation exposure from each reliable study for 

systemic effects in each species and duration category for aluminum are shown in Table 3-1 and plotted 

in Figure 3-1. 

Respiratory Effects. No studies were located regarding respiratory effects following acute-duration 

inhalation exposure to various forms of aluminum in humans. 

A number of studies have examined the potential for airborne aluminum to induce respiratory effects in 

chronically exposed workers. Exposure to aluminum fumes and dust occurs in potrooms where hot 

aluminum metal is recovered from ore, in foundries where aluminum alloys are melted and poured into 

molds, in welding operations, and the production and use of finely powdered aluminum. Because these 

workers were also exposed to a number of other toxic chemicals including sulfur dioxide, polycyclic 

aromatic hydrocarbons (PAHs), carbon monoxide, hydrogen fluoride, and chlorine, it is difficult to 

ascribe the respiratory effects to aluminum. Wheezing, dyspnea, and/or impaired lung function have been 
050

1010

20050

023

3333

404

3

7

405

10

Table 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Systemic 

1 Rat 

(Fischer- 344) 

5 x 4 hr 

System 

Resp

NOAEL 

(mg/m3) 

10 M 

Less Serious 

(mg/m3) 

200 M (multifocal 

microgranulomas in lungs) 

LOAEL 

Serious 

(mg/m3) 

Reference Chemical Form 

Thomson et al. 1986 Aluminum flakes 

50 M (increased lactate 

dehydrogenase, glucose6-phosphate dehydrogenase, and alkaline phosphatase activity in lavage fluid) 

2 Hamster 

(Golden Syrian) 

3 d 4 or 6 hr/d (NS) 

Resp 33 M (alveolar wall thickening 

and increased number of macrophages; bronchopneumonia) 

Drew et al. 1974 Aluminum chlorhydrate 

Bd Wt 33 M (unspecified decreased 

body weight) 

3 Hamster 

(Golden Syrian) 

3 d 4 or 6 hr/d (NS) 

Resp 3 M 7 M (13% increased lung 

weight) 

Drew et al. 1974 Aluminum chlorhydrate 

4 Hamster 

(Golden Syrian) 

3 d 4 hr/d (NS) 

Resp 10 M (approximately 24% 

increased lung weight) 

Drew et al. 1974 Aluminum chlorhydrate 
410

31

409

43

022

0.061

0.61

6.16.16.16.16.16.16.16.16.16.1

Table 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

5 Hamster 3 d 

(Golden Syrian) 

4 hr/d 

6 Rabbit 5 d 

4 hr/d (New

Zealand) (NS)

INTERMEDIATE EXPOSURE Systemic 

7 Rat 6 mo 

5 d/wk (Fischer- 344) 6 hr/d (NS) 

System 

Resp Resp Resp Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Dermal Ocular Bd Wt 

LOAEL 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

Serious 

(mg/m3) 

Reference Chemical Form 

31 (alveolar wall thickening 

and increased number of macrophages and heterophils) 

Drew et al. 1974 Aluminum chlorhydrate 

43 (alveolar wall thickening, 

increased number of macrophage; 65% increase in lung weight) 

Drew et al. 1974 Aluminum chlorhydrate 

0.061 0.61 (increase in alveolar 

macrophages; granulomatous lesions in lungs) 

Steinhagen et al. 1978 Aluminum chlorhydrate 

6.1 

6.1 6.1 6.1 6.1 6.1 6.1 6.1 6.1 

6.1 
580

0.065

0.65

5.45.4

021

0.061

0.61

6.16.16.16.16.16.16.16.16.16.1

Table 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (continued) 

Exposure/ 

Duration/ 

a 

Key to Species Frequency 

Figure (Strain) (Route) 

8 Rat 6 mo 

5 d/wk (Fischer- 344) 6 hr/d 

9 Gn Pig 6 mo 

5 d/wk (Hartley) 6 hr/d (NS) 

System 

Resp Hemato Bd Wt Resp Cardio Gastro Hemato Musc/skel Hepatic Renal Endocr Dermal Ocular Bd Wt 

LOAEL 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

Serious 

(mg/m3) 

Reference Chemical Form 

0.065 M 0.65 M (12% increased relative 

lung weight) 

Stone et al. 1979 Aluminum chlorhydrate 

5.4 

5.4 

0.061 0.61 (increase in alveolar 

macrophages; granulomatous lesions in lungs) 

Steinhagen et al. 1978 Aluminum chlorhydrate 

6.1 

6.1 6.1 6.1 6.1 6.1 6.1 6.1 6.1 

6.1 
581

0.65

5.4

5.45.4

019

10

020

2.45

582

0.65

5.4

5.40.65

5.4

583

0.065

5.4

Table 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (continued) 

Exposure/ LOAEL 

Duration/ 

a 

Key to 

Figure 

Species 

(Strain) 

Frequency 

(Route) System NOAEL (mg/m3) Less Serious (mg/m3) Serious (mg/m3) 

10 Gn Pig 

(Hartley) 

6 mo 5 d/wk 6 hr/d 

Resp 0.65 5.4 (19-23% increased 

relative lung weight) 

Hemato Bd Wt 

5.4 

5.4 

11 Hamster 

(Golden Syrian) 

5 or 6 wk 5 d/wk 6 hr/d 

Resp 10 M (alveolar thickening and 

increased number of foci of macrophages and heterophils) 

CHRONIC EXPOSURE Systemic 

12 Rat 

(Wistar) 

86 wk 5 d/wk 6 hr/d (NS) 

Resp 2.45 

13 Rat 

(Fischer- 344) 

12-24 mo 5 d/wk 6 hr/d 

Resp 0.65 5.4 (108-274% increased 

relative lung weight at 2 years) 

Hemato Bd Wt 

5.4 

0.65 5.4 (16-26% decrease in 

body weight at 2 years) 

14 Gn Pig 

(Hartley) 

12-21 mo 5 d/wk 6 hr/d 

Resp 0.065 M (21% increased relative 

lung weight at 2 years) 

Hemato 5.4 

Reference Chemical Form 

Stone et al. 1979 Aluminum chlorhydrate Drew et al. 1974 Aluminum chlorhydrate Pigott et al. 1981 Aluminum oxide Stone et al. 1979 Aluminum chlorhydrate Stone et al. 1979 Aluminum chlorhydrate 
5.4

Table 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (continued) 

Exposure/ LOAEL 

Duration/ 

a 

Key to Species Frequency NOAEL Less Serious Serious Reference (Route) Figure (Strain) System (mg/m3) (mg/m3) (mg/m3) Chemical Form 

Bd Wt 5.4 

a The number corresponds to entries in Figure 3-1. Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; Gn pig = guinea pig; Gastro = gastrointestinal; Hemato = hematological; hr = hour(slowest-observed-adverse-effect level; M = male; mo = month(s); Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; NS = not specified; Res= week(s); x = time(s) 
R 

B 

yrotaripse

thgie y Wdo

35 

Figure 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation 

Acute (≤14 days) 

Systemic 

mg/m3 

1000 

1r 

100 

1r 

6h 

2s 2s 5s 

10 4s 1r 

3s 

3s 

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

ALUMINUM 

3. HEALTH EFFECTS 
Respiratory 

Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal Endocrine 

Figure 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

ALUMINUM

mg/m3 

100 

10 11s 

9g 7r 9g 7r 9g 7r 9g 7r 9g 7r 9g 7r 9g 7r 10g 10g 8r 

1 

10g 8r 9g 7r 

0.1 

8r 9g 7r 

0.01 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

36
Dermal 

Ocular Body Weight 

ALUMINUM

Figure 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (Continued)

Intermediate (15-364 days) 

Systemic 

mg/m3 

100 

10 

9g 7r 9g 7r 9g 7r 10g 8r 

1 

0.1 

0.01 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

37
Respiratory 

Hematological Body Weight 

ALUMINUM

Figure 3-1 Levels of Significant Exposure to Aluminum and Compounds - Inhalation (Continued)

Chronic (≤365 days) 

Systemic 

mg/m3 

10 

13r 14g 13r 14g 13r 

12r 

1 

13r 13r 

0.1 

14g 

0.01 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

38
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 39 

3. HEALTH EFFECTS 

observed in potroom workers (Bast-Pettersen et al. 1994; Chan-Yeung et al. 1983; Radon et al. 1999; 

Simonsson et al. 1985), foundry workers (Al-Masalkhi and Walton 1994; Burge et al. 2000; Halatek et al. 

2006), workers exposed to fine aluminum dust (including grinders) (Jederlinic et al. 1990; Korogiannos et 

al. 1998; Miller et al. 1984b), a worker spray painting with an aluminum paint (Bost and Newman 1993), 

and welders (Abbate et al. 2003; Herbert et al. 1982; Hull and Abraham 2002; Vandenplas et al. 1998), 

although other studies have not found a significant effect (Musk et al. 2000). Occupational asthma has 

been reported in aluminum potroom workers (as reviewed by Abramson et al. 1989 and Kilburn 1998); 

there is some debate whether the asthma is related to exposure to respiratory irritants, such as hydrogen 

fluoride and chlorine, or due to aluminum exposure. Case reports provide suggestive evidence that 

chronic exposure to aluminum may cause occupational asthma. An asthmatic reaction was observed 

following a bronchial provocation test an aluminum foundry worker (Burge et al. 2000) and an aluminum 

welder (Vandenplas et al. 1998). 

Pulmonary fibrosis is the most commonly reported respiratory effect observed in workers exposed to fine 

aluminum dust (pyropowder), alumina (aluminum oxide), or bauxite. However, conflicting reports are 

available on the fibrogenic potential of aluminum. In some of the cases, the fibrosis was attributed to 

concomitant exposure to other chemicals. For example, pulmonary fibrosis has been observed in a 

number of bauxite workers or potroom workers (De Vuyst et al. 1986; Gaffuri et al. 1985; Gilks and 

Churg 1987; Jederlinic et al. 1990; Jephcott 1948; Musk et al. 1980; Riddell 1948; Shaver 1948; Shaver 

and Riddell 1947); in these workers, it is very likely that there was simultaneous exposure to silica and 

that the latter was the causative agent rather than the aluminum. Some of the earliest cases of pulmonary 

fibrosis were reported in German munition workers exposed to pyropowder (Goralewski 1947). Case 

reports of fibrosis in workers exposed to finely ground aluminum have been also been reported by Edling 

(1961), McLaughlin et al. (1962), Mitchell et al. (1961), and Ueda et al. (1958). However, other studies 

have not found any radiological evidence of pulmonary fibrosis in workers exposed to alumina 

(Meiklejohn and Posner 1957; Posner and Kennedy 1967) or fine aluminum powder (Crombie et al. 

1944). It is believed that the conflicting study results are due to differences in the lubricant used to retard 

surface oxidation during milling (Dinman 1987). Stearic acid is the most commonly used lubricant in the 

aluminum industry; the stearic acid combines with the aluminum to form aluminum stearate. Exposure to 

the aluminum stearate does not appear to be fibrogenic to workers (Crombie et al. 1944; Meiklejohn and 

Posner 1957; Posner and Kennedy 1967). In contrast, the previous and now discontinued use of a 

nonpolar aliphatic oil lubricant, such as mineral oil, has been associated with fibrosis (Edling 1961; 

McLaughlin et al. 1962; Mitchell et al. 1961; Ueda et al. 1958). Pulmonary fibrosis has also been 

observed in an aluminum arc welder (Vallyathan et al. 1982), an aluminum production worker exposed to 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 40 

3. HEALTH EFFECTS 

aluminum oxide fumes (Al-Masalkhi and Walton 1994), and in workers in an unspecified aluminum 

industry (Akira 1995). There is also some evidence suggesting aluminum-induced pneumoconiosis (Hull 

and Abraham 2002; Korogiannos et al. 1998; Kraus et al. 2000), pulmonary alveolar proteinosis (Miller et 

al. 1984b), interstitial pneumonia (Herbert et al. 1982), and granulomas (Cai et al. 2007; Chen et al. 1978; 

De Vuyst et al. 1987); however, these reports are based on a small number of cases, which limits their 

interpretation. 

Respiratory effects typically associated with inhalation of particulates and lung overload have been 

observed in animals. The pulmonary toxicity of alchlor (a propylene glycol complex of aluminum 

chlorhydrate), a common component of antiperspirants, was examined in hamsters in a series of studies 

conducted by Drew et al. (1974). A 3-day exposure to 31 or 33 mg Al/m3 resulted in moderate-to-marked 

thickening of the alveolar walls due to neutrophil and macrophage infiltration and small granulomatous 

foci at the bronchioloalveolar junction (a likely site of particulate deposition). A decrease in the severity 

of the pulmonary effects was observed in animals killed 3, 6, 10, or 27 days after exposure termination. 

Similar pulmonary effects were observed in rabbits exposed to 42 mg Al/m3 for 5 days (Drew et al. 1974). 

Significant increases in absolute lung weights have been observed in hamsters exposed for 3 days to 

≥7 mg Al/m3 (no effects were observed at 3 mg Al/m3

) and in rabbits exposed to 43 mg Al/m3 for 5 days 

(no effects were observed in rabbits exposed to 48 or 39 mg Al/m3 for 1 or 4 days, respectively). In rats 

exposed to aluminum flakes for 5 days, there were alterations in the cytological (increase in the number of 

polymorphonuclear neutrophils [PMNs]) and enzymatic (increased activity of alkaline phosphatase and 

lactate dehydrogenase) content of the lavage fluid at ≥50 mg Al/m3 and multifocal microgranulomas in 

the lungs and hilar lymph nodes at ≥100 mg Al/m3 (Thomson et al. 1986). The enzymatic changes in the 

lavage fluid probably resulted from the presence of PMNs, increased phagocytosis of alveolar 

macrophages, and Type II cell hyperplasia. 

Similar pulmonary effects were observed in animals following intermediate-duration exposure. An 

increase in the number of alveolar macrophages and heterophils were observed in hamsters exposed to 

10 mg Al/m3 as alchlor for 6 hours/day, 5 days/week for 2, 4, or 6 weeks (Drew et al. 1974). The severity 

was directly related to exposure duration. Granulomatous nodules and thickening of the alveolar walls 

due to infiltration of heterophils and macrophages were observed 2 weeks after termination of a 6-week 

exposure. An increase in the number of alveolar macrophages and granulomatous lesions in the lungs and 

peribronchial lymph nodes were also observed in rats and guinea pigs exposed to 0.61 or 

6.1 mg Al/m3 aluminum chlorhydrate for 6 hours/day, 5 days/week for 6 months (Steinhagen et al. 1978); 

the severity of the alterations was concentration-related. In addition, statistically significant increases in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 41 

3. HEALTH EFFECTS 

absolute and relative lung weight were observed in the rats exposed to 6.1 mg Al/m3; the authors noted 

that pulmonary edema was not observed in these rats. No statistically significant histological alterations 

or changes in lung weight were observed at 0.061 mg Al/m3

. Suggestive evidence of alveolar 

macrophage damage was observed in rats following a 5-month exposure (6 hours/day, 5 days/week) to 

either aluminum chloride (0.37 mg Al/m3

) or aluminum fluoride (0.41 mg Al/m3); increases in lysozyme 

levels, protein levels (aluminum chloride only), and alkaline phosphatase (aluminum chloride only) were 

observed in the lavage fluid (Finelli et al. 1981). Alveolar proteinosis was observed in rats, guinea pigs, 

and hamsters exposed to ≥15, 20, or 30 mg/m3 of several types of aluminum flake powders; the particle 

sizes ranged from 2.5 to 4.8 μm (Gross et al. 1973). The investigators noted that aluminum powders did 

not induce pulmonary fibrosis in the guinea pigs or hamsters; in rats, foci of lipid pneumonitis were 

observed. A similar exposure to aluminum oxide did not result in alveolar proteinosis, pulmonary 

fibrosis, or pneumonitis; effects were limited to foci consisting of alveoli filled with macrophages; the 

particle size of the aluminum oxide dust was much smaller (0.8 μm) than the aluminum flake powders. 

Interpretation of this study is limited by the lack of incidence data and the high mortality observed in 

treated and control animals. 

There are limited data on the pulmonary toxicity of aluminum in animals following chronic exposure. 

Increases in relative lung weights (21–274%) have been observed in rats and guinea pigs exposed to 

5.1 mg Al/m3 aluminum chlorhydrate for 6 hours/day, 5 days/week for approximately 2 years (Stone et al. 

1979). Lung weights were not affected at 0.61 mg Al/m3

. It should be noted that this study did not 

conduct histological examinations of the lungs. Pigott et al. (1981) did not find evidence of lung fibrosis 

in rats exposed to 2.18 or 2.45 mg/m3 manufactured or aged Saffil alumina fibers; Saffil alumina fiber is a 

refractory material containing aluminum oxide and about 4% silica. The animals were exposed for 

86 weeks followed by a 42-week observation period. 

Cardiovascular Effects. No studies were located regarding cardiovascular effects of various forms 

of aluminum following acute- or intermediate-duration inhalation exposure in humans. Dilation and 

hypertrophy of the right side of the heart were reported in male factory workers chronically exposed by 

inhalation to aluminum flake powder and who eventually died (McLaughlin et al. 1962; Mitchell et al. 

1961). The cardiac effects may have been secondary to pulmonary fibrosis and poor pulmonary function. 

Epidemiological studies of aluminum industry workers failed to identify an increase in deaths related to 

cardiovascular disease (Milham 1979; Mur et al. 1987; Rockette and Arena 1983; Theriault et al. 1984a). 

Cohort sizes ranged from 340 to 21,829 men. Results of cardiovascular tests (electrocardiogram, blood 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 42 

3. HEALTH EFFECTS 

pressure measurement) were similar between 22 aluminum workers exposed for 10 years or more and an 

unexposed control group of 16 men (Bast-Pettersen et al. 1994). 

No histological alterations were observed in the hearts of Fischer 344 rats or Hartley guinea pigs exposed 

by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months 

(Steinhagen et al. 1978). 

Gastrointestinal Effects. No studies were located regarding gastrointestinal effects of various forms 

of aluminum following acute-, intermediate-, or chronic-duration inhalation exposure in humans or acuteor chronic-duration inhalation exposure in animals. No histological changes were observed in the 

gastrointestinal tissues of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 

5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months (Steinhagen et al. 1978). 

Hematological Effects. No studies were located regarding hematological effects of various forms of 

aluminum following acute-duration inhalation exposure in humans. No adverse hematological effects 

were noted in a group of seven workers following 6 months of exposure to aluminum fumes or dust 

(Mussi et al. 1984). Exposure levels from personal sampling ranged from 1 to 6.2 mg Al/m3

, 

predominantly as aluminum oxide. Decreased red blood cell hemoglobin and increased erythrocyte 

sedimentation rates were reported in the case of a male aluminum industry worker chronically exposed by 

inhalation to aluminum flake powder (McLaughlin et al. 1962). A prolongation of prothrombin time was 

seen in 30 of 36 aluminum workers chronically exposed by inhalation to alumina dust (Waldron-Edward 

et al. 1971). The authors suggested that increasing serum aluminum levels may be used to provide 

beneficial antithrombogenic effects (Waldron-Edward et al. 1971). 

No studies were located regarding hematological effects in animals after acute-duration inhalation 

exposure to aluminum or its compounds. No hematological effects were observed in Fischer 344 rats or 

Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum 

chlorhydrate for 6–24 months (Steinhagen et al. 1978; Stone et al. 1979). 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects following 

acute- or intermediate-duration inhalation exposure to various forms of aluminum in humans. Two case 

reports have been identified in which finger clubbing was observed in male factory workers chronically 

exposed to aluminum powder (De Vuyst et al. 1986; McLaughlin et al. 1962). Joint pain was reported by 

a female worker exposed by inhalation to dried alunite residue (a hydrated sulphate of aluminum and 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 43 

3. HEALTH EFFECTS 

potassium) for 18 months (Musk et al. 1980). Schmid et al. (1995) did not find any significant alterations 

in bone mineral content (assessed via osteodensitometry) in workers exposed to aluminum powder 

(average concentration 12.1 mg/m3

) for an average duration of 12.6 years. 

No studies were located regarding musculoskeletal effects following acute- or chronic-duration inhalation 

exposure to aluminum or its compounds in animals. No histological changes were observed in the muscle 

or bone of Fischer 344 rats or Hartley guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 

6.1 mg Al/m3 as aluminum chlorhydrate for 6 months (Steinhagen et al. 1978). 

Hepatic Effects. No studies were located regarding hepatic effects in humans following acute- or 

chronic-duration inhalation exposure to various forms of aluminum. Intermediate occupational inhalation 

exposure to aluminum fumes, dusts, or powders did not affect liver function or hepatic microanatomy in a 

group of seven workers as determined from biopsy samples (Mussi et al. 1984). 

In animals, no histological or organ weight changes were observed in livers of Fischer 344 rats or Hartley 

guinea pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate 

for 6 months (Steinhagen et al. 1978). No acute- or chronic-duration inhalation studies examining the 

liver were identified. 

Renal Effects. No studies were located regarding renal effects in humans following acute-duration 

inhalation exposure to various forms of aluminum. 

No adverse effects on renal function or standard urine tests have been noted in humans following 

intermediate-duration inhalation exposure to aluminum fumes or dust (Mussi et al. 1984) or chronicduration inhalation exposure to metallic aluminum powder (De Vuyst et al. 1987; McLaughlin et al. 

1962). 

No histological or organ weight changes were observed in kidneys of Fischer 344 rats or Hartley guinea 

pigs exposed by inhalation (6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 

6 months (Steinhagen et al. 1978). 

Endocrine Effects. No studies were located regarding endocrine effects in humans following acuteor intermediate-duration inhalation exposure to various forms of aluminum. Post-mortem enlargement of 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 44 

3. HEALTH EFFECTS 

the thyroid was reported in the case of a male factory worker chronically exposed by inhalation to 

aluminum flake powder (McLaughlin et al. 1962). 

No studies were located regarding endocrine effects in animals following acute- or chronic-duration 

inhalation exposure to aluminum or its compounds. No adverse histological changes were observed in the 

adrenal, thyroid, or pituitary glands of Fischer 344 rats or Hartley guinea pigs exposed by inhalation 

(6 hours/day, 5 days/week) to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months (Steinhagen et al. 

1978). 

Dermal Effects. No studies were located regarding dermal effects in animals following acute- or 

chronic-duration inhalation exposure to various forms of aluminum. No histologic changes of the skin 

were observed in Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as 

aluminum chlorhydrate for 6 months (Steinhagen et al. 1978). 

Ocular Effects. No studies were located regarding ocular effects in humans following acute- or 

intermediate-duration inhalation exposure to various forms of aluminum. No adverse effects were 

observed during an eye examination in a man chronically exposed by inhalation to metallic aluminum and 

aluminum oxide powders (De Vuyst et al. 1987). 

No studies were located regarding ocular effects in animals following acute- or chronic-duration 

inhalation exposure to aluminum or its compounds. No histological changes were observed in the eyes of 

Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as aluminum chlorhydrate 

for 6 months (Steinhagen et al. 1978). 

Body Weight Effects. No studies were located regarding body weight effects in humans following 

inhalation exposure to aluminum or its compounds. Unspecified body weight decreases were reported for 

male Golden Syrian hamsters acutely exposed via whole-body inhalation to 3, 10, or 33 mg Al/m3 as 

alchlor, a common component of antiperspirants (Drew et al. 1974). In contrast, no body weight effects 

were observed in Sprague-Dawley rats exposed by inhalation to 0.37 mg Al/m3 as aluminum chloride or 

0.41 mg Al/m3 as aluminum fluoride dust for 5 months (Finelli et al. 1981), or in Fischer 344 rats or 

Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as aluminum chlorhydrate for 6 months 

(Steinhagen et al. 1978) or to 0.61 mg Al/m3 as aluminum chlorhydrate for up to 24 months (Stone et al. 

1979). Significant reduction in body weight (>10%) was observed in Fischer 344 rats after 24 months of 

exposure to 6.1 mg/m3 as aluminum chlorhydrate. No effect on body weight was seen in Hartley guinea 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 45 

3. HEALTH EFFECTS 

pigs similarly exposed (Stone et al. 1979). These NOAEL and LOAEL values are recorded in 

Table 3-1 and plotted in Figure 3-1. 

Metabolic Effects. No studies were located regarding metabolic effects in humans following acuteor chronic-duration inhalation exposure to various forms of aluminum. No adverse effect on phosphate 

metabolism was identified in humans following intermediate-duration inhalation exposure to aluminum 

fumes or dust (Mussi et al. 1984). 

3.2.1.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological/lymphoreticular effects in humans after acute- or 

intermediate-duration inhalation exposure to various forms of aluminum. Helper T-lymphocyte alveolitis 

and blastic transformation of peripheral blood lymphocytes in the presence of soluble aluminum 

compounds in vitro were found in an individual with sarcoid-like epitheliod granulomas and exposed to 

metallic aluminum and aluminum dust (De Vuyst et al. 1987). Additional testing 1 year after termination 

of exposure indicated the man no longer had alveolitis. A significantly higher percentage of CD4-

CD8+ T 

lymphocytes were observed in aluminum electrolytic workers (He et al. 2003). 

Several animal studies have found histological alterations in the lymphoreticular system, in particular 

granulomas in the hilar lymph nodes; these effects are secondary to the pulmonary effects (Steinhagen et 

al. 1978; Thomson et al. 1986) and resulted from the removal of aluminum from the lungs by alveolar 

macrophages. 

3.2.1.4 Neurological Effects 

No studies were located regarding neurological effects in humans following acute- or intermediateduration inhalation exposure to various forms of aluminum. A number of studies have investigated the 

neurotoxic potential in workers chronically exposed to aluminum. With the exception of isolated cases 

(for example, McLaughlin et al. 1962), none of these studies reported overt signs of neurotoxicity in 

workers exposed to aluminum dust (potroom and foundry workers) (Bast-Pettersen et al. 1994; Dick et al. 

1997; Hosovski et al. 1990; Sim et al. 1997; White et al. 1992), in aluminum welders (Hänninen et al. 

1994; Sjögren et al. 1996), or in miners exposed to McIntyre powder (finely ground aluminum and 

aluminum oxide) (Rifat et al. 1990). Higher incidences of subjective neurological symptoms (e.g., 

incoordination, difficulty buttoning, problems concentrating, headaches, depression, fatigue) were 

reported in aluminum potroom or foundry workers at aluminum smelters (Halatek et al. 2005; Iregren et 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 46 

3. HEALTH EFFECTS 

al. 2001; Sim et al. 1997; Sińczuk-Walczak et al. 2003; White et al. 1992), workers exposed to aluminum 

flake powder (Iregren et al. 2001), and aluminum welders (Bast-Pettersen et al. 2000; Riihimäki et al. 

2000; Sjögren et al. 1990). Among the studies examining the potential association between neurological 

symptoms and aluminum exposure estimates (urinary and/or blood aluminum levels), some found a 

significant association (Riihimäki et al. 2000; Sińczuk-Walczak et al. 2003) and others did not (BastPettersen et al. 2000; Iregren et al. 2001; Kiesswetter et al. 2007). 

Subclinical effects have been reported in various types of aluminum workers. Significant alterations in 

performance tests assessing reaction time, eye-hand coordination, memory, and/or motor skills were 

found in aluminum foundry workers (Hosovski et al. 1990; Polizzi et al. 2001), aluminum welders (Akila 

et al. 1999; Bast-Pettersen et al. 2000; Buchta et al. 2005; Riihimäki et al. 2000; Sjögren et al. 1990), 

electrolyte workers (He et al. 2003), and miners exposed to McIntyre powder (Rifat et al. 1990). Three 

studies of aluminum welders did not find significant decrements in neurobehavioral performance as 

compared to controls; however, significant correlations between aluminum exposure estimates (urinary or 

plasma aluminum levels or air aluminum levels) and memory and/or reaction-time tests were found (BastPettersen et al. 2000; Buchta et al. 2003; Hänninen et al. 1994). Other studies did not find alterations in 

neuroperformance tests in aluminum potroom workers (Sim et al. 1997) or aluminum welders 

(Kiesswetter et al. 2007); two studies in aluminum welders did not find effects on motor performance 

(Buchta et al. 2003, 2005). A higher incidence of subclinical tremors was found in a study of potroom 

workers (Bast-Pettersen et al. 1994); another study did not find a significant alteration (Dick et al. 1997). 

Several studies have examined aluminum’s potential to induce quantitative EEG changes; some studies 

found alterations (Hänninen et al. 1994; Riihimäki et al. 2000; Sińczuk-Walczak et al. 2003) and others 

did not (Iregren et al. 2001). In general, the available occupational exposure studies poorly characterize 

aluminum exposure. Some of the studies reported aluminum air concentrations for a single time period 

(Dick et al. 1997; Sim et al. 1997; Sjögren et al. 1996; White et al. 1992) or a couple of time periods 

(Buchta et al. 2003; Kiesswetter et al. 2007), but did not have earlier monitoring data when aluminum 

exposures may have been higher. A meta-analysis using data from most of these studies found a 

statistically significant decline in performance on the digit symbol neurobehavioral test (Meyer-Baron et 

al. 2007). Although decreases in performance were observed for other neurobehavioral tests, the 

differences were not statistically significant. The lack of adequate exposure monitoring data, potential 

exposure to other neurotoxicants, and the different types of aluminum exposure make it difficult to draw 

conclusions regarding the neurotoxic potential of inhaled aluminum in workers. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 47 

3. HEALTH EFFECTS 

Three studies have examined the possible association between occupational exposure to aluminum and 

the risk of Alzheimer’s disease. Two case-control studies did not find a significant association between 

occupational exposure to aluminum dust or fumes and the risk of Alzheimer’s disease (Graves et al. 1998; 

Salib and Hillier 1996). Another study of former aluminum dust-exposed workers (retired for at least 

10 years) found some impairment in some tests of cognitive function; the investigators raised the 

possibility that cognitive impairment may be a pre-clinical indicator of Alzheimer’s disease (Polizzi et al. 

2002). 

No studies were located regarding neurological effects in animals following acute-duration inhalation 

exposure to various forms of aluminum. No brain weight or histological changes were observed in 

Fischer 344 rats or Hartley guinea pigs exposed by inhalation to up to 6.1 mg Al/m3 as aluminum 

chlorhydrate for 6 months (Steinhagen et al. 1978). No brain weight effects were observed in SpragueDawley rats exposed by inhalation to 0.37 mg Al/m3 as aluminum chloride or 0.41 mg Al/m3 as 

aluminum fluoride for 5 months, although tissues were not examined histologically (Finelli et al. 1981). 

No brain weights were observed in Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 

6.1 mg Al/m3 as aluminum chlorhydrate for up to 24 months (Stone et al. 1979). 

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans following acute-, intermediate-, or 

chronic-duration inhalation exposure to various forms of aluminum. 

No reliable studies were located regarding reproductive effects in animals following acute- or chronicduration inhalation exposure to various forms of aluminum. No histological changes were observed in 

reproductive tissues of Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 as 

aluminum chlorhydrate for 6 months (Steinhagen et al. 1978). These NOAEL values are recorded in 

Table 3-1 and plotted in Figure 3-1. 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure 

to various forms of aluminum. 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 48 

3. HEALTH EFFECTS 

3.2.1.7 Cancer 

No studies were located regarding cancer effects in humans following acute- or intermediate-duration 

inhalation exposure to various forms of aluminum. 

A reported high incidence of bladder cancer in a region of Quebec, Canada where aluminum production 

takes place (Wigle 1977) resulted in the initiation of a case-control study (Theriault et al. 1984a). 

Workers in five aluminum reduction plants were assessed with respect to incidence of bladder cancer. 

The number of men working in the plants was 300–1,200 except for one plant with 7,800 workers. The 

number of bladder cancer cases was collected from regional hospitals over a 10-year period, and the 

number of current or former employees from the aluminum plants identified. For each case, three 

controls who had never had bladder cancer were selected. Detailed occupational histories of each man 

(case and controls) were collected from the companies and included each division, department, and job to 

which the men had been assigned; smoking history; and estimated assessment of tar and PAH exposure 

(based on benzene soluble material and benz(a)pyrene concentrations in workplace air) for each 

occupation. An index of lifetime exposure of each worker to tar and PAHs was created. Over the 10-year 

study period, 488 cases of bladder cancer were found in men from the designated regions. Of these, 

96 were identified as being current or former aluminum company employees, and 11 were eliminated 

from the study because they had worked <12 months at the companies. The distribution of tumors was as 

follows: transitional epitheliomas grade I (n=3), grade II (n=43), grade III (n=18), and grade IV (n=21). 

The mean age at diagnosis was 61.7 years, and the mean age at first employment in aluminum work was 

28.2 years. The interval between beginning of employment in the aluminum industry and diagnosis was 

23.9 years. A higher proportion of cases than controls were smokers. The risk for bladder cancer was 

highest in workers in Soderberg reactor rooms (where the reduction process takes place), and risk 

increased steadily with time worked in this department. The risk also increased steadily with estimated 

exposure to tar and PAHs. The interaction between cigarette smoking and PAH exposure in the 

generation of bladder cancer was more than additive. 

Several studies on cancer mortality patterns have been conducted in aluminum reduction factory workers 

(Gibbs and Horowitz 1979; Milham 1979; Mur et al. 1987; Rockette and Arena 1983). The workplace 

inhalation exposure was to aluminum dust or fumes for chronic durations, but the exposure levels were 

not determined. In addition to aluminum, most workers were concurrently exposed by inhalation to 

known carcinogens, such as tobacco smoke or PAHs from coal tars. In a historical prospective study of 

2,103 aluminum production workers, standardized mortality ratios (SMRs) of 117 for lung cancer 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 49 

3. HEALTH EFFECTS 

(35 cases), 180 for pancreatic cancer (9 cases), and 184 for all lymphatic and hematopoietic cancers 

(17 cases) were observed (Milham 1979). Smoking histories were not available, and only the SMR for 

lymphatic and hematopoietic cancers were statistically significant. In a study that focused on mortality 

from lung cancer in a group of 5,406 aluminum production workers (Gibbs and Horowitz 1979), a doseresponse relationship was observed between lung cancer mortality and both years of exposure to tar and 

“tar-years” in specific occupations. A study of mortality patterns in 21,829 aluminum production workers 

in the United States (Rockette and Arena 1983) indicated that the risk of lung cancer mortality increased 

among workers with ≥25 years of experience in the carbon bake department, who presumably had higher 

exposure to potential hydrocarbon carcinogens than other workers. Increased deaths from bladder and 

hematolymphopoietic cancers were also reported. 

Based on current evidence, the International Agency for Research on Cancer (IARC) has stated (IARC 

1984) that “the available epidemiological studies provide limited evidence that certain exposures in the 

aluminum production industry are carcinogenic to humans, giving rise to cancer of the lung and bladder. 

A possible causative agent is pitch fume.” It is important to emphasize that the potential risk of cancer in 

the aluminum production industry is probably due to the presence of known carcinogens (e.g., PAHs) in 

the workplace and is not due to aluminum or its compounds. 

No reliable studies were located regarding cancer effects in animals following acute- or intermediateduration inhalation exposure to aluminum or its compounds. An increase in cancer was not observed in 

male and female Wistar rats exposed via whole-body inhalation to atmospheres containing 2.18– 

2.45 mg Al/m3 as alumina fibers (≈96% aluminum oxide) for 86 weeks (Pigott et al. 1981). 

3.2.2 Oral Exposure 

Major sources of human oral exposure to aluminum include food (due to its use in food additives, food 

and beverage packaging, and cooking utensils), drinking water (due to its use in municipal water 

treatment), and aluminum-containing medications (particularly antacid/antiulcer and buffered aspirin 

formulations) (Lione 1985b). Dietary intake of aluminum, estimated to be in the 0.10–0.12 mg Al/kg/day 

range in adults (Pennington and Schoen 1995), has not been of historical concern with regard to toxicity 

due to its presence in food and the generally recognized as safe (GRAS) status of aluminum-containing 

food additives by the FDA. Users of aluminum-containing medications that are healthy (i.e., have normal 

kidney function) can ingest much larger amounts of aluminum than in the diet, possibly as high as 12– 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 50 

3. HEALTH EFFECTS 

71 mg Al/kg/day from antacid/antiulcer products and 2–10 mg Al/kg/day from buffered analgesics when 

taken at recommended dosages (Lione 1985b). 

The oral toxicity of aluminum in animals is well-studied, although many of the studies are limited by a 

lack of reported information on aluminum content in the base diet. Commercial grain-based feeds for 

laboratory animals contain high levels of aluminum that typically far exceed the aluminum content of the 

human diet. Commercial laboratory animal chow can significantly contribute to total experimental 

exposure, as well as provide excess and variable amounts of essential and nonessential trace minerals and 

metal binding ligands that can alter aluminum uptake in comparison to diets that are semipurified or 

purified in which trace metal levels are precisely determined (Golub et al. 1992b). Base diets containing 

250–350 ppm Al were used in some rat and mouse studies, but this cannot be assumed to be a normal or 

representative concentration range because analyses for aluminum were not routinely performed, 

substantial brand-to-brand and lot-to-lot variations are apparent, and formal surveys of aluminum content 

of laboratory animal feed are not available. For example, concentrations ranging from 60 to 280 ppm Al 

for Panlab rodent standard diet (Colomina et al. 1998; Domingo et al. 1987a, 1993) and 120–8,300 ppm 

for Purina Rodent Laboratory Chow (Fleming and Joshi 1987; Provan and Yokel 1990; Varner et al. 

1994, 1998) have been reported. Due to the likelihood of significant base dietary exposure to aluminum, 

studies with insufficient information on aluminum content in the base diet must be assumed to 

underestimate the actual aluminum intake. The magnitude of the underestimate can be considerable. For 

example, based on approximate values of 250 ppm (Colomina et al. 1998; Domingo et al. 1993) and 

350 ppm (Oteiza et al. 1993) for Al in feed used in some studies in rats and mice, respectively, and using 

reference values for food consumption and body weight in rats and mice (EPA 1988) for ingestion during 

the period from weaning to 90 days, estimated doses of 25 mg Al/kg/day (rats) and 68 mg Al/kg/day 

(mice) may be provided by diet alone. These figures can represent a significant portion of the intake for 

which Table 3-2 reports health effects in animal studies. Consequently, although studies with inadequate 

data on base dietary levels of aluminum provide useful information on health effects of aluminum, 

NOAELs and LOAELs from these studies cannot be assumed to be accurate, they may not be suitable for 

comparison with effect levels from studies that used diets with known amounts of aluminum, and are not 

included in Table 3-2 and Figure 3-2. Studies for which data on base dietary aluminum content are 

available are mainly limited to those conducted by Golub and coworkers (Donald et al. 1989; Golub and 

Germann 1998, 2001; Golub et al. 1989, 1992a, 1992b, 1994, 1995, 2000; Oteiza et al. 1993) and 

Domingo and coworkers (Colomina et al. 1992, 1994, 1998, 2005; Domingo et al. 1987a, 1987b, 1989, 

1993; Gomez et al. 1986, 1991; Paternain et al. 1988; Roig et al. 2006). 
062

261

496

370

498

162

503

286

504

222

506

164

011

770

432

980

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Death 

1 Rat 

(SpragueDawley) 

once (G) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

261 (LD50) 

Reference Chemical Form 

Llobet et al. 1987 

Aluminum nitrate 

2 Rat 

(SpragueDawley) 

once (G) 370 (LD50) Llobet et al. 1987 Aluminum chloride 

3 Rat 

(SpragueDawley) 

once (G) 162 (LD50) Llobet et al. 1987 Aluminum bromide 

4 Mouse 

(SwissWebster) 

once (G) 286 (LD50) Llobet et al. 1987 Aluminum nitrate 

5 Mouse 

(SwissWebster) 

once (G) 222 (LD50) Llobet et al. 1987 Aluminum chloride 

6 Mouse 

(SwissWebster) 

once (G) 164 (LD50) Llobet et al. 1987 Aluminum bromide 

7 Mouse 

(Dobra Voda) 

once (G) 770 M (LD50) Ondreicka et al. 1966 Aluminum chloride 

8 Mouse 

(Dobra Voda) 

once (G) 980 M (LD50) Ondreicka et al. 1966 Aluminum sulfate 
607

540

042

110

038

141

843

97

005

284284284284284

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) System 

Exposure/ 

Duration/ 

Frequency 

(Route) NOAEL (mg/kg/day) 

LOAEL 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

9 Rabbit 

(New Zealand) 

once (GW) 

Developmental 

10 Rat 

(SpragueDawley) 

Gd 6-19 (F) 110 

540 F (5/5 died) Yokel and McNamara 1

Aluminum lactate McCormack et al. 1979 Aluminum chloride 

11 Mouse 

(Swiss) 

Gd 6-15 (GW) 

INTERMEDIATE EXPOSURE Systemic 

12 Bd Wt Rat (NS) 100 d (W) 

141 F 

97 M (decreased body weight 

gain in aged rats) 

Domingo et al. 1989 Aluminum hydroxide Colomina et al. 2002 Aluminum nitrate 

13 Cardio Rat (SpragueDawley) 100 d (W) 284 F Domingo et al. 1987b Aluminum nitrate 

Hemato 284 F Hepatic Renal 

284 F 284 F 

Bd Wt 284 F 
063

13313313352

79

79

133

133133

1

9090

876

230

472

330

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

14 Rat 

(SpragueDawley) 

15 Rat 

(Wistar) 

16 Rat 

(SpragueDawley) 

17 Mouse 

(SwissWebster) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

1 mo (W) 10 wk (F) 8 mo (W) 

Gd 1- Ld 21 (F) 

System 

Resp Cardio Gastro Hemato Hepatic Renal Bd Wt Musc/skel Bd Wt Hemato Bd Wt 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

133 F Gomez et al. 1986 

Aluminum nitrate 

133 F 133 F 

52 F 79 F (hyperemia in the red 

pulp of the spleen) 

79 F 133 F (hyperemia in the liver, 

periportal monocytic infiltrate in liver) 

133 F 133 F 

90 M 

90 M 

Konishi et al. 1996 Aluminum lactate 

230 F (decreased hemoglobin, 

hematocrit and haptoglobin levels, increased reticulocyte levels; inhibition of CFU-E proliferation) 

Vittori et al. 1999 Aluminum citrate 

330 F Donald et al. 1989 

Aluminum lactate 
419

130

671

250

676

195

727

170

750

195195195

065

888888888888

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

18 Mouse 

(SwissWebster) 

6 wk (F) 

19 Mouse 

(SwissWebster) 

Gd 1-21 Ld 1-21 Gd 1- Ld 21 (F) 

20 Mouse 

(SwissWebster) 

90 d (F) 

21 Mouse 

(SwissWebster) 

7-10 wk (F) 

22 Mouse 

(SwissWebster) 

5 or 7 wk (F) 

23 Dog 

(Beagle) 

6 mo (F) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

Bd Wt Bd Wt Bd Wt Bd Wt Hemato Hepatic Bd Wt Cardio Hemato Hepatic Renal Endocr Ocular 

LOAEL 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

Serious 

(mg/kg/day) 

Reference Chemical Form 

130 F Golub et al. 1989 

Aluminum lactate 

250 F (decreased body weight 

gain in lactating mice) 

Golub et al. 1992a Aluminum lactate 

195 F Golub et al. 1992b 

Aluminum lactate 

170 F Oteiza et al. 1989 

Aluminum lactate 

195 F 195 F 195 F 

Oteiza et al. 1993 Aluminum chloride 

88 88 88 88 88 88 

Katz et al. 1984 Aluminum phosphate 
200

75757575

877

25

410

259

413

52

79

1

200

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

24 Dog 

(Beagle) 

26 wk (F) Cardio 

Hemato 

75 75 

Pettersen et al. 1990 Aluminum phosphate 

Renal 75 

Immuno/ Lymphoret 

25 Human 3 x/d 

6 wk (F) 

Endocr 75 

25 Gräske et al. 2000 

Aluminum hydroxide 

26 Rat 

(SpragueDawley) 

100 d (W) 259 F Domingo et al. 1987b Aluminum nitrate 

27 Rat 

(SpragueDawley) 

1 mo (W) 52 F 79 F (hyperemia in the red pulp of the spleen) Gomez et al. 1986 Aluminum nitrate 

28 Mouse 

(SwissWebster) 

Gd 0- pnd 180 (F) 200 (in offspring: 19% increased absolute 

spleen weights; depressed spleen cell concentrations of interleukin-2, interferon-g and tumor necrosis factor-a; deficiency of CD4+ cells in T-cell populations) 

Golub et al. 1993 Aluminum lactate 
2

107

3

155

842

97

1

125

878

21.5

43.1

091

330

833

100

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

29 Mouse 

(SwissWebster) 

30 Mouse 

(SwissWebster) 

Neurological 

31 Rat 

(NS) 

32 Rat 

(SpragueDawley) 

33 Rat 

(Wistar) 

34 Mouse 

(SwissWebster) 

35 Mouse 

(SwissWebster) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

6 wk (F) 107 F Yoshida et al. 1989 Aluminum lactate 

Gd 1- pnd 31 (F) 155 F (increased susceptibility to bacterial infection in 

dams) 

Yoshida et al. 1989 Aluminum lactate 

100 d (W) 97 M Colomina et al. 2002 Aluminum nitrate 

6.5 mo (W) daily 3 mo (W) 

125 M 

21.5 M 43.1 M (impairment of 

post-rotatory nystagmus) 

Domingo et al. 1996 

Aluminum nitrate Mameli et al. 2006 Aluminum chloride 

Gd 1- Ld 21 (F) 330 F Donald et al. 1989 Aluminum lactate 

NR (F) 100 M Golub and Germann 19

Aluminum lactate 
048

62

130

672

250

677

195

868

100

200

751

195

627

75

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

36 Mouse 

(SwissWebster) 

37 Mouse 

(SwissWebster) 

38 Mouse 

(SwissWebster) 

39 Mouse 

(SwissWebster) 

40 Mouse 

(SwissWebster) 

41 Dog 

(Beagle) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

6 wk (F) 62 F 130 F (decreased total activity and vertical activity) Golub et al. 1989 Aluminum lactate 

Gd 1-21 Ld 1-21 Gd 1- Ld 21 (F) 

250 F Golub et al. 1992a 

Aluminum lactate 

90 d (F) 195 F (decreased forelimb and hindlimb grip strengths 

and startle response, decreased total activity, horizontal activity, and percent interval with high activity counts) 

Golub et al. 1992b Aluminum lactate 

Gd 1- pnd 170 (F) 100 M 200 M (increased cage mate aggression) Golub et al. 1995 Aluminum lactate 5 or 7 wk (F) 195 F (reduced forelimb and hindlimb grip strength) Oteiza et al. 1993 Aluminum chloride 26 wk (F) 75 Pettersen et al. 1990 Aluminum phosphate 
473

155

673

250

841

10353

474

155

1

330

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

Reproductive 

42 Mouse 

(SwissWebster) 

43 Mouse 

(SwissWebster) 

Developmental 

44 Rat 

(SpragueDawley) 

45 Mouse 

(SwissWebster) 

46 Mouse 

(SwissWebster) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Gd 1- Ld 21 (F) 155 F (altered gestational length) Donald et al. 1989 Aluminum lactate 

Gd 1-21 Ld 1-21 Gd 1- Ld 21 (F) 

250 F Golub et al. 1992a 

Aluminum lactate 

15 d premating Gd 1- Ld 21 (W) 

103 (decreased forelimb grip 

strength, decreased pup body weight) 

Colomina et al. 2005 

Aluminum nitrate 

53 (delay in vaginal 

opening) 

Gd 1- Ld 21 (F) 155 (decreased forelimb and increased hindlimb grip 

strength and increased foot splay in weanlings) 

Donald et al. 1989 Aluminum lactate 

Gd 1- pnd 35 (F) 330 M Golub and Germann 19

Aluminum lactate 
862

26

130

840

330

674

250

781

155

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

47 Mouse 

(SwissWebster) 

48 Mouse 

(SwissWebster) 

49 Mouse 

(SwissWebster) 

50 Mouse 

(SwissWebster) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

Gd 0- Ld 21, pnd 21-35 (F) 

b

26 130 (impaired performance 

on the water maze test in females, shorter latency to fall in wire suspension test in males) 

Golub and Germann 20

Aluminum lactate 

Gd 1- pnd 35 (F) 330 (altered myelination in spinal cord) Golub and Tarara 1999 Aluminum lactate 

Gd 1-19 Gd 1- Ld 21 Ld 1-21 (F) 

250 (decrease in pup weight, 

crown-rump length, forelimb grip strength in gestation exposed group, increase in hindlimb grip and tail withdrawal times in gestation and lactation exposed groups, increase in negative geotaxis latency in lactation exposed groups) 

Golub et al. 1992a Aluminum lactate 

Gd 1- pnd 21 (F) 155 (decreased fore- and hindlimb grip strengths 

and startle response) 

Golub et al. 1995 Aluminum lactate 
830

330

845

103

015

0.60.60.60.60.6

825

100

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL (mg/kg/day) Less Serious (mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

51 Mouse 

(SwissWebster) 

Gd 1- pnd 31 (F) 

CHRONIC EXPOSURE Systemic 

52 Rat 

(SpragueDawley) 

Gd 1- Ld 21 weaning-1 yr of 

age or 2 yr of age (W) 

Bd Wt 

330 103 M 

Yoshida et al. 1989 

Aluminum lactate Roig et al. 2006 Aluminum nitrate 

53 Rat 

(Long- Evans) 

2.5 yr (W) Resp 0.6 Schroeder and Mitchen

1975a Aluminum sulfate 

Cardio 0.6 Hepatic Renal 

0.6 0.6 

Bd Wt 0.6 

54 Mouse 

(SwissWebster) 

2 yr conception to 24 mo (F) 

Bd Wt 100 F (20% decrease in body 

weight gain) 

Golub et al. 2000 Aluminum lactate 
835

1.21.21.21.21.2

850

103

826

100

Table 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (continued) 

a 

Key to Species 

Figure (Strain) 

55 Mouse 

(Swiss) 

Neurological 

56 Rat 

(SpragueDawley) 

57 Mouse 

(SwissWebster) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

lifetime (W) 

Gd 1- Ld 21 weaning-1 yr of 

age or 2 yr of age (W) 2 yr conception to 24 mo (F) 

System 

Resp Cardio Hepatic Renal Bd Wt 

NOAEL 

(mg/kg/day) 

1.2 

1.2 

1.2 1.2 

1.2 

103 M 

LOAEL 

Less Serious Serious 

(mg/kg/day) (mg/kg/day) 

c

100 (decreased forelimb and 

hindlimb grip strength, decreased thermal sensitivity) 

Reference Chemical Form 

Schroeder and Mitchen1975b 

Aluminum sulfate 

Roig et al. 2006 

Aluminum nitrate Golub et al. 2000 Aluminum lactate 

a The number corresponds to entries in Figure 3-2. b Used to derive an intermediate-duration oral minimal risk level (MRL) of 0.9 mg Al/kg/day; dose divided by an uncertainty factor of 30 (3 for extrapolation from aniand 10 for human variability). c Used to derive a chronic-duration oral MRL of 0.3 mg Al/kg/day; dose divided by an uncertainty factor of 300 (10 for the use of a LOAEL, 3 for extrapolation from humans, and 10 for human variability). Bd Wt = body weight; Cardio = cardiovascular; CFU-E = colony-forming unit-erythroid; d = day(s); (F) = feed; F = Female; (G) = gavage; Gastro = gastrointestinal; Gday; (GW) = gavage in water; Hemato = hematological; Ld = lactation day; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; Immuno/Lyimmunological/lymphoreticular; M = male; mo = month(s); NOAEL = no-observed-adverse-effect level; NR = not reported; pnd = post-natal day; Resp = respiratory; water; wk = week(s); x = time(s); yr = year(s) 
Death 

Developmental 

ALUMINUM

Figure 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral 

Acute (≤14 days) 

mg/kg/day 

1000 8m 

7m 

9h 

2r 

4m 

1r 

5m 

6m 3r 

11m 

10r 

100 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

62
Respiratory 

Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Renal Endocrine Ocular 

Body Weight 

Immuno/Lymphor 

Neurological 

Reproductive Developmental 

Figure 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (Continued)
 

Intermediate (15-364 days)
	

Systemic 

ALUMINUM

mg/kg/day 

1000 

17m 34m 46m 13r 13r 13r 13r 13r 

16r 19m 26r 37m 43m

22m 22m 20m 22m 28m 38m 39m 40m 21m 30m 42m 45m 14r 14r 14r 14r 14r 18m 14r 36m 32r 47m 

100 12r 29m 35m 39m 31r 15r 15r
	 24d

23d 23d 23d 23d 23d 23d

24d 14r 14r 24d 24d 27r 41d 

36m 

14r 27r 

33r 

47m 

33r 25 

10 

1 

0.1 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

63
Developmental 

Figure 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (Continued)
 

Intermediate (15-364 days)

ALUMINUM

mg/kg/day 

1000 

48m 51m 

49m 

50m 

44r 

44r 

100 

10 

1 

0.1 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

64
Respiratory 

Cardiovascular Hepatic Renal Body Weight Neurological 

ALUMINUM

Figure 3-2 Levels of Significant Exposure to Aluminum and Compounds - Oral (Continued)

Chronic (≥365 days) 

Systemic 

mg/kg/day 

1000 

100 54m 52r 57m 56r

10 

55m 55m 55m 55m 55m 

1 

53r 53r 53r 53r 53r 

0.1 

3. HEALTH EFFECTS

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans Minimal Risk Level 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans for effects

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans other than

q-Cow a-Sheep g-Guinea Pig Cancer 

65
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 66 

3. HEALTH EFFECTS 

Although levels of human oral intake of aluminum may be characterized, it is important to recognize that 

the amount of aluminum ingested does not provide an actual estimate of exposure without information on 

bioavailability of the form of aluminum ingested. Similarly, effective doses in the animal studies, 

including the exact underestimate of aluminum intake in animal studies with insufficient information on 

aluminum in the base diet, cannot be known without information on bioavailability of the aluminum. As 

discussed in Section 3.3.1.2, the bioavailability of aluminum is influenced by the form in which it is 

ingested and the presence of other substances in the gastrointestinal tract, particularly complexing 

moieties in foods, which may significantly enhance or hinder absorption. 

3.2.2.1 Death 

No aluminum-related deaths in healthy humans have been reported after oral exposure. One aluminum 

compound that can be life threatening to humans is aluminum phosphide, a grain fumigant. Accidental or 

volitional ingestion (to commit suicide) of large amounts has caused death (Chopra et al. 1986; Khosla et 

al. 1988). The toxicity from this compound is due to the exposure to phosphine gas, which is produced in 

the gastrointestinal tract after the aluminum phosphide is ingested. 

Aluminum caused death in laboratory animals only at doses that are high compared to normal human 

exposure. Data on acute lethality of ingested aluminum are summarized below. For aluminum bromide, 

LD50 (lethal dose, 50% kill) values of 162 and 164 mg Al/kg have been reported in Sprague-Dawley rats 

and Swiss Webster mice, respectively (Llobet et al. 1987). For the nitrate form, LD50 values of 261 and 

286 mg Al/kg have been reported for Sprague-Dawley rats and Swiss Webster mice, respectively (Llobet 

et al. 1987). For the chloride form, LD50 values of 370, 222, and 770 mg Al/kg have been reported for 

Sprague-Dawley rats, Swiss Webster mice, and male Dobra Voda mice, respectively (Llobet et al. 1987; 

Ondreicka et al. 1966). The LD50 for aluminum sulfate in male Dobra Voda mice was reported as 

980 mg Al/kg (Ondreicka et al. 1966). Time to death and clinical signs were not reported in these studies. 

A single gavage exposure to 540 mg Al/kg as aluminum lactate was fatal to all 5 lactating female New 

Zealand rabbits tested (Yokel and McNamara 1985). Time to death was reported as 8–48 hours. 

Intermediate-duration oral exposure to aluminum has also been shown to cause death. Mortality occurred 

in female Swiss Webster mice exposed to aluminum lactate in the diet for 42 days throughout gestation 

and lactation at doses of 184 or 280 mg Al/kg/day (Golub et al. 1987), but not at 330 mg Al/kg/day in a 

different study (Donald et al. 1989) by the same group of investigators. Severe signs of neurotoxicity 

(ataxia, paralysis) were noted prior to the deaths. The effects in the Golub et al. (1987) study appear to be 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 67 

3. HEALTH EFFECTS 

related to semipurified diet composition. In particular, the formulation of the diet was revised by Donald 

et al. (1989) (and in subsequent studies by Golub and coworkers) by adding a “more generous provision” 

of several essential nutrients, particularly trace minerals (including calcium, magnesium, phosphate), to 

avoid the toxicity associated with the aluminum in the original diet. One of nine pregnant Swiss Webster 

mice that consumed 250 mg Al/kg/day as aluminum lactate in the revised purified diet died (Golub et al. 

1992a). No mortality was observed in male Sprague-Dawley rats (7–10 per group) orally exposed to 

70 mg Al/kg/day as aluminum chloride in water for 30, 60, or 90 days (Dixon et al. 1979), or up to 

158 mg Al/kg/day as aluminum hydroxide in the feed for 16 days (Greger and Donnaubauer 1986); these 

doses do not include aluminum in the base diet. No male or female Beagle dogs (4/sex/group) died 

following dietary exposure to 75–80 mg Al/kg/day as sodium aluminum phosphate and base levels of 

aluminum in the feed for 26 weeks (Pettersen et al. 1990). In chronic-duration studies, exposure to 

aluminum at 100 mg Al/kg/day as aluminum lactate in the diet or 103 mg Al/kg/day as aluminum nitrate 

with added citric acid in drinking water did not result in significant alterations in mortality (Golub et al. 

2000; Roig et al. 2006). 

All reliable LOAEL values for death in each species and duration category are recorded in Table 3-2 and 

plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

The highest NOAEL values and all LOAEL values for oral exposure from each reliable study for 

systemic effects in each species and duration category for aluminum are shown in Table 3-2 and plotted 

in Figure 3-2; only studies providing information on the levels of aluminum in the base diet are included 

in Table 3-2 and Figure 3-2. 

Respiratory Effects. No studies were located regarding respiratory effects of various forms of 

aluminum following intermediate- or chronic-duration oral exposure in humans. Acute-duration oral 

exposure to aluminum phosphide has been shown to cause pulmonary edema in persons following 

accidental or volitional ingestion (Chopra et al. 1986; Khosla et al. 1988). The toxicity was probably due 

to the formation of highly toxic phosphine gas rather than to aluminum exposure. 

No studies were located regarding respiratory effects of various forms of aluminum following acuteduration oral exposure in animals. Intermediate- and chronic-duration studies found no organ weight or 

histological changes in the lungs in rats exposed to 70 mg Al/kg/day as aluminum chloride in drinking 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 68 

3. HEALTH EFFECTS 

water (base dietary aluminum not reported) for 30, 60, or 90 days (Dixon et al. 1979), rats exposed to 

133 mg Al/kg/day as aluminum nitrate in drinking water and base diet for 1 month (Gomez et al. 1986), 

rats or mice exposed to 0.6 and 1.2 mg Al/kg/day as aluminum potassium sulfate in drinking water (base 

dietary aluminum not reported), respectively, for 2–2.5 years (Schroeder and Mitchener 1975a, 1975b), or 

mice exposed to 979 mg Al/kg/day as aluminum potassium sulfate in the feed (base dietary aluminum not 

reported) for 20 months (Oneda et al. 1994). 

Cardiovascular Effects. No studies were located regarding cardiovascular effects of various forms 

of aluminum following intermediate- or chronic-duration oral exposure in humans. Acute-duration oral 

exposure to aluminum phosphide has been shown to cause tachycardia, hypotension, cardiovascular 

electrocardiographic abnormalities, subendocardial infarction, and transient atrial fibrillation in persons 

who either ingested it accidentally or in suicide attempts (Chopra et al. 1986; Khosla et al. 1988). 

However, toxicity was probably due to the formation of highly toxic phosphine gas rather than to 

aluminum exposure. 

No studies were located regarding cardiovascular effects of aluminum or its compounds following acuteduration oral exposure in animals. No histological changes were observed in the hearts of male SpragueDawley rats given up to 70 mg Al/kg/day as aluminum chloride in drinking water (base dietary aluminum 

not reported) for 30, 60, or 90 days (Dixon et al. 1979). Similarly, no organ weight or histological 

changes were found in the hearts of female Sprague-Dawley rats that ingested 133 or 284 mg Al/kg/day 

as aluminum nitrate in drinking water and base diet for up to 1 month (Gomez et al. 1986) or 100 days, 

respectively (Domingo et al. 1987b). No organ weight or histological changes were observed in the 

hearts of dogs that consumed up to 75 mg Al/kg/day (Katz et al. 1984) or 88 mg Al/kg/day (aluminum 

levels of base diet not provide) (Pettersen et al. 1990) as sodium aluminum phosphate in the diet for 

6 months. 

Cardiovascular effects were not observed in animals following chronic-duration exposure to aluminum 

compounds. No histological changes were observed in the hearts of male and female Long Evans rats or 

Swiss mice given 0.6 or 1.2 mg Al/kg/day as aluminum potassium sulfate in drinking water, respectively, 

for 2–2.5 years (Schroeder and Mitchener 1975a, 1975b) or B6C3F1 mice that ingested 979 mg Al/kg/day 

as aluminum potassium sulfate in the diet for 20 months (Oneda et al. 1994). Aluminum levels in the 

base diet were not reported in these rat and mouse studies, although the animals were fed a low-metal diet 

in metal-free environmental conditions in the Schroeder and Mitchener (1975a, 1975b) studies. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 69 

3. HEALTH EFFECTS 

Gastrointestinal Effects. No studies were located regarding gastrointestinal effects of various forms 

of aluminum following intermediate- or chronic-duration exposure in humans. Unspecified 

gastrointestinal and bowel problems were reported by people who, for 5 days or more, may have 

consumed water that contained unknown levels of aluminum sulfate accidentally placed in a water 

treatment facility in England (Ward 1989). Forty-eight of the exposed persons were examined, but the 

number of people with gastrointestinal complaints was not reported. It should be noted that the water 

supply also contained elevated levels of copper and lead which leached from the plumbing systems due to 

the greater acidity of the water (pH <4). Aluminum and copper levels in body tissues were reported as 

elevated in scalp hair and fingernails. Acute-duration oral exposure to aluminum phosphide has been 

shown to cause vomiting and abdominal pain in persons who ingested it either accidentally or in suicide 

attempts (Chopra et al. 1986; Khosla et al. 1988). However, as noted above, toxicity was probably due to 

the formation of highly toxic phosphine gas rather than to aluminum exposure. 

No studies were located regarding gastrointestinal effects of aluminum or its compounds following acuteduration oral exposure in animals. No organ weight or histological changes were observed in the 

gastrointestinal tissues of female Sprague-Dawley rats given 133 mg Al/kg/day as aluminum nitrate in 

drinking water and base diet for up to 1 month (Gomez et al. 1986), or in male or female B6C3F1 mice 

that ingested 979 mg Al/kg/day as aluminum potassium sulfate in the feed (base dietary aluminum not 

reported) for 20 months (Oneda et al. 1994). 

Hematological Effects. No studies were located regarding hematological effects of various forms of 

aluminum following acute-, intermediate-, or chronic-duration exposure in humans after oral exposure to 

aluminum or its compounds. 

Repeated exposure to aluminum appears to adversely affect the hematological system of rats and mice. 

Significant decreases in hemoglobin, hematocrit, and/or erythrocyte osmotic fragility were observed in 

rats exposed to 420 mg Al/kg/day as aluminum citrate in drinking water for 15 weeks (Garbossa et al. 

1998), mice exposed to 13 mg Al/kg as aluminum citrate administered via gavage 5 days/week for 

22 weeks (Garbossa et al. 1996), rats exposed to 230 mg Al/kg/day as aluminum citrate in drinking water 

for 8 months (Vittori et al. 1999), and rats exposed via drinking water to 54.7 mg Al/kg/day as aluminum 

sulfate in a sodium citrate solution for 18 months (Farina et al. 2005). Exposure to lower concentrations 

or for shorter durations resulted in no significant damage to the erythrocytes. No alterations in 

hemoglobin, hematocrit, and/or erythrocyte osmotic fragility were observed in mice exposed to 13 mg 

Al/kg as aluminum citrate or aluminum chloride administered via gavage 5 days/week for 2 weeks 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 70 

3. HEALTH EFFECTS 

(Garbossa et al. 1996), rats exposed to 133 mg Al/kg/day as aluminum nitrate in drinking water for 

1 month (Gomez et al. 1986), mice exposed to 195 mg Al/kg/day as aluminum citrate in the diet for 5 or 

7 weeks (Oteiza et al. 1993), rats exposed to 284 mg Al/kg/day as aluminum nitrate in drinking water for 

100 days (Domingo et al. 1987b), rats exposed to 27 mg Al/kg as aluminum citrate administered via 

gavage 5 days/week for 15 weeks (Garbossa et al. 1996), or dogs exposed to 75 or 88 mg Al/kg/day as 

aluminum phosphate in the diet for 6 months (Katz et al. 1984; Pettersen et al. 1990). The studies 

conducted by Domingo et al. (1987b), Gomez et al. (1986), Oteiza et al. (1993), Pettersen et al. (1990), 

and Vittori et al. (1999) provided information on the levels of aluminum in the base diet; the remaining 

studies did not provide this information. As highlighted by the Garbossa et al. (1996) study, which used 

multiple durations, the erythrocytic effects appear to be duration sensitive. No alterations in hemoglobin 

or hematocrit levels were observed in mice exposed to 13 mg Al/kg as aluminum citrate administered via 

gavage for 2 weeks; however, significant decreases in these parameters were observed when the exposure 

was continued for 22 weeks. Additionally, aluminum can alter mature erythrocyte morphology; 

anisocytosis (abnormal variations in cell size), anisochromia (unequal degree of cell staining), and 

poikilocytosis (abnormal variation in cell shape) have been observed in rats exposed to 230 mg Al/kg/day 

as aluminum citrate in drinking water for 8 months (Vittori et al. 1999). Hyperemia in the red pulp of the 

spleen was reported in rats exposed to 79 mg Al/kg/day as aluminum nitrate in drinking water for 

1 month (Gomez et al. 1986); this may be indicative of erythrocyte damage. 

There is some evidence that aluminum may affect iron levels in blood; however, this has not been well 

studied and the results are not consistent across studies. Vittori et al. (1999) did not find significant 

alterations in plasma iron levels or total iron binding capacity in rats exposed to 230 mg Al/kg/day as 

aluminum citrate in drinking water for 8 months; however, impaired iron uptake and decreased iron 

incorporation into heme were measured in bone marrow cells. Farina et al. (2005) found significant 

decreases in blood iron concentrations and no change in total iron binding capacity in rats exposed to 

54.7 mg Al/kg/day as aluminum sulfate in a sodium citrate solution in drinking water for 18 months. 

Florence et al. (1994) reported decreases in serum iron levels, total iron binding capacity, and transferring 

saturation in rats exposed to 75 mg Al/kg/day as aluminum citrate in the diet for 6 months; however, the 

statistical significance of these findings was not reported. 

Several studies have shown that aluminum can adversely affect erythropoeisis. Intermediate-duration 

exposure has been associated with significant inhibition of colony forming units-erythroid (CFU-E) 

development in bone marrow of mice exposed to 13 mg Al/kg as aluminum citrate or aluminum chloride 

administered via gavage 5 days/week for 2 or 22 weeks (Garbossa et al. 1996), rats exposed to 27 mg 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 71 

3. HEALTH EFFECTS 

Al/kg as aluminum citrate administered via gavage 5 days/week for 15 weeks (Garbossa et al. 1998), rats 

exposed to 420 mg Al/kg/day as aluminum citrate in drinking water for 15 weeks (Garbossa et al. 1998), 

and rats exposed to 230 mg Al/kg/day as aluminum citrate in drinking water for 8 months (Vittori et al. 

1999); the aluminum content of the base diet was not reported in the Garbossa et al. (1996, 1998) studies. 

Chronic-duration studies did not examine this end point. 

Musculoskeletal Effects. Joint pains were common symptoms reported in people in England who, 

for 5 days or more, consumed unknown levels of aluminum sulfate in drinking water which also 

contained elevated levels of copper and lead (Ward 1989). Osteomalacia has been observed in healthy 

individuals following long-term use of aluminum-containing antacids and in individuals with kidney 

disease. There are numerous case reports of osteomalacia and rickets in otherwise healthy infants and 

adults using aluminum-containing antacids for the treatment of gastrointestinal illnesses (i.e., ulcers, 

gastritis, colic) (Carmichael et al. 1984; Chines and Pacifici 1990; Pivnick et al. 1995; Woodson 1998). 

The aluminum in the antacids binds with dietary phosphorus and prevents its absorption resulting in 

hypophosphatemia and phosphate depletion. Osteomalacia, characterized by a softening of the bone and 

resulting in increased spontaneous fractures and pain, has been well documented in dialyzed uremic 

adults and children exposed to aluminum-contaminated dialysate or orally administered aluminumcontaining phosphate-binding agents (Andreoli et al. 1984; Griswold et al. 1983; King et al. 1981; Mayor 

et al. 1985; Wills and Savory 1989). Decreased aluminum urinary excretion caused by impaired renal 

function and possibly an increase in gastrointestinal absorption of aluminum (Alfrey 1993) results in 

increased aluminum body burden leading to markedly increased bone aluminum levels and the presence 

of aluminum between the junction of calcified and noncalcified bone. For more information on renal 

patients and aluminum, see Section 3.10. 

Although long-term oral exposure to aluminum results in an increase in aluminum levels in the bone (Ahn 

et al. 1995; Konishi et al. 1996), there is no histological evidence that under normal physiological 

conditions that the accumulation of aluminum alters the bone structure. No histological alterations were 

observed in the tibias of male Wistar rats fed 100 mg Al/kg/day as aluminum lactate (aluminum levels in 

the base diet not reported) for 10 weeks (Konishi et al. 1996). 

Hepatic Effects. No studies were located regarding hepatic effects of various forms of aluminum 

following intermediate- or chronic-duration exposure in humans. Hepatic dysfunction was reported in 

1 of 15 people acutely exposed to unspecified amounts of aluminum phosphide (Khosla et al. 1988). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 72 

3. HEALTH EFFECTS 

However, the toxicity, as noted above was probably due to the formation of highly toxic phosphine gas 

rather than to aluminum exposure. 

Most animal studies did not find significant alterations in liver weights or liver histology following 

intermediate- or chronic-duration oral exposure. Hyperemia and periportal monocytic infiltrate were 

observed in the livers of female Sprague-Dawley rats given 133 mg Al/kg/day as aluminum nitrate in 

drinking water for 1 month (Gomez et al. 1986). Mild hepatocyte vacuolation was found in male dogs 

exposed to 75 mg Al/kg/day in the diet for 26 weeks (Pettersen et al. 1990), but the study authors 

concluded that the hepatic effects probably resulted from a drastic reduction in food consumption and a 

decrease in body weight. 

The remaining studies conducting liver histopathological examinations did not find significant alterations 

in rats exposed to 70 mg Al/kg/day as aluminum chloride in drinking water for 30, 60, or 90 days (Dixon 

et al. 1979), rats exposed to 284 mg Al/kg/day as aluminum nitrate in drinking water for 100 days 

(Domingo et al. 1987b), mice exposed to 49 mg Al/kg/day as aluminum chloride in drinking water for 

180 days (Ondreicka et al. 1966), dogs exposed to 88 mg Al/kg/day as aluminum phosphate in the diet for 

6 months (Katz et al. 1984), mice exposed to 979 mg Al/kg/day as aluminum sulfate in the diet for 

20 months (Oneda et al. 1994), or rats or mice exposed to 0.6 or 1.2 mg Al/kg/day as aluminum sulfate, 

respectively, in drinking water for a lifetime (Schroeder and Mitchener 1975a, 1975b). Only the 

Domingo et al. (1987b) and Ondreicka et al. (1966) studies included the levels of aluminum in the base 

diet. 

Renal Effects. No studies were located regarding renal effects of various forms of aluminum 

following intermediate- or chronic-duration exposure in humans. Acute-duration oral exposure to 

aluminum phosphide has been shown to cause renal failure, significant proteinuria, and anuria in persons 

who ingested it either accidentally or in suicide attempts (Chopra et al. 1986; Khosla et al. 1988). 

However, toxicity was probably due to the formation of highly toxic phosphine gas rather than to 

aluminum exposure. 

Several intermediate- or chronic-duration studies examined for possible effects on the kidneys; most 

studies did not find any adverse effects. Mild tubular “glomerularnephritis” was observed in dogs 

exposed to 75 mg Al/kg/day as sodium aluminum phosphate in the diet for 26 weeks (Pettersen et al. 

1990); however, the study investigators did not consider this effect to be adverse because it was not 

accompanied by clinical evidence of kidney dysfunction. The effect may have been secondary to the 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 73 

3. HEALTH EFFECTS 

drastic reduction in feed intake and decreased body weight also observed in these dogs. No alterations in 

kidney histopathology were observed in rats exposed to 70 mg Al/kg/day as aluminum chloride in 

drinking water for 30–90 days (Dixon et al. 1979), rats exposed to 284 mg Al/kg/day as aluminum nitrate 

in drinking water for 100 days (Domingo et al. 1987b), mice exposed to 49 mg Al/kg/day as aluminum 

chloride in drinking water for 180 days (Ondreicka et al. 1966), dogs exposed to 88 mg Al/kg/day as 

aluminum phosphate in the diet for 6 months (Katz et al. 1984), mice exposed to 979 mg Al/kg/day as 

aluminum sulfate in the diet for 20 months (Oneda et al. 1994), or rats or mice exposed to 0.6 or 1.2 mg 

Al/kg/day as aluminum sulfate, respectively, in drinking water for a lifetime (Schroeder and Mitchener 

1975a, 1975b). With the exception of the Domingo et al. (1987b), Pettersen et al. (1990), and Ondreicka 

et al. (1966) studies, information on the levels of aluminum in the base diet was not reported. 

Endocrine Effects. No studies were located regarding endocrine effects of various forms of 

aluminum following acute-, intermediate-, or chronic-duration oral exposure in humans. 

No studies were located regarding endocrine effects of aluminum or its compounds following acuteduration exposure in animals. No organ weight or histological changes were observed in the thyroid, 

adrenal, or pituitary glands of male and female Beagle dogs that consumed up to 75 (Pettersen et al. 1990) 

or 88 (Katz et al. 1984) mg Al/kg/day as sodium aluminum phosphate in the diet for 6 months; the doses 

in the Katz et al. (1984) study do not include aluminum in the base diet. 

Dermal Effects. No studies were located regarding dermal effects of various forms of aluminum 

following intermediate- or chronic-duration oral exposure in humans. Skin rashes were common 

symptoms reported by 48 people in England who consumed drinking water containing unknown levels of 

aluminum sulfate for approximately 5 days (Ward 1989). The water also contained elevated levels of 

copper and lead. 

No studies were located regarding dermal effects of aluminum or its compounds following acute-duration 

exposure in animals. A localized loss of fur on the tip of the snout was observed in mice that ingested 

130 mg Al/kg/day as aluminum lactate and base dietary aluminum for 6 weeks, but the effect was 

considered to be a sign of poor condition in the colony and not clearly attributable to aluminum exposure 

(Golub et al. 1989). 

Ocular Effects. No studies were located regarding ocular effects of various forms of aluminum 

following acute-, intermediate-, or chronic-duration oral exposure in humans. 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 74 

3. HEALTH EFFECTS 

No studies were located regarding ocular effects of various forms of aluminum following acute-duration 

exposure in animals. No adverse ocular changes were found in male and female Beagle dogs that 

consumed up to 88 mg Al/kg/day as sodium aluminum phosphate in the diet for 6 months (Katz et al. 

1984); these doses do not include aluminum in the base diet. 

Body Weight Effects. No studies were located regarding body weight effects of various forms of 

aluminum following acute-, intermediate-, or chronic-duration oral exposure in humans. 

Most studies have not found significant alterations in body weight gain in rats or mice following acute 

exposure to 73–192 mg Al/kg/day as aluminum lactate or aluminum hydroxide with citric acid (Bernuzzi 

et al. 1986; Domingo et al. 1989; Gomez et al. 1991; Misawa and Shigeta 1992), intermediate-duration 

exposure to 20–399 mg Al/kg/day as aluminum lactate, aluminum chloride, aluminum hydroxide, or 

aluminum nitrate (Bernuzzi et al. 1989b; Bilkei-Gorzo 1993; Domingo et al. 1987b; Donald et al. 1989; 

Golub et al. 1989, 1992b, 1995; Gomez et al. 1986; Greger and Donnaubauer 1986; Konishi et al. 1996; 

Ondreicka et al. 1966; Oteiza et al. 1989), or chronic-duration exposure to 0.6–979 mg Al/kg/day as 

aluminum nitrate with citric acid, aluminum lactate, or aluminum sulfate (Golub et al. 2000; Oneda et al. 

1994; Roig et al. 2006; Schroeder and Mitchener 1975a, 1975b). Of the studies reporting reductions of 

body weight gain, many involved gestational and/or lactational exposure; significant decreases in body 

weight gain were observed in rats administered via gavage 409 mg Al/kg/day as aluminum hydroxide 

with citric acid on gestation days 6–15 (Gomez et al. 1991), rats administered via gavage 38 mg 

Al/kg/day as aluminum nitrate on gestation days 6–14 (Paternain et al. 1988), rats administered via 

gavage 70 mg Al/kg/day as aluminum chloride on gestation days 0–16 (Sharma and Mishra 2006), and 

mice exposed to 200 or 250 mg Al/kg/day aluminum lactate in the diet on gestation day 0 through 

lactation day 21 (Golub et al. 1987, 1992a). A decrease in body weight was also observed in aged rats 

exposed to 97 mg Al/kg/day as aluminum nitrate with citric acid for 100 days (Colomina et al. 2002) and 

rats administered via gavage 53 mg Al/kg/day as aluminum chloride for 30 days (Rajasekaran 2000). In a 

lifetime exposure study, Golub et al. (2000) reported a 20% decrease in body weight gain in female mice 

exposed to 100 mg Al/kg/day as aluminum lactate in the diet; however, in a separate group of mice 

similarly exposed to 100 mg Al/kd/day as aluminum lactate, no significant alterations in body weight gain 

were observed (Golub et al. 2000). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 75 

3. HEALTH EFFECTS 

3.2.2.3 Immunological and Lymphoreticular Effects 

There are limited data on the potential for aluminum to induce immunological effects in humans. 

Intermediate-duration exposure to 25 mg Al/kg/day as aluminum hydroxide in the form of an antacid 

suspension for 6 weeks did not affect immunoglobulin and interleukin concentrations or production, 

natural killer (NK) cells, or B- and T-lymphocyte populations or proliferation; a significant reduction in, 

primed cytotoxic T- cells (CD8+CD45R0+ population) was observed (Gräske et al. 2000). The 

toxicological significance of this finding in the absence of other alterations is not known. 

Very few animal studies examined the potential immunotoxicity of aluminum. Intermediate-duration 

exposure of mice to 13 mg Al/kg/day as aluminum citrate administered via gavage 5 days/week for 

22 weeks resulted in a significantly higher proliferation of lymph node cells and had no effect on spleen 

cell proliferation (Lauricella et al. 2001). This suggests that while aluminum might induce alterations in 

cell immune response, the stimulating or suppressing effects could depend on the dose, route of 

administration, exposure duration, or cell population. There is some evidence that developmental 

exposure to aluminum may adversely affect the immune system in young animals. A 19% increase in 

spleen weights, depressed spleen cell concentrations of interleukin-2, interferon-γ and tumor necrosis

factor-α, and a deficiency of CD4+ cells in T-cell populations were observed in Swiss Webster mice 

exposed to aluminum from conception through 6 months of age (Golub et al. 1993). The maternal 

animals consumed 200 mg Al/kg/day as aluminum lactate in the diet from conception through lactation 

and the offspring were subsequently fed the same diet as the dams. Susceptibility to bacterial infection 

was increased in offspring of Swiss-Webster mice exposed to dietary aluminum lactate in a dose of 

155 mg Al/kg from conception through 10 days of age, but not in 6-week-old mice exposed to 

107 mg Al/kg/day for 6 weeks (Yoshida et al. 1989). Susceptibility to infection was evaluated by 

assessing survival following intravenous inoculation with Listeria monocytogenes at the end of the 

exposure periods. 

No organ weight or histological changes in spleen and/or thymus were observed in female SpragueDawley rats exposed to 284 mg Al/kg/day as aluminum nitrate in drinking water for 100 days (Domingo 

et al. 1987b), male Sprague-Dawley rats given 70 mg Al/kg/day as aluminum chloride in drinking water 

for 30, 60, or 90 days (Dixon et al. 1979), or male and female mice exposed to 979 mg Al/kg/day as 

aluminum potassium sulfate in the diet for 20 months (Oneda et al. 1994). The doses in all of the above 

studies except Lauricella et al. (2001), Dixon et al. (1979), and Oneda et al. (1994) include aluminum in 

the base diet. 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 76 

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The highest reliable NOAEL value and all reliable LOAEL values in each species and duration category 

are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.4 Neurological Effects 

The neurotoxicity of aluminum following oral exposure has been well established in humans with renal 

insufficiency and animals; however, it has not been adequately investigated in healthy humans. The 

human database consists of case reports of acute accidental or intentional exposure to aluminum, an acute 

exposure study in healthy individuals, studies of patients undergoing dialysis treatment, and studies 

examining the possible association between aluminum ingestion and Alzheimer’s disease. 

Memory loss, fatigue, depression, behavioral changes, and learning impairment were reported in five 

children who, over a 5-day period, consumed drinking water containing unknown levels of aluminum 

sulfate, which was accidentally placed in a water-treatment facility in England (Ward 1989). The water 

also contained elevated levels of copper and lead, a highly neurotoxic element, which leached from the 

plumbing systems due to the greater acidity of the water. Thus, the role of aluminum in the onset of the 

neurological symptoms is unclear. Acute-duration oral exposure to aluminum phosphide (19– 

157 mg Al/kg) caused altered sensorium in 4 of 16 persons who ingested it either accidentally or in 

suicide attempts (Khosla et al. 1988). Restlessness and loss of consciousness were observed in 10 of 

15 people who ingested unknown amounts of aluminum phosphide (Chopra et al. 1986). The toxicity 

associated with aluminum phosphide ingestion was probably due to the formation of highly toxic 

phosphine gas rather than the aluminum exposure. 

Uremic persons represent a population at risk for aluminum-related dementia (Alfrey 1993). Prolonged 

dialysis with aluminum-containing dialysates, possibly combined with oral treatment with aluminum 

hydroxide to control hyperphosphatemia, has produced a characteristic neurotoxicity syndrome which has 

been referred to as “dialysis dementia” (Alfrey 1987; King et al. 1981; Mayor et al. 1985; Wills and 

Savory 1989). Alfrey (1993) describes two types of aluminum neurotoxicity in uremic patients: acute 

and classical. The acute form is caused by high levels of aluminum in the dialysate, the co-ingestion of 

aluminum-containing phosphate binders and citrate, or the rapid rise in serum aluminum following 

desferoxamine treatment. The onset of neurotoxicity is rapid and marked by confusion, muscle twitching, 

grand mal seizures, coma, and death. Plasma levels of aluminum are typically >500 μg/L; normal levels

are approximately 1–3 μg/L (House 1992; Liao et al. 2004). The classical type results from chronic 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 77 

3. HEALTH EFFECTS 

parenteral or oral aluminum exposures and is characterized by a gradual onset of neurobehavioral 

disorders and, eventually, death. These neurological effects have been observed in adults and children 

(Alfrey 1993; Griswold et al. 1983). Plasma levels are estimated to be 100–200 μg/L. Limiting

aluminum exposure in uremic persons (for example, the use of aluminum-free dialysates and aluminumfree phosphate binding agents) essentially eliminates these neurotoxic effects. 

Alzheimer’s disease is a neurodegenerative disorder, which is manifested clinically as a progressive 

deterioration of memory and cognition. The primary neuropathological characteristics of Alzheimer’s 

disease are neuronal loss and the formation of neurofibrillary tangles, senile plaques with amyloid 

deposits and neuropil threads, and cerebrovascular amyloid deposition. The etiology of Alzheimer’s 

disease is complex, with genetics playing a critical role; there is also evidence that the environment may 

modify the risk. The possible association between aluminum and Alzheimer’s disease was proposed over 

40 years ago; however, the evidence that aluminum may or may not be a risk factor is inconsistent and 

inconclusive. A number of lines of evidence have been used to support the relationship between 

aluminum and Alzheimer’s disease (Flaten 2001; Munoz 1998); these include elevated levels of 

aluminum in the brains of individuals with Alzheimer’s disease, the well-established neurotoxicity of 

aluminum, and epidemiology studies finding a geographical association between aluminum levels in 

drinking water and Alzheimer’s disease. In the last 25 years, a number of epidemiology and animal 

studies have investigated this possible association; an animal model that fully mimics human Alzheimer’s 

disease has not been identified. Many of the epidemiology studies have been criticized for flawed patient 

selection, poor comparability of exposed and control groups, poor exposure assessment, inaccurate 

diagnosis of Alzheimer’s disease, and weak statistical correlations (Nieboer et al. 1995; Schupf et al. 

1989). A number of these studies have found significant associations between individuals living in areas 

with elevated aluminum levels in drinking water and the prevalence of Alzheimer’s disease (or a 

surrogate such as dementia or cognitive impairment) (Flaten 1990; Forbes et al. 1992, 1994; Gauthier et 

al. 2000; Jacqmin et al. 1994; Jacqmin-Gadda et al. 1996; Martyn et al. 1989; McLachlan et al. 1996; 

Michel et al. 1990; Neri and Hewitt 1991; Rondeau et al. 2000, 2001); the aluminum content of the water 

typically exceeded 0.10 mg Al/L. The odds ratios (or relative risks) were typically <2.0 (Flaten 1990; 

Jacqmin et al. 1994; Martyn et al. 1989; McLachlan et al. 1996; Neri and Hewitt 1991), although some 

studies, particularly studies that controlled for other risk factors such as age, education level, and family 

history of dementia, estimated higher odds ratios (Gauthier et al. 2000; Rondeau et al. 2000). In contrast, 

several studies did not find significant associations between aluminum exposure and the risk of 

Alzheimer’s disease (or cognitive impairment (Forster et al. 1995; Martyn et al. 1997; Sohn et al. 1996; 
 

 

 

 

 

 

 

 

ALUMINUM 78 

3. HEALTH EFFECTS 

Wettstein et al. 1991; Wood et al. 1988); the levels of aluminum in the drinking water were similar to the 

levels in studies finding positive associations. 

Additionally, there are studies that examined the possible association between Alzheimer’s disease and 

ingestion of aluminum from sources other than drinking water, particularly tea and antacids. The 

aluminum levels in tea are typically 10–50 times higher than levels found in drinking water; similarly, the 

levels of aluminum in antacids (typically containing aluminum hydroxide) are very high compared to 

drinking water levels. No significant associations between tea consumption (Forster et al. 1995; 

McDowell et al. 1994) or antacid use (Amaducci et al. 1986; Broe et al. 1990; Colin-Jones et al. 1989; 

Forster et al. 1995; Graves et al. 1990; Heyman et al. 1984; McDowell et al. 1994) and Alzheimer’s 

disease have been found. A small scale study did find a significant relationship between consumption of 

food containing aluminum additives and the risk of Alzheimer’s disease (Rogers and Simon 1999); 

however, this was based on a very small number of cases. The contrast between the results of the 

drinking water studies, many of which found a weak association between living in areas with high 

aluminum levels in drinking water and Alzheimer’s disease, and the tea and antacid studies may be due to 

the difference in aluminum bioavailability. The presence of tannins and other organic constitutes found in 

tea may significantly reduce aluminum absorption; the aluminum hydroxide found in antacids is poorly 

absorbed. Although the aluminum speciation was not provided in most drinking water studies, in a study 

by Gauthier et al. (2000), organic monomeric aluminum was the only aluminum species significantly 

associated with Alzheimer’s disease. The bioavailability of organic aluminum compounds such as 

aluminum citrate, aluminum lactate, and aluminum maltolate is much greater than for inorganic 

aluminum compounds (Froment et al. 1989a; Yokel and McNamara 1988). 

In conclusion, the available data suggest that aluminum is not likely the causative agent in the 

development of Alzheimer’s disease. However, aluminum may play a role in the disease development by 

acting as a cofactor in the chain of pathological events resulting in Alzheimer’s disease (Flaten 2001). 

Amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia (PD) are neurodegenerative diseases that 

have also been associated with aluminum exposure. ALS is a progressive disease of the central nervous 

system that is characterized by an accumulation of neurofibrillary tangles. In Guam, Southwest New 

Guinea, and the Kii Peninsula of Honshu Island in Japan, there is an unusually high prevalence of ALS 

and PD. This may be related to the natural abundance of highly bioavailable aluminum compounds 

coupled with the virtual lack of magnesium and calcium in the areas’ drinking water supplies and soil. 

The consumption of the neurotoxic seed of the false sago palm tree may also play a key role in the 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 79 

3. HEALTH EFFECTS 

prevalence of ALS and PD in these areas. It has been proposed that long-term dietary deficiencies of 

calcium, rendering a secondary hyperparathyroid state, in the presence of highly bioavailable aluminum 

compounds and enhanced gastrointestinal absorption of aluminum can result in neuronal degeneration. In 

a study designed to evaluate effects of high aluminum and low calcium levels in the diet, much like the 

conditions associated with Guam and other similar areas, Cynomolgus monkeys were placed on a low 

calcium diet either with or without supplemental aluminum and manganese (Garruto et al. 1989). 

Chronic calcium deficiency alone produced neurodegenerative effects, although neurofibrillary changes 

were most frequently seen in the monkey on a low calcium diet supplemented with aluminum and 

manganese. 

There are limited data on the neurotoxicity of ingested aluminum in healthy individuals. An acute 

exposure study conducted by Molloy et al. (2007) did not find any significant alterations in performance 

in neurobehavioral tests with a mean aluminum blood level of 280–300 μg/L at the time of testing. 

Although neurotoxicity of aluminum has not been established or adequately studied in people who are 

healthy (i.e., have normal renal function), there is conclusive evidence that aluminum compounds are 

neurotoxic in orally-exposed animals. As discussed below and in Section 3.2.2.6, numerous intermediateduration studies in mice and rats found various neurotoxic effects in exposed adults and developing 

offspring. 

Many of the animal neurotoxicity studies are complicated by a lack of reported information on aluminum 

content in the base diet. This is an important issue because, as discussed in the introduction to 

Section 3.2.2, commercial rodent laboratory feed has a high aluminum content which can significantly 

contribute to total exposure. Dosages in studies with insufficient information on aluminum content in the 

base diet therefore must be assumed to underestimate the actual experimental dosages. The magnitude of 

the underestimate may be considerable, particularly for maternal dietary intake during lactation (an 

exposure period used in many neurobehavioral studies of aluminum in mice), which can be markedly 

(often 2-fold) higher than in nonlactating adults. Consequently, although aluminum studies with 

inadequate data on base dietary levels of aluminum provide useful information on neurotoxicity, 

NOAELs and LOAELs from these studies cannot be assumed to be accurate and are not suitable for 

comparing with effect levels from studies that used diets with known amounts of aluminum. There is 

particular concern for the adequacy of neurotoxicity NOAEL and LOAEL values for aluminum because 

sensitive neurotoxic effects may occur in rodents at aluminum intake levels close to those provided by 

commercial diet alone. Based on these concerns, only neurotoxicity studies providing information on 

base dietary aluminum content are included in Table 3-2. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 80 

3. HEALTH EFFECTS 

In general, oral exposure to aluminum is not associated with marked signs of neurotoxicity in animals. In 

a study by Golub et al. (1987), ataxia, splaying and dragging of hindlimbs, and paralysis were observed in 

mouse dams exposed to 200 mg Al/kg/day as aluminum lactate during gestation and lactation. Other 

studies involving exposure to higher aluminum doses have not noted significant increases in the incidence 

of overt signs of neurotoxicity (Donald et al. 1989; Golub et al. 1992a). It is possible that the levels of 

essential trace minerals in the diet used by Golub et al. (1987) were too low and may have contributed to 

the severity of the observed effects. The diet formulation used by this group was revised by adding a 

“more generous provision” of several essential nutrients, particularly trace minerals (including calcium, 

magnesium, phosphate), to avoid the marked maternal neurotoxicity associated with their absence in the 

original diet (Donald et al. 1989). Due to the apparent nutritional insufficiency of the diet used by Golub 

et al. (1987), the results of this study are not included in Table 3-2. Another overt sign of toxicity is an 

increase in cage mate aggression in male mice exposed to 200 mg Al/kg/day from gestation day 1 through 

postnatal day 170 (Golub et al. 1995). 

The overall weight of evidence strongly indicates that oral exposure to aluminum results in functional and 

cognitive alterations. Motor function and sensory function are affected by aluminum exposure. 

Decreases in forelimb and/or hindlimb grip strength have been observed in mice exposed to 

195 mg Al/kg/day as aluminum lactate in the diet for 5–7 weeks (Oteiza et al. 1993) or 13 weeks (Golub 

et al. 1992b; Oteiza et al. 1993) and in mice exposed to 100 mg Al/kg/day for over 2 years (Golub et al. 

2000). In contrast, no alterations in grip strength were observed in mouse dams exposed to 

250 mg Al/kg/day (Golub et al. 1992a) or 330 mg Al/kg/day (Donald et al. 1989) as aluminum lactate in 

the diet on gestation day 1 through lactation day 21 or in mice exposed to 200 mg Al/kg/day on gestation 

day 1 through postnatal day 170 (Golub et al. 1995). No significant alterations have been observed for 

footsplay or negative geotaxis following intermediate duration exposure to 195 mg Al/kg/day or 

200 mg Al/kg/day as aluminum lactate in the diet (Golub et al. 1992b, 1995; Oteiza et al. 1993) or mouse 

dams exposed to 250 mg Al/kg/day (Golub et al. 1992a) or 330 mg Al/kg/day as aluminum lactate in diet 

on gestation day 1 through lactation day 21 (Donald et al. 1989). A chronic-duration study found 

impaired performance on the negative geotaxis test after 18 months of exposure to 100 mg Al/kg/day as 

aluminum lactate in the diet, but not after 24 months of exposure (Golub et al. 2000). 

Significant decreases in spontaneous motor activity have also been reported in rats and mice exposed to 

aluminum chloride or aluminum lactate in the diet for at least 6 weeks. Effects are typically observed at 

doses of 130 mg Al/kg/day and higher. A decrease in total spontaneous activity, vertical activity 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 81 

3. HEALTH EFFECTS 

(rearing), and horizontal activity were observed in mice exposed to 130 mg Al/kg/day for 6 weeks (Golub 

et al. 1989). In mice exposed to 195 mg Al/kg/day, decreases in total activity, horizontal activity, and 

percentage of intervals with high activity counts were found after 90 days of exposure, but not after 

45 days of exposure (Golub et al. 1992b). Decreases in spontaneous motor activity have also been 

observed in rats exposed to aluminum chloride in the diet for 7 weeks or 11 months (Commissaris et al. 

1982); the amounts of aluminum added to the diet were 184 and 66 mg Al/kg/day, respectively; however, 

the aluminum content of the basal diet was not reported. Gavage exposure to a relatively low dose 

(53 mg Al/kg/day as aluminum chloride; aluminum content of the diet not reported) was also associated 

with a decrease in spontaneous motor activity. Exposure to lower doses of aluminum lactate or aluminum 

nitrate (with added citric acid) has not been associated with decreases in motor activity. No alterations in 

motor activity (as assessed in open field tests) were found in rats exposed to 97 mg Al/kg/day for 

100 days (Colomina et al. 2002), 125 mg Al/kg/day for 6.5 months (Domingo et al. 1996), or 

103 mg Al/kg/day for 1 or 2 years (Roig et al. 2006). Similarly, no alterations in total activity or 

horizontal activity were observed in mice exposed to 100 mg Al/kg/day as aluminum lactate in the diet 

during gestation, lactation, and postnatally until 2 years of age (Golub et al. 2000). However, the 

investigators noted that the automated activity monitor used in this study did not detect vertical movement 

of the older rats and that their previous study (Golub et al. 1989) found that vertical movement was more 

sensitive than horizontal movement. Another chronic-duration study (Roig et al. 2006) found no 

significant alterations in the total distance traveled or the total number of rearings in rats exposed to 

103 mg Al/kg/day as aluminum nitrate in drinking water (citric acid added) from gestation day 1 through 

2 years of age. Exposure to doses as high as 1,252 mg Al/kg/day as aluminum hydroxide (aluminum 

content of the basal diet was not reported) for 30 or 60 days (Thorne et al. 1986, 1987); the poor 

absorption of aluminum hydroxide probably contributed to this very high NOAEL. 

Several tests of sensory function have resulted in significant alterations. Decreases in thermal sensitivity 

were observed following chronic exposure of mice to 100 mg Al/kg/day as aluminum lactate in the diet 

(Golub et al. 2000). Changes in thermal sensitivity was not observed in mice exposed to 

195 mg Al/kg/day as aluminum lactate for 5–7 weeks (Oteiza et al. 1993) or 13 weeks (Golub et al. 

1992b) or mouse dams exposed to 250 mg Al/kg/day (Golub et al. 1992a) or 330 mg Al/kg/day as 

aluminum lactate in the diet on gestation day 1 through lactation day 21 (Donald et al. 1989). As with 

thermal sensitivity, conflicting results have been observed for startle responsiveness. Decreased 

responses to auditory and/or air puff stimuli were observed in mice exposed to 195 mg Al/kg/day as 

aluminum lactate in the diet for 5–7 weeks (Oteiza et al. 1993) or 90 days (Golub et al. 1992b). However, 

no changes in startle responsiveness were observed in mice exposed to 250 or 330 mg Al/kg/day as 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 82 

3. HEALTH EFFECTS 

aluminum lactate in the diet on gestation day 1 through lactation day 21 (Donald et al. 1989; Golub et al. 

1992a). Impairment of post-rotatory nystagmus was observed in rats exposed to 43.1 mg Al/kg/day as 

aluminum chloride in drinking water (dietary aluminum levels not reported) for 3 months; no alterations 

were observed at 21.5 mg Al/kg/day (Mameli et al. 2006). 

The potential effect of aluminum on cognitive function has been assessed in a number of studies using 

passive avoidance, operant training, or water maze tests. Aluminum does not appear to adversely affect 

performance on passive avoidance or operant training tests at lower oral doses. No significant alterations 

have been observed in rats exposed to 97 mg Al/kg/day as aluminum nitrate in drinking water (with added 

citric acid) for 100 days (Colomina et al. 2002), rats exposed to 125 mg Al/kg/day as aluminum nitrate in 

drinking water (with added citric acid) for 6.5 months (Domingo et al. 1996), or rats exposed to 

830 mg Al/kg/day or as high as 1,252 mg Al/kg/day as aluminum hydroxide in the diet (aluminum levels 

of basal diet were not reported) for 60 or 30 days, respectively (Thorne et al. 1987). Another study found 

improved performance on operant training tasks in mice exposed to 100 mg Al/kg/day in the diet for an 

intermediate duration (Golub and Germann 1998); the authors attributed this to an increase in food 

motivation in the aluminum-exposed mice. It is not known if an increased food motivation also 

influenced the results of the other studies. At higher aluminum doses, performance on operant training 

tasks is adversely affected. Impaired retention of learned responses were observed in rats exposed to 

346 mg Al/kg/day as aluminum sulfate in the drinking water (aluminum content of the diet was not 

reported) (Connor et al. 1989) or 70 mg Al/kg/day as aluminum chloride in drinking water (aluminum 

content of the basal diet was not reported) for 90 days (Zhang et al. 2003). Another study found impaired 

learning (more trials were needed to reach the acquisition criterion), but no effect on retention or recall in 

rats exposed to 66 mg Al/kg/day as aluminum chloride in the diet (aluminum content of the basal diet was 

not reported) (Commissaris et al. 1982). 

Because maze tests did not typically involve a food reward, these studies controlled for the potential 

confounder of food motivation. Impaired learning in a labyrinth maze test was observed in rats receiving 

gavage doses of 6 mg Al/kg/day as aluminum chloride or 35 mg Al/kg/day as aluminum hydroxide with 

citric acid (aluminum content of the diet was not reported) for 90 days (Bilkei-Gorzo 1993). In Morris 

water maze tests, impaired learning and memory was observed following gavage doses of 

500 mg Al/kg/day of an unreported aluminum compound for 90 days (Jing et al. 2004). In contrast, no 

significant alterations in performance on the water maze test were found in rats exposed to 

103 mg Al/kg/day as aluminum nitrate in the drinking water for a chronic duration (Roig et al. 2006). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 83 

3. HEALTH EFFECTS 

A number of studies have conducted histopathological examinations of the brain of rats, mice, and dogs 

following oral exposure to aluminum and have not found significant alterations (Dixon et al. 1979; 

Domingo et al. 1987b; Gomez et al. 1986; Katz et al. 1984; Oneda et al. 1994; Pettersen et al. 1990); the 

aluminum doses ranged from 70 to 979 mg Al/kg/day. In contrast to these results, Abd El-Rahman 

(2003) reported spongioform changes in the neurons of the hippocampus, nuclear deformity, 

neurofibrillary degeneration, and foci of demyelination in rats receiving gavage doses of 

85.9 mg Al/kg/day as aluminum sulfate (aluminum content of the diet was not reported). 

Neurotoxicity has been extensively studied in developing mice and rats that were exposed to aluminum 

during gestation, lactation, and/or directly via diet following weaning. As summarized in Section 3.2.2.6, 

effects on reflexes and simple motor behaviors were commonly found in aluminum-exposed developing 

animals, whereas effects on learning and memory have not been consistently shown. 

All reliable NOAEL and LOAEL values for neurological effects in adults in each species and duration 

category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects of various forms of aluminum following acute-, 

intermediate-, or chronic-duration oral exposure in humans. 

Several studies evaluated reproductive effects of acute-duration oral exposure to aluminum in animals. 

An increased incidence of resorptions occurred in female BALB/c mice treated with 41 mg Al/kg/day as 

aluminum chloride by gavage (aluminum in base diet not reported) on gestation days 7–16 (Cranmer et al. 

1986). No reproductive effects were observed in female Sprague-Dawley rats exposed to 

158 mg Al/kg/day as aluminum hydroxide or aluminum citrate by gavage and base diet from gestation 

day 6 to 15 (Gomez et al. 1991), or in THA rats treated with 73.1 mg Al/kg/day as aluminum chloride by 

gavage (aluminum in base diet not reported) from gestation day 7 to 16 (Misawa and Shigeta 1992). In a 

study of female reproductive system development (Agarwal et al. 1996), offspring of rats that were 

gavaged with aluminum lactate on gestation days 5–15 showed a transient irregularity of the estrus cycle 

(increased number of abnormal cycle lengths) at 250 mg Al/kg/day; doses as high as 1,000 mg Al/kg/day 

did not affect other end points (gonad weights, anogenital distance, time to puberty, duration of induced 

pseudopregnancy, or numbers of superovulated oocytes). The inconsistent findings summarized above 

may reflect differences in susceptibility among different strains/species of animals or compound 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 84 

3. HEALTH EFFECTS 

differences in toxicity or bioavailability. Additionally, because levels of aluminum in the base diet were 

not reported by Agarwal et al. (1996), Misawa and Shigeta (1992), or Cranmer et al. (1986), the doses in 

these studies are likely to underestimate actual aluminum intake. 

In a combination acute- and intermediate-duration study, no adverse effects on fertility or other general 

reproductive indices were found in female rats that were exposed to 38–77 mg Al/kg/day as aluminum 

nitrate by gavage and base diet for 14 days prior to mating with males that were similarly treated for 

60 days pre-mating (Domingo et al. 1987c). These exposures were continued throughout mating, 

gestation, parturition, and weaning and caused a reduction in the growth of the offspring in all treated 

groups, but the effects were negligible and transient (slight decreases in body weight, body length, and 

tail length observed on postpartum days 1 and 4 were no longer evident at time of weaning). An 

intermediate-duration oral study in male rats found that sperm count was decreased following exposure to 

2.5 mg Al/kg/day as aluminum chloride for 6–12 months (Krasovskii et al. 1979). The method of oral 

exposure was not specified but is presumed to be gavage, no information on aluminum in the base diet 

was reported, and reproductive function was not evaluated. No adverse reproductive effects were seen in 

male Sprague-Dawley rats, as assessed by plasma gonadotropin levels, histopathological evaluation, and 

serial matings, following exposure to 70 mg Al/kg/day as aluminum chloride in drinking water for up to 

90 days (Dixon et al. 1979); this dose does not include base dietary aluminum. 

Mating success (numbers of litters and offspring) was not affected in a three-generation study with Dobra 

Voda mice that were exposed to 49 mg Al/kg/day as aluminum chloride in drinking water and base diet 

over a period of 180–390 days (Ondreicka et al. 1966). No reproductive effects were observed in 

pregnant Swiss Webster mice that consumed 250 mg Al/kg/day as aluminum lactate throughout gestation 

and lactation (Golub et al. 1992a). However, an alteration in gestation length was observed in pregnant 

Swiss Webster mice that consumed 155 mg Al/kg/day as aluminum lactate in the diet during gestation 

and lactation (Donald et al. 1989). The effect on gestation length was small but statistically significant; 

all litters in the control group (7.5 mg Al/kg/day) were born on gestation day 18, whereas 4 of 17 litters 

exposed to ≥155 mg Al/kg/day were born earlier or later (gestation days 17, 19, or 20). 

No organ weight or histological changes were observed in the gonads of male and female Beagle dogs 

that consumed 93 mg Al/kg/day as acidic sodium aluminum phosphate (a common human food additive) 

in the diet for 6 months (Katz et al. 1984); this dose does not include base dietary aluminum. In another 

study with dogs, two of four male Beagles that were fed 75 mg Al/kg/day as basic sodium aluminum 

phosphate and base dietary aluminum for 26 weeks had decreased testicular weight and moderate 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 85 

3. HEALTH EFFECTS 

seminiferous tubule germinal epithelial cell degeneration and atrophy (Pettersen et al. 1990). No changes 

in reproductive tissue weight or histology occurred in the males at lower doses (≤27 mg Al/kg/day) or in 

female Beagles similarly exposed to ≤80 mg Al/kg/day. The investigators concluded that the testicular 

changes appeared to be secondary to palatability-related reductions in food consumption and body weight, 

and therefore, are not clearly direct effects of aluminum. 

Chronic studies showed no histological changes in the testes or ovaries of male and female Wistar rats fed 

a diet containing unspecified levels of aluminum phosphide/ammonium carbamate for 24 months 

(Hackenberg 1972), or in B6C3F1 mice that ingested 979 mg Al/kg/day as dietary aluminum potassium 

sulfate for 20 months (Oneda et al. 1994). The doses in the latter study do not include aluminum in the 

base diet. Neither mouse study assessed reproductive function. 

The highest reliable NOAEL and all reliable LOAEL values for reproductive effects in each species and 

duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects of various forms of aluminum following acuteor chronic-duration oral exposure in healthy humans. The only human data on developmental effects 

come from infants with renal failure and premature infants. Their responses are probably not indicative 

of responses expected in normal infants. Osteomalacia and increased bone and serum levels of aluminum 

were reported in three infants with kidney failure who had been treated orally with >100 mg of Al/kg/day 

as aluminum hydroxide from the first or sixth month of life (Andreoli et al. 1984; Griswold et al. 1983), 

and in healthy infants ingesting aluminum-containing antacids (Pivnick et al. 1995). Progressive 

encephalopathy was also observed among children with severe renal disease ingesting aluminumcontaining phosphate binders (Finberg et al. 1986; Griswold et al. 1983). 

A large number of studies have examined the developmental toxicity of aluminum in rats and mice. A 

variety of effects have been found including decreased pup survival/increased pup mortality, decreased 

growth, delayed maturation, and impaired neurodevelopment. Increases in pup mortality, typically 

occurring within the first 4 postnatal days, have been observed in rats exposed to 155 mg Al/kg/day as 

aluminum chloride in the diet on gestational days 8–20 (Bernuzzi et al. 1986), 200 mg Al/kg/day as 

aluminum lactate administered via gavage on postnatal days (PND) 5–14 (Bernuzzi et al. 1989a), and 

272 mg Al/kg/day as aluminum chloride or 378 mg Al/kg/day as aluminum lactate in the diet on gestation 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 86 

3. HEALTH EFFECTS 

days 1–20. Interpretation of the results of these studies is limited by the lack of information on the 

aluminum content of the basal diet. Another study found a decrease in the number of live pups per litter 

and an increase in the number of dead young per litter on PND 21 in the offspring of rats administered via 

gavage 51 mg Al/kg/day as aluminum nitrate for 14 days prior to mating, on gestation days 1–20, and 

lactation days 1–21 (Domingo et al. 1987c). The gavage administration route may have influenced the 

results of this study; other studies involving exposure to aluminum nitrate, aluminum citrate, or aluminum 

lactate via drinking water or diet have not reported increases in mortality at doses as high as 

330 mg Al/kg/day as aluminum lactate in the diet on gestation days 1 through PND 35 (Colomina et al. 

1992, 2005; Golub and Germann 1998, 2001; Golub et al. 1992a, 1995; McCormack et al. 1979). 

Numerous studies have reported decreases in pup body weight gain (Bernuzzi et al. 1986, 1989a, 1989b; 

Colomina et al. 2005; Domingo et al. 1987a, 1987c, 1989; Golub and Germann 2001; Golub et al. 1992a; 

Gomez et al. 1991; Misawa and Shigeta 1992; Paternain et al. 1988; Sharma and Mishra 2006). Since 

some of these studies did not report the aluminum content of the basal diet, their usefulness in 

establishing dose-response relationships is limited. With few exceptions, most studies have shown that 

aluminum does not adversely affect birth weight in the absence of effects on maternal body weight 

(Colomina et al. 2005; Domingo et al. 1989; Donald et al. 1989; Golub and Germann 1998, 2001; Golub 

et al. 1992a, 1995; Gomez et al. 1991; McCormack et al. 1979). The possible exception to this finding 

was decreases in birth weight observed in the offspring of rats administered aluminum nitrate via gavage 

at doses of ≥38 mg Al/kg/day on gestation day 1 through lactation day 21 (Domingo et al. 1987c) or 

77 mg Al/kg/day on gestation day 14 through lactation day 21 (Domingo et al. 1987a); neither study 

reported whether there were significant effects on maternal body weight gain. Paternain et al. (1988) also 

reported a decrease in pup body weight in rats receiving gavage doses of 38 mg Al/kg/day as aluminum 

nitrate on gestation days 6–14; a decrease in maternal weight gain was also reported at this dose level. 

Although most studies did not find effects on birth weights, several studies did find decreases in postbirth pup body weights; however, this finding was not consistent across studies. Lower pup body weights 

starting on PND 10 were observed in mouse pups exposed to aluminum during gestation only, during 

lactation only, or during gestation and lactation (Golub et al. 1992a); a decrease in maternal body weight 

gain was observed in the dams exposed during lactation. This study suggests that aluminum may 

influence growth directly and may not be only related to changes in maternal body weight during 

lactation. Similarly, decreases in body weights were observed on PND 12, 16, and 21 in the pups 

exposed to 100 mg Al/kg/day as aluminum nitrate in the drinking water (with added citric acid) on 

gestation day 1 through lactation day 21; a decrease in maternal food and water intake was also observed 

at this dose level (Colomina et al. 2005). A third study found decreases in pup body weight at PND 21 in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 87 

3. HEALTH EFFECTS 

mice exposed to 130 mg Al/kg/day as aluminum lactate in the diet on gestation day 1 through PND 

35 (Golub and Germann 2001). The lower body weights were still present at 5 months of age even 

though aluminum exposure was stopped on PND 35; an increase in food intake was also observed in these 

animals. In contrast to these studies, no adverse effects on body weight were observed in mouse pups 

exposed to 330 mg Al/kg/day as aluminum lactate in the diet on gestation day 1 through PND 21 or 

35 (Donald et al. 1989; Golub and Germann 1998; Golub et al. 1995). 

Gestational exposure to aluminum does not appear to result in an increase in the occurrence of 

malformation and anomalies, although reductions in ossification have been observed (Gomez et al. 1991; 

Sharma and Mishra 2006). Delays in ossification were observed at doses that also resulted in decreases in 

pup body weight. Some alterations in physical maturation have been observed in rats exposed to 

aluminum nitrate in drinking water (with added citric acid) on gestation day 1 through lactation 

day 21 (Colomina et al. 2005). The observed effects included significant delay in vagina opening at 53 or 

103 mg Al/kg/day, testes descent at 103 mg Al/kg/day, and incisor eruption in males at 53 mg Al/kg/day. 

No effects on days to pinna detachment or eye opening were observed. No delays on pinna detachment, 

eye opening, or incisor eruption were observed in rats administered via gavage 73 mg Al/kg/day as 

aluminum chloride (aluminum content of the diet not reported) on gestation days 8–20 (Misawa and 

Shigeta 1992). 

Animal studies provide strong evidence that gestational and/or lactational exposure to aluminum impairs 

the development of the nervous system. Potential neurodevelopmental effects have been evaluated using 

a variety of functional tests and cognitive tests. Because comparisons between studies are difficult due to 

differences in the exposure period, subroute of exposure, lack of information on the aluminum levels in 

the basal diet, and age of assessment, the results for each test will be presented separately. Significant 

impairment in the righting reflex and grasping reflex were observed in rat pups exposed to 

272 mg Al/kg/day as aluminum chloride or 194 mg Al/kg/day as aluminum lactate in the diet (aluminum 

content of the basal diet was not reported) on gestation days 1–20 (Bernuzzi et al. 1989b); no reflex 

alterations were observed at 96 mg Al/kg/day for aluminum chloride or aluminum lactate. Impairment of 

the righting reflex was also observed in the offspring of rats exposed to 155 mg Al/kg/day as aluminum 

chloride on gestation days 8–20 (Bernuzzi et al. 1986); grasping reflex was not significantly affected at 

this dose level or at 192 mg Al/kg/day. Exposure of pups to gavage doses of 300 mg Al/kg/day as 

aluminum lactate on PND 5–14 did not adversely affect the grasping reflex (Bernuzzi et al. 1989a). 

Righting reflex was also not affected in pups exposed to 103 mg Al/kg/day as aluminum nitrate in 

drinking water (citric acid added) on gestation day 1 through lactation day 21 (Colomina et al. 2005). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 88 

3. HEALTH EFFECTS 

Four studies examined temperature sensitivity; increases in sensitivity were observed in the offspring of 

mice exposed to 250 mg Al/kg/day as aluminum lactate in the diet on lactation days 1–21 (Golub et al. 

1992a) or 330 mg Al/kg/day as aluminum lactate in the diet on gestation day 1 through PND 42 (Golub et 

al. 1995). No effects were observed in mice exposed to 330 mg Al/kg/day as aluminum lactate in the diet 

on gestation day 1 through lacation day 21 or to 250 mg Al/kg/day as aluminum lactate in the diet on 

gestation days 1–21 (Golub et al. 1992a). 

A variety of motor function tests have been used to assess neurodevelopmental toxicity. Dosing pups 

with 300 mg Al/kg/day as aluminum lactate on PND 5–14 resulted in impairment of the suspension test 

and locomotor coordination (Bernuzzi et al. 1989a). Locomotor coordination was also altered in rat 

offspring exposed to 399 mg Al/kg/day as aluminum chloride in the diet on gestation days 1– 

20 (Bernuzzi et al. 1989b). No effects on the suspension test or locomotor coordination were observed in 

the offspring of rats exposed to 192 mg Al/kg/day as aluminum chloride in the diet on gestation days 8– 

20 (Bernuzzi et al. 1986). No information on the aluminum content of the basal diet was reported in the 

Bernuzzi studies. Alterations in the performance on the negative geotaxis test were found in mouse pups 

exposed to 250 mg Al/kg/day as aluminum lactate in the diet on lactation days 1–21 (Golub et al. 1992a) 

and in rat pups exposed to 399 mg Al/kg/day as aluminum chloride in the diet on gestation days 1– 

20 (Bernuzzi et al. 1989b), 200 mg Al/kg/day as aluminum lactate administered to pups on PND 5– 

14 (Bernuzzi et al. 1989a), or 155 mg Al/kg/day as aluminum chloride in the diet on gestation days 8– 

20 (Bernuzzi et al. 1986). No alterations in negative geotaxis results were found in mice exposed to 

330 mg Al/kg/day as aluminum lactate in the diet on gestation day 1 through PND 21 (Donald et al. 1989; 

Golub et al. 1995) or in rat pups exposed to 103 mg Al/kg/day as aluminum nitrate in the drinking water 

(citric acid added) on gestation day 1 through lactation day 21 (Colomina et al. 2005). 

Exposure to aluminum during gestation and/or lactation has consistently resulted in decreases in forelimb 

and/or hindlimb grip strength. Decreases in grip strength have been observed in mice exposed to 

155 mg Al/kg/day as aluminum lactate in diet on gestation day 1 through lactation day 21 (Donald et al. 

1989; Golub et al. 1995), 250 mg Al/kg/day as aluminum lactate on gestation days 1–21 or lactation 

days 1–21 (Golub et al. 1992a), or 130 mg Al/kg/day as aluminum lactate in the diet on gestation 

day 1 through PND 35 (Golub and Germann 2001) and in rats exposed to 103 mg Al/kg/day as aluminum 

nitrate in drinking water (with citric acid added) on gestation day 1 through lactation day 21 (Colomina et 

al. 2005). In other motor tests, increases in the number of rotations on a rotorod and a shorter latency to 

fall in a wire suspension test were observed in mice exposed to 260 or 130 mg Al/kg/day, respectively, as 

aluminum lactate in the diet on gestation day 1 through PND 35 (Golub and Germann 2001). Foot splay 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 89 

3. HEALTH EFFECTS 

has been observed in the mice exposed to 155 mg Al/kg/day as aluminum lactate in the diet on gestation 

day 1 through lactation day 21 (Donald et al. 1989), but not in mice exposed to 250 mg Al/kg/day as 

aluminum lactate in the diet on gestation days 1–21 or lactation days 1–21 (Golub et al. 1992a). In open 

field tests of motor activity, significant delays in pivoting, longer latencies, and more rearings were 

observed in the offspring of rats administered via gavage 73 mg Al/kg/day as aluminum chloride 

(aluminum content of the diet was not reported) (Misawa and Shigeta 1992). No effect on open field tests 

were observed in rat pups exposed to 103 mg Al/kg/day as aluminum nitrate in drinking water (citric acid 

added) on gestation day 1 through lactation day 21 (Colomina et al. 2005). 

Cognitive function effects were evaluated in passive avoidance tests, operant conditioning tests and water 

maze tests. No adverse effects were observed in operant conditioning tests in mice exposed to 

155 mg Al/kg/day as aluminum lactate in the diet on gestation day 1 through lactation day 21 (Golub et 

al. 1995) or 330 mg Al/kg/day as aluminum lactate in the diet on gestation day 1 through PND 35 (Golub 

and Germann 1998) and in passive avoidance tests in rats exposed to 103 mg Al/kg/day as aluminum 

nitrate in the drinking water (with added citric acid) on gestation day 1 through lactation 

day 21 (Colomina et al. 2005). The studies in mice noted that the aluminum-exposed pups often 

performed better than the controls; this may be due to an increase in food motivation in the aluminumexposed rats rather than a direct effect on cognitive function. Impaired learning, as measured using the 

Morris water maze, was observed in mice exposed to 260 mg Al/kg/day as aluminum lactate in the diet 

from gestation day 0 to PND 21 and on PND 21–35 (tested at 90 days of age) (Golub and Germann 

2001). When the salient and nonsalient cues were rotated, an increase in the escape latency was found at 

130 and 260 mg Al/kg/day. The investigators found exposure to >130 mg Al/kg/day resulted in 

differences in how the mice used the salient and nonsalient cues; no effects were observed at 

26 mg Al/kg/day. A study in rats exposed to 103 mg Al/kg/day (Colomina et al. 2005) did not find any 

significant effects in the water maze test. However, this study did not use probe trials; the alteration 

observed in the Golub and Germann studies were detected in the probe trials. 

The highest reliable NOAEL values and all reliable LOAEL values for developmental effects in each 

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

3.2.2.7 Cancer 

No studies were located regarding cancer in humans after oral exposure to various forms of aluminum. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 90 

3. HEALTH EFFECTS 

Animal bioassays have found no conclusive evidence for carcinogenicity of aluminum. Significantly 

increased incidences of gross tumors were reported for Long Evans rats (only in males) and Swiss mice 

(only in females) given 0.6 or 1.2 mg Al/kg/day as aluminum potassium sulfate in drinking water, 

respectively, for 2–2.5 years (Schroeder and Mitchener 1975a, 1975b). Aluminum levels in the base diet 

were not reported in these studies, although the animals were fed a low-metal diet in metal-free 

environmental conditions. At gross necropsy, 13/25 (52%) aluminum-treated male rats were found to 

have tumors compared to 4/26 (15.4%) controls. Six of the tumors in the aluminum-treated males were 

malignant compared to two malignancies in the control rats. The incidences of gross tumors in the female 

mice were 19/41 (46.3%) and 14/47 (29.8%) in exposed and control groups, respectively. The incidence 

of “lymphoma leukemia” was significantly increased (10/41 versus 3/47 in controls) in the female mice. 

A dose-response relationship could not be determined for either species because only one aluminum dose 

was used and the types of tumors and organs in which they were found were not specified. Very few 

study details were reported in this paper and it is unclear if the investigators grouped several types of 

tumors into the “lymphoma leukemia” category. Another study in rats (Wistar) found no increase in the 

incidence of neoplasms in male and female rats fed diets containing unspecified amounts of aluminum 

phosphide/ammonium carbamate for 24 months (Hackenberg 1972). 

There were no exposure-related increased incidences of tumors, other proliferative lesions or 

nonneoplastic lesions in 60 male or 60 female B6C3F1 mice that ingested ≤979 mg Al/kg/day as 

aluminum potassium sulfate in the diet for 20 months (Oneda et al. 1994). The level of aluminum in the 

base diet was not reported. The incidence of spontaneous hepatocellular carcinoma was significantly 

decreased in the high-dose males (5.5% compared to 20.5% in controls). 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to various forms of 

aluminum. 

3.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, hepatic, 

renal, endocrine, ocular, body weight, or metabolic effects in humans or animals after dermal exposure to 

various forms of aluminum. 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 91 

3. HEALTH EFFECTS 

The highest NOAEL values and all LOAEL values for dermal exposure from each reliable study for 

systemic effects in each species and duration category for aluminum are shown in Table 3-3. 

Musculoskeletal Effects. Information on potential musculoskeletal effects associated with dermal 

exposure of aluminum is limited to a case report of a woman reporting bone pain after a 4-year exposure 

to aluminum chlorhydrate in antiperspirant (Guillard et al. 2004). No osseous abnormalities were 

detected via radiography, and C-reactive protein levels and bone-specific serum parameters (alkaline 

phosphatase, γ-glutamyl transferase, calcium, phosphate) were within reference ranges; however, plasma 

aluminum levels were approximately 10 times higher than reference levels. Termination of aluminum 

exposure resulted in decreases in plasma aluminum levels and a disappearance of bone pain. 

No studies were located regarding musculoskeletal effects in animals following dermal exposure to 

aluminum. 

Dermal Effects. No studies were located regarding dermal effects in humans after dermal exposure to 

various forms of aluminum. Aluminum compounds are widely used in antiperspirants without harmful 

effects to the skin or other organs (Sorenson et al. 1974). Some people, however, are unusually sensitive 

to topically applied aluminum compounds. Skin irritation was reported in subjects following the 

application of aluminum chloride hexahydrate in ethanol used for the treatment of axillary or palmar 

hyperhidriosis (excessive sweating) (Ellis and Scurr 1979; Goh 1990) or the use of a crystal deodorant 

containing alum (Gallego et al. 1999). 

No studies were located regarding dermal effects in animals following intermediate- or chronic- duration 

dermal exposure to various forms of aluminum. 

Skin damage has been observed in female TF1 Carworth mice, New Zealand rabbits, and Large White 

pigs following the application of 10% aluminum chloride (0.005–0.1 g Al) or aluminum nitrate (0.006– 

0.013 g Al) for 5 days; but not from aluminum sulfate, hydroxide, acetate, or chlorhydrate (Lansdown 

1973). The damage consisted of hyperplasia, microabscess formation, dermal inflammatory cell 

infiltration, and occasional ulceration. These results suggest that the development of adverse dermal 

effects from exposure to aluminum depends upon its chemical form. 
024

Percent (%) Percent (%) Percent (%)

027

Percent (%)

034

Percent (%)

049

Percent (%)

079

Percent (%)

082

Percent (%)

Table 3-3 Levels of Significant Exposure to Aluminum and Compounds - Dermal 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System NOAEL Less Serious 

LOAEL 

Serious 

Reference Chemical Form 

ACUTE EXPOSURE 

Systemic 

Mouse 5 d Dermal Lansdown 1973 

(TFI) 1 x/d 2.5 F Percent (%) 5 F (slight to moderate Percent (%) hyperplasia) 25 F (severe hyperplasia with Percent (%) focal ulceration) Aluminum chloride 

Mouse 5 d Dermal Lansdown 1973 

(TFI) 1 x/d 25 F Percent (%) Aluminum chlorhydrate Mouse 5 d Dermal Lansdown 1973 

(TFI) 1 x/d 10 F Percent (%) Aluminum sulfate 

Mouse 5 d Dermal Lansdown 1973 

(TFI) 1 x/d 10 F (epidermal damage; hyperkeratosis, 

acanthosis, microabscesses; aluminum deposition in keratin) 

Percent (%) Aluminum chloride 

Mouse 5 d Dermal Lansdown 1973 

(TFI) 1 x/d 10 F Percent (%) Aluminum hydroxide Mouse 5 d Dermal Lansdown 1973 

(TFI) 1 x/d 10 F Aluminum acetate 

Percent (%) 
085

Percent (%)

025

Percent (%)

028 Percent (%)067 Percent (%)080 Percent (%)

Table 3-3 Levels of Significant Exposure to Aluminum and Compounds - Dermal (continued) 

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

Mouse (TFI) Rabbit (New Zealand) Rabbit (New Zealand) Rabbit (New Zealand) Rabbit (New Zealand) 

5 d 1 x/d Dermal 10 F 

Percent (%) 

(epidermal change: hyperkeratosis, acanthosis, 

Lansdown 1973 

Aluminum nitrate 

microabscesses; aluminum deposition in keratin) 

5 d 1 x/d Dermal 10 

Percent (%) 

(epidermal damage; 

hyperkeratosis, acanthosis, 

Lansdown 1973 

Aluminum chloride 

microabscesses; aluminum deposition in keratin) 

5 d 1 x/d Dermal 25 

Percent (%) 

Lansdown 1973 

Aluminum acetate 

5 d 1 x/d Dermal 10 

Percent (%) 

Lansdown 1973 

Aluminum sulfate 

5 d 1 x/d Dermal 10 

Percent (%) 

Lansdown 1973 

Aluminum hydroxide 
083 Percent (%)

086

Percent (%)

026

Percent (%)

029

Percent (%)

078

Percent (%)

081

Percent (%)

Table 3-3 Levels of Significant Exposure to Aluminum and Compounds - Dermal (continued) 

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

Rabbit(NewZealand)Rabbit(NewZealand)Pig(Large White)Pig(Large White)Pig(Large White)Pig(Large White)

5 d 1 x/d 5 d 1 x/d 5 d 1 x/d 5 d 1 x/d 5 d 1 x/d 5 d 1 x/d 

Dermal Dermal Dermal Dermal Dermal Dermal 

10

Percent (%)

25

Percent (%)

10

Percent (%)

10

Percent (%)

10

Percent (%)

10

Percent (%)

(epidermal change: 

hyperkeratosis, acanthosis, microabscesses; aluminum deposition in keratin) 

(epidermal damage; 

hyperkeratosis, acanthosis, microabscesses; aluminum deposition in keratin) 

Lansdown 1973 

Aluminum acetate 

Lansdown 1973 

Aluminum nitrate 

Lansdown 1973 

Aluminum chloride 

Lansdown 1973 

Aluminum chlorhydrate 

Lansdown 1973 

Aluminum sulfate 

Lansdown 1973 

Aluminum hydroxide 
084

Percent (%)

087

Percent (%)

Table 3-3 Levels of Significant Exposure to Aluminum and Compounds - Dermal (continued) 

Exposure/ LOAEL

Duration/

Species Frequency Reference (Route) (Strain) System NOAEL Less Serious Serious Chemical Form 

(Large White) Pig 5 d 

1 x/d Dermal 10 F 

Percent (%) 

Lansdown 1973 

Aluminum acetate 

(Large White) Pig 5 d 

1 x/d Dermal 10 (epidermal change: 

hyperkeratosis, acanthosis, microabscesses; aluminum deposition in keratin) 

Percent (%) 

Lansdown 1973 

Aluminum nitrate 

d = day(s); F = female; LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; x = time(s) 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 96 

3. HEALTH EFFECTS 

3.2.3.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological/lymphoreticular effects in humans after intermediateor chronic-duration dermal exposure to various forms of aluminum. 

Several children and one adult who had previous injections of vaccines or allergens in an aluminum-based 

vehicle showed hypersensitivity to aluminum chloride in a patch test (Böhler-Sommeregger and 

Lindemayr 1986; Veien et al. 1986). Dermal hypersensitivity to aluminum appears to be rare in humans. 

No studies were located regarding immunological/lymphoreticular effects in animals after dermal 

exposure to various forms of aluminum. 

3.2.3.4 Neurological Effects 

No studies were located regarding neurological effects in humans after acute- or intermediate-duration 

dermal exposure to various forms of aluminum. Graves et al. (1990) examined the association between 

Alzheimer’s disease and the use of aluminum-containing antiperspirants in a case-control study using 

130 matched pairs. The Alzheimer’s disease was clinically diagnosed at two geriatric psychiatric centers; 

the controls were friends or nonblood relatives of the Alzheimer patients. Information on lifetime use of 

antiperspirants/deodorant was collected via a telephone interview with the subject’s spouse. No 

association was found between Alzheimer’s disease and antiperspirant/deodorant use, regardless of 

aluminum content (odds ratio of 1.2; 95% confidence interval of 0.6–2.4). When only users of aluminumcontaining antiperspirants/deodorants were examined, the adjusted odds ratio was 1.6 (95% confidence 

interval of 1.04–2.4). A trend (p=0.03) toward a higher risk of Alzheimer’s with increasing use of 

aluminum-containing antiperspirants/ deodorants was also found. 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 97 

3. HEALTH EFFECTS 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to various forms of aluminum: 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.3 GENOTOXICITY 

Although aluminum complexes with deoxyribonucleic acid (DNA), particularly at lower pHs (Dyrssen et 

al. 1987; Karlik et al. 1980), negative results have been observed in in vitro assays (summarized in Table 

3-4) for reverse mutations in Salmonella typhimurium (Marzin and Phi 1985), DNA damage in 

Escherichia coli (Olivier and Marzin 1987), rec assay using Bacillus subtilis (Kada et al. 1980; 

Kanematsu et al. 1980; Nishioka 1975), forward mutations in the thymidine kinase locus of L5178Y 

mouse lymphoma cells (Oberly et al. 1982), and morphological transformation in Syrian hamster cells 

(DiPaola and Casto 1979). However, other studies have shown that aluminum can induce DNA crosslinking in rat ascites hepatoma cells (Wedrychowski et al. 1986), micronuclei formation in human 

peripheral blood lymphocytes (Banasik et al. 2005; Migliore et al. 1999; Roy et al. 1990), and 

chromosome aberrations in human peripheral blood lymphocytes (Roy et al. 1990). Using FISH analysis, 

Migliore et al. (1999) was unable to conclude whether the micronuclei resulted from clastogenic and 

aneuploidogenic mechanism, although a higher (not statistically significant) percentage of micronuclei 

contained whole chromosomes. An in vivo study also found significant increases in chromosome 

aberrations in the mone marrow cells of mice receiving an intraperitoneal dose of aluminum chloride 

(Manna and Das 1972). There was a significant increase in chromatid-type aberrations over the controls, 

and these occurred in a nonrandom distribution over the chromosome complement; no dose-response 

relationship could be demonstrated, although the highest dose of aluminum chloride did produce the 

greatest number of aberrations. 

3.4 TOXICOKINETICS 

Aluminum is poorly absorbed following either oral or inhalation exposure and is essentially not absorbed 

dermally. Approximately 0.1–0.6% of ingested aluminum is usually absorbed, although absorption of 

less bioavailable forms, such as aluminum hydroxide, can be on the order of 0.1%. The unabsorbed 

aluminum is excreted in the feces. The bioavailability of aluminum is strongly influenced by the 

aluminum compound and the presence of dietary constituents which can complex with aluminum and 
 

 

 

 

ALUMINUM 98 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Aluminum In Vitro 

Species (test system) End point Results Reference 

Salmonella typhimurium Gene mutation –	 Marzin and Phi 1985 

Escherichia coli DNA damage –	 Olivier and Marzin 1987 

Bacillus subtilis Rec assay –	 Kada et al. 1980; Kanematsu et al. 

1980; Nishioka 1975 

L5178Y mouse lymphoma Forward mutation –	 Oberly et al. 1982 

cells 

Syrian hamster embryo Transformation assay –	 DiPaola and Casto 1979 

cells 

Rat ascites hepatoma DNA cross-linking +	 Wedrychowski et al. 1986 

cells 

Human peripheral blood Micronuclei formation +	 Banasik et al. 2005; Migliore et al. 1999; 

lymphocytes	 Roy et al. 1990 

Human peripheral blood Chromosome +	 Roy et al. 1990 

lymphocytes abberrations 

– = negative result; + = positive result 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 99 

3. HEALTH EFFECTS 

thereby enhance or inhibit its absorption. The main mechanism of absorption is probably passive 

diffusion through paracellular pathways. Aluminum binds to various ligands in the blood and distributes 

to every organ, with highest concentrations found in bone and lung tissues. Absorbed aluminum is 

excreted principally in the urine and, to a lesser extent, in the bile. Studies on aluminum uptake and 

elimination rates indicate that a near steady-state is maintained in most healthy adults, with aluminum 

body burdens varying slightly up and down over time with an overall small rate of increase over the 

lifespan. Nevertheless, blood and tissue aluminum levels are increased in persons exposed to high levels 

of aluminum, such as those associated with long-term use of antacids. The levels return to normal upon 

cessation of exposure. Under certain atypical conditions (e.g., poor renal function with increased 

aluminum load), levels of aluminum in the body may raise high enough to cause toxicity in humans. The 

main target organs under these conditions appear to be the central nervous system and bone. The 

molecular mechanism of aluminum bone and neurotoxicity has not been established. 

Aluminum can form complexes with many molecules in the body (organic acids, amino acids, 

nucleotides, phosphates, carbohydrates, macromolecules). Many aluminum compounds have low 

solubility products, so their “free” aluminum ions (e.g., hydrated Al(H2O)6

3+) occur in very low 

concentrations. The toxicokinetics of aluminum can vary, depending on the nature of these complexes. 

For example, aluminum bound in a low-molecular-weight complex could be filtered at the renal glomeruli 

and excreted, while aluminum in a high-molecular-weight complex (aluminum transferrin) would not. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Evidence for absorption of aluminum after inhalation exposure in humans is available from several 

occupational studies. Occupational exposure to aluminum fumes, dusts, and flakes has resulted in 

increases in serum, tissue, and urinary levels of aluminum. Significantly higher serum aluminum levels 

were observed in 279 workers exposed to aluminum powder as compared to unexposed workers; the 

preshift plasma levels were 4.92 and 3.60 μg/L, respectively (Gitelman et al. 1995); no significant 

differences in postshift plasma levels were found between the aluminum workers (5.12 μg/L) and 

unexposed controls (4.16 μg/L). Results of an autopsy on a stone mason presumably exposed to 

aluminum showed that tissue levels of aluminum were substantially higher than those of a group of 

24 individuals presumably not exposed to aluminum in the workplace (Teraoka 1981). Following an 

8-hour exposure to a time-weighted average (TWA) concentration of 2.4 mg/m3 aluminum, urinary levels 

in 3 previously unexposed volunteers rose from 3 to 4–414 μg/L (Sjögren et al. 1985). Increased urinary 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 100 

3. HEALTH EFFECTS 

aluminum levels have also been observed in workers exposed to 0.025 (median respirable concentration) 

or 5 mg/m3 (TWA concentrations) aluminum dust (Gitelman et al. 1995; Mussi et al. 1984) or 2.4 or 

5 mg/m3 (TWA concentrations) aluminum fumes (Mussi et al. 1984; Sjögren et al. 1985). Indirect 

evidence for inhalation absorption of aluminum was reflected in a fall in urinary aluminum levels from 

82 to 29 μg/L in workers following a 16–37-day exposure-free interval (Sjögren et al. 1988). 

The percentage of aluminum absorbed following inhalation exposure was not reported in occupational 

toxicokinetic studies (Gitelman et al. 1995; Mussi et al. 1984; Pierre et al. 1995; Sjögren et al. 1985, 

1988). However, a fractional absorption of 1.5–2% was estimated based on the relationship between 

urinary aluminum excretion and the airborne soluble aluminum to which workers were exposed (Yokel 

and McNamara 2001). Data from Mussi et al. (1984) suggest that the fractional absorption of aluminum 

from lung to blood is higher in individuals exposed to aluminum fumes as compared to aluminum dust. 

This is consistent with knowledge that particle size influences the deposition pattern in the lungs and 

absorption. 

It is considered that systemic absorption of airborne aluminum occurs via the lungs, gastrointestinal tract 

after mucociliary clearance from the respiratory tract (ICRP 1994), or intranasal absorption via olfactory 

neurons. Gitelman et al. (1995) found a better correlation between respirable aluminum air 

concentrations and urinary aluminum output than between total aluminum air concentrations and urinary 

aluminum output, suggesting that some of the aluminum was absorbed through the lungs. Studies by Perl 

and Good (1987) and Zatta et al. (1993) have demonstrated that aluminum may directly enter the brain via 

the olfactory tract; the aluminum crosses the nasal epithelium and reaches the brain via axonal transport. 

Several animal studies indicate that aluminum is retained in the lung after inhalation exposure to 

aluminum oxide (Christie et al. 1963; Thomson et al. 1986) and aluminum chlorhydrate (Steinhagen et al. 

1978; Stone et al. 1979). However, no significant increases in aluminum in tissues other than the lungs or 

serum were seen, indicating that lung retention rather than absorption was taking place (Steinhagen et al. 

1978; Stone et al. 1979). 

3.4.1.2 Oral Exposure 

Aluminum present in food and drinking water is poorly absorbed through the gastrointestinal tract. 

Several small scale human studies estimated aluminum absorption efficiencies of 0.07–0.39% following 

administration of a single dose of the radionuclide aluminum-26 (26Al) in drinking water (Hohl et al. 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 101 

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1994; Priest et al. 1998; Stauber et al. 1999; Steinhausen et al. 2004). Fractional absorption was 

estimated by measuring aluminum levels in urine; it is likely that most of these studies (with the 

exception of Stauber et al. 1999) underestimated gastrointestinal absorption because the amount of 

aluminum retained in tissues or excreted by non-renal routes was not factored into the absorption 

calculations. Several animal studies also utilized 26Al to estimate aluminum bioavailability from drinking 

water. When aluminum levels in urine and bone were considered, absorption rates of 0.04–0.06% were 

estimated in rats (Drueke et al. 1997; Jouhanneau et al. 1993); when liver and brain aluminum levels were 

also considered, an absorption rate of 0.1% was estimated (Jouhanneau et al. 1997). Another study that 

utilized a comparison of the area under the plasma aluminum concentration-time curve after oral and 

intravenous administration of 26Al estimated an oral aluminum bioavailability of 0.28% (Yokel et al. 

2001a). 

Two human studies examined the bioavailability of aluminum in the diet. An absorption efficiency of 

0.28–0.76% was estimated in subjects ingesting 3 mg Al/day (0.04 mg Al/kg/day) or 4.6 mg Al/day 

(0.07 mg Al/kg/day) (Greger and Baier 1983; Stauber et al. 1999). When 125 mg Al/day (1.8 mg 

Al/kg/day) as aluminum lactate in fruit juice was added to the diet, aluminum absorption decreased to 

0.094% (Greger and Baier 1983). Yokel and McNamara (2001) suggested that the bioavailability of 

aluminum from the diet is 0.1% based on daily urinary excretion levels of 4–12 μg and average aluminum

intakes by adults in the United States of 5,000–10,000 μg/day. 

The bioavailability of aluminum is dependent on the form in which it is ingested and the presence of 

dietary constituents with which the metal cation can complex (see Section 3.5.1). Ligands in food can 

have a marked effect on absorption of aluminum, as they can either enhance uptake by forming 

absorbable (usually water soluble) complexes (e.g., with carboxylic acids such as citric and lactic), or 

reduce it by forming insoluble compounds (e.g., with phosphate or dissolved silicate). Evidence strongly 

suggests that the complexing agent of most importance to aluminum uptake in humans is citric acid (or its 

conjugate base citrate), which is a constituent of many foods and beverages and can be present in the gut 

in high concentrations (Reiber et al. 1995). It is well-documented in both human and animal studies that 

blood and tissue levels of aluminum can be increased by simply increasing the consumption of citric acid 

(i.e., with no concurrent increase in aluminum ingestion), or other dietary chelators such as ascorbic acid 

and lactic acid (DeVoto and Yokel 1994; Domingo et al. 1991; Florence et al. 1994; Molitoris et al. 1989; 

Partridge et al. 1989; Slanina et al. 1984, 1985, 1986; Testolin et al. 1996; Weberg and Berstad 1986). 

The amount of a 976 mg (approximately 14 mg/kg) dose of aluminum as aluminum hydroxide in antacid 

tablets absorbed by 7–10 volunteers were estimated as 0.004, 0.03, or 0.2% when the antacids were 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 102 

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suspended in tap water (pH 9.2), orange juice (pH 4.2), or citric acid (pH 2.4), respectively (Weberg and 

Berstad 1986). Absorption was estimated as the amount excreted in urine in 72 hours divided by the 

amount ingested. A more recent study using 26Al estimated aluminum absorption rates of 0.523, 0.0104, 

and 0.136% in two subjects receiving a single dose of aluminum citrate, aluminum hydroxide, or 

aluminum hydroxide dissolved in a citrate solution, respectively (Priest et al. 1996). This is consistent 

with another study reporting absorption levels of 0.37–0.57% in humans ingesting 280 mg Al as 

aluminum hydroxide in sodium citrate and citric acid (Taylor et al. 1998). A fourth study reported a 

higher absorption level (1%) in one subject administered 26Al in a sodium citrate solution (Day et al. 

1991). 

A comparison of the bioavailability of different aluminum compounds was conducted by Yokel and 

McNamara (1988). Bioavailability in rabbits following a single maximum safe dose was estimated by 

comparing areas under the plasma concentration-time curves after oral and intravenous dosing. The 

estimated bioavailability of the water-soluble compounds aluminum chloride (333 mg Al/kg), aluminum 

nitrate (934 mg Al/kg), aluminum citrate (1,081 mg Al/kg), and aluminum lactate (2,942 mg Al/kg) in 

rabbits was 0.57, 1.16, 2.18, and 0.63%, respectively. Aluminum absorption in rabbits similarly treated 

with the water-insoluble compounds aluminum hydroxide (780 mg Al/kg), aluminum borate 

(2,736 mg Al/kg), aluminum glycinate (1,351 mg Al/kg), and aluminum sucrose sulfate 

(20,867 mg Al/kg) was 0.45, 0.27, 0.39, and 0.60%, respectively (Yokel and McNamara 1988). 

Similarly, Schönholzer et al. (1997) examined aluminum absorption following oral exposure to 26Al in 

rats. The bioavailability of aluminum hydroxide, aluminum citrate, aluminum citrate with added sodium 

citrate, or aluminum maltolate following a single gavage dose was 0.1, 0.7, 5.1, and 0.1%, respectively. 

The presence of food in the stomach appeared to delay the absorption of 26Al, but did not significantly 

alter the amount of aluminum absorbed in rats (Yokel et al. 2001a). Aluminum bioavailability was 0.23% 

with no food in the stomach and 0.21% when food was present. Similarly, there were no differences in 

absorption when the 26Al was added to hard water (300 mg calcium carbonate/L added) or soft water. 

Considering the available human and animal data as discussed above, it is likely that the oral absorption 

of aluminum can vary 10-fold based on chemical form alone. Although bioavailability appears to 

generally parallel water solubility, insufficient data are available to directly extrapolate from solubility in 

water to bioavailability. Additionally, due to available dietary ligands such as citrate, lactate, and other 

organic carboxylic acid complexing agents, the bioavailability of any particular aluminum compound can 

be markedly different in the presence of food than under empty stomach conditions. 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 103 

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3.4.1.3 Dermal Exposure 

There are limited human data on the dermal absorption of aluminum. Aluminum compounds are common 

additives in underarm antiperspirants. The active ingredient is usually an aluminum chlorhydrate salt, 

which is thought to form an obstructive plug of aluminum hydroxide within the sweat duct (Hostynek et 

al. 1993; Reiber et al. 1995). Using 26Al labeled aluminum chlorohydrate applied to the underarm of two 

subjects, Flarend et al. (2001) estimated that 0.012% of the applied aluminum was absorbed through the 

skin. The study investigators cautioned against using these results to extrapolate dermal absorption 

following repeated exposure to aluminum. 

Dermal absorption studies were not located for animals; however a study by Anane et al. (1995) found 

increased levels of aluminum in the urine of mice exposed to 0.1 or 0.4 μg/day aluminum chloride (0.01– 

0.04 μg Al/day) applied daily to a 4 cm2 shaved area for 130 days. Interpretation of this study is limited 

due to the lack of control measures to prevent the animals from licking their fur and thus ingesting 

aluminum. 

3.4.1.4 Other Routes of Exposure 

Flarend et al. (1997) estimated aluminum absorption in rabbits following intramuscular injection of 26Al 

labelled aluminum hydroxide or aluminum phosphate adjuvants used for vaccines. Aluminum from both 

solutions was absorbed, appearing in the blood as early as 1 hour after injection. Three times as much 

aluminum from the aluminum phosphate adjuvant was absorbed during the first 28 days after exposure; 

since the terminal phase of the blood concentration curve was not reached by that time, this difference 

may be due to differences in the rate of absorption. 

3.4.2 Distribution 

Aluminum occurs normally in all body tissues of humans (Ganrot 1986). The total body burden of 

aluminum in healthy human subjects is approximately 30–50 mg (Alfrey 1981, 1984; Alfrey et al. 1980; 

Cournot-Witmer et al. 1981; Ganrot 1986; Hamilton et al. 1973; Tipton and Cook 1963). Normal levels 

of aluminum in serum are approximately 1–3 μg/L (House 1992; Liao et al. 2004). Of the total body

burden of aluminum, about one-half is in the skeleton, and about one-fourth is in the lungs (Ganrot 1986). 

The normal level of aluminum in adult human lungs is about 20 mg/kg wet weight (w/w) and increases 

with age due to an accumulation of insoluble aluminum compounds that have entered the body via the 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 104 

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airways (Ganrot 1986). Most of the aluminum in other parts of the body probably originates from food 

intake. Reported normal levels in human bone tissue range from 5 to 10 mg/kg (Alfrey 1980; Alfrey et al. 

1980; Cournot-Witmer et al. 1981; Flendrig et al. 1976; Hamilton et al. 1973; Tipton and Cook 1963). 

Aluminum is also found in human skin (Alfrey 1980; Tipton and Cook 1963), lower gastrointestinal tract 

(Tipton and Cook 1963), lymph nodes (Hamilton et al. 1973), adrenals (Stitch 1957; Tipton and Cook 

1963), and parathyroid glands (Cann et al. 1979). Low aluminum levels (0.3–0.8 mg/kg w/w) are found 

in most soft tissue organs, other than the lungs (Hamilton et al. 1973; Tipton and Cook 1963). 

The normal level of aluminum in the human brain ranges from 0.25 to 0.75 mg/kg w/w, with gray matter 

containing about twice the concentration found in the white matter (Alfrey et al. 1976; Arieff et al. 1979; 

McDermott et al. 1978; Roider and Drasch 1999). There is evidence that with increasing age of humans, 

aluminum concentrations may increase in the brain tissue (Alfrey 1980; Crapper and DeBoni 1978; 

Markesbery et al. 1981; McDermott et al. 1979; Stitch 1957; Tipton and Shafer 1964); aluminum levels in 

serum may also increase with aging (Zapatero et al. 1995). 

3.4.2.1 Inhalation Exposure 

Limited information is available regarding the distribution of aluminum following inhalation exposure in 

humans or animals. Results of an autopsy of a stone mason presumed to have been exposed to aluminum 

by inhalation indicated elevated concentrations of aluminum in the lungs (2,000 ppm), hilar lymph nodes 

(3,200 ppm), liver (130 ppm), and spleen (520 ppm) (Teraoka 1981). The aluminum levels in the tissues 

of control subjects were 230, 2,000, 19, and 22 ppm, respectively. Rats and guinea pigs given 

intermediate or chronic inhalation exposures to aluminum chlorhydrate accumulated aluminum primarily 

in the lungs (Steinhagen et al. 1978; Stone et al. 1979). The only other organs with significant 

accumulation of aluminum were the adrenal glands (Stone et al. 1979) and the peribronchial lymph nodes 

(Steinhagen et al. 1978; Stone et al. 1979). No appreciable aluminum accumulation was observed in the 

brain, heart, spleen, kidneys, or liver of either species. 

During inhalation exposure to aluminum and its compounds, the lungs distribute and deposit the material 

based on particle size (ICRP 1994). A portion of the particles are exhaled, some are trapped in the 

nasopharyngeal and upper respiratory areas and deposited in the gastrointestinal tract by mucosal 

movement and mucocilliary action, and a portion of the small particles reach the alveoli where they can 

be transferred to blood (especially for soluble compounds), or taken up by alveolar macrophages through 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 105 

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phagocytosis and transported to pulmonary lymph nodes for insoluble compounds. Pulmonary 

concentration of aluminum increases with age. 

3.4.2.2 Oral Exposure 

There are limited data on the distribution of aluminum in humans. Clearance of 26Al from the blood was 

assessed in two male volunteers orally exposed to 100 mg aluminum as aluminum chloride (Hohl et al. 

1994). Plots of the serum and urine concentrations showed several slope changes, indicating that the 

clearance from blood involves one central and three peripheral compartments with turnover rates ranging 

from 0.003 to 9 h-1 . 

The distribution of aluminum in animals after oral exposure has been evaluated in a number of studies 

(Cranmer et al. 1986; Deng et al. 2000; Dlugaszek et al. 2000; Domingo et al. 1993; Gomez et al. 1997a, 

1997b; Greger and Donnaubauer 1986; Julka et al. 1996; Ogasawara et al. 2002; Santos et al. 1987; 

Sutherland and Greger 1998; Walton et al. 1995; Yokel and McNamara 1985; Yokel et al. 1999; Zafar et 

al. 1997). These studies are particularly informative because they demonstrate that, although 

bioavailability of aluminum is low, aluminum tissue concentrations can increase substantially following 

oral exposure, and provide information on distribution of aluminum in various tissues. Aluminum is not 

equally distributed throughout the body following oral exposure. Aluminum accumulation was typically 

higher in the spleen, liver, bone, and kidneys than in the brain, muscle, heart, or lung (Greger and 

Sutherland 1997). Eight days after a single gavage dose of 2.6 mg of 26Al as aluminum chloride, the 

descending order of aluminum levels was bone>spleen>liver>kidney (Zafar et al. 1997). To evaluate the 

retention of aluminum in tissues following oral exposure, rats were fed a diet supplemented with 

aluminum hydroxide for an intermediate-duration exposure period (Greger and Donnaubauer 1986). 

Relative to controls, treated rats had increased aluminum concentrations in bone, muscle, and kidneys. 

Aluminum concentrations in these tissues decreased significantly 3 days after withdrawal of aluminum 

hydroxide from the diet. Tissue concentrations of aluminum were similar for treated and control rats 

7 days after withdrawal. 

Once into the blood, aluminum is believed to be present almost exclusively in the plasma where it is 

bound mainly to transferrin (Ganrot 1986; Harris and Messori 2002; Martin 1986); recent data suggest 

that over 90% of the aluminum in serum is bound to transferrin (Harris and Messori 2002). There is in 

vitro evidence indicating that aluminum can bind to the iron-binding sites of transferrin (Moshtaghie and 

Skillen 1986), and that Al+3 may compete with similar ions in binding to transferrin (Ganrot 1986). As 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 106 

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reviewed by Priest (2004), approximately 10% of the aluminum in blood is found in the erythrocytes; 

peak levels occur 1 day after peak serum aluminum levels were reached. The half-life of aluminum in the 

erythrocytes appears to longer than the half-life in plasma. In addition to binding with transferrin, Al+3 is 

also known to bind to a considerable extent to bone tissue, primarily in the metabolically active areas of 

the bone (Ganrot 1986). 

Cellular uptake of aluminum by organs and tissues is believed to be relatively slow and most likely occurs 

from the aluminum bound to transferrin (Ganrot 1986). It is likely that the density of transferrin receptors 

in different organs influences the distribution of aluminum to organs (Morris et al. 1989). Within cells, 

Al+3 accumulates in the lysosomes, cell nucleus, and chromatin. In organs composed of postmitotic cells, 

this accumulation would be expected to lead to an increase of the Al+3 concentration; however, in other 

organs, a steady state is expected to be reached between the Al+3 accumulation and the elimination of 

dead cells that are replaced by cells with a lower Al+3 content. The cells that accumulate the most 

aluminum are large, long-lived postmitotic cells, such as in neurons (Ganrot 1986). 

In addition to distribution of aluminum to the brain (hippocampus), bone, muscle, and kidneys of orally 

exposed animals, there is evidence in animals that aluminum crosses the placenta and accumulates in the 

fetus and distributes to some extent to the milk of lactating mothers (Cranmer et al. 1986; Golub et al. 

1996; Yokel 1985; Yokel and McNamara 1985). Aluminum levels were increased in both fetuses and 

placentas of mice treated throughout gestation with aluminum chloride (Cranmer et al. 1986). The 

concentration of aluminum in milk of rats that ingested 420 mg Al/kg/day as aluminum lactate in the diet 

during gestation and lactation increased at least 4-fold beginning on postnatal day 12 (Golub et al. 1996). 

Peak concentrations of aluminum were detected in the milk of lactating rabbits 12–24 hours after a single 

large gavage dose of aluminum lactate; however, the amount of aluminum in milk as a percentage of the 

total oral dose was not reported (Yokel and McNamara 1985). Aluminum levels of rabbit pups exposed 

during lactation were not significantly different from levels in control pups, suggesting that only a small 

amount of the aluminum in breast milk is absorbed by the offspring (Yokel 1985). 

Age-related differences in the distribution of aluminum has been observed in rats exposed to 0, 50, or 

100 mg Al/kg/day as aluminum nitrate in the drinking water with added citrate (Gomez et al. 1997a). The 

levels of aluminum in the brain and bone were significantly higher in the older rats (16 months of age at 

study beginning) compared to young (21 days of age) or adult (8 months of age) rats; this was observed in 

the control and aluminum-treated rats. Liver aluminum levels were significantly higher in adult and older 

rats as compared to the young rats. 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 107 

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3.4.2.3 Dermal Exposure 

No studies were located regarding distribution in humans after dermal exposure to aluminum or its 

compounds. Elevated levels of aluminum have been observed in the liver, brain, lung, and kidneys of 

Swiss mice dermally exposed to 0.4 μg/day aluminum chloride (0.04 μg Al/day) for 20 days during 

gestation (Anane et al. 1997). Elevated levels of aluminum were also observed in the fetus, providing 

evidence of transplacental transfer of aluminum. As noted previously, this study did not prevent the mice 

from licking their fur. 

3.4.2.4 Other Routes of Exposure 

When there is inadequate elimination of aluminum from the body, as in nondialyzed uremic patients, 

increased aluminum concentrations are detected in serum, bone tissue, liver, spleen, brain, and skeletal 

muscle (Alfrey et al. 1980; Arieff et al. 1979). In hemodialysis patients exposed by infusion to large 

amounts of aluminum over long periods of time (with inadequate removal of aluminum by the kidneys 

and dialysis machines), increased aluminum concentrations are observed mostly in the spleen, followed 

by the liver and skeletal system (Alfrey 1980; Alfrey et al. 1980). A study in rabbits found a significantly 

lower serum half-life in renally-impaired animals, as compared to renally-intact animals (27 hours versus 

14 hours); this is likely due to the diminished volume of distribution in the renally-impaired rabbits 

(Yokel and McNamara 1988). 

The distribution of aluminum following intravenous, subcutaneous, intraperitoneal, and intramuscular 

exposure has been evaluated in studies with experimental animals (Cranmer et al. 1986; Du Val et al. 

1986; Flarend et al. 1997; Leblondel and Allain 1980; Yokel and McNamara 1985, 1989; Yokel et al. 

2001b). Results of these animal studies indicate that aluminum distributes to a number of tissues, organs, 

and biological fluids (Du Val et al. 1986; Leblondel and Allain 1980; Yokel and McNamara 1989). 

In rabbits given a single intravenous dose of aluminum lactate, aluminum concentrations did not increase 

above controls in the cerebellum, white brain tissue, hippocampus, spinal cord, adrenal glands, bone, 

heart, testes, or thyroid (Yokel and McNamara 1989). Treated animals did have significant increases of 

aluminum in the liver, serum, bile, kidneys, lungs, and spleen. Throughout the 128 day study, the liver of 

exposed rabbits had over 80% of the total body burden of aluminum. Persistence of aluminum in the 

various tissues, organs, and fluids varied. Estimated half-times of aluminum were 113, 74, 44, and 

42 days in the spleen, liver, lungs, and serum, respectively. The kidneys of treated rabbits demonstrated 
 

 

 

 

 

 

 

 

 

ALUMINUM 108 

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two half-times with an initial time of 4.2 and 2.3 days for the renal cortex and renal medulla, respectively, 

and a second half-time of >100 days for kidney in general; the relative amounts subject to each half-time 

were not addressed. The half-life of aluminum in the brain of rats receiving an intravenous dose of 

aluminum citrate was approximately 150 days (Yokel et al. 2001b). 

Subcutaneous injection of rabbits with aluminum chloride daily for 28 days was associated with 

significant accumulation of aluminum (measured at the end of the exposure period) in bone, followed in 

order by significantly increased aluminum concentrations in renal cortex, renal medulla, liver, testes, 

skeletal muscle, heart, brain white matter, hippocampus, and plasma (Du Val et al. 1986). Because the 

brain tissue of treated rabbits had the lowest aluminum concentrations of the tissues evaluated, the authors 

suggested that there was a partial blood-brain barrier to entry of aluminum. 

Distribution of aluminum to tissues following intraperitoneal exposure depends in part on the type of 

aluminum compound administered and on the aluminum concentration in blood (Leblondel and Allain 

1980). Mice were administered 54 mg Al/kg as aluminum chloride, nitrate, lactate, or gluconate by a 

single intraperitoneal injection. The blood concentrations of aluminum, which reached a peak within 

20 minutes, increased significantly with gluconate (99.5 mg/L), increased to high levels with lactate 

(4.5 mg/L), and increased marginally with nitrate and chloride (0.3 mg/L). Aluminum concentrations in 

the brain tissue of treated mice significantly increased only with aluminum gluconate and only at 

extremely high blood aluminum concentrations of 20–100 mg/L; the half-life of aluminum in the brain 

was approximately 90 minutes. At blood aluminum concentrations of 2–4 mg/L, there was no increase in 

brain aluminum with any of the compounds evaluated. Interpretation of this study is limited by the short 

monitoring period (apparently 80 minutes); thus, the study does not take into consideration possible 

differences in absorption rate between aluminum compounds. Differences in brain aluminum levels 

following administration of different aluminum compounds may also be due to the presence of carrier 

systems that can transport aluminum into or out of the brain; this has been demonstrated for aluminum 

citrate (Allen et al. 1995). 

Following intramuscular administration of aluminum hydroxide or aluminum phosphate vaccine 

adjuvants in rabbits, increased levels of 26Al were found in the kidney, spleen, liver, heart, lymph nodes, 

and brain (in decreasing order of aluminum concentration) (Flarend et al. 1997). 

There is also evidence from animal studies indicating that aluminum administered parenterally 

accumulates to a small extent in the milk of lactating mothers, and that aluminum crosses the placenta and 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 109 

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accumulates in fetal tissue (Cranmer et al. 1986; Yokel and McNamara 1985; Yumoto et al. 2000). 

Intraperitoneal exposure of pregnant mice to aluminum chloride on gestation days 7–16 has been 

associated with significantly increased concentrations of aluminum in both placental and fetal tissues 

(Cranmer et al. 1986). Following a single subcutaneous injection of 26Al on gestation day 15, 0.2 and 

0.21% of the dose was detected in the placenta and fetus, respectively, 5 days after the injection (Yumoto 

et al. 2000). Within the fetus, the level of 26Al in the brain was as high as 30% of that in the fetal liver; in 

contrast, the level of 26Al in the brain of the dam was only 1% of the level in the liver. Intravenous, 

intraperitoneal, or subcutaneous exposure of lactating rats, rabbits, or mice to aluminum lactate or 

aluminum chloride has been associated with increased concentrations of aluminum in milk (Muller et al. 

1992; Yokel and McNamara 1985). The amount of aluminum detected in milk 24 hours after exposure 

was estimated to be 2.4% of the intravenous dose and 3.3% of the subcutaneous dose (Yokel and 

McNamara 1985). Subcutaneous injection of 26Al in rats on lactation day 1 through 20, resulted in 

significant elevation in aluminum levels in the suckling rats (Yumoto et al. 2000, 2003). On lactation 

day 2, elevated levels of 26Al were detected in the liver, but not in the kidney, brain, or blood; 26Al was 

detected in these tissues on lactation day 9 (Yumoto et al. 2000). 

3.4.3 Metabolism 

As an element, aluminum is always found attached to other chemicals, and these affinities can change 

within the body. In living organisms, aluminum is believed to exist in four different forms: as free ions, 

as low-molecular-weight complexes, as physically bound macromolecular complexes, and as covalently 

bound macromolecular complexes (Ganrot 1986). The free ion, Al+3, is easily bound to many substances 

and structures; therefore, its fate is determined by its affinity to each of the ligands and their relative 

amounts and metabolism. Aluminum may also form low-molecular-weight complexes with organic 

acids, amino acids, nucleotides, phosphates, and carbohydrates. These low-molecular-weight complexes 

are often chelates and may be very stable. The complexes are metabolically active, particularly the 

nonpolar ones. Because aluminum has a very high affinity for proteins, polynucleotides, and 

glycosaminoglycans, much of the aluminum in the body may exist as physically bound macromolecular 

complexes with these substances. Metabolically, these macromolecular complexes would be expected to 

be much less active than the smaller, low-molecular-weight complexes. Aluminum may also form 

complexes with macromolecules that are so stable that they are essentially irreversible. For example, 

evidence suggests that the nucleus and chromatin are often sites of aluminum binding in cells (Crapper 

McLachlan 1989; Dyrssen et al. 1987; Ganrot 1986; Karlik et al. 1980). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 110 

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3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Urinary excretion is the primary route of elimination of absorbed aluminum after inhalation exposure in 

humans. Elevated levels of aluminum in urine have been detected in aluminum welders and aluminum 

flake workers (Letzel et al. 1996; Ljunggren et al. 1991; Mussi et al. 1984; Pierre et al. 1995; Rossbach et 

al. 2006; Schaller et al. 2007; Sjögren et al. 1985, 1988). Six volunteers had urinary levels of 14– 

414 μg/L aluminum compared to concentrations of <3 μg/L prior to a 1-day exposure to 0.3– 

10.2 mg Al/m3 in welding fumes (Sjögren et al. 1985). The urinary aluminum levels of 7 welders 

exposed occupationally to aluminum fumes or dust for 6 months were increased 3-fold after an 8-hour 

workshift compared to concentrations at the beginning of the day (Mussi et al. 1984). Several 

investigators (Letzel et al. 1996; Rossbach et al. 2006; Sjögren et al. 1988) have found a linear 

relationship between post-shift urinary aluminum levels and levels of aluminum in air among welders. 

Occupational exposure studies suggest that the urinary excretion of aluminum is biphasic. The excretion 

half-time for the first phase ranged from 7.5 to 9 days among workers exposed to welding fumes or 

aluminum dust (Pierre et al. 1995; Sjögren et al. 1985, 1988). The half-times for the second phase ranged 

from 6.8 to 24 weeks (Schaller et al. 2007; Sjögren et al. 1988, 1991); the wide range of half-times may 

reflect the character of the inhaled aluminum (welding fume particles or aluminum flake particles) and the 

duration of exposure. 

No studies were located regarding excretion in animals after inhalation exposure to aluminum or its 

compounds. 

3.4.4.2 Oral Exposure 

Following ingestion in humans, absorbed aluminum from the blood is eliminated in the kidney and 

excreted in the urine (Gorsky et al. 1979; Greger and Baier 1983; Kaehny et al. 1977; Recker et al. 1977; 

Sutherland and Greger 1998). The unabsorbed aluminum is excreted primarily in the feces. An acute 

exposure of 4 days to 54.3 mg Al/kg as aluminum carbonate produced peak concentrations ranging from 

4- to 10-fold elevation in base-line urinary levels; the average urinary excretion rate being 495 μg/day 

during exposure (Recker et al. 1977). In humans, 0.09 and 96% of the aluminum intake per day was 

cleared through the urine and feces, respectively, during exposure to 1.71 mg Al/kg/day as aluminum 

lactate in addition to 0.07 mg Al/kg/day in basal diet for 20 days (Greger and Baier 1983). Urinary 
 

 

 

 

 

 

 

ALUMINUM 111 

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aluminum concentrations were significantly elevated in volunteers who received aluminum hydroxide and 

aluminum carbonate (Kaehny et al. 1977). Patients taking aluminum antacids in the diet had only a 3-fold 

increase in urinary aluminum levels (Gorsky et al. 1979), suggesting that most of the aluminum hydroxide 

was not absorbed and was excreted directly into the feces. 

Excretion of aluminum may be lower in premature compared to full-term infants (Bougle et al. 1991). 

Plasma levels of aluminum in premature infants were 14.6 μg/L compared to 7.8 μg/L in full-term infants, 

and absolute urinary excretion was reduced. The aluminum-creatinine ratio in the urine was similar in 

both groups, indicating that the lower excretion in the premature infants may be due to lower metabolic 

and glomerular filtration rates, thus increasing the risk of aluminum accumulation in this group. 

Excretion data collected in animal studies are consistent with the results from human studies. A single 

oral dose of 11 mg aluminum resulted in a 14-fold increase in urine aluminum levels, as compared to 

baseline levels, in healthy Sprague-Dawley rats (Ittel et al. 1987). The aluminum was primarily excreted 

during the first 24-hour period, and was comparable to baseline levels 5 days postexposure. Similarly 

exposed uremic rats excreted more aluminum than the healthy rats; the study authors postulated that this 

increase in excretion was probably due to increased gastrointestinal absorption. Rats administered a 

single dose of one of eight aluminum compounds (all contained 35 mg aluminum) excreted in the urine 

0.015–2.27% of the initial dose (Froment et al. 1989b). The range most likely reflects differences in 

gastrointestinal absorption. Following administration of a single dose of 6.7–27 mg Al/kg, 1.3–2.8% of 

the dose was excreted within the first 3 hours; the percent of the dose excreted in the urine did not differ 

among the three dose groups (Sutherland and Greger 1998). 

Fecal aluminum represents unabsorbed aluminum as well as aluminum excreted via bile. Within 

15 minutes of rats receiving a gavage dose of 6.7–27 mg Al/kg, the levels of aluminum in bile were 

significantly higher than in controls (Sutherland and Greger 1998). The percentage of the total dose 

excreted in bile during the first 3 hours after dosing ranged from 0.06 to 0.14%. In the control group, 

25.0 mmol aluminum were excreted in the bile compared to 7.9 mmol in the urine. 

3.4.4.3 Dermal Exposure 

No studies were located regarding the excretion in humans and animals after dermal exposure to 

aluminum or its compounds. 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 112 

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3.4.4.4 Other Routes of Exposure 

Human and animal studies have investigated the aluminum retention in the body. Within the first day of 

receiving a single injection of 26Al citrate, approximately 59% of the dose was excreted in the urine of six 

subjects; 72 and 1.2% was excreted in the urine and feces, respectively, during the first 5 days (Talbot et 

al. 1995). At the end of 5 days, it was estimated that 27% of the dose was retained in the body (Priest et 

al. 1995; Talbot et al. 1995). When 26Al levels were monitored more than 3 years after a single subject 

received the injection, a half-life of approximately 7 years was calculated (Priest et al. 1995). However, 

when the subject was re-examined approximately 10 years after the injection, a half-life of about 50 years 

was estimated (Priest 2004). 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen and 

Krishnan 1994; Andersen et al. 1987). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parameterization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 113 

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1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 

numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

Figure 3-3 shows a conceptualized representation of a PBPK model. 

If PBPK models for aluminum exist, the overall results and individual models are discussed in this section 

in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. 

A PBPK/PD model that can be used in risk assessment to predict the concentrations of aluminum 

delivered to target tissues (particularly the brain) or to examine the relationship between target tissue dose 

and the observed responses was not located. However, a biokinetic model has been developed to describe 

the absorption, distribution, and excretion of aluminum (Kislinger et al. 1997; Nolte et al. 2001; 

Steinhausen et al. 2004). This model allows for the prediction of aluminum levels under different 

physiological conditions such as renal failure or iron deficiency/overload. The model is an open 

compartment model comprised of a central compartment, three peripheral compartments, additional 

compartments for the gastrointestinal tract (stomach, duodenum, and residual intestinal tract), and 

excretion primarily via kidney output into urine. The central compartment comprises the blood plasma 

and interstitial fluid; in both compartments, the aluminum is bound to large proteins such as transferrin 
 

 

ALUMINUM 114 

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Figure 3-3. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance
 

Inhaled chemical Exhaled chemical 

Ingestion 

 Chemicals in air 

contacting skin 

Lungs 

Liver 

Fat 

Slowly 

perfused 

tissues 

Richly 

perfused 

tissues 

Kidney 

Skin 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

Vmax Km 

GI 

Tract 

Feces 

Urine

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by 

ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Source: adapted from Krishnan et al. 1994 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 115 

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and to small soluble molecules such as citrate. The peripheral compartments are: (1) the liver and spleen, 

which are supplied by aluminum from plasma transferrin (this compartment is characterized by a rapid 

exchange with the central compartment and no significant long-term storage of aluminum); (2) the 

muscles, heart, and kidney tissues, which are supplied aluminum from interstitial transferrin; and (3) the 

bones, which are supplied by aluminum from interstitial tissue citrate (this compartment is characterized 

by rapid accumulation of aluminum and long-term storage). Aluminum is primarily excreted via 

ultrafilterable citrate-bound aluminum of plasma via the kidneys into the urine; a minor excretion path is 

transport of transferrin-bound aluminum of plasma via the liver into the residual intestinal tract. 

3.5 MECHANISMS OF ACTION 

The mechanism of action for aluminum toxicity is not known, but the element is known to compete in 

biological systems with cations, especially magnesium (Macdonald and Martin 1988) despite an oxidation 

state difference, and to bind to transferrin and citrate in the blood stream (Ganrot 1986). It may also 

affect second messenger systems and calcium availability (Birchall and Chappell 1988), and irreversibly 

bind to cell nucleus components (Crapper McLachlan 1989; Dyrssen et al. 1987). Aluminum has also 

been shown to inhibit neuronal microtubule formation. However, much more work is needed before a 

mechanism can be proposed. 

3.5.1 Pharmacokinetic Mechanisms 

Gastrointestinal absorption of aluminum is low, generally in the range of 0.01–0.6% in humans as 

discussed in Section 3.3.1.2. Absorption of aluminum compounds is largely determined by its ionic 

availability in the aqueous conditions of the gut, which is mainly related to pH, the presence of 

complexing ligands with which the metal can form absorbable aluminum species, and the chemical form 

(type of anion) of the ingested compound (DeVoto and Yokel 1994; Reiber et al. 1995). In acidic 

aqueous conditions such as in the stomach (pH≈2) aluminum primarily occurs as a monomolecular

hexahydrate, Al(H2O)6

+3, which is generally abbreviated Al+3 and referred to as “free” aluminum (Reiber 

et al. 1995). The acidic conditions and mixing/residence time in the stomach appear to ensure that the 

majority of consumed aluminum will be solubilized to monomolecular species (most likely free Al+3), 

regardless of the compound and form (e.g., food, drinking water or antacid tablets) in which it was 

ingested. The solubilized aluminum that is in the stomach can recomplex with the anion from the original 

aluminum compound that was ingested or form new complexes with dietary ligands. The dietary 

constituents that appear to play a particularly important role in the complexation process include simple 

mono-, di-, and tricarboxylic acids (particularly citric acid). The vast majority of the solubilized 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 116 

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aluminum is not complexed. As pH increases in the duodenum, a series of aluminum hydroxy complexes 

are formed by successive deprotonation so that in near-neutral conditions such as in the intestines, the 

predominant form is aluminum hydroxide ([Al(OH)3]), which is rapidly precipitated as insoluble by the 

near-neutral pH conditions, and is ultimately excreted in the feces. 

The mechanism by which aluminum is absorbed and the chemical forms of aluminum able to pass 

through the intestinal wall are not completely understood (DeVoto and Yokel 1994; Exley et al. 1996; 

Lione 1985a; Priest 1993; Reiber et al. 1995; van der Voet 1992; Wilhelm et al. 1990). Available data, 

mainly results of in vitro (everted gut) and in situ (intestinal perfusion) studies in rats (e.g., Feinroth et al. 

1982; Froment et al. 1989b; Provan and Yokel 1990), suggest that aluminum is mainly absorbed as 

neutral complexes by passive diffusion through intercellular tight junction (paracellular channel) 

pathways (i.e., via spaces between cells rather than through the cells themselves). However, adequate 

information is not available to rule out transcellular transport (cellular internalization), and both 

paracellular and transcellular pathways may be involved. Transcellular transport is also likely to be a 

passive process; possible mechanisms include cell-mediated endocytosis, simple diffusion of neutral and 

possibly lipophilic aluminum complexes, and facilitative diffusion via cation-specific channels (Exley et 

al. 1996). Active transport of Al+3 via iron absorption pathways may also contribute to the absorption of 

aluminum, but the role of iron pathways in aluminum absorption is incompletely elucidated (DeVoto and 

Yokel 1994) and complicated by the primary differences in oxidation states (2+ and 3+), which would 

argue against the two following an identical pathway. The predominant uptake mechanism remains 

unresolved due to insufficient data in the existing studies, particularly failure to characterize or control for 

intraluminal conditions affecting aluminum absorption, especially pH differences which can influence 

aluminum speciation, presence of dietary and other gut substances that can influence solubility of 

aluminum via formation of complexes, and quantity of available aluminum. These data insufficiencies 

complicate reconciling different results and postulated mechanisms between studies, and extrapolating to 

human in vivo physiochemical conditions (i.e., identifying the chemical form and mechanism of 

aluminum absorption in humans). 

As previously discussed, absorption of aluminum is markedly increased by the presence of citrate. The 

mechanism is not fully characterized, but it is thought that citrate enhances gut bioavailability by 

increasing the permeability of the paracellular channels, possibly via disruption in calcium homeostasis 

(DeVoto and Yokel 1994; Exley et al. 1996; Froment et al. 1989b; Molitoris et al. 1989; Provan and 

Yokel 1988). It currently appears that aluminum is not absorbed across the gastrointestinal epithelium as 

a citrate complex, but that citrate expedites the absorption of aluminum by maintaining the aluminum in a 
 

 

 

 

 

 

 

 

 

ALUMINUM 117 

3. HEALTH EFFECTS 

form that can be readily incorporated into one or more mechanisms of absorption (Exley et al. 1996). 

This mechanism may be unique to the aluminum-citrate complex, which would be consistent with the 

apparent greater bioavailability of aluminum citrate compared to other carboxylic acid chelates. Other 

factors such as parathyroid hormone (through stimulation of 1,25(OH)2D3 production) and vitamin D 

have also been suggested to enhance the absorption of aluminum, but the data are largely inconclusive. 

Mechanisms of inhalation absorption of aluminum are not well characterized, although it seems likely 

that relatively large aluminum-containing particles retained in the respiratory tract are cleared to the 

gastrointestinal tract by ciliary action. As has been observed with typical particulates (ICRP 1994), it is 

hypothesized that aluminum particles that are small enough (<5 μm diameter) to penetrate the lung’s

protective removal mechanisms may contribute to overall body levels by dissolution and direct uptake 

from alveoli into the blood stream, or by macrophage phagocytosis (Priest 1993; Reiber et al. 1995). 

3.5.2 Mechanisms of Toxicity 

In the cases in which human aluminum toxicity has occurred, the target organs appear to be the lung, 

bone, and the central nervous system. No specific molecular mechanisms have been elucidated for 

human toxicity to aluminum. In animal models, aluminum can also produce lung, bone, and 

neurotoxicity, as well as developmental effects in offspring. 

Bone Toxicity. Two types of osteomalacia have been associated with aluminum exposure. The first type 

has been observed in healthy individuals using aluminum-containing antacids to relieve the symptoms of 

gastrointestinal disorders such as ulcers, colic, or gastritis. The aluminum in the antacids binds with 

dietary phosphorus and impairs gastrointestinal absorption of phosphorus. The observed osteomalacia 

and rickets is directly related to the decreased phosphate body burden. Osteomalacia is well documented 

in dialyzed uremic patients exposed to aluminum via dialysis fluid or orally administered aluminum used 

to control hyperphosphatemia. In the case of the uremic patient, bone aluminum levels are markedly 

increased and the aluminum is present between the junction of calcified and noncalcified bone (Alfrey 

1993). The osteomalacia is characterized by increased mineralization lag time, osteoid surface, and 

osteoid area, relatively low parathyroid hormone levels, and mildly elevated serum calcium levels. 

Neurotoxicity. Various neurotoxic effects of aluminum have been induced in animals, ranging from 

neurobehavioral and neurodevelopmental alterations following repeated oral exposures in mice and rats to 

neurodegenerative pathological changes in the brain caused by acute parenteral administration in 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 118 

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nonrodent species. Numerous mechanistic studies of aluminum neurotoxicity have been performed, but 

no single unifying mechanism has been identified (Erasmus et al. 1993; Jope and Johnson 1992; Strong et 

al. 1996); it is likely that more than one mechanism is involved. The main sites of action of aluminum are 

difficult to discern because the studies have been performed using a variety of exposure methods 

(including a number of different in vivo injections and in vitro systems) and animal species, and a number 

of typical effects are not common to all species and exposure circumstances (i.e., are only expressed using 

certain models of neurotoxicity). Although insufficient data are available to fully understand the 

mechanism(s) of aluminum toxicity, some general processes that are involved have been identified. 

Changes in cytoskeletal proteins, manifested as hyperphosphorylated neurofilamentous aggregates within 

the brain neurons, is a characteristic response to aluminum in certain species (e.g., rabbits, cats, ferrets, 

and nonhuman primates) and exposure situations (e.g., intracerebral and intracisternal administration). 

Similar neurofibrillary pathological changes have been associated with several neurodegenerative 

disorders, suggesting that the cause of aluminum-related abnormal neuronal function may involve 

changes in cytoskeletal protein functions in affected cells. The neurofilamentous aggregates appear to 

mainly result from altered phosphorylation, apparently by posttranslational modifications in protein 

synthesis, but may also involve proteolysis, transport and synthesis (Jope and Johnson 1992; Strong et al. 

1996). Interactions between these processes probably contribute to the induction of the phosphorylated 

neurofilaments. Each of the processes can be influenced by kinases, some of which are activated by 

second messenger systems. For example, aluminum appears to influence calcium homeostasis and 

calcium-dependent processes in the brain via impairment of the phosphoinositide second messengerproducing system (which modulates intracellular calcium concentrations); calcium-activated proteinases 

may be affected, which could alter the distribution and concentration of cytoskeletal proteins and other 

substates (Gandolfi et al. 1998; Jope and Johnson 1992; Julka and Gill 1995; Kaur and Gill 2005; Kaur et 

al. 2006; Mundy et al. 1995; Nostrandt et al. 1996; Sarin et al. 1997; Shafer and Mundy 1995). Another 

process that may contribute to neurodegeneration is apoptosis (Fu et al. 2003; Ghribi et al. 2001; Johnson 

et al. 2005; Suarez-Fernandez et al. 1999). 

The species (rodents) in which aluminum-induced neurobehavioral effects (e.g., changes in locomotor 

activity, learning and memory) have been observed fail to develop significant cytoskeletal pathology, but 

exhibit a number of neurochemical alterations following in vivo or in vitro exposure (Erasmus et al. 1993; 

Strong et al. 1996). Studies in these animals indicate that exposure to aluminum can affect permeability 

of the blood-brain barrier (Yokel et al. 2002; Zheng 2001), cholinergic activity (Kaizer et al. 2005; Kohila 

et al. 2004; Zatta et al. 2002), signal transduction pathways (Montoliu and Felipo 2001), lipid 

peroxidation (Deloncle et al. 1999; El-Demerdash 2004; Fraga et al. 1990; Khanna and Nehru 2007; 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 119 

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Nehru and Anand 2005), and impair neuronal glutamate nitric oxide-cyclic GMP pathway (Cucarella et 

al. 1998; Hermenegildo et al. 1999; Llansola et al. 1999; Rodella et al. 2004), as well as interfere with 

metabolism of essential trace elements (e.g., iron) because of similar coordination chemistries and 

consequent competitive interactions. 

3.5.3 Animal-to-Human Extrapolations 

The appropriateness of extrapolating health effects of aluminum in animals to humans cannot be 

conclusively determined due to limitations of the human database. Information on toxicity of aluminum 

in humans is not extensive because the preponderance of studies are in patients with reduced renal 

function who accumulated aluminum as a result of long-term intravenous hemodialysis therapy with 

aluminum-containing dialysis fluid and, in many cases, concurrent administration of high oral doses of 

aluminum to regulate phosphate levels. No clinical studies on health effects of aluminum medicinals in 

people with normal renal function have been performed, largely due to the fact that exposures typically 

consist of over-the-counter products such as antacids and buffered aspirins that have been assumed to be 

safe in healthy individuals at recommended doses based on historical use. The assumed safety of 

aluminum is also partly due to the FDA-approved GRAS status of aluminum-containing food additives. 

Other human data largely consist of studies of aluminum-exposed workers that are limited by the lack of 

quantitative exposure data and/or co-exposure to other chemicals. Subtle neurological effects have been 

observed in workers chronically exposed to aluminum dust or aluminum fumes, but these studies only 

provide suggestive evidence that there may be a relationship between chronic aluminum exposure and 

neurotoxic effects in humans. Aluminum is generally considered to be neurotoxic in animals, and there is 

an adequate basis to conclude that neurotoxicity/neurodevelopmental toxicity is the critical effect of oral 

exposure in animals. Whether the subtle neurotoxic effects seen in adult and developing animals exposed 

to relatively low doses of aluminum would definitely manifest in humans under similar exposure 

conditions remains to be determined. 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Thomas and Colborn (1992), was also used in 1996 when Congress mandated the EPA to 

develop a screening program for “...certain substances [which] may have an effect produced by a 
 

 

 

 

 

 

 

 

ALUMINUM 120 

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naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 

are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

No studies were located regarding endocrine disruption in humans and/or animals after exposure to 

aluminum. No in vitro studies were located regarding endocrine disruption of aluminum. 

3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 
 

 

 

 

 

 

 

 

ALUMINUM 121 

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Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6, Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects, and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life, and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water, and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 122 

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alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

There is a limited amount of information available on the toxicity of aluminum in children. As with 

adults, neurological and skeletal (osteomalacia) effects have been observed in children with impaired 

renal function (Andreoli et al. 1984; Griswold et al. 1983). These effects are related to an abnormal 

accumulation of aluminum due to exposure to aluminum-contaminated dialysate, use of aluminum 

containing phosphate binding gels, and impaired renal excretion of aluminum. These effects are not 

likely to occur in children with normal renal function. Skeletal effects have also been observed in 

children on long-term total parenteral nutrition containing elevated levels of aluminum. Another 

subpopulation of children that may be particularly sensitive to the toxicity of aluminum is preterm infants. 

The observed elevated plasma aluminum levels may be due to the higher aluminum content of premature 

infant formula and/or limited renal capacity of preterm infants to excrete aluminum (Tsou et al. 1991). 

Bougle et al. (1991) reported plasma aluminum levels of 14.6 μg/L in preterm infants compared to 

7.8 μg/L in full-term infants; decreased urinary aluminum levels at comparable creatinine normalized 

rates were also found. Bishop et al. (1997) found significant decreases in the Bayley Mental 

Development Index in pre term infants receiving a standard intravenous feeding solution compared to pre 

term infants receiving an aluminum-depleted feeding solution. Growth reduction, hypotonia, muscle 

weakness, and craniosynostosis (premature ossification of the skull and obliteration of the sutures) have 

been observed in healthy infants following prolonged used of oral antacids for the treatment of colic 

(Pivnick et al. 1995). These effects were related to secondary hypophosphatemia caused by aluminum 

binding to phosphate in the gut and markedly reduced phosphate absorption. 

Most of the available data come from animal studies that examined the distribution, neurotoxicity, and 

skeletal toxicity of aluminum at several ages (e.g., gestationally exposed, neonatal, young, adult, and 

older animals). Yokel and McNamara (1985) did not find any age-related differences in the systemic 

clearance or half-time of aluminum lactate in rabbits following intravenous, oral, or subcutaneous 

exposure. Oral exposure to aluminum nitrate resulted in higher brain aluminum levels in young rats as 

compared to older rats, but there was no difference in toxicity between young and adult rats (Gomez et al. 

1997a). In other tissues examined, the aluminum levels in the young rats tended to be lower than in the 

adult or older animals (Gomez et al. 1997b). Fetal exposure may result in a higher distribution of 

aluminum to the brain, as compared to adults. In the fetuses of rats receiving a single subcutaneous 

injection of aluminum on gestation day 5, the amount of the radiolabelled aluminum in the brain was 30% 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 123 

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higher than in the liver; in the dams, brain aluminum levels were only 1% of the levels found in the liver 

(Yumoto et al. 2000). 

Aluminum is distributed transplacentally, and elevated levels of aluminum have been measured in the 

fetus and placenta following oral, dermal, or parenteral exposure to aluminum (Anane et al. 1997; 

Cranmer et al. 1986; Yumoto et al. 2000). There is also evidence that oral or parenteral exposure to 

aluminum can result in elevated levels in breast milk (Golub et al. 1996; Muller et al. 1992; Yokel 1985; 

Yokel and McNamara 1985; Yumoto et al. 2000, 2003); the form of aluminum in breast milk was not 

reported. Although levels of aluminum in breast milk were elevated in aluminum-exposed rabbit does, 

the concentrations in the pups were not significantly different from control levels, suggesting that the 

aluminum was poorly absorbed (Yokel 1985). In contrast, subcutaneous injection of 26Al in rats on 

lactation day 1 through 20 resulted in significant elevation in aluminum levels in the suckling rats 

(Yumoto et al. 2000). 

The most sensitive known effect following oral exposure to aluminum is neurotoxicity. Neurotoxic 

effects have been observed in adult animals, weanling animals, and in animals exposed during gestation, 

gestation and lactation, and lactation-only (Colomina et al. 2005; Donald et al. 1989; Golub and Germann 

1998, 2001; Golub et al. 1987, 1992a, 1992b, 1994, 1995; Oteiza et al. 1993). When neurological tests 

were performed in adult mice exposed to aluminum during development (gestation and lactation 

exposure) (Golub et al. 1995), the pattern of neurological effects (alterations in grip strength and startle 

response) was similar to those observed in mice exposed to aluminum as adults (Golub et al. 1992b; 

Oteiza et al. 1993) and in mice exposed to aluminum during development and adulthood (Golub et al. 

1995). Additionally, the LOAELs for these effects were similar in the three groups, thus suggesting that 

the developing fetus and children may have a similar sensitivity as adults to the neurotoxic effects of 

aluminum. 

A series of studies in which rabbits received subcutaneous doses of aluminum lactate suggest that the 

neurotoxicity of aluminum may be age-dependent. Subcutaneous administration of aluminum lactate 

resulted in alterations in learning and memory in gestationally-exposed rabbits and adult rabbits. A 

biphasic effect (enhancement after low doses and attenuation after high doses) on learning and memory 

was observed in the in utero-exposed rabbits (treatment on gestational days 2 through 27) (Yokel 1985) 

and an attenuated effect was observed in the adults (Yokel 1987), but no effects were observed in 

neonatal or immature rabbits (Yokel 1987). The apparent age-dependence of the toxicity of aluminum in 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 124 

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this study may be a reflection of the different ages at evaluation rather than age of exposure (Golub et al. 

1995). 

Another aluminum effect which appears to be age-related is skeletal toxicity. Increased carpal joint 

width, suggestive of poor bone calcification, was observed in immature rabbits receiving 20 subcutaneous 

doses of aluminum lactate, but was not seen in neonatal or adult rabbits (Yokel 1987). 

A study by Sanchez et al. (1997) found significant age-related effects on aluminum interactions with 

essential elements (e.g., calcium, magnesium, zinc). Decreases in concentration of some essential 

elements in a number of tissues were observed in young rats orally exposed to aluminum lactate (as 

compared to adults); the decreases included liver and spleen calcium levels, bone magnesium levels, and 

brain manganese levels. 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself, substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to aluminum are discussed in Section 3.8.1. 
 

 

 

 

 

 

 

 

 

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Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by aluminum are discussed in Section 3.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10, Populations That Are Unusually Susceptible. 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Aluminum 

Aluminum can be measured in the blood, bone, urine, and feces (see Chapter 7 for description of 

available methods). Since aluminum is found naturally in a great number of foods, it is found in 

everyone. Unfortunately, exposure levels cannot be related to serum or urine levels very accurately, 

primarily because aluminum is very poorly absorbed by any route and its oral absorption in particular can 

be quite affected by other concurrent intakes. There is an indication that high exposure levels are 

reflected in urine levels, but this cannot be well quantified as much of the aluminum may be rapidly 

excreted. Aluminum can also be measured in the feces, but this cannot be used to estimate absorption. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Aluminum 

There are no known simple, noninvasive tests which can be used as biomarkers of effects caused by 

aluminum. D’Haese et al. (1995) proposed the use of the DFO (deferoxamine) test to identify individuals 

with aluminum-related bone disease/aluminum overload. This test involves administering a challenge 

dose of the chelator deferoxamine to individuals with suspected aluminum-induced bone disease. 

However, iron supplementation may interfere with the test results (Huang et al. 2001). 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 126 

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For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC 

Subcommittee Report on Biological Indicators of Organ Damage (Agency for Toxic Substances and 

Disease Registry 1990) and for information on biomarkers for neurological effects see OTA (1990). 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

It is well documented that citrate, a common component of food, markedly enhances the gastrointestinal 

absorption of concurrently ingested aluminum (Alfrey 1993; Day et al. 1991; DeVoto and Yokel 1994; 

Froment et al. 1989b; Molitoris et al. 1989; Priest et al. 1996; Provan and Yokel 1988; Slanina et al. 1986; 

Weberg and Berstad 1986; Yokel and McNamara 1988). The effect has been shown with a variety of 

aluminum compounds and several forms of citrate in both experimental and clinical studies. The 

combination of citrate and aluminum has been responsible for a number of deaths in uremic patients, and 

the clinical implications of the interaction has led some investigators to advise against concomitant 

exposure to aluminum and citrate in any form (e.g., antacids and orange juice), especially to patients with 

impaired renal function. As discussed in Sections 3.3.1.2 and 3.5.1, citrate complexes with aluminum to 

form a species that is particularly bioavailable in the near-neutral pH conditions of the intestines. 

Unlike citrate, it is likely that the presence of silicic acid in food and drink will decrease the 

bioavailability of aluminum by providing a strong competitive binding site for it within the gut contents, 

thus making the metal less available for absorption (Priest 1993). This is supported by two studies that 

show a decrease in retention of aluminum in response to higher doses of silicon when human volunteers 

ingested both chemicals together (Bellia et al. 1996; Edwardson et al. 1993; Jugdaohsingh et al. 2000); 

Jugdaohsingh et al. (2000) only found this effect when oligometric silica was administered (monomeric 

silica did not affect aluminum absorption). As discussed in Section 3.5.1, there are some data that suggest 

that aluminum absorption can be enhanced by parathyroid hormone and vitamin D, but the data are 

inconclusive. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to aluminum than will most 

persons exposed to the same level of aluminum in the environment. Reasons may include genetic 

makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). 

These parameters result in reduced detoxification or excretion of aluminum, or compromised function of 

organs affected by aluminum. Populations who are at greater risk due to their unusually high exposure to 

aluminum are discussed in Section 6.7, Populations with Potentially High Exposures. 
 

 

 

 

 

 

 

 

 

 

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The major population at risk for aluminum loading and toxicity consists of individuals with renal failure. 

In a study by Alfrey (1980), 82% of nondialyzed uremic patients and 100% of dialyzed uremic patients 

had an increased body burden of aluminum. The decreased renal function and loss of the ability to 

excrete aluminum, ingestion of aluminum compounds to lessen gastrointestinal absorption of phosphate, 

the aluminum present in the water used for dialysate, and the possible increase in gastrointestinal 

absorption of aluminum in uremic patients can result in elevated aluminum body burdens. The increased 

body burdens in uremic patients has been associated with dialysis encephalopathy (also referred to as 

dialysis dementia), skeletal toxicity (osteomalacia, bone pain, pathological fractures, and proximal 

myopathy), and hematopoietic toxicity (microcytic, hypochromic anemia). Preterm infants may also be 

particularly sensitive to the toxicity of aluminum due to reduced renal capacity (Tsou et al. 1991). 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to aluminum. However, because some of the treatments discussed may be experimental and 

unproven, this section should not be used as a guide for treatment of exposures to aluminum. When 

specific exposures have occurred, poison control centers and medical toxicologists should be consulted 

for medical advice. The following texts provide specific information about treatment following exposures 

to aluminum: 

Schonwald S. 2004. Aluminum. In: Dart RC, ed. Medical toxicology. 3rd ed. New York, NY: 

Lippincott, Williams, and Wilkins, 1387-1390. 

Haddad, CM, Shannon MW, Winchester, JF. 1998. Clinical management of poisoning and drug 

overdose. 3rd ed. Philadelphia, PA: WB Saunders, 186. 

Leikin JB, Paloucek FP. 2002. Leikin and Paloucek’s poisoning and toxicology handbook. 3rd ed. 

Hudson, OH: Lexi-Comp, Inc., 214-217. 

3.11.1 Reducing Peak Absorption Following Exposure 

There are limited data on reducing aluminum absorption following exposure. There is good evidence that 

aluminum is absorbed by a pericellular energy-independent and sodium-dependent process (Provan and 

Yokel 1988). If this is correct, then treatments that block pericellular processes can be used to minimize 

or prevent intestinal uptake of aluminum. Ranitidine may also decrease aluminum absorption (Leikin and 

Paloucek 2002). 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 128 

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3.11.2 Reducing Body Burden 

In persons with normal renal function, the body burden can be reduced simply by limiting exposure 

(Schonwald 2004). Avoidance of aluminum-containing products, such as aluminum-containing 

phosphate binding gels, dialysate, and parenteral solutions, is recommended for patients with renal 

failure. Avoidance of co-administration of aluminum compounds and citrate compounds is also advised. 

Administration of a chelator such as desferrioxamine (DFO) may also help reduce aluminum body 

burden. DFO is a chelating agent that competes with complexing ligands such as transferrin and citrate 

that might deliver aluminum to tissues or otherwise redistribute it within the body. For example, DFO 

treatment has been used to facilitate the removal of aluminum from bone and its entry into the blood 

where it can be removed by hemodialysis (Haddad et al. 1998). DFO is also used in dialyzed uremic 

patients for the treatment of neurological, hematopoietic, and skeletal toxicity. In rats, administration of 

DFO resulted in a large reduction in the half life of aluminum in the brain; 55 days in the DFO-treated 

rats versus 150 days in controls (Yokel et al. 2001b). It should be noted that the clinical usefulness of 

DFO is limited by a variety of toxic effects including hypotension, skin rashes, stimulation of fungal 

growth, and possibly cataract formation. There is some evidence that other chelators may also be 

effective in reducing aluminum body burden. 1,2-Dimethyl-3-hydroxypyrid-4-one was shown to enhance 

urinary aluminum excretion in aluminum-loaded rats (Gomez et al. 1999; Yokel et al. 1997). Another 

study showed that (4-methyl-6-trifluoromethyl-6-pyrimidin-2-il)-hydrazine was effective in decreasing 

the levels of aluminum in the brains of mice (Missel et al. 2005), although DFO was more effective in 

lowering the brain aluminum levels. Tiron (4,5-dihydroxy-1,3-benzene disulfonic acid di-sodium salt) 

administered during aluminum exposure to pregnant rats resulted in significant decreases in aluminum 

levels in the blood, brain, placenta, and fetus (Sharma and Mishra 2006). Another chelator tested in this 

study, 4-tricloromethyl-1-H-pyrimidin-2-one, was not effective. Administration of folic acid, me 

-

- . 2007). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The mechanism of action for aluminum toxicity is not fully understood; thus, there are no known ways of 

interfering with its mechanism of action. Some pathways of aluminum chloride toxicity include induced 

lipid peroxidation, altered enzyme activity, overexpression of hippocampal Aβ immunoreactivity, and 

biochemical parameters. These toxic effects were shown to be improved in rats or mice when 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 129 

3. HEALTH EFFECTS 

administered vitamin E, vitamin C, selenium, beer (due to its silicon content), centrophenoxine (an antiaging drug), and the herbal medicines Dipsacus asper Wall extract and Bacopa moniera 

- - . 2007; Jyoti and Sharma 2006; Nedzvetsky et al. 2006; 

Nehru and Bhalla 2006; Nehru et al. 2007; Saba-El Rigal 2004; Zhang et al. 2003). 

3.12 ADEQUACY OF THE DATABASE 

Section 104(I)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of aluminum is available. Where adequate information is not 

available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the 

initiation of a program of research designed to determine the health effects (and techniques for developing 

methods to determine such health effects) of aluminum. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

3.12.1 Existing Information on Health Effects of Aluminum 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

aluminum are summarized in Figure 3-4. The purpose of this figure is to illustrate the existing 

information concerning the health effects of aluminum. Each dot in the figure indicates that one or more 

studies provide information associated with that particular effect. The dot does not necessarily imply 

anything about the quality of the study or studies, nor should missing information in this figure be 

interpreted as a “data need”. A data need, as defined in ATSDR’s Decision Guide for Identifying 

Substance-Specific Data Needs Related to Toxicological Profiles (Agency for Toxic Substances and 

Disease Registry 1989), is substance-specific information necessary to conduct comprehensive public 

health assessments. Generally, ATSDR defines a data gap more broadly as any substance-specific 

information missing from the scientific literature. 

Information on human health effects from inhaled aluminum is available from epidemiological studies 

and case studies of aluminum workers. This includes data on death, chronic effects, and cancer. 
 

 

 

ALUMINUM 130 

3. HEALTH EFFECTS 

Figure 3-4. Existing Information on Health Effects of Aluminum 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Human 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Inhalation 

Oral 

Dermal 

Animal 

Existing Studies 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 131 

3. HEALTH EFFECTS 

Information on oral exposure is available only from specialized cases, such as people who consumed a 

grain fumigant to try to commit suicide, individuals consuming large doses of aluminum-containing 

antacids, and dialyzed and nondialyzed uremic patients consuming aluminum compounds prescribed as 

phosphate binding agents. Information on dermal effects in humans is available from patch tests. 

In animals, information on effects from inhalation exposure is available for pure aluminum flakes, 

aluminum chlorhydrate antiperspirants, and a propylene glycol complex of aluminum chlorhydrate. 

Effects following oral exposure to several aluminum salts are available for adults and newborn animals. 

One acute dermal study is available. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. There are no studies that examined the acute toxicity of aluminum 

following inhalation, oral, or dermal exposure. A small number of animal studies have examined the 

acute toxicity of inhaled aluminum. The results of these inhalation studies suggest that the lung may be a 

sensitive target for toxicity (Drew et al. 1974; Thomson et al. 1986); the observed effects are similar to 

those that would occur with dust overload. The data are insufficient to determine if these effects are 

solely due to dust overload or to an interaction between aluminum and lung tissue; thus, an inhalation 

MRL was not derived. Additional inhalation studies are needed to evaluate whether the respiratory tract 

is a target of aluminum toxicity; these studies should also examine potential neurological effects, another 

sensitive target of aluminum toxicity. The acute systemic toxicity of orally administered aluminum has 

not been well investigated; most of the available data examined the developmental toxicity of aluminum 

(Bernuzzi et al. 1986, 1989a; Cranmer et al. 1986; Domingo et al. 1989; Gomez et al. 1991; McCormack 

et al. 1979; Misawa and Shigeta 1992; Paternain et al. 1988) or aluminum lethality (Llobet et al. 1987; 

Ondreicka et al. 1966). Two studies examining potential effects other than developmental toxicity only 

examined a small number of end points (Garbossa et al. 1996; Ondreicka et al. 1966). The Ondreicka et 

al. (1966) study examined potential body weight effects and Garbossa et al. (1996) examined 

hematological indices; neither study examined for potential neurological effects, which has been shown to 

be the most sensitive end point following intermediate- or chronic-duration exposure. Oral exposure 

studies that examined a wide range of potential effects, including neurotoxicity, are needed to identify the 

critical target of toxicity and establish dose-response relationships. There are limited data on the dermal 

toxicity of aluminum. A mouse study conducted by Lansdown (1973) found skin damage following 

application of a number of aluminum compounds. Because aluminum is found in a number of topical 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 132 

3. HEALTH EFFECTS 

products, additional dermal exposure studies would be useful to fully assess the potential toxicity of 

aluminum following dermal exposure. 

Intermediate-Duration Exposure. There is a limited amount of intermediate-duration human data 

on the toxicity of aluminum. Neurological and skeletal effects have been observed in uremic patients 

(Alfrey 1987; King et al. 1981; Mayor et al. 1985; Wills and Savory 1989); however, it is not likely that 

individuals with normal renal function would experience these effects. Intermediate-duration inhalation 

studies in animals identified the lung as a sensitive target of toxicity (Drew et al. 1974; Steinhagen et al. 

1978; Stone et al. 1979). It is not known if these effects, particularly the granulomatous lesions, are a 

response to dust overload or an interaction of aluminum with lung tissue; thus, an intermediate-duration 

inhalation MRL was not derived for aluminum. Additional inhalation studies are needed to evaluate the 

mechanisms of lung toxicity to determine whether the effects are due to dust overload or aluminum; 

inhalation studies examining a wide-range of potential end points, including the nervous system, would 

be useful for identifying the most sensitive effect of inhaled aluminum. A fair number of studies have 

examined the toxicity of aluminum following intermediate-duration oral exposure. Although most of the 

studies focused on the neurotoxicity and neurodevelopmental toxicity of aluminum, the available studies 

have examined potential systemic (Dixon et al. 1979; Domingo et al. 1987b; Farina et al. 2005; Garbossa 

et al. 1996, 1998; Gomez et al. 1986; Katz et al. 1984; Ondreicka et al. 1966; Oteiza et al. 1993; Pettersen 

et al. 1990; Vittori et al. 1999), immunological (Golub et al. 1993; Lauricella et al. 2001; Yoshida et al. 

1989), and reproductive (Dixon et al. 1979; Donald et al. 1989; Katz et al. 1984; Krasovskii et al. 1979; 

Ondreicka et al. 1966; Pettersen et al. 1990) end points. A series of studies conducted by Mahieu and 

associates (Mahieu et al. 1998, 2003, 2005, 2006) found small changes in sodium and phosphate 

excretion and urine concentrating ability (under conditions of water deprivation), but no changes in 

overall renal function (glomerular filtration rate or clearance), in rats administered aluminum hydroxide 

or aluminum lactate via intraperitoneal injection. Although several oral exposure studies did not find 

histological alterations in the kidneys, none of these studies examined renal function; the results of the 

Mahieu studies suggest the need for a study examining renal function following oral exposure to 

aluminum. The available intermediate-duration studies clearly identify the nervous system as the most 

sensitive target of aluminum toxicity (Colomina et al. 2005; Donald et al. 1989; Golub and Germann 

2001; Golub et al. 1989, 1992a, 1992b, 1995; Oteiza et al. 1993). An intermediate-duration oral MRL 

was derived based on Golub and Germann (2001) and Colomina et al. (2005) co-principal studies; the 

critical effect was neurodevelopmental effects and delays in physical maturation. No studies have 

examined the dermal toxicity of aluminum; animal studies would provide useful information on 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 133 

3. HEALTH EFFECTS 

aluminum’s potential to induce dermal effects following repeated exposure and whether it can cause 

systemic or neurological effects. 

Chronic-Duration Exposure and Cancer. Aluminum has been implicated in causing neurological 

(Banks et al. 1988; Liss and Thornton 1986), musculoskeletal, (Alfrey 1987; King et al. 1981; Mayor et 

al. 1985; Wills and Savory 1989), and hematopoietic (Jeffery et al. 1996) effects in individuals with 

impaired renal function. Respiratory and neurological effects have been observed in workers exposed to 

finely ground aluminum and aluminum welding fumes. Impaired lung function has been observed in 

workers employed in various aluminum industries including potrooms, foundry, and welders (Abbate et 

al. 2003; Al-Masalkhi and Walton 1994; Bast-Pettersen et al. 1994; Bost and Newman 1993; Burge et al. 

2000; Chan-Yeung et al. 1983; Hull and Abraham 2002; Jederlinic et al. 1990; Korogiannos et al. 1998; 

Miller et al. 1984b; Radon et al. 1999; Simonsson et al. 1985; Vandenplas et al. 1998). Other studies 

have provided some suggestive evidence that aluminum exposure can result in occupational asthma 

(Abramson et al. 1989; Akira 1995; Al-Masalkhi and Walton 1994; Burge et al. 2000; Vandenplas et al. 

1998) or pulmonary fibrosis (De Vuyst et al. 1986; Edling 1961; Gaffuri et al. 1985; Jederlinic et al. 

1990; Jephcott 1948; McLaughlin et al. 1962; Mitchell et al. 1961; Musk et al. 1980; Riddell 1948; 

Shaver 1948; Shaver and Riddell 1947; Ueda et al. 1958; Vallyathan et al. 1982). A common limitation 

of most of these occupational exposure studies is co-exposure to other compounds, such as silica, which 

can also damage the respiratory tract. Subtle neurological effects have been observed in workers exposed 

to aluminum dust in the form of McIntyre powder, aluminum dust and fumes in potrooms, and aluminum 

fumes during welding (Bast-Pettersen et al. 1994; Buchta et al. 2003, 2005; Dick et al. 1997; Hänninen et 

al. 1994; Hosovski et al. 1990; Iregren et al. 2001; Rifat et al. 1990; Riihimäki et al. 2000; Polizzi et al. 

2001; Sim et al. 1997; Sjögren et al. 1990, 1996; White et al. 1992). Inhalation animal studies have 

focused on the pulmonary toxicity of aluminum (Pigott et al. 1981; Stone et al. 1979). Data were 

considered inadequate for derivation of a chronic-duration inhalation MRL. Additional inhalation studies 

are needed to identify the critical target of aluminum toxicity following inhalation exposure. Several 

studies have examined the systemic toxicity of aluminum following chronic oral exposure (Farina et al. 

2005; Golub et al. 2000; Oneda et al. 1994; Roig et al. 2006; Schroeder and Mitchener 1975a, 1975b). 

These studies identified two potential targets of toxicity: the nervous system (Golub et al. 2000) and the 

hematopoeitic system (Farina et al. 2005). A chronic-duration oral MRL was derived based on the 

neurotoxicity observed in the Golub et al. (2000) study. A comparison between the dose-response 

relationship of neurotoxicity and the alterations in hematological parameters cannot be conducted because 

the Farina et al. (2005) study did not provide information on the level of aluminum in the base diet and 

both studies only utilized one aluminum-exposure group. Additional studies on the toxicity of aluminum 
 

 

 

 

 

 

 

 

 

ALUMINUM 134 

3. HEALTH EFFECTS 

following chronic-duration exposure utilizing multiple dose levels would be useful in comparing the 

sensitivity of these two effects. 

The available data do not indicate that aluminum is a potential carcinogen. It has not been shown to be 

carcinogenic in epidemiological studies in humans, nor in animal studies using inhalation, oral, and other 

exposure routes (Oneda et al. 1994; Ondreicka et al. 1966; Pigott et al. 1981; Schroeder and Mitchener 

1975a, 1975b). Although these studies have limitations ranging from use of only one species to a single 

exposure level and limited histological examinations, the evidence strongly suggests that aluminum is not 

carcinogenic, indicating that additional carcinogenicity testing is not warranted at this time. 

Genotoxicity. Several in vitro studies have found significant increases in the occurrence of 

micronuclei formation (Banasik et al. 2005; Migliore et al. 1999; Roy et al. 1990) and chromosome 

aberrations (Roy et al. 1990) in human lymphocytes; no human in vivo studies were identified. One study 

examined the in vivo genotoxicity of aluminum and found clastogenic changes in mice receiving an 

intraperitoneal injection of aluminum chloride (Manna and Das 1972). In vitro studies in mammalian and 

bacterial systems have not found mutagenic alterations (DiPaola and Casto 1979; Kada et al. 1980; 

Kanematsu et al. 1980; Marzin and Phi 1985; Nishioka 1975; Oberly et al. 1982; Olivier and Marzin 

1987). Further genotoxicity studies, particularly in vivo exposures, would be useful for verifying the 

results of the Manna and Das (1972) study and for evaluating other potential end points of genotoxicity. 

Reproductive Toxicity. No studies were located regarding reproductive effects of various forms of 

aluminum following inhalation, oral, or dermal exposure in humans. No histological alterations were 

observed in the reproductive tissues of rats or guinea pigs exposed to airborne aluminum chlorhydrate 

(Steinhagen et al. 1978); this study did not examine reproductive function. A number of oral-exposure 

studies examining reproductive end points in several animal species were identified. In general, the 

results of these studies suggest that aluminum is not associated with alterations in fertility (Dixon et al. 

1979; Domingo et al. 1987c), mating success (Dixon et al. 1979; Ondreicka et al. 1966), or number of 

implantations, implantation losses, or litter size (Bernuzzi et al. 1989b; Domingo et al. 1987c, 1989; 

Golub et al. 1992a; Gomez et al. 1991; Misawa and Shigeta 1992). Further studies in this area do not 

appear to be necessary at this time. 

Developmental Toxicity. No studies human studies examining the potential of aluminum to induce 

developmental effects in humans exposed to aluminum via inhalation, ingestion, or dermal contact were 

located. Developmental toxicity studies in animals have shown that oral gestational exposure to 
 

 

 

 

 

 

 

ALUMINUM 135 

3. HEALTH EFFECTS 

aluminum induced skeletal variations such as delayed ossification in rats and mice under conditions that 

enhanced its uptake, particularly maternal intake of compounds that are highly bioavailable (e.g., 

aluminum citrate and nitrate), concurrent exposure to dietary constituents that contribute to increased 

absorption of aluminum (e.g., citrate), and/or bolus administration by gavage (Colomina et al. 1992; 

Gomez et al. 1991; Paternain et al. 1988). There is some evidence that oral developmental exposure to 

aluminum affected the immune system in young mice (Golub et al. 1993; Yoshida et al. 1989) and may 

delay physical maturation (Colomina et al. 2005). Neurobehavioral deficits have been observed in oral 

studies of weanling and young developing mice and rats exposed to aluminum by gestation, combined 

gestation and lactation, combined gestation and lactation followed by postweaning ingestion, or 

postweaning ingestion alone (Bernuzzi et al. 1986, 1989a, 1989b; Colomina et al. 2005; Donald et al. 

1989; Golub and Germann 1998, 2001; Golub et al. 1987, 1992a, 1992b, 1994, 1995; Misawa and Shigeta 

1992; Muller et al. 1990). The most frequently affected neurobehavioral effects in the exposed weanlings 

and young mice included increases in grip strength and landing foot splay and decreased thermal 

sensitivity. The effects most commonly found in mice exposed during development and tested as adults, 

or tested only as adults, included decreases in spontaneous motor activity, grip strength, and startle 

responsiveness, indicating that the pattern of neurobehavioral impairment in developing animals was 

different from adults. 

Although the neurodevelopmental toxicity of aluminum is well-documented in animals, there are a 

number of data needs that preclude fully assessing the significance of the findings to human health (Golub 

and Domingo 1996). An important issue not adequately addressed in the existing studies is the potential 

for effects on more complex central nervous system functions, including learning and memory and 

sensory abilities. This type of animal testing would help determine the generality or specificity of 

aluminum neurodevelopmental toxicity and provide a better basis for its assessment in children. 

Additional information that is needed to more fully characterize the neurodevelopmental toxicity of 

aluminum includes data on whether effects are transient and reversible or whether they persist and cause 

permanent changes after exposures are terminated. Additionally, it would be informative to verify that 

the central nervous system is the critical developmental end point for aluminum by obtaining data on 

effects in noncentral nervous system organs known to be targets of aluminum toxicity in adults. 

Additional investigations of the skeletal component of the aluminum developmental toxicity syndrome 

are particularly needed because permanent effects on bone growth and strength could occur during 

periods of rapid mineralization not investigated in existing studies, such as early infancy and adolescence. 

New developmental toxicity studies should include a range of low oral doses that encompasses the 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 136 

3. HEALTH EFFECTS 

neurotoxicity NOAEL on which the intermediate-duration MRL is based, as well adequately 

characterized levels of aluminum in the base diet. 

Additional information on compound bioavailability is also needed to better evaluate the developmental 

toxicity of aluminum. Because the developmental effects of orally administered aluminum appear to be 

dependent on the bioavailability of the form in which it is administered and the presence of dietary 

components that promote aluminum uptake, additional information on compound-related differences in 

aluminum uptake and effectiveness during pregnancy and postnatal development would help in assessing 

the relevance of the animal data to oral exposures in humans. For example, gavage administration of low 

doses of aluminum (38–77 mg Al/kg/day) as aluminum nitrate during gestation induced skeletal 

variations in rats (Paternain et al. 1988), indicating that the LOAEL for this effect is below the 

neurotoxicity NOAEL of 62 mg Al/kg/day for aluminum lactate in adult mice used to derive the MRL. 

The Paternain et al. (1988) LOAEL was not considered to be appropriate for MRL consideration due to 

concern that gavage does not realistically represent environmental aluminum intake (i.e., the LOAEL 

could be unnaturally low compared to dietary exposure because the skeletal effects could be related to 

phosphate binding caused by the bolus administration), and that nitrate represents an unusually 

bioavailable form of aluminum. Additional information on the bioavailability of different forms and 

amounts of aluminum exposure would help establish how well oral aluminum exposure regimens in 

animals (e.g., gavage as tested by Paternain et al. [1988]) approximate the oral bioavailability of 

aluminum from water or food in humans. This kind of information is needed to verify that the MRL is 

based on the most appropriate end point (i.e., neurotoxicity in adults rather than skeletal developmental 

toxicity), especially considering that no NOAEL has been identified for either skeletal developmental 

effects (Paternain et al. 1988) or neurodevelopmental effects (Donald et al. 1989; Golub and Germann 

1998; Golub et al. 1992a, 1992b, 1994, 1995). Information on fetal uptake of aluminum administered in 

forms that have been already evaluated for prenatal developmental toxicity could indicate if the aluminum 

nitrate in the Paternain et al. (1988) study was effective because it is the most available to the fetus. 

Immunotoxicity. A few reports indicate hypersensitivity in children and adults who have received 

aluminum-containing vaccines (Bergfors et al. 2005; Böhler-Sommeregger and Lindemayr 1986; 

Castelain et al. 1988; Veien et al. 1986). A human oral exposure study (Gräske et al. 2000) did not find 

alterations in the concentrations of immunoglobulin, interleukin, natural killer cells, or B- or 

T-lymphocyte populations in humans ingesting an antacid suspension for 6 weeks. No other human 

exposure studies examining immunological end points were located. Histological alterations have been 

observed in the lymphoreticular system, particularly granulomas in the hilar lymph nodes, of animals 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 137 

3. HEALTH EFFECTS 

exposed to airborne aluminum (Steinhagen et al. 1978; Thomson et al. 1986); these effects were probably 

secondary to the pulmonary effects rather than the result of direct damage to lymphoreticular tissue. The 

available inhalation studies did not conduct function tests. Histopathological examination of 

lymphoreticular tissues has shown no effect after oral administration of aluminum in rats (Dixon et al. 

1979; Domingo et al. 1987b; Gomez et al. 1986; Katz et al. 1984; Ondreicka et al. 1966). Alteration in 

lymph node proliferation was observed in rats (Lauricella et al. 2001), and there is some evidence that 

developmental exposure to aluminum can affect the immune system in young mice (Golub et al. 1993; 

Yoshida et al. 1989). A battery of immune function tests following developmental and intermediate- or 

chronic-duration oral exposure may provide important information on characterizing the immunotoxic 

potential of aluminum, especially the age-sensitivity of effects. Aluminum-related dermal sensitivity 

appears to be very rare in humans; further studies do not appear to be necessary. 

Neurotoxicity. There are suggestive data that the nervous system may be a sensitive target in humans. 

Subtle neurological effects, such as impaired performance on neurobehavioral tests and increases in 

objective symptoms, have been observed in workers exposed to aluminum dust and fumes, McIntyre 

powder, or welding fumes (Bast-Pettersen et al. 1994; Buchta et al. 2003, 2005; Dick et al. 1997; 

Hänninen et al. 1994; Hosovski et al. 1990; Iregren et al. 2001; Rifat et al. 1990; Riihimäki et al. 2000; 

Polizzi et al. 2001; Sim et al. 1997; Sjögren et al. 1990, 1996; White et al. 1992). Although a number of 

studies have examined the possible association between aluminum exposure and Alzheimer’s disease 

(Flaten 1990; Forbes et al. 1992, 1994; Forster et al. 1995; Gauthier et al. 2000; Graves et al. 1998; 

Jacqmin et al. 1994; Jacqmin-Gadda et al. 1996; Martyn et al. 1989, 1997; McLachlan et al. 1996; Michel 

et al. 1990; Neri and Hewitt 1991; Polizzi et al. 2002; Rondeau et al. 2000, 2001; Salib and Hillier 1996; 

Sohn et al. 1996; Wettstein et al. 1991; Wood et al. 1988), a causal link between aluminum exposure and 

Alzheimer’s disease has not been shown, and a number of factors may influence the risk of developing 

Alzheimer’s disease. Nevertheless, continued monitoring of aluminum intake and incidence of 

neurological disease in humans is important to clarify aluminum's role in the Alzheimer’s disease process. 

The neurotoxicity of aluminum is well-documented in animals and has been manifested following oral or 

parenteral routes of exposure; however, there are very limited data on neurotoxicity following inhalation 

or dermal exposure. Inhalation studies have conducted histological examinations of the brain (Steinhagen 

et al. 1978; Stone et al. 1979), but have not conducted neurobehavioral function tests; no dermal exposure 

neurotoxicity studies were located. Studies are needed by these routes of exposure to establish whether it 

is a sensitive target following inhalation or dermal exposure. In rats and mice orally exposed to 

aluminum for intermediate or chronic durations, the neurotoxicity is manifested in neuromotor, 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 138 

3. HEALTH EFFECTS 

behavioral, and cognitive changes (Bilkei-Gorzo 1993; Commissaris et al. 1982; Connor et al. 1989; 

Donald et al. 1989; Golub and Germann 1998; Golub et al. 1987, 1989, 1992a, 1992b, 1995, 2000; Jing et 

al. 2004; Oteiza et al. 1993; Zhang et al. 2003). Additional low-dose studies in which levels of aluminum 

in the base diet are adequately characterized would be useful in establishing the NOAEL/LOAEL 

boundary. Oral exposure studies are also needed to evaluate the potential neurotoxicity of aluminum 

following acute-duration exposure and to confirm or refute the potential for aluminum to induce cognitive 

effects. Additionally, neurotoxicology studies measuring blood aluminum levels would be useful in 

determining the relevance of the animal data to humans. Research issues related to neurodevelopmental 

effects of aluminum are discussed in the Data Needs section on Developmental Toxicity. 

Epidemiological and Human Dosimetry Studies. There are numerous reports of adverse health 

effects, primarily respiratory and neurological effects, in workers exposed to airborne aluminum (Abbate 

et al. 2003; Abramson et al. 1989; Akira 1995; Al-Masalkhi and Walton 1994; Bast-Pettersen et al. 1994; 

Bost and Newman 1993; Buchta et al. 2003, 2005; Burge et al. 2000; Chan-Yeung et al. 1983; De Vuyst 

et al. 1986; Dick et al. 1997; Edling 1961; Gaffuri et al. 1985; Hänninen et al. 1994; Hosovski et al. 1990; 

Hull and Abraham 2002; Iregren et al. 2001; Jederlinic et al. 1990; Jephcott 1948; Korogiannos et al. 

1998; McLaughlin et al. 1962; Miller et al. 1984b; Mitchell et al. 1961; Musk et al. 1980; Polizzi et al. 

2001; Radon et al. 1999; Riddell 1948; Rifat et al. 1990; Riihimäki et al. 2000; Shaver 1948; Shaver and 

Riddell 1947; Sim et al. 1997; Simonsson et al. 1985; Sjögren et al. 1990, 1996; Ueda et al. 1958; 

Vallyathan et al. 1982; Vandenplas et al. 1998; White et al. 1992). However, a common limitation of the 

occupational exposure data is that the exposure levels have not been well quantified and workers were 

often exposed to a number of other chemicals. A number of studies have examined the possible 

association between Alzheimer’s disease and aluminum exposure in air (Polizzi et al. 2002; Salib and 

Hillier 1996) and drinking water (Flaten 1990; Forbes et al. 1992, 1994; Forster et al. 1995; Gauthier et 

al. 2000; Graves et al. 1998; Jacqmin et al. 1994; Jacqmin-Gadda et al. 1996; Martyn et al. 1989, 1997; 

McLachlan et al. 1996; Michel et al. 1990; Neri and Hewitt 1991; Rondeau et al. 2000, 2001; Sohn et al. 

1996; Wettstein et al. 1991; Wood et al. 1988). These studies have reported conflicting results and have 

been criticized for poor subject selection, exposure assessment, and diagnosis of Alzheimer’s disease. 

Further studies are important in helping to determine whether there is a cause-and-effect relationship 

between chronic aluminum exposure and the development of Alzheimer’s disease. There are also a 

number of studies reporting bone damage and neurological effects in individuals with chronic renal 

failure (Alfrey 1993); however, kidney failure increases the risk for developing aluminum-related effects; 

thus, these data have limited usefulness in predicting health effects in the general population. Aluminum 

is found in a number of over-the-counter products, such as antacids; however, controlled studies 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 139 

3. HEALTH EFFECTS 

examining potential adverse effects in healthy individuals ingesting these products long-term have not 

been located and are needed. 

Biomarkers of Exposure and Effect. Reliable methods for determining tissue and plasma levels of 

aluminum exist. The mechanism of action for aluminum toxicity is not known, hence it is not known 

whether biomarkers of effect exist or not. 

Exposure. Although aluminum can be measured in blood (Alfrey et al. 1980; Arieff et al. 1979; Ganrot 

1986), urine (Gorsky et al. 1979; Greger and Baier 1983; Kaehny et al. 1977; Mussi et al. 1984; Recker et 

al. 1977; Sjögren et al. 1985, 1988), and feces (Greger and Baier 1983), the aluminum body burden 

rapidly declines upon termination of exposure (except in the lungs, where retention takes place). Also, 

tissue levels do not correlate with exposure except that higher-than-average tissues levels of aluminum 

correlate with increased exposure. There is some suggestive evidence that erythrocyte aluminum levels 

may be reflective of long-term aluminum exposure (Priest 2004), but a possible relationship between 

ingestion and erythrocyte aluminum levels has not been established. Additional studies examining the 

possible relationship between urine, blood, or other tissue levels and aluminum exposure would be useful 

in establishing biomarkers of exposure. 

Effect. No biomarkers of effect have been identified for aluminum. The mechanisms of action for 

aluminum toxicity is not known and there is considerable research in identifying the mechanism(s) of 

neurotoxicity (Cucarella et al. 1998; Deloncle et al. 1999; El-Demerdash 2004; Fraga et al. 1990; 

Hermenegildo et al. 1999; Kaizer et al. 2005; Kohila et al. 2004; Llansola et al. 1999; Montoliu and 

Felipo 2001; Nehru and Anand 2005; Rodella et al. 2004; Yokel et al. 2002; Zatta et al. 2002; Zheng 

2001). Studies on the mechanism of action of aluminum may lead to biochemical tests that can be used in 

the early identification of aluminum toxicity. 

Absorption, Distribution, Metabolism, and Excretion. Available data indicate that the 

gastrointestinal absorption of aluminum is often in the range of 0.1–0.6% in humans, although absorption 

of poorly available aluminum compounds such as aluminum hydroxide can be <0.01% (Day et al. 1991; 

DeVoto and Yokel 1994; Ganrot 1986; Greger and Baier 1983; Hohl et al. 1994; Jones and Bennett 1986; 

Nieboer et al. 1995; Priest 1993; Priest et al. 1998; Stauber et al. 1999; Steinhausen et al. 2004). 

Bioavailability of aluminum varies mainly due to differences in the form of the ingested compound and 

dietary constituents (i.e., the kinds and amounts of ligands in the stomach with which absorbable 

aluminum species can be formed). The apparent 10-fold range in aluminum absorption has not been 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 140 

3. HEALTH EFFECTS 

systematically documented using a variety of aluminum compounds and the most suitable analytical 

techniques. Radiochemical studies are desired because they facilitate accurate quantitation of the small 

percentages of ingested aluminum that are absorbed and provide a means to distinguish endogenous 

aluminum from administered aluminum and from aluminum contamination of samples (Priest 1993). 

Additional toxicokinetic studies using 26Al would help to better characterize the likely range of aluminum 

bioavailability. This kind of information is needed because an amount of aluminum ingested does not 

provide an estimate of exposure without information on bioavailability of the form in which it is ingested. 

In particular, if bioavailability in a particular human scenario differs from bioavailability in the MRL 

study, or is not known, extrapolation may not be appropriate because exposure depends on bioavailability 

as well as intake. Information on the bioavailability of aluminum in rodent laboratory feed would also be 

useful for extrapolating from animal to human exposure. Studies investigating the extent of absorption of 

aluminum into the placenta and fetal blood circulation would be useful in assessing the relevance of 

developmental effects in animals to human exposures. 

There are limited data on the distribution of aluminum following inhalation or dermal exposure, although 

it is likely that the distribution would be similar to distribution following oral exposure. Ingested 

aluminum is not equally distributed throughout the body; higher levels are found in the bone, spleen, 

liver, and kidney (Greger and Donnaubauer 1986; Greger and Sutherland 1997; Zafar et al. 1997). In the 

blood, aluminum is primarily found in the plasma bound to transferrin (Ganrot 1986; Harris and Messori 

2002; Martin 1986). Metabolism of the element does not occur (Ganrot 1986). Absorbed aluminum is 

primarily excreted in the urine with a small amount of absorbed aluminum excreted in the feces (Gorsky 

et al. 1979; Greger and Baier 1983; Kaehny et al. 1977; Recker et al. 1977; Sjögren et al. 1985, 1988). A 

main deficiency is whether aluminum can cross into the brains of healthy humans in sufficient amounts to 

cause neurological diseases. Further animal experiments, possibly using 26Al as a tracer, would be useful 

in determining which, if any, levels and routes of exposure may lead to increased aluminum uptake in the 

brain. 

Comparative Toxicokinetics. The animal data indicate that the nervous system is a sensitive target 

of toxicity for aluminum following oral exposure, as summarized in the Data Needs sections on 

Neurotoxicity and Developmental Toxicity. Human data also suggest that the nervous system is a 

sensitive target; a number of neurological effects have been observed in aluminum workers (BastPettersen et al. 1994; Buchta et al. 2003, 2005; Dick et al. 1997; Hänninen et al. 1994; Hosovski et al. 

1990; Iregren et al. 2001; Polizzi et al. 2001; Rifat et al. 1990; Riihimäki et al. 2000; Sim et al. 1997; 

Sjögren et al. 1990, 1996; White et al. 1992). The toxicokinetic properties of aluminum have been 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 141 

3. HEALTH EFFECTS 

studied in human and animals. The results of these studies suggest that the absorption, distribution, and 

excretion properties of aluminum are similar across species. There are very few comparative studies 

examining the toxicokinetic properties of different aluminum compounds; these studies would be useful 

in extrapolating toxicity data across species. 

Methods for Reducing Toxic Effects. The mechanisms of absorption of aluminum have not been 

established. Studies that elucidated these mechanisms would be useful for establishing methods or 

treatments for reducing absorption and distribution of aluminum to sensitive targets. The chelating agent 

DFO has been used to reduce the aluminum body burden (Haddad et al. 1998; Yokel et al. 2001b); 

however, the clinical usefulness of DFO is limited by a variety of toxic effects. Other chelators such as 

1,2-dimethyl-3-hydroxypyrid-4-one and (4-methyl-6-trifluoromethyl-6-pyrimidin-2-il)-hydrazine have 

also been shown to reduce the aluminum body burden (Gomez et al. 1999; Missel et al. 2005;Yokel et al. 

1997). Studies that identify other methods for reducing aluminum body burden would be useful. The 

mechanism of toxicity has not been established for most of the toxic end points. Additional information 

on the mechanisms of toxicity would be useful for developing methods for reducing the toxicity of 

aluminum. 

Children’s Susceptibility. Data needs relating to both prenatal and childhood exposures, and 

developmental effects expressed either prenatally or during childhood, are discussed in detail in the 

Developmental Toxicity subsection above. 

The available data suggest that the targets of aluminum toxicity in children would be similar to those in 

adults. However, there is conflicting evidence on whether the threshold of toxicity, particularly 

neurotoxicity, would be lower in children. Multiple species studies using a relevant route of exposure, 

such as ingestion, and examining a wide range of effects in immature, mature, and older animals would be 

useful in assessing the children’s susceptibility to the toxicity of aluminum. Additionally, there are no 

studies on the influence of immature renal function on aluminum retention in the body and no studies on 

the long-term effects of aluminum exposure on skeletal maturation or neurotoxicity. There are some data 

suggesting age-related differences in the toxicokinetic properties of aluminum. A study in rats found 

higher levels of aluminum in the brain and bone of aged rats (aged 18 months) compared to young rats 

(aged 21 days) (Gomez et al. 1997a); similar findings were observed in the controls and aluminum-treated 

rats. 
 

 

 

 

 

ALUMINUM 142 

3. HEALTH EFFECTS 

Child health data needs relating to exposure are discussed in Section 6.8.1, Identification of Data Needs: 

Exposures of Children. 

3.12.3 Ongoing Studies 

There are a large number of ongoing studies covering many aspects of aluminum toxicity. Studies 

supported by the federal government are listed in Table 3-5. 
 

 

ALUMINUM 143 

3. HEALTH EFFECTS 

Table 3-5. Ongoing Studies on Aluminum 

Investigator Study Topic Institution Sponsor 

Longnecker M Use of aluminum in toenails as National Institute of 

a biomarker of exposure Environmental Health Sciences 

Yokel R Aluminum bioavailability from University of National Institute of 

foods Kentucky Environmental Health Sciences 

Bondy S Aluminum/iron interactions in University of National Institute of 

neurodegenerative disease California Irvine Environmental Health Sciences 

DeWitt DA Mechanism of aluminum- Liberty University National Institutes of Health 

induced neurodegeneration in 

Alzheimer’s disease 

Swyt-Thomas CR Role of aluminum in Alzheimer’s National Institutes of Health 

disease 

Source: FEDRIP 2006 
 

 

 

ALUMINUM 144
 

3. HEALTH EFFECTS 

This page is intentionally blank. 
 

 

ALUMINUM 145 

4. CHEMICAL AND PHYSICAL INFORMATION
 

4.1 CHEMICAL IDENTITY 

Aluminum is a naturally occurring element that appears in the second row of Group 13 (IIIA) of the 

periodic table (O’Neil et al. 2001). Table 4-1 lists common synonyms and other pertinent identification 

information for aluminum and selected aluminum compounds. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Aluminum is a silvery-white, malleable, and ductile metal. In moist air, a protective oxide coating of 

aluminum oxide is formed on its surface. In compounds, aluminum typically occurs in its +3 oxidation 

state (Lide 2005; O’Neil et al. 2001). Table 4-2 lists important physical and chemical properties of 

aluminum and selected aluminum compounds. 
 

 

 

ALUMINUM 146 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Aluminum and Compoundsa 

Characteristic Information 

Chemical name Aluminum Aluminum chloride Aluminum chlorohydrate 

(anhydrous) 

Synonym(s) Aluminiumb; alumina fibre; Aluminum trichloride; Aluminol ACH; aluminum 

metana; aluminium aluminum chloride chloride hydroxide oxide, 

bronze; aluminum (1:3); Pearsall basic; aluminum chloride 

dehydrated; aluminium oxide; aluminum oxychloride; 

flake; aluminum powder; PAC 250A; Astringen; 

aluminum-27; Noral Chlorhydrol; Locron 

aluminum; PAP-1 

Chemical formula Al AlCl3 Unspecifiedd 

Chemical structure Al Al3+ (Cl-

)3 Unspecified 

Identification numbers: 

CAS registry 7429-90-5 7446-70-0 1327-41-9 

EINECS 231-072-3 231-208-1 215-477-2 

NIOSH RTECS BD330000 BD0525000 No data 

EPA hazardous waste No data D003 No data 

code 

EPA Pesticide 000111 013901 No data 

Chemical Code 

DOT/UN/NA/IMCO UN 1309; UN 1396; IMO UN 1726; UN 2581; No data 

shipping 4.1; IMO 4.3; NA 9260 IMO 8.0 

HSDB 507 607 No data 
 

 

 

ALUMINUM 147 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Aluminum and Compoundsa 

Characteristic Information 

Chemical name 

Synonym(s) 

Chemical formula 

Chemical structure 

Identification numbers: 

CAS registry 

EINECS 

NIOSH RTECS 

EPA hazardous waste 

code 

EPA Pesticide 

Chemical Code 

DOT/UN/NA/IMCO 

shipping 

HSDB 

Aluminum hydroxide 

alpha-Alumina trihydrate; 

alumina hydrate; alumina 

hydrated; aluminum oxide 

trihydrate; aluminum 

oxide hydrate; aluminum 

(III) hydroxide; hydrated 

alumina; hydrated 

aluminum oxide; 

aluminum hydrate; 

aluminum trihydrate; 

hydrated alumina; Alcoa 

331/C 30BF/C 330/C 333; 

Alugel; Alumigel; BACO 

AF260; British Aluminum 

AF260; Calmogastrin; 

Higilite H 31S/ H 32/ H 42; 

Hychol 705; Hydrafil; 

Hydral 705/710; Martinal 

A/A-S/F-A; Reheis F 1000 

Al(OH)3 

Al3+ (OH-

)3 

21645-51-2 

244-492-7 

BD0940000 

No data 

No data 

No data 

575 

Aluminum lactate 

Aluminum, tris (2­

hydroxypropanoatoO1

,O2); propanoic acid, 

2-hydroxy-, aluminum 

complex; aluminum tris 

(α-hydroxypropionate) 

C9H15AlO9 

O 

Al3+ O OH 

3 

18917-91-4 

242-670-9 

No data 

No data 

No data 

No data 

No data 

Aluminum nitrate 

Aluminum trinitrate; 

aluminum (III) nitrate (1:3); 

nitric acid, aluminum salt; 

nitric acid, aluminum (3+) 

salt 

Al(NO3)3 

Al3+ (NO3

-

)3 

13473-90-0f 

236-751-8 

No data 

No data 

No data 

UN 1438; IMO 5.1 

574 
 

 

ALUMINUM 148 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Aluminum and Compoundsa 

Characteristic Information 

Chemical name Aluminum oxide Aluminum phosphate Aluminum phosphide 

Synonym(s) Activated aluminum oxide; Aluminum ortho- Aluminum monophosphide; 

α-alumina; aluminum phosphate; phosphoric AL-Phos; AlP; Celphos; 

sesquioxide; aluminum acid; aluminum salt Delicia; Delicia Gastoxin; 

trioxide; β-aluminum (1:1); Aluphos; Detia; Phostoxin; Quickphos 

oxide; γ-alumina; Almite; Phosphaljel; 

Alon; Aloxite; Alumite; Phosphalugel; 

Alundum; Campalox; aluminum 

Dispal Alumina; Exolon monophosphate 

XW 60; Faserton; Hypalox 

II; Ludox CL; Martoxin; 

Microgrit WCA; Poraminar 

Chemical formula Al2O3 AlPO4 AlP 

Chemical structure 

(Al3+)2 (O2-)3 Al3+ PO4

3- Al P 

Identification numbers: 

CAS registry 1344-28-1 7784-30-7 20859-73-8 

EINECS 215-691-6 232-056-9 244-088-0 

NIOSH RTECS BD1200000 TB6450000 BD1400000c 

EPA hazardous waste No data No data P006 

code 

EPA Pesticide No data No data 066501 

Chemical Code 

DOT/UN/NA/IMCO No data No data UN 1397; UN 3048; IMO 4.3; 

shipping IMO 6.1
 

HSDB 506 No data 6035
 
ALUMINUM	 149 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Aluminum and Compoundsa 

Characteristic	 Information 

Chemical name Aluminum fluoride	 Aluminum sulfate Aluminum carbonate 

anhydrous 

Synonym(s) Aluminum trifluoride	 Alum; aluminum sulfate Carbonic acid, aluminium 

(2:3); cake alum; filter salt 

alum; papermaker’s 

alum; pearl alum; pickle 

alum; aluminum 

trisulfate; sulfuric acid, 

aluminum salt (3:2) 

Chemical formula AlF3 Al2(SO4)3	 Al2O3•CO2; normal aluminum 

carbonate Al2(CO3)3 is not 

known as an individual 

compounde 

Chemical structure No data 

Al3+ (F-

)3 (Al3+)2 (SO4

2-)3 

Identification numbers: 

CAS registry 7784-18-1 10043-01-3 53547-27-6 

EINECS 232-051-1 233-135-0 238-440-2 

NIOSH RTECS BD0725000 BD1700000 No data 

EPA hazardous waste No data No data No data 

code 

EPA Pesticide No data 013906 No data
 

Chemical Code
 

DOT/UN/NA/IMCO No data NA 9078; NA 1760 No data
 

shipping
 

HSDB 600 5067 No data
 
 

 

ALUMINUM 150 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Aluminum and Compoundsa 

Characteristic Information 

Chemical name Aluminum potassium sulfate Alchlor 

Synonym(s) Alum potassium; burnt alum; sulfuric acid, Aluminum chloride hydroxide 

aluminum potassium salt (2:1:1); Tai-Ace K propylene glycol complex 

150; Tai-Ace K 20 

Chemical formula AlKO8S2 Unspecified 

Chemical structure K+ Al3+ (SO4

2-)2 Unspecified 

Identification numbers: 

CAS registry 10043-67-1 52231-93-3 

EINECS 233-141-3 No data 

NIOSH RTECS No data No data 

EPA hazardous waste No data No data 

code 

EPA pesticide No data No data
 

chemical code
 

DOT/UN/NA/IMCO No data No data
 

shipping
 

HSDB No data No data
 

a

All information obtained from ChemIDplus 2006, ChemFinder 2008, and HSDB 2008, except where noted. b

British spelling (Lewis 2001)
 c

NIOSH 1997
 d

Aluminum chlorohydrate: CAS No. 12042-91-0; Chemical formula: Al2ClH5O5·xH2O (ChemIDplus 2006)
 e

Lewis 2001
 f

Aluminum nitrate nonahydrate (CAS No. 7784-27-2)
 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMO = Department of Transportation/United Nations/North America/
 

Intergovernmental Maritime Dangerous Goods Code; EINECS = European Inventory of Existing Commercial
 

Chemical Substances; EPA = Environmental Protection Agency; HSDB = Hazardous Substances Data Bank;
 

NIOSH = National Institute for Occupational Safety and Health; RTECS = Registry of Toxic Effects of Chemical
 

Substances
 
 

 

 

ALUMINUM 151 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Aluminum and Compoundsa 

Property Information 

Chemical name Aluminum Aluminum chloride Aluminum chlorohydrate 

Molecular weight 26.98 133.34 No data 

Color Silver white White when pure, ordinarily Glassyb 

gray or yellow to greenish 

Physical state Malleable, ductile metal; White hexagonal Solidb 

cubic crystal deliquescent or moisture 

sensitive plates 

Melting point 660 °C 192.6 °C No data 

Boiling point 2,327 °C 182.7 °C at 752 mm Hg No data 

(sublimation temperature) 

Density (g/cm3) 2.70 2.48 No data 

Odor Odorless Strong odor of hydrogen No data 

chloride 

Odor threshold: 

Water No data 0.5 mg/L (calculating on the No data 

aluminum ion) 

Air No data No data No data 

Solubility: 

Water Insoluble in water Reacts violently with water Dissolves in H2O, 

producing hydrochloric acid forming slightly turbid 

and heat colloidal solutions (up to 

55% w/w)b 

Other solvents Soluble in HCl, H2SO4, hot Soluble in benzene, carbon No data 

water, and alkalies tetrachloride, chloroform 

Partition coefficients: 

Log Kow No data No data No data 

Log Koc No data No data No data 

pH No data No data ~4.3 (15% aqueous 

solution)b 

Vapor pressure 1 mm Hg at 1,284 °C 1 mm Hg at 100 °C No data 

Henry’s law constant No data No data No data 

Autoignition No data No data No data 

temperature 

Flashpoint No data No data No data 

Flammability Finely divided aluminum Not combustible, but heating No data 

dust is easily ignited may produce irritants and 

toxic gases 

Explosive limits No data No data No data 
ALUMINUM 152 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Aluminum and Compoundsa 

Property Information 

Chemical name Aluminum hydroxide Aluminum lactate Aluminum nitrate 

Molecular weight 78.01 294.19b 213.00 

Color White Colorlessc Colorlessd 

Physical state Bulky, amorphous powder Powderc Rhombic crystalsd 

Melting point 300 °C No data 73 °Cd 

Boiling point No data No data Decomposes at 135 °Cd 

Density (g/cm3) 2.42 No data No data 

Odor No data No data No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water Insoluble in water Freely soluble in waterb Very soluble in waterd 

Other solvents Soluble in alkaline or acid No data Very soluble in alcohol; 

solutions very slightly soluble in 

acetone; almost 

insoluble in ethyl 

acetate, pyridined 

Partition coefficients: 

Log Kow No data No data No data 

Log Koc No data No data No data 

pH No data No data Aqueous solution is 

acidicd 

Vapor pressure No data No data No data 

Henry's law constant No data No data No data 

Autoignition No data No data No data 

temperature 

Flashpoint No data No data No data 

Flammability No data No data No data 

Explosive limits No data No data No data 
 

ALUMINUM	 153 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Aluminum and Compoundsa 

Property	 Information 

Chemical name Aluminum oxide Aluminum phosphate Aluminum phosphide 

Molecular weight 101.94 121.95b 57.95 

Color White Whiteb Dark gray or dark yellow 

Physical state Crystalline powder Infusible powderb Cubic crystals 

Melting point approximately 2,000 °C >1,460 °Cb 2,550 °C 

Boiling point 2,980 °C No data No data 

Density (g/cm3) 4.0 at 20 °C 2.56b 2.85 at 15 °C 

Odor Odorless No data	 Garlic odor 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water Soluble in cold water, Practically insoluble in Decomposesb 

0.000098 g/100 cc; waterb 

insoluble in hot water 

Other solvents Very slightly soluble in acid, Practically insoluble in acetic No data 

alkali acid; very slightly soluble in 

concentrated HCl and HNO3 

acidsb 

Partition coefficients: 

Log Kow No data No data No data 

Log Koc No data No data No data 

pH No data No data No data 

Vapor pressure 1 mm Hg at 2,158 °C No data No data 

Henry's law constant No data No data No data 

Autoignition No data No data No data 

temperature 

Flashpoint No data No data No data 

Flammability No data No data No data 

Explosive limits No data No data No data 
 

ALUMINUM 154 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Aluminum and Compoundsa 

Property Information 

Chemical name Aluminum fluoride Aluminum sulfate Aluminum carbonate 

Molecular weight 83.98 342.14 No data 

Color White White, lustrous Whitec 

Physical state Hexagonal crystals Crystals, pieces, granules or Lumps or powderc 

powder 

Melting point 1,291 °C Decomposes at 770 °C No data 

Boiling point Sublimes at 1,272 °C and No data No data 

760 mm Hg 

Density (g/cm3) 3.10 1.61 No data 

Odor No data Odorless No data 

Odor threshold: No data 

Water No data No data 

Air No data No data 

Solubility: 

Water 0.559 g/100 mL at 25 °C Soluble in 1 part H2O Insolublec 

Other solvents Sparingly soluble in acids 

and alkalies; insoluble in 

Insoluble in ethanol Dissolves in hot HCl or 

H2SO4 acidc 

alcohol and acetone 

Partition coefficients: 

Log Kow No data No data No data 

Log Koc No data No data No data 

pH No data Aqueous solution (1 g/mL) No data 

not less than 2.9 

Vapor pressure 1 mm Hg at 1,238 °C Essentially zero No data 

Henry's law constant No data No data No data 

Autoignition No data No data No data 

temperature 

Flashpoint No data No data No data 

Flammability No data No data No data 

Explosive limits No data No data No data 
ALUMINUM 155 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Aluminum and Compoundsa 

Property Information 

Chemical name Aluminum potassium sulfate Alchlor 

Molecular weight 258.20 No data 

Color White No data 

Physical state Powder No data 

Melting point 92 oCe No data 

Boiling point Loses 18 H2O at 64.5 °C; anhydrous at 200 °Ce No data 

Density (g/cm3) 1.75e No data 

Odor Odorlesse No data 

Odor threshold: 

Water No data No data 

Air No data No data 

Solubility: 

Water 1 gram dissolves in about 20 mL of cold water, No data 

about 1 mL of boiling water 

Other solvents Practically insoluble in alcohol No data 

Partition coefficients: 

Log Kow No data No data 

Log Koc No data No data 

pH Aqueous solutions are acidic No data 

Vapor pressure No data No data 

Henry’s law constant No data No data 

Autoignition No data No data 

temperature 

Flashpoint No data No data 

Flammability limits Noncombustiblee No data 

Explosive limits No data No data 

a

All information obtained from HSDB 2008, except where noted. b

O’Neil et al. 2001
 c

Lewis 2001
 d

Aluminum nitrate nonahydrate (CAS No. 7784-27-2) e

Al2(SO4)3·K2SO4·24H2O (Lewis 2001)
 
ALUMINUM 156
 

4. CHEMICAL AND PHYSICAL INFORMATION 

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ALUMINUM 157 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Aluminum is the most abundant metal and the third most abundant element in the earth’s crust, 

comprising about 8.8% by weight (88 g/kg). It is rarely found free in nature and is found in most rocks, 

particularly igneous rocks, which contain aluminum as aluminosilicate minerals (Staley and Haupin 

1992). Bauxite is a naturally occurring, heterogeneous material consisting of primarily one or more 

aluminum hydroxide minerals in addition to a variety of aluminosilicates, iron oxide, silica, titania, and 

other impurities in trace amounts. It is the most important raw material for the production of aluminum. 

More than 90% of the bauxite consumed in the United States in 2006 was converted to alumina (Al2O3) 

for the production of aluminum (USGS 2007d). Other raw materials sometimes used in the production of 

aluminum include cryolite, aluminum fluoride, fluorspar, corundum, and kaolin minerals (Browning 

1969; Dinman 1983; IARC 1984; Lide 2005; O’Neil et al. 2001; USGS 2007a). 

In 2006, primary aluminum was produced in 42 countries, with China, Russia, Canada, and the United 

States, in decreasing order of metal produced, accounting for 53% of the total world production of 

31.9 million metric tons. In 2006, 5 U.S. companies, operating 13 primary aluminum smelters, produced 

an estimated 2.3 million metric tons of aluminum metal. Six smelters were temporarily idled. In the 

United States, about 3 million metric tons of aluminum were recovered from purchased scrap in 2006, 

with 64% of this coming from new (manufacturing) scrap and 36% from old scrap (discarded aluminum 

products) (USGS 2007b, 2007c). 

In 2006, Australia, Brazil, and China accounted for approximately 58% of the total world bauxite product 

of 178 million metric tons. World production of alumina was estimated to be 69.2 million metric tons in 

2006, with Australia and China as leading producers, accounting for 46% of the world’s alumina 

production. U.S. production of alumina, which is nearly all derived from imported metallurgical-grade 

bauxite, was 4.61 million metric tons in 2006 (USGS 2007a, 2007d). 

The principal method used in producing aluminum metal involves three major steps: refining of bauxite 

by the Bayer process to produce alumina, electrolytic reduction of alumina by the Hall-Héroult process to 

produce aluminum, and casting of aluminum into ingots (Browning 1969; Dinman 1983; IARC 1984). 

In the first step (Bayer process), bauxite (Al2O3·H2O) is digested at high temperature and pressure in a 

strong solution of caustic soda. The resulting hydrate is then crystallized and calcined in a kiln to produce 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 158 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

alumina (aluminum oxide). In the second step (Hall-Héroult process), alumina is reduced to aluminum 

metal by an electrolytic process involving carbon electrodes and cryolite flux (3NaF ·AlF3). The 

electrolytic reduction process of transforming alumina into aluminum is carried out in electrolytic cells or 

pots. The areas where this occurs are called potrooms. Two types of electrolytic cells may be used, a 

prebake or a Söderberg cell. Their design differs, but the principle is the same. Alumina is dissolved in 

the cell in an electrolyte at a high temperature (950–970 °C) and a low voltage (4–6 volts). A high 

current is applied to the melted fraction. The alumina is reduced to aluminum at the cathode and the 

metal sinks to the bottom of the electrolytic cell. The aluminum is then removed by siphoning. The 

oxygen from the alumina migrates to the carbon anode of the cell, where it reacts to form carbon dioxide 

and carbon monoxide. The aluminum produced using the Hall-Héroult electrolytic reduction process may 

be refined to a maximum purity of 99.9%. In the third step (casting), aluminum is taken from the cell to 

holding furnaces from which it is poured into molds and cast into aluminum ingots (IARC 1984; Lewis 

2001; Staley and Haupin 1992). Current U.S. manufacturers of aluminum are given in Table 5-1. 

Aluminum is also an integral part of a variety of aluminum compounds used in industrial, domestic, 

consumer, and medicinal products. The methods of production for these compounds are described in the 

following section. Current U.S. manufacturers of selected aluminum compounds are given in Table 5-2. 

Aluminum chloride can be produced by the reaction of purified gaseous chlorine with molten aluminum, 

as well as by the reaction of bauxite with coke and chlorine at about 875 °C (Lewis 2001). 

Aluminum fluoride can be produced by heating ammonium hexafluoroaluminate to red heat in a stream of 

nitrogen. Other methods include the action of hydrogen fluoride gas on aluminum trihydrate; the reaction 

of hydrogen fluoride on a suspension of aluminum trihydrate followed by calcining the hydrate formed; 

fusion of cryolite or sodium fluoride with aluminum sulfate; or the reaction of fluosilicic acid on 

aluminum hydrate (HSDB 2007; Lewis 2001; O’Neil et al. 2001). 

Aluminum hydroxide is produced from bauxite. The bauxite ore is first dissolved in a solution of sodium 

hydroxide, and then the aluminum hydroxide is precipitated from the sodium aluminate solution by 

neutralization (as with carbon dioxide) or by autoprecipitation (Bayer process) (Lewis 2001). 

Aluminum nitrate as the nonahydrate is formed by dissolving aluminum or aluminum hydroxide in dilute 

nitric acid and allowing the resulting solution to crystallize (Grams 1992; Lewis 2001). 
 

ALUMINUM 159 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. U.S. Manufacturers of Aluminuma 

Company Location 

Alcan Aluminum Corporation, Alcan Specialty Aluminas Sebree, Kentucky 

Alcoa, Inc., Alcoa Primary Metals Alcoa, Tennessee 

Badin, North Carolina 

Goose Creek, South Carolina 

Massena, New York 

Wenatchee, Washington 

Alcoa Intalco Works Ferndale, Washington 

Century Aluminum Hawesville, Kentucky 

Ravenswood, West Virginia 

Columbia Falls Aluminum Company Columbia Falls, Montana 

Eastalco Aluminum Company Frederick, Maryland 

Noranda Aluminum Inc. New Madrid, Missouri 

Northwest Aluminum Company The Dalles, Oregon 

Ormet Primary Aluminum Corporation Hannibal, Ohio 

a

Derived from SRI 2007 
 

ALUMINUM 160 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. U.S. Producers of Selected Aluminum Compoundsa 

Annual capacity 

Company Location (103 metric tons)b 

Alumina, calcined (Aluminum oxide) 

Alcoa, Inc., Alcoa World Alumnia Point Comfort, Texas 

Almatis, Inc. Bauxite, Arkansas 

Gramercy Alumina LLC Gramercy, Louisiana 

Ormet Primary Aluminum Corporation Burnside, Louisiana 

Sherwin Alumina Company Corpus Christi, Texas 

Aluminas (specialty grades) 

Albemarle Corporation Pasadena, Texas 

Almatis, Inc. Bauxite, Arkansas 

AluChem, Inc. Cincinnati, Ohio 

Axens North America Savannah, Georgia 

BASF Catalysts LLC, Adsorbents and Catalysts Port Allen, Louisiana 

Vidalia, Louisiana 

Huber Engineered Materials Fairmount, Georgia 

Porocel Corporation Little Rock, Arkansas 

Saint-Gobain Ceramics & Plastics, Inc., Grains Worcester, Massachusetts 

& Powders Division 

Sasol North America Inc., Ceralox Division Westlake, Louisiana 

Tucson, Arizona 

SPI Pharma Group Lewes, Delaware 

Treibacher Schleifmittel North America, Inc. Niagara Falls, New York 

UOP, LLC Baton Rouge, Louisiana 

Washington Mills Electro Minerals Company Niagara Falls, New York 

Aluminum ammonium sulfate 

Holland Company, Inc. Adams, Massachusetts 

Aluminum chlorhydrate (aluminum chloride, basic) 

GEO Specialty Chemicals, Inc., Aluminum Baltimore, Maryland 

Products Group 

Bastrop, Louisiana 

Counce, Tennessee 

The Gillette Company, North Chicago North Chicago, Illinois 

Manufacturing Center 

Gulbrandsen Companies, Gulbrandsen Orangeburg, South Carolina 

Chemicals, Inc. 

Gulbrandsen Companies, Gulbrandsen La Porte, Texas 

Technologies, Inc. Phillipsburg, New Jersey 

Puerto Rico Alum Corporation Penuelas, Puerto Rico 

Reheis, Inc. Berkeley Heights, New Jersey 
 

 

 

ALUMINUM 161 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. U.S. Producers of Selected Aluminum Compoundsa 

Company Location 

Annual capacity 

(103 metric tons)b 

Summit Research Labs Huguenot, New York 

Phoenix, Arizona 

Somerset, New Jersey 

Thatcher Company Salt Lake City, Utah 

Aluminum chloride (anhydrous)c 

Gulbrandsen Companies, Gulbrandsen Orangeburg, South Carolina 25 

Chemicals, Inc. 

Toth Aluminum Corporation Vacherie, Louisiana 10d 

Vanchlor Company, Inc. Lockport, New York 15 

Aluminum chloride (hydrous)e 

Arkema, Inc., Specialty Chemicals Division Axis, Alabama 2 

Chattem, Chemicals, Inc. Chattanooga, Tennessee 1 

Delta Chemical Corporation Ashtabula, Ohio 10 

Baltimore, Maryland 50 

GEO Specialty Chemicals, Inc., Aluminum Baltimore, Maryland 9 

Products Group 

Bastrop, Louisiana 6 

The Gillette Company, North Chicago North Chicago, Illinois Not applicable 

Manufacturing Center 

Gulbrandsen Companies, Gulbrandsen Phillipsburg, New Jersey 9 

Technologies, Inc. 

Holland Company, Inc. Adams, Massachusetts Not applicable 

Puerto Rico Alum Corporation Penuelas, Puerto Rico 1 

Reheis, Inc. Berkeley Heights, New Jersey 3 

Southern Ionics, Inc. Westlake, Louisiana 60 

Summit Research Labs Huguenot, New York Not applicable 

Phoenix, Arizona Not applicable 

Somerset, New Jersey Not applicable 

Aluminum chloride (aluminum trichloride) 

Mallinckrodt, Inc., Pharmaceuticals Group St. Louis, Missouri 

Aluminum chlorohydrate (polyaluminum chloride) 

Delta Chemical Corporation Ashtabula, Ohio 

Baltimore, Maryland 

GEO Specialty Chemicals, Inc., Aluminum Baltimore, Maryland 

Products Group Bastrop, Louisiana 

Gulbrandsen Companies, Gulbrandsen Orangeburg, South Carolina 

Chemicals, Inc. 

Gulbrandsen Companies, Gulbrandsen La Porte, Texas 

Technologies, Inc. Phillipsburg, New Jersey 

Holland Company, Inc. Adams, Massachusetts 
 

ALUMINUM	 162 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. U.S. Producers of Selected Aluminum Compoundsa 

Annual capacity 

Company Location (103 metric tons)b 

Kemiron Companies, Inc.	 Kalama, Washington
 

Savannah, Georgia
 

Spokane, Washington
 

Puerto Rico Alum Corporation	 Penuelas, Puerto Rico 

Summit Research Labs	 Huguenot, New York
 

Phoenix, Arizona
 

Somerset, New Jersey
 

Aluminum fluoride 

Alcoa, Inc., Alcoa World Alumina Point Comfort, Texas 60 

CERAC, Inc. Milwaukee, Wisconsin Not applicable 

ConocoPhillips Billings, Montana <1f 

Ponca City, Oklahoma <1f
 

Ozark Fluorine Specialties, Inc. Tulsa, Oklahoma <2
 

Aluminum hydroxide 

Almatis, Inc. Bauxite, Arkansas 

Franklin Industries, Inc., Franklin Industrial Dalton, Georgia 

Minerals
 

Gramercy Alumina LLC Gramercy, Louisiana
 

Huber Engineered Materials Fairmount, Georgia
 

Kennesaw, Georgia 

Quincy, Illinois
 

IMERYS Pigments & Additives Talking Rock, Georgia
 

Sherwin Alumina Company Corpus Christi, Texas
 

Aluminum nitrate 

Blue Grass Chemical Specialties, LLC New Albany, Indiana 

Mallinckrodt Baker, Inc. Phillipsburg, New Jersey 

Mineral Research and Development Harrisburg, North Carolina 

Thatcher Company Salt Lake City, Utah 

Aluminum phosphate (aluminum orthophosphate) 

Innophos, Inc. Chicago Heights, Illinois 

Johnson Matthey, Inc., Alfa Aesar Ward Hill, Massachusetts 

PCS Phosphate Co., Inc. Cincinnati, Ohio 

United-Erie, Inc. Erie, Pennsylvania 

Aluminum phosphideg 

Bernardo Chemical, Ltd, Inc. 

Degesch America, Inc. 

Inventa Corporation 

Midland Fumigant, Inc. 

Pestcon Systems, Inc. 
 

ALUMINUM 163 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. U.S. Producers of Selected Aluminum Compoundsa 

Annual capacity 

Company Location (103 metric tons)b 

Aluminum potassium sulfate (Potash alum) 

Holland Company, Inc. Adams, Massachusetts 

Aluminum sodium sulfate (Soda alum) 

General Chemical Corporation East St. Louis, Illinois 

Aluminum sulfate (Alum, commercial) 

Alchem, Inc. Rockwell, North Carolina 

Bay Chemical and Supply Company Odem, Texas 

C & S Chemicals, Inc. Austell, Georgia 

Bartow, Florida 

Joliet, Illinois 

Randolph, Minnesota 

Waycross, Georgia 

Delta Chemical Corporation Ashtabula, Ohio 

Baltimore, Maryland
 

GAC Chemical Corporation Searsport, Maine
 

Gemini Industries, Inc. Santa Ana, California
 

General Chemical Corporation Ashdown, Arkansas
 

Augusta, Georgia 

Catawba, South Carolina 

Cedar Springs, Georgia 

Cleveland, Ohio 

Covington, Virginia 

Denver, Colorado 

Detroit, Michigan 

East Point, Georgia 

East St. Louis, Illinois 

Hopewell, Virginia 

Indianapolis, Indiana 

Jacksonville, Florida 

Johnsonburg, Pennsylvania 

Kalamazoo, Michigan 

Macon, Georgia 

Marrero, Louisiana 

Menasha, Wisconsin 

Middletown, Ohio 

Pine Bluff, Arkansas 

Pittsburg, California 

Port St. Joe, Florida 

Saukville, Wisconsin 

Savannah, Georgia 
 

ALUMINUM	 164 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. U.S. Producers of Selected Aluminum Compoundsa 

Annual capacity 

Company Location (103 metric tons)b 

Springfield, Tennessee 

Tacoma, Washington 

Tampa, Florida 

Toledo, Ohio 

Vancouver, Washington 

Wisconsin Rapids, Wisconsin 

GEO Specialty Chemicals, Inc., Aluminum Bastrop, Louisiana 

Products Group 

Chattanooga, Tennessee 

Childersburg, Alabama 

Counce, Tennessee 

Demopolis, Alabama 

De Ridder, Louisiana 

Georgetown, South Carolina 

Monticello, Mississippi 

Pennington, Alabama 

Plymouth, North Carolina 

Savannah, Georgia 

W. R. Grace & Co., Grace Davison	 Curtis Bay, Maryland 

Lake Charles, Louisiana 

Holland Company, Inc. Adams, Massachusetts 

Kemira Companies, Inc. Antioch, California 

Savannah, Georgia 

Spokane, Washington 

Mallinckrodt Baker, Inc. Paris, Kentucky 

Mallinckrodt, Inc., Pharmaceuticals Group St. Louis, Missouri 

National Alum Corporation Woodbine, Georgia 

Puerto Rico Alum Corporation Penuelas, Puerto Rico 

Rhodia, Inc., Services & Specialties Division Dominguez, California 

Portland, Oregon 

Russ Chemical Company, Inc. Odessa, Texas 

Southern Ionics, Inc. Baton Rouge, Louisiana 

Calhoun, Tennessee 

Chickasaw, Alabama 

Pasadena, Texas 

Westlake, Louisiana 

West Point, Mississippi 

Thatcher Company	 Henderson, Nevada 

Missoula, Montana 

Salt Lake City, Utah 
 

 

 

ALUMINUM	 165 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. U.S. Producers of Selected Aluminum Compoundsa 

Annual capacity 

Company Location (103 metric tons)b 

U.S. Aluminate Company, Inc.	 Fairfield, Ohio 

Michigan City, Indiana 

Sodium aluminosilicate 

Albemarle Corporation Pasadena, Texas 

W.R. Grace & Co., Grace Division	 Curtis Bay, Maryland 

Lake Charles, Louisiana 

Huber Engineered Materials	 Etowah, Tennessee 

Havre de Grace, Maryland 

Longview, Washington 

The PQ Corporation, Zeolyst and Catalyst Kansas City, Kansas 

Division 

UOP, LLC Chickasaw, Alabama 

Zeolyst International Kansas City, Kansas 

Sodium aluminum phosphate 

ICL Performance Products L.P. Carondelet, Missouri 

Innophos, Inc. Chicago Heights, Illinois 

Nashville, Tennessee 

a

Derived from SRI 2007
 b

SRI Consulting estimates as of February 1, 2007; annual capacities were only reported for aluminum chloride 

(anhydrous), aluminum chloride (hydrous), and aluminum fluoride.

d

Unit is currently idle.
 c

Capacities are on 100% AlCl3 basis.
 e

Capacities, which are expressed as 100% AlCl3, are nominal and easily expandable.
 f

Aluminum fluoride is reclaimed from refinery operations in small quantities.
 g

Manufacturers for aluminum phosphide were obtained from EPA 1998.
 
 

 

 

 

 

 

 

 

 

ALUMINUM 166 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Aluminum oxide is produced during the recovery of bauxite, which is crushed, ground, and kiln dried, 

followed by leaching with sodium hydroxide, forming sodium aluminate, from which alumina trihydrate 

is precipitated and calcined (Bayer process). Aluminum sulfate obtained from coal mine waste waters can 

be reduced to aluminum oxide (HSDB 2007; Lewis 2001). 

Aluminum phosphide can be manufactured in a high degree of purity, by heating aluminum and 

phosphorus. It can also be prepared from red phosphorus and aluminum powder, or from aluminum and 

zinc phosphide (HSDB 2007; O’Neil et al. 2001). 

Aluminum sulfate is manufactured by reacting freshly precipitated pure aluminum hydroxide, bauxite, or 

kaolin, with an appropriate quantity of sulfuric acid. The resulting solution is evaporated and allowed to 

crystallize. Aluminum sulfate can also be produced by the treatment of pure kaolin or aluminum 

hydroxide or bauxite with sulfuric acid. The insoluble silic acid is removed by filtration and the sulfate is 

obtained by crystallization. It can be prepared similarly from waste coal mining shale and sulfuric acid 

(HSDB 2007; Lewis 2001). 

Table 5-3 lists the facilities in each state that manufacture or process aluminum (fume or dust), the 

intended use, and the range of maximum amounts of aluminum that are stored on site. Table 5-4 lists the 

facilities in each state that manufacture or process aluminum oxide (fibrous form), the intended use, and 

the range of maximum amounts of aluminum oxide that are stored on site. The data listed in Tables 5-3 

and 5-4 are derived from the Toxics Release Inventory (TRI05 2007). Only certain types of facilities 

were required to report (EPA 1995). Therefore, this is not an exhaustive list. 

5.2 IMPORT/EXPORT 

In 2006, nearly all of the 12.3 million metric tons of bauxite used in the United States was imported. 

Domestic mines have supplied <1% of the U.S. requirements for bauxite for many years. Import sources 

for bauxite (2002–2005) are Jamaica (31%), Guinea (30%), Brazil (17%), Guyana (12%), and other 

(10%). Import sources for alumina (2002–2005) are Australia (19%), Suriname (29%), Jamaica (9%), 

and other (12%). More than 90% of the bauxite consumed in the United States in 2006 was converted to 

alumina (USGS 2007a, 2007d). 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 167 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. Facilities that Produce, Process, or Use Aluminum (Fume or Dust) 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AK 1 10,000 99,999 12 

AL 37 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

AR 39 0 499,999,999 1, 3, 4, 5, 6, 7, 8, 11, 12, 13, 14 

AZ 17 0 9,999,999 1, 3, 4, 5, 6, 7, 8, 11, 12, 13 

CA 71 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CO 11 1,000 999,999 1, 2, 4, 5, 8, 11, 12 

CT 20 0 9,999,999 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

DE 4 1,000 9,999 2, 3, 4, 6, 7, 8, 11 

FL 15 0 999,999 1, 5, 7, 8, 9, 11, 12 

GA 21 0 9,999,999 1, 2, 3, 4, 5, 7, 8, 9, 11, 12, 13, 14 

IA 41 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 

ID 7 10,000 999,999 1, 3, 4, 5, 7, 12, 13 

IL 93 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

IN 113 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

KS 25 0 9,999,999 1, 2, 3, 5, 7, 8, 9, 10, 11, 12 

KY 63 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

LA 16 0 9,999,999 1, 5, 6, 7, 8, 10, 11, 12, 13 

MA 10 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 

MD 13 1,000 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9 

ME 5 100 99,999 1, 3, 4, 5, 8, 9, 12 

MI 80 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MN 28 100 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

MO 49 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MS 16 0 9,999,999 1, 3, 5, 7, 8, 10, 11, 12 

NC 39 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

ND 2 1,000 9,999 1, 5, 8 

NE 5 1,000 99,999 1, 5, 6, 7, 8, 11, 12 

NH 3 100 499,999,999 8 

NJ 52 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13 

NV 11 100 499,999,999 1, 2, 3, 5, 7, 8, 9, 10, 12, 13 

NY 36 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 12 

OH 120 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OK 26 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13 

OR 29 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

PA 105 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

PR 6 100 99,999 4, 8, 12 

RI 3 1,000 999,999 7, 8, 9 

SC 29 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12 

TN 60 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 
 

 

 

 

 

 

 

 

ALUMINUM 168 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. Facilities that Produce, Process, or Use Aluminum (Fume or Dust) 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

TX 64 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

UT 18 0 9,999,999 1, 4, 5, 7, 8, 11, 12, 13 

VA 27 0 999,999 1, 2, 3, 5, 7, 8, 11, 12 

VT 3 0 999,999 8, 11, 12 

WA 20 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13 

WI 49 0 499,999,999 1, 2, 3, 5, 6, 7, 8, 9, 11, 12, 13, 14 

WV 17 0 9,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12 

WY 1 1,000 9,999 7 

a

Post office state abbreviations used b

Amounts on site reported by facilities in each state 

c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

Source: TRI05 2007 (Data are from 2005) 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 169 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-4. Facilities that Produce, Process, or Use Aluminum Oxide 

(Fibrous Forms) 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

AK 2 10,000 999,999 10 

AL 56 1,000 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13 

AR 41 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

AZ 16 1,000 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13 

CA 96 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

CO 13 100 9,999,999 2, 5, 7, 8, 10, 11, 12, 13 

CT 35 0 99,999,999 2, 3, 4, 7, 8, 10, 11, 12 

DE 5 10,000 9,999,999 6, 7, 8, 10 

FL 24 1,000 9,999,999 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

GA 59 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

HI 3 10,000 999,999 10, 12 

IA 21 100 49,999,999 1, 2, 3, 4, 5, 7, 8, 11, 12 

IL 89 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

IN 89 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

KS 25 100 9,999,999 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12 

KY 55 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

LA 47 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MA 38 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MD 22 1,000 499,999,999 1, 2, 3, 4, 5, 6, 7, 10, 11, 12, 13 

ME 7 1,000 999,999 6, 7, 8, 11, 12 

MI 67 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MN 27 100 99,999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12 

MO 56 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MS 22 1,000 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

MT 11 0 499,999,999 2, 3, 6, 10, 11, 12 

NC 50 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

ND 4 1,000 9,999,999 7, 10 

NE 10 1,000 999,999 2, 4, 8, 10, 11, 12, 13 

NH 12 1,000 499,999,999 1, 2, 3, 4, 7, 8, 9, 11, 12 

NJ 45 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

NM 6 1,000 999,999 7, 8, 10, 11, 12 

NV 3 100 999,999 1, 5, 6, 8, 9, 10 

NY 78 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

OH 145 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

OK 41 1,000 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13 

OR 14 100 99,999,999 2, 3, 4, 6, 8, 10, 11, 12 

PA 115 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

PR 9 100 9,999,999 2, 3, 7, 8, 10, 11, 12 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 170 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-4. Facilities that Produce, Process, or Use Aluminum Oxide 

(Fibrous Forms) 

Minimum Maximum 

Number of amount on site amount on site 

Statea facilities in poundsb in poundsb Activities and usesc 

RI 2 10,000 99,999 2, 3, 7 

SC 42 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12 

SD 4 1,000 99,999 5, 8, 11 

TN 70 100 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

TX 103 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

UT 19 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13 

VA 30 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

VI 1 1,000,000 9,999,999 10 

VT 6 1,000 99,999 8, 11, 12 

WA 38 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

WI 43 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

WV 34 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

WY 5 10,000 999,999 6, 10, 11 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state c

Activities/Uses: 

1. Produce 6. Impurity 11. Chemical Processing Aid 

2. Import 7. Reactant 12. Manufacturing Aid 

3. Onsite use/processing 8. Formulation Component 13. Ancillary/Other Uses 

4. Sale/Distribution 9. Article Component 14. Process Impurity 

5. Byproduct 10. Repackaging 

Source: TRI05 2007 (Data are from 2005) 
 

 

 

 

 

 

 

ALUMINUM 171 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.3 USE 

In 2006, transportation accounted for an estimated 40% of domestic consumption of aluminum, 

predominantly as automotive applications, with the remainder used in packaging, 28%; building, 13%; 

consumer durables, 7%; electrical, 5%; and other, 7% (USGS 2007c). 

Aluminum chloride, anhydrous form, is used as an acid catalyst (especially in Friedel-Crafts-type 

reactions), as a chemical intermediate for other aluminum compounds, in the cracking of petroleum, in the 

manufacture of rubbers and lubricants, and as an antiperspirant. The hexahydrate form is used in 

preserving wood, disinfecting stables and slaughterhouses, in deodorants and antiperspirants, in cosmetics 

as a topical astringent, in refining crude oil, dyeing fabrics, and manufacturing parchment paper (O’Neil 

et al. 2001). 

Aluminum chlorohydrate is an ingredient in commercial antiperspirant and deodorant preparations and is 

also used for water purification and treatment of sewage and plant effluent (Lewis 2001) 

Aluminum hydroxide (alumina trihydrate) is used as an adsorbent, emulsifier, ion-exchanger, mordant in 

dyeing, and filtering medium. It is also used in the manufacturing of glass, paper, ceramics and pottery, 

printing inks, lubricating compositions, detergents, in the waterproofing of fabrics, in antiperspirants, 

dentifrices, and as a vaccine adjuvant (Baylor et al. 2002; Lewis 2001; O’Neil et al. 2001). Aluminum 

hydroxide is used as a flame retardant in the interiors of automobiles, commercial upholstered furniture, 

draperies, wall coverings, and carpets (Subcommittee on Flame-Retardant Chemicals 2000). Aluminum 

hydroxide is used as an antacid (O’Neil et al. 2001). Finely divided (0.1–0.6 microns) aluminum 

hydroxide is used for rubber reinforcing agent, paper coating, filler, and cosmetics (Lewis 2001). 

Aluminum hydroxide is also used pharmaceutically, as an antihyperphosphatemic, to lower the plasma 

phosphorus levels of patients with renal failure (O’Neil et al. 2001). 

Aluminum nitrate is used in textiles (mordant), leather tanning, the manufacturing of incandescent 

filaments, catalysts in petroleum refining, nucleonics, anticorrosion agent, nitrating agent, and 

antiperspirants (Lewis 2001; O’Neil et al. 2001). 

In 2006, 96% of the bauxite consumed in the United States was refined to alumina (aluminum oxide), 

with the remaining 4% consumed in nonmetallurgical uses, such as abrasives, chemicals, and refactories. 

Of the total alumina used in the United States in 2006, approximately 87% was used for primary 
 

 

 

 

 

 

 

 

ALUMINUM 172 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

aluminum smelters and the remainder was used for nonmetallurgical uses, including abrasives, chemicals, 

refactories, and in specialty industries (USGS 2007a, 2007d). Other uses of aluminum oxide are in the 

manufacture of ceramics, electrical insulators, catalyst and catalyst supports, paper, spark plugs, crucibles 

and laboratory works, adsorbent for gases and water vapors, chromatographic analysis, fluxes, light bulbs, 

artificial gems, heat resistant fibers, food additive (dispersing agent), and in hollow-fiber membrane units 

used in water desalination, industrial ultrafiltration, and hemodialysis (HSDB 2007; Lewis 2001). 

Another application of aluminum oxide, which may have wide occupational use in the future, is as a 

dosimeter for measuring personnel radiation exposure (McKeever et al. 1995; Radiation Safety Guide 

1999; Radiation Safety Newsletter 1998). 

Aluminum phosphate is used in ceramics, dental cements, cosmetics, paints and varnishes, 

pharmaceuticals (antacid), and in paper and pulp industries (Lewis 2001; O’Neil et al. 2001). It is also 

used as a vaccine adjuvant (Baylor et al. 2002; Malakoff 2000). Aluminum phosphate, as basic sodium 

aluminum phosphate (SALP), is used as an emulsifying agent in pasteurized processed cheese, cheese 

food, and cheese spread. Acidic SALP is used as a leavening agent in cereal foods and related products, 

such as self-rising flour, prepared cake mixes, pancakes, waffles, and refrigerated or frozen dough or 

batter products (Chung 1992; Saiyed and Yokel 2005). 

Aluminum phosphide is a fumigant used primarily for indoor fumigation of raw agricultural commodities, 

animal feeds, processed food commodities, and non-food commodities in sealed containers or structures 

to control insects, and for outdoor fumigation of burrows to control rodents and moles in nondomestic 

areas, noncropland, and agricultural areas. Aluminum phosphide reacts with the moisture in the 

atmosphere to produce phosphine gas, which is the substance that is active as a pesticide. Based on 

available pesticide survey usage information for 1987–1996, the estimated annual usage of aluminum 

phosphide is about 1.6 million pounds active ingredient. Major uses of aluminum phosphide include 

fumigation of wheat, peanuts, and stored corn. It was noted that usage estimates for aluminum phosphide 

are not precise due to scarcity of usage data sources for postharvest agriculture and non-agriculture 

uses/sites. All aluminum phosphide containing products have been classified as restricted use (EPA 

1998). According to the National Pesticide Information Retrieval System, there are five active registrants 

for aluminum phosphide (NPIRS 2008). 

Aluminum sulfate (alum) is used in leather tanning, sizing paper, as a mordent in dyeing, water 

purification, fireproofing and waterproofing of cloth, clarifying oils and fats, treating sewage, 

waterproofing concrete, deodorizing and decolorizing of petroleum, antiperspirants, and agricultural 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 173 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

pesticide. It is also used as a food additive, a foaming agent in fire foams, and in the manufacturing of 

aluminum salts (Lewis 2001; O’Neil et al. 2001). Aluminum sulfate, as sodium aluminum sulfate, is a 

component of household baking powder (Chung 1992). Alum is also used as a vaccine adjuvant (Baylor 

et al. 2002; Malakoff 2000). Aluminum potassium sulfate (potash alum) is used in dyeing (mordant), 

paper, matches, paints, tanning agents, waterproofing agents, aluminum salts, food additives, baking 

powder, water purification, astringent, and cement hardener (Lewis 2001). Aluminum ammonium sulfate 

(ammonium alum) is used in dyeing (mordant), water and sewage purification, sizing paper, retanning 

leather, clarifying agent, food additive, the manufacture of lakes and pigments, and fur treatment (Lewis 

2001). 

Other aluminum compounds that are used as food additives include aluminum silicates (anticaking 

agents) and aluminum color additives (lakes) (Saiyed and Yokel 2005; Soni et al. 2001). 

5.4 DISPOSAL 

Production of finished aluminum products by industrial facilities typically results in the generation of 

very large amounts of solid aluminum hydroxide anodizing residues (Saunders 1988). These aluminumanodizing residues are currently classified as nonhazardous under the Federal Resource Conservation and 

Recovery Act (RCRA) regulations. These residues are typically dewatered to reduce the volume of waste 

prior to being landfilled. However, the heavy metal content of these solid waste residues can be of 

concern, especially in production processes using two-step anodizing systems that employ solutions 

containing elevated heavy metal concentrations. For these types of plants, Saunders (1988) has proposed 

implementation of a caustic-etch recovery system that will limit both the volume of aluminum-anodizing 

residue and the heavy metal content of the residue. Additional information on regulations and standards 

for aluminum and aluminum compounds is summarized in Chapter 8. 

Approximately 24.7x106 and 1.15x105 pounds of aluminum (fume or dust) and aluminum oxide (fibrous 

forms) were reported for on-site disposal and other releases in 2004. On-site disposal or other releases 

include emissions to the air, discharges to bodies of water, disposal at the facility to land, and disposal in 

underground injection wells. Approximately 23.7x106 and 1.20x106 pounds of aluminum (fume or dust) 

and aluminum oxide (fibrous forms), respectively, were reported for off-site disposal and other releases in 

2004. An off-site disposal or other release is a discharge of a toxic chemical to the environment that 

occurs as a result of a facility’s transferring a waste containing a TRI chemical off-site for disposal or 
 

 

 

ALUMINUM 174 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

other release (TRI04 2006). The TRI data should be used with caution because only certain types of 

facilities are required to report (EPA 2005). This is not an exhaustive list. 

In the United States, about 3 million metric tons of aluminum was recovered from purchased scrap in 

2006, with 64% of this coming from new (manufacturing) scrap and 36% from old scrap (discarded 

aluminum products). Aluminum used beverage cans accounted for about 54% of the reported old scrap 

consumption in 2006. According to the Aluminum Association, Inc., the recycling rate for used 

aluminum beverage cans in 2004 was 51.6% (USGS 2007b, 2007c). 
 

 

 

 

 

 

 

ALUMINUM 175 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Aluminum has been identified in at least 596 of the 1,699 hazardous waste sites that have been proposed 

for inclusion on the EPA National Priorities List (NPL) (HazDat 2008). However, the number of sites 

evaluated for aluminum is not known. The frequency of these sites can be seen in Figure 6-1. Of these 

sites, 590 are located within the United States, 2 are located in Guam, 3 are located in the Commonwealth 

of Puerto Rico, and 1 is located in the Virgin Islands (not shown). 

Aluminum is the most abundant metal and the third most abundant element in the earth’s crust, 

comprising about 8.8% by weight (88 g/kg). It is never found free in nature and is found in most rocks, 

particularly igneous rocks as aluminosilicate minerals (Lide 2005; Staley and Haupin 1992). Aluminum 

is also present in air, water, and many foods. Aluminum enters environmental media naturally through 

the weathering of rocks and minerals. Anthropogenic releases are in the form of air emissions, waste 

water effluents, and solid waste primarily associated with industrial processes, such as aluminum 

production. Because of its prominence as a major constituent of the earth's crust, natural weathering 

processes far exceed the contribution of releases to air, water, and land associated with human activities 

(Lantzy and MacKenzie 1979). 

The behavior of aluminum in the environment depends upon its coordination chemistry and the 

characteristics of the local environment, especially pH. The major features of the biogeochemical cycle 

of aluminum include leaching of aluminum from geochemical formations and soil particulates to aqueous 

environments, adsorption onto soil or sediment particulates, and wet and dry deposition from the air to 

land and surface water. 

Generally, aluminum is not bioaccumulated to a significant extent. However, certain plants can 

accumulate high concentrations of aluminum. For example, tea leaves may contain very high 

concentrations of aluminum, >5,000 mg/kg in old leaves (Dong et al. 1999). Other plants that may 

contain high levels of aluminum include Lycopodium (Lycopodiaceae), a few ferns, Symplocos 

(Symplocaceae), and Orites (Proteaceae) (Jansen et al. 2002). Aluminum does not appear to accumulate 

to any significant degree in cow's milk or beef tissue and is, therefore, not expected to undergo 

biomagnification in terrestrial food chains (DOE 1984). Similarly, because of its toxicity to many aquatic 

organisms, including fish, aluminum does not bioconcentrate in aquatic organisms to any significant 

degree (Rosseland et al. 1990). 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

Background concentrations of aluminum in rural air typically range from 0.005 to 0.18 μg/m3 (Hoffman 

et al. 1969; Pötzl 1970; Sorenson et al. 1974), whereas concentrations in urban and industrial areas can be 

considerably higher, ranging from 0.4 to 8.0 μg/m3 (Cooper et al. 1979; Dzubay 1980; Kowalczyk et al. 

1982; Lewis and Macias 1980; Moyers et al. 1977; Ondov et al. 1982; Pillay and Thomas 1971; Sorenson 

et al. 1974; Stevens et al. 1978). Concentrations of aluminum are highly variable in drinking water, 

ranging from <0.001 to 1.029 mg/L (Schenk et al. 1989). The use of alum (aluminum sulfate) as a 

flocculent in water treatment facilities typically leads to high aluminum concentrations in finished waters 

(DOI 1970; Letterman and Driscoll 1988; Miller et al. 1984a). In a survey of 186 community water 

systems, the median aluminum concentration in finished water receiving coagulation treatment using 

alum was 0.112 mg/L, compared to 0.043 mg/L in finished water that received no coagulation treatment 

(Miller et al. 1984a). Dissolved aluminum concentrations in surface and groundwater vary with pH and 

the humic acid content of the water. High aluminum concentrations in natural water occur only when the 

pH is <5; therefore, concentrations in most surface water are very low. 

Since aluminum is ubiquitous in the environment, the general population will be exposed to aluminum by 

the inhalation of ambient air and the ingestion of food and water. The consumption of foods containing 

aluminum-containing food additives are a major sources of aluminum in the diet (Saiyed and Yokel 2005; 

Soni et al. 2001). The use of other consumer items such as antiperspirants, cosmetics, internal analgesics 

(buffered aspirins), anti-ulcerative medications, antidiarrheals, and antacids that also contain aluminum 

compounds will result in exposure to aluminum. The intake of aluminum from food and drinking water is 

low, especially compared with that consumed by people taking aluminum-containing medicinal 

preparations. Daily intakes of aluminum from food range from 3.4 to 9 mg/day (Biego et al. 1998; MAFF 

1999; Pennington and Schoen 1995), whereas aluminum-containing medications contain much higher 

levels of aluminum, for example 104–208 mg of aluminum per tablet/capsule/5 mL dose for many 

antacids (Zhou and Yokel 2005). While aluminum is naturally present in food and water, the greatest 

contribution to aluminum in food and water by far is the aluminum-containing additives used in water 

treatment and processing certain types of food such as grain-based products and processed cheese. 

Aluminum has no known physiological role in the human body (Nayak 2002). 

The aluminum content of human breast milk generally ranged from 9.2 to 49 μg/L (Fernandez-Lorenzo et 

al. 1999; Hawkins et al. 1994; Koo et al. 1988; Simmer et al. 1990; Weintraub et al. 1986). Soy-based 

infant formulas contain higher concentrations of aluminum, as compared to milk-based infant formulas or 

breast milk. Recent reports provide average aluminum concentrations of 460–930 μg/L for soy-based 
 

 

 

 

 

 

 

ALUMINUM 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

infant formulas and 58–150 μg/L for milk-based formulas (Fernandez-Lorenzo et al. 1999; Ikem et al. 

2002; Navarro-Blasco and Alvarez-Galindo 2003). 

Occupational exposures to aluminum occur during the mining and processing of aluminum ore into metal, 

recovery of scrap metal, production and use of aluminum compounds and products containing these 

compounds, and in aluminum welding. Individuals living in the vicinity of industrial emission sources 

and hazardous waste sites; individuals with chronic kidney failure requiring long-term dialysis or 

treatment with phosphate binders; patients requiring intravenous fluids; infants, especially premature 

infants fed soy-based formula containing high levels of aluminum; and individuals consuming large 

quantities of antacids, anti-ulcerative medications, antidiarrheal medications may also be exposed to high 

levels of aluminum. 

According to the Toxic Chemical Release Inventory, in 2005, total releases of aluminum (fume or dust) to 

the environment (including air, water, and soil) from 329 large processing facilities were 

45.6 million pounds (~2.07x104 metric tons) (TRI05 2007). In addition, in 2005, total releases of 

aluminum oxide (fibrous forms) to the environment (including air, water, and soil) from 59 large 

processing facilities were 2.59 million pounds (~1180 metric tons) (TRI05 2007). Tables 6-1 and 6-2 list 

amounts released from these facilities grouped by state. The TRI data should be used with caution 

because only certain types of facilities are required to report (EPA 2005). This is not an exhaustive list. 

6.2 RELEASES TO THE ENVIRONMENT 

The Toxics Release Inventory (TRI) data should be used with caution because only certain types of 

facilities are required to report (EPA 2005). This is not an exhaustive list. Manufacturing and processing 

facilities are required to report information to the TRI only if they employ 10 or more full-time 

employees; if their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 

1081, and 1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the 

purpose of generating electricity for distribution in commerce), 4931 (limited to facilities that combust 

coal and/or oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to 

facilities that combust coal and/or oil for the purpose of generating electricity for distribution in 

commerce), 4953 (limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 

5169, 5171, and 7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities 

primarily engaged in solvents recovery services on a contract or fee basis); and if their facility produces, 
ALUMINUM 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Aluminum (Fume or Dust)a
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

AK 1 0 0 0 0 1 0 0 0 

AL 4 2,453 0 0 45,887 48,344 2,453 45,887 48,340 

AR 3 0 0 0 0 3 0 750 750 

AZ 4 7,167 0 0 230,729 237,900 7,217 230,679 237,896 

CA 16 182,017 0 0 1,662,654 1,844,688 1,802,363 42,364 1,844,727 

CO 1 1,500 0 0 53,058 54,559 1,500 53,058 54,558 

CT 2 0 0 0 0 2 0 0 0 

FL 5 1,624 0 0 23 1,652 1,624 23 1,647 

GA 10 37,680 0 0 108,219 145,909 37,680 108,871 146,551 

IA 8 11,570 0 0 43,052 54,630 11,570 43,052 54,622 

ID 2 2,864 0 0 653,345 656,211 518,203 138,006 656,209 

IL 16 62,008 0 0 520,607 582,631 62,008 525,882 587,890 

IN 29 149,220 0 0 10,023,429 10,172,678 149,225 10,024,174 10,173,399 

KS 3 0 0 0 0 3 0 0 0 

KY 13 254,892 0 0 2,799,380 3,054,285 2,419,281 634,991 3,054,272 

LA 4 1,184 0 0 13 1,201 1,197 0 1,197 

MA 2 No dataNo data No data No data No data No data 0 0 

MD 2 0 0 0 0 2 0 0 0 

MI 16 17,862 0 0 1,215,365 1,233,243 17,862 1,224,508 1,242,370 

MN 6 58,268 0 0 157,233 215,507 58,268 157,277 215,545 

MO 8 29,495 0 0 1,941,390 1,970,893 1,828,685 7,037,274 8,865,959 

MS 1 0 0 0 550 551 0 550 550 

NC 8 62,432 0 0 55,340 117,780 63,182 54,590 117,772 

NE 2 0 0 0 31,105 31,107 21,263 9,842 31,105 

NJ 6 4,413 0 0 5,222 9,641 4,413 5,222 9,635 

NM 1 No dataNo data No data No data No data No data 0 0 

NV 4 259 0 0 330,084 330,347 330,343 0 330,343 

NY 7 58,438 312 0 198,222 256,979 60,436 213,027 273,463 

OH 33 50,159 2 0 2,170,512 2,220,706 253,161 2,237,892 2,491,053 

OK 9 9,654 0 0 447,920 457,583 10,416 447,158 457,574 

OR 4 646 0 0 1,295 1,945 646 1,295 1,941 

PA 23 8,594 0 0 294,833 303,450 8,866 317,627 326,493 

RI 1 No dataNo data No data No data No data No data 0 0 

SC 4 7,841 0 0 750 8,595 7,841 1,500 9,341 

TN 21 93,021 0 0 887,911 980,953 185,281 795,651 980,932 

TX 19 89,879 0 0 7,670,584 7,760,481 2,590,719 5,171,544 7,762,262 
 

ALUMINUM 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that Produce, Process, or
 

Use Aluminum (Fume or Dust)a
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

UT 6 187 0 0 372,634 372,827 147,182 225,639 372,821 

VA 2 137 0 0 1,000 1,139 137 1,000 1,137 

WA 4 846 0 0 128,819 129,669 846 129,421 130,267 

WI 14 75,933 0 0 289,933 365,880 75,933 290,099 366,032 

WV 5 3,112 0 0 4,732,012 4,735,129 3,112 4,732,012 4,735,124 

Total 329 1,285,354 314 0 37,073,110 38,359,108 10,682,912 34,900,865 45,583,777 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used.
 d

Number of reporting facilities.

e

The sum of fugitive and point source releases are included in releases to air by a given facility.
 f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal
 

and metal compounds).

g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills.

i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for
 

disposal, unknown

j

The sum of all releases of the chemical to air, land, water, and underground injection wells.

k

Total amount of chemical transferred off-site, including to POTWs.
 

RF = reporting facilities; UI = underground injection 

Source: TRI05 2007 (Data are from 2005) 
ALUMINUM 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or
 

Use Aluminum Oxide (Fibrous Forms)a
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

AL 2 0 0 0 0 0 0 0 0 

AR 1 0 0 0 0 0 0 0 0 

CA 1 0 No data 0 0 0 0 0 0 

CO 1 0 5 0 480 2,749 485 2,749 3,234 

CT 1 0 0 0 0 0 0 0 0 

GA 2 16 175 0 2,957 0 191 2,957 3,148 

IA 2 0 0 0 40,320 0 0 40,320 40,320 

IL 5 76 0 0 122,002 22,660 76 144,662 144,738 

IN 3 901 250 0 5 10 1,156 10 1,166 

KY 3 243 0 0 26,631 0 243 26,631 26,874 

LA 2 0 0 0 0 0 0 0 0 

MI 2 0 0 0 375,000 0 0 375,000 375,000 

MO 1 250 0 0 750 0 1,000 0 1,000 

NC 4 56 10 0 60,797 4,342 61 65,144 65,205 

NE 1 2 0 0 20 0 22 0 22 

NM 1 0 0 0 0 0 0 0 0 

NY 2 250 0 0 0 29,808 250 29,808 30,058 

OH 2 980 0 0 110,958 0 980 110,958 111,938 

OK 1 0 No data 0 0 0 0 0 0 

PA 6 247 0 0 178,893 6,781 247 185,674 185,920 

SC 2 14 0 7 23,556 424 14 23,987 24,001 

TN 4 3 0 0 0 0 3 0 3 

TX 4 11 0 0 431,166 0 11 431,166 431,177 

VA 2 500 0 0 37,159 0 37,409 250 37,659 

WI 3 260 0 0 1,059,128 0 1,059,138 250 1,059,388 
 

ALUMINUM 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that Produce, Process, or
 

Use Aluminum Oxide (Fibrous Forms)a
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

WV 1 0 0 0 48,000 0 48,000 0 48,000 

Total 59 3,810 440 7 2,517,822 66,774 1,149,287 1,439,565 2,588,852 

a

The TRI data should be used with caution since only certain types of facilities are required to report. This is not an 

exhaustive list. Data are rounded to nearest whole number.
 b

Data in TRI are maximum amounts released by each facility.
 c

Post office state abbreviations are used.
 d

Number of reporting facilities.

e

The sum of fugitive and point source releases are included in releases to air by a given facility.
 f

Surface water discharges, waste water treatment-(metals only), and publicly owned treatment works (POTWs) (metal
 

and metal compounds).

g

Class I wells, Class II-V wells, and underground injection. h

Resource Conservation and Recovery Act (RCRA) subtitle C landfills; other on-site landfills, land treatment, surface 

impoundments, other land disposal, other landfills.

i

Storage only, solidification/stabilization (metals only), other off-site management, transfers to waste broker for
 

disposal, unknown

j

The sum of all releases of the chemical to air, land, water, and underground injection wells.

k

Total amount of chemical transferred off-site, including to POTWs.
 

RF = reporting facilities; UI = underground injection 

Source: TRI05 2007 (Data are from 2005) 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

imports, or processes ≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI 

chemical in a calendar year (EPA 2005). 

6.2.1 Air 

Estimated releases of 1.29 million pounds (~586 metric tons) of aluminum (fume or dust) to the 

atmosphere from 329 domestic manufacturing and processing facilities in 2005, accounted for about 2.8% 

of the estimated total environmental releases from facilities required to report to the TRI (TRI05 2007). 

Estimated releases of 3,810 pounds (~1.73 metric tons) of aluminum oxide (fibrous forms) to the 

atmosphere from 59 domestic manufacturing and processing facilities in 2005, accounted for about 1.5% 

of the estimated total environmental releases from facilities required to report to the TRI (TRI05 2007). 

These releases are summarized in Tables 6-1 and 6-2. 

Aluminum is released to the environment by both natural processes and anthropogenic sources. Because 

of its prominence as a major constituent of the earth's crust, natural processes far exceed the contribution 

of anthropogenic releases to the environmental distribution of aluminum (Lantzy and MacKenzie 1979). 

Anthropogenic releases are primarily to the atmosphere. The largest source of airborne aluminumcontaining particulates is the flux of dust from soil and the weathering of rocks (Lee and Von Lehmden 

1973; Sorenson et al. 1974). In addition, aluminum-containing dust is generated by volcanic activity 

(Varrica et al. 2000). Human activities, such as mining and agriculture, contribute to this wind-blown 

dust (Eisenreich 1980; Filipek et al. 1987). About 13% of atmospheric aluminum is attributed to 

anthropogenic emissions (Lantzy and MacKenzie 1979). The major anthropogenic sources of aluminumcontaining particulate matter include coal combustion, aluminum production, and other industrial 

activities, such as smelting, that process crustal minerals (Lee and Von Lehmden 1973). Aluminum 

concentrations in air particulate emissions from iron and steel foundries and brass and bronze refineries 

range from about 100 to 1,000 ppm (Lee and Von Lehmden 1973). Que Hee et al. (1982) also found that 

aluminum was one of the most abundant elements quantified in coal stack emissions from power plants 

located in both the eastern and western United States. In addition, in U.S. cities, motor vehicle emissions 

contribute an estimated 0.9–9% of the observed elemental concentration of aluminum in these 

atmospheres (Ondov et al. 1982). 

Aluminum has been identified in air samples collected at 14 of the 596 NPL hazardous waste sites where 

it has been detected in some environmental media (HazDat 2008). 
 

 

 

 

 

 

 

 

 

ALUMINUM 184 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.2 Water 

Estimated releases of 314 pounds (~0.14 metric tons) of aluminum (fume or dust) to surface water from 

329 domestic manufacturing and processing facilities in 2005, accounted for about 0.0007% of the 

estimated total environmental releases from facilities required to report to the TRI (TRI05 2007). 

Estimated releases of 440 pounds (~0.20 metric tons) of aluminum oxide (fibrous forms) to surface water 

from 59 domestic manufacturing and processing facilities in 2005, accounted for about 0.017% of the 

estimated total environmental releases from facilities required to report to the TRI (TRI05 2007). These 

releases are summarized in Tables 6-1 and 6-2. 

Aluminum occurs ubiquitously in natural waters as a result of the weathering of aluminum-containing 

rocks and minerals. Of the known geochemical responses to environmental acidification, the best 

documented is the mobilization of aluminum from terrestrial to aquatic environments (Campbell et al. 

1992). This mobilization of aluminum is often episodic in nature and is associated with pH depressions 

(acidification) occurring during the spring snowmelt or associated with erosion from specific storm events 

(Campbell et al. 1992; Nelson and Campbell 1991; Rosseland et al. 1990). 

Aluminum concentrations in surface waters can be increased directly or indirectly by human activity 

through industrial and municipal discharges, surface run-off, tributary inflow, groundwater seepage, and 

wet and dry atmospheric deposition (Eisenreich 1980). For example, aluminum is released to surface 

waters in the effluent from bauxite processing and aluminum manufacturing facilities at concentrations 

that can be toxic to aquatic life (His et al. 1996; Trieff et al. 1995). However, the effluents of these 

facilities typically contain not only aluminum, but also a complex mixture of heavy metals such as iron, 

chromium, and mercury, as well as minerals, silica, and other compounds, and synergistic effects of these 

metals and compounds cannot be ruled out. The use of aluminum sulfate and other aluminum compounds 

as coagulating agents in the treatment of raw drinking water supplies can significantly increase the total 

aluminum content in finished water (Cech and Montera 2000; Henshaw et al. 1993; Miller et al. 1984a; 

Qureshi and Malmberg 1985; USGS 1984b). Weathering of sulfide ores exposed to the atmosphere in 

inactive mines and tailings dumps releases large quantities of sulfuric acid and metals such as aluminum 

(Filipek et al. 1987). Increasingly, acid environments caused by such acid mine drainage or by acid rain 

will subsequently cause an increase in the dissolved aluminum content of the surrounding waters 

(Brusewitz 1984; Filipek et al. 1987). In addition, atmospheric deposition is a source of aluminum input 

to surface water. The atmospheric loading of aluminum to Lake Michigan was estimated to be 5 million 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 185 

6. POTENTIAL FOR HUMAN EXPOSURE 

kg/year, of which 74% was to the southern basin where the influence of agricultural and industrial activity 

(e.g., steel manufacturing and cement production) was greatest (Eisenreich 1980). 

Aluminum has been identified in surface water and groundwater samples collected at 251 and 391 of the 

596 NPL hazardous waste sites, respectively, where it has been detected in some environmental media 

(HazDat 2008). 

6.2.3 Soil 

Estimated releases of 37.1 million pounds (~1.68x104 metric tons) of aluminum (fume or dust) to soils 

from 329 domestic manufacturing and processing facilities in 2005, accounted for about 81% of the 

estimated total environmental releases from facilities required to report to the TRI (TRI05 2007). 

Estimated releases of 2.52 million pounds (~1,140 metric tons) of aluminum oxide (fibrous forms) to soils 

from 59 domestic manufacturing and processing facilities in 2005, accounted for about 97% of the 

estimated total environmental releases from facilities required to report to the TRI (TRI05 2007). An 

additional 7 pounds (3 kilograms ) of aluminum oxide (fibrous forms) were released via underground 

injection (TRI05 2007). These releases are summarized in Tables 6-1 and 6-2. 

Aluminum is the most abundant metal and the third most abundant element in the earth’s crust, 

comprising about 8.8% by weight (88 g/kg) (Staley and Haupin 1992). Aluminum can be released 

naturally by the weathering of aluminum-containing rocks. Aluminum is also released to soil as a major 

constituent of many mining wastes and is also contained in solid wastes from coal combustion and 

aluminum reduction and other metal processing operations (DOI 1983, 1984). Wilson et al. (2002) 

estimated that several hundred thousand pounds of aluminum containing chaff have been release to the 

Chesapeake Bay during research and training operations by the Naval Research Laboratory-Chesapeake 

Bay Detachment over the past 25 years. 

Aluminum has been identified in soil and sediment samples collected at 253 and 190 of the 596 NPL 

hazardous waste sites, respectively, where it has been detected in some environmental media (HazDat 

2008). 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 186 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Aluminum is the most abundant metal in the earth’s crust, but is never found in its elemental state in 

nature. In compounds, aluminum occurs in its only oxidation state (+3) (Lide 2005). Aluminum occurs 

widely in nature with silicates, such as mica and feldspar, as the hydroxo oxide (bauxite), and as cryolite 

(Na3AlF6) (Cotton et al. 1999). Aluminum’s behavior in the environment is strongly influenced by its 

coordination chemistry. Aluminum partitions between solid and liquid phases by reacting and 

complexing with water molecules and anions such as chloride, fluoride, sulfate, nitrate, phosphate, and 

negatively charged functional groups on humic materials and clay. 

The transport and partitioning of aluminum in the environment is determined by its chemical properties, 

as well as the characteristics of the environmental matrix that affect its solubility. At a pH >5.5, naturally 

occurring aluminum compounds exist predominantly in an undissolved form such as gibbsite, Al(OH)3, or 

as aluminosilicates except in the presence of high amounts of dissolved organic material or fulvic acid, 

which binds with aluminum and can cause increased dissolved aluminum concentrations in streams and 

lakes (Brusewitz 1984). Organic acids have been found to be important weathering agents for dissolving 

and transporting aluminum in an alpine soil environment (Litaor 1987). The ability of these organic acids 

to complex aluminum in sub-alpine soil solutions was found to increase as the pH rose from 3.8 to 

5 (Dahlgren and Ugolini 1989). In this study, dissolved aluminum was found primarily as organic 

complexes when organic carbon/metal ratios were >50 (Dahlgren and Ugolini 1989). 

In general, decreasing pH (acidification) results in an increase in mobility for monomeric forms of 

aluminum (Goenaga and Williams 1988), which is of concern with respect to the occurrence of acid rain 

and the release of acid mine drainage. Aluminum in soil solutions and surface waters in a mining region 

rich in metallic sulfides was in a labile form, as Al-SO4 and Al3+ species. Acidic conditions are created 

by the microbial oxidation of sulfides in tailing piles, resulting in sulfuric acid. In contrast, in areas not 

affected by acidification, aluminum in solution was partitioned between labile and non-labile forms, the 

latter being predominantly bound to fluorine (Alvarez et al. 1993). In soils, the most soluble form of 

aluminum under acidic conditions is nonsilicaceous, organically-bound aluminum (Mulder et al. 1989). 

In groundwater or surface water systems, an equilibrium with a solid phase form is established that 

largely controls the extent of aluminum dissolution which can occur. In acid sulfate waters resulting from 

mine drainage, gibbsite and kaolinite are not stable, and the solubility of the minerals jurbanite 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 187 

6. POTENTIAL FOR HUMAN EXPOSURE 

(Al(SO4)(OH)·H2O) or alunite (KAl3(SO4)2(OH)6) may control aluminum levels (Filipek et al. 1987). In a 

Colorado alpine watershed soil, the chemical equilibria of aluminum in interstitial water at a pH range of 

4.4–7.2 were controlled by amorphous aluminosilicate rather than gibbsite (Litaor 1987). 

In addition to the effect of pH on mobility, the type of acid entering environmental systems may also be 

important. Nitric acid was found to leach more aluminum from soil columns representative of highelevation forest floor soils than did sulfuric acid (James and Riha 1989). However, in mineral horizons 

below the forest floor, the study found that concentrations of aluminum leached by these acids did not 

differ from concentrations of aluminum leached by distilled, deionized water at a pH of 5.7. The authors 

concluded that soluble constituents from the forest floor affected the aluminum solubility in the 

underlying mineral horizons under the leaching conditions that they used. These constituents may have 

included natural buffering agents which resist changes in pH and, therefore, negate or mediate the effect 

of the acid. 

The ability of mineralized soil to control the migration of aluminum was observed in another study. 

Acidic leachate from coal waste containing aluminum was percolated through soil containing varying 

amounts of calcium carbonate (Wangen and Jones 1984). Soluble aluminum was found to decrease 

dramatically as the pH of the percolating leachate increased and aluminum oxide precipitates formed; at 

pH 6, no dissolved aluminum was measured. The authors concluded that alkalinized carbonaceous soils 

provide the best control material for acidic leachates from coal mineral wastes. 

The adsorption of aluminum onto clay surfaces can be a significant factor in controlling aluminum 

mobility in the environment, and these adsorption reactions, measured in one study at pH 3.0–4.1, have 

been observed to be very rapid (Walker et al. 1988). However, clays may act either as a sink or a source 

for soluble aluminum depending on the degree of aluminum saturation on the clay surface (Walker et al. 

1988). 

The presence of high levels of suspended solids in stream surface water during storm episodes resulted in 

higher concentrations of adsorbed aluminum than in the absence of suspended solids (Goenaga and 

Williams 1988). The increased adsorption was not strictly linear, with higher concentrations of 

suspended solids due to variations in the particle size distribution and the nature of the particles. 

Within the pH range of 5–6, aluminum complexes with phosphate and is removed from solution. 

Because phosphate is a necessary nutrient in ecological systems, this immobilization of both aluminum 
 

 

 

 

 

 

 

 

ALUMINUM 188 

6. POTENTIAL FOR HUMAN EXPOSURE 

and phosphate may result in depleted nutrient states in surface water (Brusewitz 1984). Conversely, 

aluminum has been added to a nutrient-rich lake in Sweden with some success in an effort to arrest the 

"aging process" caused by an overabundance of phosphate (Jernelov 1971). 

Aluminum salt coagulants are used in the treatment of potable drinking water, and unretained aluminum 

(approximately 11% of the added aluminum) was found to be transported through a water distribution 

system (Driscoll and Letterman 1988). 

Aluminum, as a constituent of soil, weathered rock, and solid waste from industrial processes, is 

transported through the atmosphere as windblown particulate matter and is deposited onto land and water 

by wet and dry deposition. Atmospheric loading rates of aluminum to Lake Michigan were estimated at 

5 million kg/year (Eisenreich 1980). In this study, most of the aluminum was generally associated with 

large particles that were deposited near their source. In a study, the wet and dry deposition of aluminum 

was measured biweekly for 1 year at two sites on Massachusetts Bay, Turro and Nahant. The average 

total deposition rate was 0.1 g/m2

-year, of which 29% was in rain (wet deposition) (Golomb et al. 1997). 

Plant species and cultivars of the same species differ considerably in their ability to take up and 

translocate aluminum to above-ground parts (Kabata-Pendias and Pendias 1984). Tea leaves may contain 

very high concentrations of aluminum, >5,000 mg/kg in old leaves (Dong et al. 1999). Other plants that 

may contain high levels of aluminum include Lycopodium (Lycopodiaceae), a few ferns, Symplocos 

(Symplocaceae), and Orites (Proteaceae) (Jansen et al. 2002). Aluminum is often taken up and 

concentrated in root tissue (Kabata-Pendias and Pendias 1984). In sub-alpine ecosystems, the large root 

biomass of the Douglas fir, Abies amabilis, takes up aluminum and immobilizes it, preventing large 

accumulation in above-ground tissue (Vogt et al. 1987). It is unclear to what extent aluminum is taken up 

into root food crops and leafy vegetables. An uptake factor (concentration of aluminum in the 

plant/concentration of aluminum in soil) of 0.004 for leafy vegetables and 0.00065 for fruits and tubers 

has been reported (DOE 1984), but the pH and plant species from which these uptake factors were 

derived are unclear. Based upon these values, however, it is clear that aluminum is not taken up in plants 

from soil, but is instead biodiluted. 

Transfer coefficients of 0.0002 (kg/day)-1 for uptake into milk and 0.0015 (kg/day)-1 for uptake into beef 

tissue have been reported (DOE 1984). The transfer coefficients represent the fraction of daily aluminum 

intake in feed that is transferred to a kilogram of milk or beef muscle. Based upon the above values, 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 189 

6. POTENTIAL FOR HUMAN EXPOSURE 

aluminum is not transferred to beef muscle or milk from feed to any appreciable extent and therefore 

would not be expected to bioaccumulate in terrestrial food chains. 

The potential for accumulation of aluminum has been studied in several aquatic species including fish 

(Buckler et al. 1995; Cleveland et al. 1991; Hamdy 1993; McDonald et al. 1991; Wilkinson and Campbell 

1993), amphibians (Freda and McDonald 1990), crustaceans (Madigosky et al. 1991), snails (Brooks et al. 

1992), aquatic insects (Frick and Herrmann 1990; Guerold et al. 1995; Krantzberg and Stokes 1990), and 

aquatic plants (Albers and Camardese 1993; Vuori et al. 1990). Bioconcentration of aluminum in fish is a 

function of the water quality (e.g., pH and total organic carbon) (Cleveland et al. 1989). 

Brook trout have been shown to accumulate slightly more aluminum (measured as whole-body residues) 

at pH 5.6–5.7 than at pH 6.5–6.6 (Cleveland et al. 1989). Cleveland et al. (1991) reported that the 

estimated steady-state bioconcentration factors (BCF) for aluminum in brook trout were 215, 123, and 

36 at pH 5.3, 6.1, and 7.2, respectively. When transferred to water of the same pH without added 

aluminum, brook trout eliminated aluminum from tissues more rapidly at pH 5.3 than at pH 6.1 and 7.2. 

In tissues of smallmouth bass, aluminum concentrations were higher and more variable in gill tissue than 

in other tissues (Brumbaugh and Kane 1985). Aluminum concentrations in rainbow trout from an alumtreated lake, an untreated lake, and a hatchery were highest in gill tissue and lowest in muscle (Buergel 

and Soltero 1983). Aluminum residue analyses in brook trout have shown that whole-body aluminum 

content decreases as the fish advance from larvae to juveniles (Cleveland et al. 1989). These results 

imply that the aging larvae begin to decrease their rate of aluminum uptake, to eliminate aluminum at a 

rate that exceeds uptake, or to maintain approximately the same amount of aluminum while the body 

mass increases. The decline in whole-body aluminum residues in juvenile brook trout may be related to 

growth and dilution by edible muscle tissue that accumulated less aluminum than did the other tissues 

(Cleveland et al. 1989). Wilkinson and Campbell (1993) studied aluminum uptake in Atlantic salmon at a 

pH of 4.5 under conditions simulating spring snowmelt. These authors reported that gill uptake was slow, 

approaching a steady state only after 3 days of exposure. The greatest fraction of the gill-associated 

aluminum was not sorbed to the gill tissue, but to the gill mucus. The authors believe that the mucus 

appears to retard aluminum transport from solution to the membrane surface, thus delaying the acute 

biological response of the fish. Buckler et al. (1995) reported concentrations of aluminum in whole-body 

tissue of the Atlantic salmon exposed to high concentrations of aluminum ranging from 3 μg/g (for fish 

exposed to 33 μg/L) to 96 μg/g (for fish exposed to 264 μg/L) at pH 5.5. After 60 days of exposure, 

BCFs ranged from 76 to 190 and were directly related to the aluminum exposure concentration. In acidic 

waters (pH 4.6–5.3) with low concentrations of calcium (0.5–1.5 mg Ca/L), labile aluminum between 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 190 

6. POTENTIAL FOR HUMAN EXPOSURE 

25 and 75 μg/L is toxic (Rosseland et al. 1990). Because aluminum is toxic to many aquatic species, it is

not bioaccumulated to a significant degree (BCF <300) in most fish and shellfish; therefore, consumption 

of contaminated fish does not appear to be a significant source of aluminum exposure in humans. 

Aluminum uptake for the leopard frog (Rana pipiens) was positively correlated to exposure time and pH; 

however, no BCF values were reported because the authors felt that the body aluminum accumulation was 

too variable for useful prediction of the exposure history or physiological status of the frogs (Freda and 

McDonald 1990). 

Bioconcentration of aluminum has also been reported for several aquatic invertebrate species. BCF 

values ranging from 0.13 to 0.5 in the whole-body were reported for the snail, Helix aspersa, fed a single 

24-hour meal containing aluminum in a barley-flour pellet (Brooks et al. 1992). Madigosky et al. (1991) 

reported high tissue residues of aluminum in the red swamp crayfish (Procambarus clarkii) collected 

from roadside drainage ditches in Louisiana. Mean aluminum concentrations as μg/g dry weight in 

crayfish from roadside ditches ranged from 1.75 to 6.39 in abdominal muscle, 3.1–22.74 in the 

hepatopancreas, 309.4–981.50 in the alimentary tract, 10.85–77.45 in the exoskeleton, and 30–140 in the 

blood. These values were significantly elevated above those of control crayfish where the concentrations 

(μg Al/g dry weight) were 1.22 in abdominal muscle, 1.42 in the hepatopancreas, 26.97 in the alimentary 

tract, 4.28 in the exoskeleton, and 37.9 in the blood. 

Bioconcentration of aluminum has also been reported for aquatic insects. Frick and Herrmann (1990) 

reported aluminum accumulation in mayfly nymphs (Heptagenia sulphurea) at low pH (4.5). The 

nymphs were exposed at two concentrations (0.2 and 2 mg Al/L) and for two exposure times (2 and 

4 weeks), the longer time period including a molting phase. When nymphs were exposed to the higher 

concentration of aluminum for two instar periods, with a molt in between, the aluminum content (2.34 mg 

Al/g dry weight) nearly doubled compared with that of a one-instar treatment (1.24 mg Al/g dry weight). 

The major part of the aluminum was deposited in the exuviae of the nymphs, as the aluminum 

determination in the nymphs showed a 70% decrease in aluminum content after molting. These authors 

speculate that internally accumulated aluminum in the nymphs may be transferred to terrestrial predators 

(e.g., birds). They also hypothesized that externally deposited aluminum may be transferred to terrestrial 

food chains by aquatic invertebrates that leave the water in their last instar to molt on shore. An 

important contribution to the idea of biomagnification of aluminum was made by Nyholm (1981). Using 

semi-quantitative multi-element microanalysis, he related impaired breeding of pied flycatchers (Ficedula 

hypoleuca) in Sweden to the occurrence of aluminum in the bone marrow of the birds. A diet of 
 

 

 

 

 

 

 

 

ALUMINUM 191 

6. POTENTIAL FOR HUMAN EXPOSURE 

stoneflies was suspected of forming a link between the lake and the terrestrial predators. Although the 

matter is far from clear, Nyholm (1981) seems to imply that the insects (stoneflies) were adults and that 

these could contain significant amounts of aluminum even after having left the exuviae behind (Frick and 

Herrmann 1990). 

Vuori et al. (1990) sampled tufts of the aquatic moss, Fontinalis dalecarlica, from the River Lestijoki in 

Western Finland. The concentrations of aluminum in the water were low (87–196 μg/L, pH 6.5–7.0) 

relative to the concentrations in the young terminal shoots of F. dalecarlica appeared to be quite high 

(303–1,852 μg/g dry weight). The authors concluded that there was an effective accumulation of 

aluminum in the moss tissue. Albers and Camardese (1993) compared concentrations of aluminum and 

other metals in aquatic species of three acidified (pH ≈5) and three nonacidified (pH≈6.5)constructed 

wetlands. They found that the metal content of Sparganium americanum (bur-reed) was only slightly 

affected by acidification. 

6.3.2 Transformation and Degradation 

As an element, aluminum cannot be degraded in the environment, but may undergo various precipitation 

or ligand exchange reactions. Aluminum in compounds has only one oxidation state (+3), and would not 

undergo oxidation-reduction reactions under environmental conditions. Aluminum can be complexed by 

various ligands present in the environment (e.g., fulvic and humic acids). The solubility of aluminum in 

the environment will depend on the ligands present and the pH. 

6.3.2.1 Air 

Aluminum-containing particulate matter in the atmosphere is mainly derived from soil and industrial 

processes where crustal materials (e.g., minerals) are processed. Aluminum is found as silicates, oxides, 

and hydroxides in these particles (Eisenreich 1980). Aluminum compounds cannot be oxidized and 

atmospheric transformations would not be expected to occur during transport. If aluminum metal 

particulates were released to air during metal processing, they would be rapidly oxidized. 

6.3.2.2 Water 

The trivalent aluminum ion is surrounded by six water molecules in solution (Cotton et al. 1999). The 

hydrated aluminum ion, [Al(H2O)6]

3+, undergoes hydrolysis, in which a stepwise deprotonation of the 

coordinated water ligands forms bound hydroxide ligands (e.g., [Al(H2O)5(OH)]2+, [Al(H2O)4(OH)2]

+

) 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 192 

6. POTENTIAL FOR HUMAN EXPOSURE 

(Snoeyink and Jenkins 1980). The speciation of aluminum in water is pH dependent. The hydrated 

trivalent aluminum ion is the predominant form at pH levels below 4. Between pH 5 and 6, the 

predominant hydrolysis products are Al(OH)2+ and Al(OH)2

+

, while the solid Al(OH)3 is most prevalent 

between pH 5.2 and 8.8. The soluble species Al(OH)4

- is the predominant species above pH 9, and is the 

only species present above pH 10 (Martell and Motekaitis 1989). Polymeric aluminum hydroxides appear 

between pH 4.7 and 10.5, and increase in size until they are transformed into colloidal particles of 

amorphous Al(OH)3, which crystalize to gibbsite in acid waters (Brusewitz 1984). Polymerization is 

affected by the presence of dissolved silica; when enough silica is present, aluminum is precipitated as 

poorly crystallized clay mineral species (Bodek et al. 1988). 

Hydroxyaluminum compounds are considered amphoteric (e.g., they can act as both acids and bases in 

solution) (Cotton et al. 1999). Because of this property, aluminum hydroxides can act as buffers and 

resist pH changes within the narrow pH range of 4–5 (Brusewitz 1984). 

Monomeric aluminum compounds, typified by aluminum fluoride, chloride, and sulfate, are considered 

reactive or labile compounds, whereas polymeric aluminum species react much more slowly in the 

environment (USGS 1984a). Aluminum has a stronger attraction for fluoride in an acidic environment 

compared to other inorganic ligands (Brusewitz 1984). Fulvic acid is also an important ligand for 

aluminum under acidic conditions, and it has been observed that as the temperature is lowered, the rate of 

complexation of aluminum with fluoride is considerably slowed, while the rate of complexation between 

aluminum and fulvic acid is only slightly decreased in rate (Plankey and Patterson 1987). This suggests 

that during snow-melt conditions, when aluminum and hydrogen ion concentrations increase, 

complexation with fulvic acid could preferentially occur over complexation with fluoride. 

6.3.2.3 Sediment and Soil 

Aluminum is present in many primary minerals. The weathering of these primary minerals over time 

results in the deposition of sedimentary clay minerals, such as the aluminosilicates kaolinite and 

montmorillonite. The weathering of soil results in the more rapid release of silicon, and aluminum 

precipitates as hydrated aluminum oxides such as gibbsite and boehmite, which are constituents of 

bauxites and laterites (Bodek et al. 1988). Aluminum is found in the soil complexed with other anions, 

such as fluoride, sulfate, and phosphate. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 193 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to aluminum depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of 

aluminum in unpolluted atmospheres and in pristine surface waters are often so low as to be near the 

limits of current analytical methods. In reviewing data on aluminum levels monitored or estimated in the 

environment, it should also be noted that the amount of chemical identified analytically is not necessarily 

equivalent to the amount that is bioavailable. The analytical methods available for monitoring aluminum 

in a variety of environmental media are detailed in Chapter 7. 

6.4.1 Air 

There are varying levels of aluminum in the atmosphere, depending on the location of the sampling site, 

meteorologic conditions, and the level of industrial activity or traffic in the area. Aluminum levels are 

expected to be low in areas influenced by the ocean and high in areas with wind-blown soil. Background 

concentrations of aluminum in the atmosphere generally range from 0.005 to 0.18 μg/m3 (Hoffman et al. 

1969; Pötzl 1970; Sorenson et al. 1974). In rural areas of Hawaii, aluminum concentrations have been 

measured at a range of 0.005–0.032 μg/m3 (Hoffman et al. 1969), whereas a concentration range of 0.27– 

0.39 μg/m3 has been reported in Manitoba National Park in Canada (AEC 1971). Atmospheric aluminum 

concentrations in U.S. cities and industrial areas are considerably higher, ranging from about 0.4 to 

8.0 μg/m3 (Cooper et al. 1979; Dzubay 1980; Kowalczyk et al. 1982; Lewis and Macias 1980; Moyers et 

al. 1977; Ondov et al. 1982; Pillay and Thomas 1971; Sorenson et al. 1974; Stevens et al. 1978). The 

range of the concentration of aluminum in fine (<1–2.5 μm) and course (2.5–10 μm) particles from two 

industrial areas, Southeast Chicago, Illinois and East St. Louis, Illinois were 22–539 ng/m3 

(125 ng/m3 mean) and 24–1,370 ng/m3 (153 ng/m3 mean), respectively, for fine particles and 8.2– 

1760 ng/m3 (390 ng/m3 mean) and 17–2,120 ng/m3 (442 ng/m3 mean), respectively, for coarse particles. 

At a rural site (Bondville, Illinois), the aluminum concentrations in fine and coarse particles ranged from 

32 to 293 ng/m3 (95 ng/m3 mean) and from 32 to 3,120 ng/m3 (338 ng/m3 mean), respectively which was 

not much different than the aluminum concentration from the industrial sites (Sweet et al. 1993). A mean 

aluminum concentration of 474.6 ng/m3 (range 38.4–2,619.6 ng/m3

) was reported in particulate matter 

collected in air from downtown Rio de Janeiro, Brazil; samples were collected during the period from 

September 2001 to August 2002 (Quiterio et al. 2004). Mean aluminum concentrations in winter and 

summer indoor air sampled in 1999 were 41 and 39 ng/m3 in the homes of 46 high school students from 

West Central Harlem, New York City who participated in the Toxic Exposure Assessment a 

Columbia/Harvard (TEACH) study (Kinney et al. 2002). Aluminum concentrations can also vary with 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 194 

6. POTENTIAL FOR HUMAN EXPOSURE 

seasonal meteorological conditions. For example, in Mackinac Island, Michigan, summer concentrations 

averaged about 0.25 μg/m3

, while winter concentrations were only about 0.18 μg/m3 (AEC 1971). 

6.4.2 Water 

The concentrations of dissolved aluminum in water vary with pH and the humic-derived acid content of 

the water (Brusewitz 1984). Aluminum is only sparingly soluble in water between pH 6 and 8. Because 

the pH of about 95% of naturally-occurring water is between 6 and 9 and since high aluminum 

concentrations occur in surface water bodies only when the pH is <5, the aluminum concentration in most 

natural waters is extremely low (Filipek et al. 1987; Snoeyink and Jenkins 1980; Sorenson et al. 1974). In 

general, aluminum concentrations in surface waters at pH levels above 5.5 will be <0.1 mg/L (Brusewitz 

1984; Miller et al. 1984a; Sorenson et al. 1974; Taylor and Symons 1984). However, even at neutral pH 

levels, higher aluminum concentrations have been found in lakes with a high humic acid content 

(Brusewitz 1984). Aluminum concentrations in marinewaters tend to be much lower (i.e., <0.001 mg/L) 

than those found in freshwater lakes and streams (Brusewitz 1984), probably because of increased 

alkalinity in marinewater compared to fresh water. 

At lower pH levels, the aluminum content significantly increases because of increased solubility of 

aluminum oxide and salts in acidic solutions. For example, aluminum has been found at concentrations 

of up to 90 mg/L in tributaries that drain mines containing massive sulfide deposits (Filipek et al. 1987). 

In heavily contaminated surface waters in a mining region rich in sulfides, the water was highly acidic 

(pH <3.5) and the levels of soluble aluminum were >2 mmol/L (50 mg/L) (Alvarez et al. 1993). 

Similarly, surface water samples contaminated with acidic mine drainage collected at seven different 

locations in the vicinity of abandoned coal mines in west-central Indiana had aluminum concentrations of 

6.0–269 mg/L (Allen et al. 1996). The pH ranged from 2.1 to 3.4 at these sites. 

Aluminum was detected at dissolved aluminum concentrations ranging from 0.001 to 2.760 mg/L with a 

mean concentration of 0.074 mg/L in 456 of 1,577 raw surface water samples collected during a 5-year 

survey at various locations across the United States (DOI 1970). Dissolved aluminum concentrations 

were detected in about 48% of the 380 finished drinking waters sampled and ranged from 0.003 to 

1.6 mg/L with a mean of 0.179 mg/L (DOI 1970). In another survey of 186 community water systems, 

median aluminum concentrations for all finished drinking water samples ranged from 0.026 to 

0.161 mg/L (Miller et al. 1984a). These authors further reported that the median aluminum concentration 

in finished water that received no coagulation treatment was 0.043 mg/L (range, 0.016–1.167 mg/L) 
 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 195 

6. POTENTIAL FOR HUMAN EXPOSURE 

compared to the median of 0.112 mg/L (range, 0.014–2.670 mg/L) in finished water receiving alum 

(aluminum sulfate) coagulation treatment. In the supplies in which no coagulant was used during 

treatment, 29% of supplies using surface water as their source had aluminum concentrations exceeding 

0.05 mg/L, whereas only 4% of supplies using groundwater sources exceeded this level. When aluminum 

coagulants were used, 69% of all supplies had residual aluminum concentrations >0.05 mg/L (Miller et al. 

1984a). In another study, the aluminum content in treated water at facilities using alum coagulation 

treatment of raw waters ranged from about 0.01 to 1.3 mg/L with a mean of about 0.157 mg/L (Letterman 

and Driscoll 1988). Tap water samples were collected in 1998 in the service area of East Houston, Texas 

water purification plant; 44% of these samples had aluminum concentrations >0.2 mg/L. Aluminum 

concentrations as high as 0.53 mg/L were observed in samples collected near the treatment plant that used 

an alum coagulant. An average decrease of 7 μg/L/km was observed along the distribution system (Cech 

and Montera 2000). 

Schenk et al. (1989) measured aluminum concentrations in drinking water collected primarily in the 

western and central parts of the United States from outlets from which water was consumed rather than 

from the original water treatment plant. Aluminum concentrations in drinking water in various regions of 

the United States are listed in Table 6-3. Although aluminum concentrations in drinking water may range 

from undetectable to 1.029 mg/L, aluminum concentrations in most drinking water in the United States 

were generally <0.1 mg/L (Schenk et al. 1989). While several water sources in the west coast states 

(California, Oregon, and Washington) were found to contain undetectable concentrations of aluminum 

(<0.001 mg/L), several cities in other geographic areas of the United States had high aluminum 

concentrations (>0.4 mg/L). These included Peoria, Illinois (0.467 mg/L); Coos Bay, Oregon 

(0.483 mg/L); Watertown, South Dakota (0.502 mg/L); Waco, Texas (0.520 mg/L); Yellowstone National 

Park, Wyoming (0.608 mg/L); Philadelphia, Pennsylvania (0.688 mg/L); and Charleston, South Carolina 

(1.029 mg/L). 

Henshaw et al. (1993) studied concentrations of various components, including aluminum, in drinking 

water derived from the Great Lakes in six communities in the United States and Ontario, Canada. Alum 

was used as a coagulant in all six communities. It was found that aluminum concentrations were 

generally higher in treated waters as compared to raw water. Between 1986 and 1990, mean aluminum 

concentrations in raw water were 0.020–0.053, 0.058–0.070, 0.012–0.023, 0.020–0.037, and 0.058– 

0.476 mg/L in Milwaukee, Wisconsin; Rochester, New York; Thunder Bay, Ontario; Toronto, Ontario; 

and Windsor, Ontario, respectively. Between 1986 and 1990, mean aluminum concentrations in treated 

water were 0.085–0.200, 0.070–0.115, 0.027–0.032, 0.080–0.139, and 0.113–0.727 mg/L in Gary, 
 

 

ALUMINUM 196 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Aluminum Concentrations Detected in Drinking Water in Various
 

Regions of the United States
 

U.S. States Aluminum concentration (μg/L)a 

California 0–274 

Colorado 42–166 

Hawaii 12–124 

Idaho 28–63 

Illinois 3–467 

Indiana 1–137 

Kansas 12–245 

Kentucky 9–400 

Louisiana 12–210 

Michigan 6–123 

Minnesota 24–93 

Missouri 2–368 

Montana 11–98 

New Yorkb 254–299 

Nevada 5–126 

Ohio 2–245 

Oregon 0–483 

Pennsylvaniac 688 

South Carolina 2–1,029 

South Dakota 2–502 

Tennesseed 45 

Texas 1–520 

Utah 19–51 

Washington 0–118 

Wisconsin 12–118 

Wyoming 16–608 

a

Range in values reported for each state

b

Water sampled in New York City only 

c

Water sampled in Philadelphia only (one sample)

d

Water sampled in Memphis only (one sample) 

Source: Schenk et al. 1989 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 197 

6. POTENTIAL FOR HUMAN EXPOSURE 

Indiana; Rochester, New York; Thunder Bay, Ontario; Toronto, Ontario; and Windsor, Ontario, 

respectively. Data for raw water in Gary, Indiana and treated water in Milwaukee, Wisconsin were not 

provided (Henshaw et al. 1993). Aluminum concentrations in 172 samples of bottled water sold in 

Canada ranged from <0.010 to 0.568 μg/g (<0.010–0.567 mg/L), with a mean of 0.027 μg/g (0.027 mg/L) 

(Dabeka et al. 1992). Drinking water from 35 cities and villages in Galicia, northwest Spain were 

analyzed for dissolved aluminum during 1997 to 2003; an average aluminum concentration of 0.126 mg/L 

was reported, with concentrations ranging from 0.008 to 0.650 mg/L (Rubinos et al. 2007). 

Aluminum has been measured in atmospheric precipitation (i.e., rain and snow) in the United States at 

concentrations up to 1.2 mg/L (Dantzman and Breland 1970; DOI 1971; Fisher et al. 1968; USGS 1964). 

Aluminum has been measured in rainwater samples collected during the Global Change Expedition in the 

North Atlantic Ocean (Lim and Jickells 1990). These authors reported that comparisons between acidleachable and total (dissolved plus particulate) trace aluminum concentrations suggest that the acidleachable fraction of aluminum can significantly underestimate total concentrations of aluminum in 

rainwater. Acid-leached mean concentrations of aluminum in rainwater collected during three rainfall 

events in the North Atlantic were 33.7, 12.2, and 1.99 μg/L. Overall, the acid-leached concentrations of 

aluminum in rainwater for seven rainfall events ranged from 1.14 to 35.2 μg/L. These values were 

compared with acid-leachable aluminum concentrations in precipitation from remote areas which ranged 

from 2.1 to 15.44 μg/L. Total (dissolved plus particulate) aluminum concentrations in North Atlantic

precipitation samples collected in 1988 ranged from 6.1 to 827 μg/L (Lim and Jickells 1990). 

Aluminum concentrations in groundwater wells at neutral pH generally fall below 0.1 mg/L (Brusewitz 

1984). In areas receiving acid precipitation, aluminum concentrations in groundwater may be >10 times 

the concentrations found in areas with neutral pH levels in the water (Brusewitz 1984), possibly due to 

precipitation of aluminum compounds in the more alkaline medium, or the reaction of aluminum with 

available silicates. In another study, Miller et al. (1984a) reported that the median concentration of 

aluminum in finished water obtained from groundwater was 0.031 mg/L (range, 0.014–0.290 mg/L) as 

compared to the median concentration in surface water of 0.043 mg/L (range, 0.016–1.167 mg/L). These 

authors also reported that, while 55% of the raw surface waters sampled contained aluminum 

concentrations >0.05 mg/L, only 4% of the raw groundwater samples contained aluminum concentrations 

>0.05 mg/L. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 198 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.3 Sediment and Soil 

Aluminum is the most abundant metal and the third most abundant element in the earth’s crust, 

comprising about 8.8% by weight (88 g/kg) (Staley and Haupin 1992). Its concentration in soils varies 

widely, ranging from about 0.07% by weight (0.7 g/kg) to over 10% by weight (100 g/kg) (Sorenson et al. 

1974; USGS 1984c). Varying concentrations are found in different soil samples taken from the same area 

and in areas with different vegetation types (Brusewitz 1984; Sorenson et al. 1974). In Hawaii, aluminum 

contents were much higher with concentrations ranging from 79 to 317 g/kg (Moomaw et al. 1959). Soils 

in Florida and parts of Georgia, Texas, Oklahoma, and Michigan contain <20 g/kg of soil, whereas soils 

from portions of the Pacific Northwest, New England, Colorado, and Nevada have concentrations 

>80 g/kg (Sparling and Lowe 1996). Mean aluminum concentrations in cultivated and uncultivated soil 

samples collected during a number of field studies were 33 g/kg (range 7–>100 g/kg) for subsurface soils 

in the eastern United States, 54 g/kg (range 5–>100 g/kg) in subsurface soils in the western United States, 

and 57 g/kg (range 13–76 g/kg) in surface soils collected in Colorado (Connor and Shacklette 1975). Ma 

et al. (1997) reported a mean aluminum concentration of 0.730 g/kg (range 0.01–4.300 g/kg) in 40 surface 

soil samples from Florida. Aluminum concentrations in 1,903 soils samples collected from the United 

States, as well as the Virgin Islands, Guam, and Puerto Rico, were reported to range from 0.5 to 142 g/kg, 

with a median value of 46 g/kg (Burt et al. 2003). A median aluminum concentration of 1.8 mg/kg was 

reported in soils collected form 25 playgrounds located in urban Uppsala, Sweden’s fourth largest city 

(Ljung et al. 2006). 

Aluminum concentrations in soil also vary with different vegetation types. For example, aluminum 

concentrations in the soils of coniferous forests are often higher than in soils of beech forests since 

coniferous forests tend to have more acid soils (Brusewitz 1984). Alternate views of the data are that the 

acidic soil produced by conifers can preferentially mobilize aluminum from deeper layers toward surface 

soil, or that conifers over beech preferentially grow in soils rich in aluminum and it is their metabolic 

processes which produce more acidic soil. 

Concentrations of various elements in 541 streambed-sediment samples collected from 20 study areas in 

the conterminous United States (1992–1996) were analyzed as part of the National Water-Quality 

Assessment Program of the U.S. Geological Survey. Aluminum was present in all samples; 

concentrations ranged from 1.4 to 14% by weight (14–140 g/kg), with a median of 6.4% by weight 

(64 g/kg) (Rice 1999). Mean aluminum concentrations in sediments collected in 1993 and 1994 from 

Lake Erie, Lake Ontario, and the Niagara River ranged from 1.339 to 13.823 g/kg dry weight (Lowe and 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 199 

6. POTENTIAL FOR HUMAN EXPOSURE 

Day 2002). Mean aluminum concentrations in sediments collected from three lakes in central Texas near 

a coal-fired power plant were 5.32, 8.16, and 8.64% in the Gibbons Creek Reservoir, Hall Lake, and 

Yarboro Lake, respectively (Menounou and Presley 2003). A mean aluminum concentration of 56.1 g/kg 

was reported in sediments form Terra Nova Bay, Antarctica (Giordano et al. 1999). 

6.4.4 Other Environmental Media 

Aluminum occurs naturally in many edible plants and is added to many processed foods. The 

concentrations in foods and beverages vary widely, depending upon the food product, the type of 

processing used, and the geographical areas in which food crops are grown (Brusewitz 1984; Sorenson et 

al. 1974). In general, the foods highest in aluminum are those that contain aluminum additives (e.g., 

processed cheese, grain products, and grain-based desserts) (Greger 1992; Pennington 1987; Saiyed and 

Yokel 2005). Because of the variability of reported concentrations of aluminum in foods, the many new 

manufactured food products on the market, and the increasing use of aluminum as a packaging material, a 

wide range of beverages and foods have been analyzed. The aluminum concentrations in a number of 

beverages, foods, and food products are listed in Table 6-4. Most unprocessed foods, (with the exception 

of some herbs and tea leaves) typically contain <5 mg/kg aluminum (Greger 1992; MAFF 1999; 

Pennington 1987; Schenk et al. 1989). Concentrations of aluminum in foods generally ranged from 

<0.15 mg/kg in eggs, apples, raw cabbage, corn, and potatoes to 695 mg/kg in American cheese (Greger 

1992; MAFF 1999; Pennington 1987; Schenk et al. 1989). López et al. (2000) measured aluminum 

concentrations in 17 different spices and aromatic herbs widely consumed in Spain and in the 

Mediterranean diet; concentrations ranged from 3.74 to 56.50 mg/kg dry weight in cinnamon and 

oregano, respectively. 

The high aluminum concentrations seen in some processed foods (e.g., processed cheeses, baked goods, 

and nondairy cream substitutes) are likely to have been introduced into the foods as additives, such as the 

anti-caking agent, sodium aluminosilicate, which is present in salt, nondairy creamers, and many other 

powdered materials (Table 6-4) (Saiyed and Yokel 2005; Schenk et al. 1989). The most commonly used 

food additives containing aluminum are: acidic sodium aluminum phosphate (leavening agent in baked 

goods); basic sodium aluminum phosphate (emulsifying agent in processed cheese); aluminum sulfates 

(acidifying agents); bentonite (materials-handling aid); aluminum color additives (lakes) from various 

food dyes; and aluminum silicates (anti-caking agents) (Greger 1992; Saiyed and Yokel 2005). 
 

ALUMINUM 200 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Estimated Aluminum Concentrations of Selected Foods 

Aluminum 

Foods concentration Reference 

Beverages (mg/L) 

Fruit juices (e.g., orange, reconstituted 0.043–4.130 Schenk et al. 1989 

lemon, peach) 

Soft drinks (e.g., ginger ale, diet cola) 0.103–2.084 Schenk et al. 1989 

Alcoholic beverages (e.g., beer, wine, 0.067–3.20 Schenk et al. 1989 

wine coolers, champagne) 

Spirits (e.g., brandy, vodka, whiskey) 0.148–0.635 Schenk et al. 1989 

Tea, steeped from tea bags 0.424–2.931 Schenk et al. 1989 

Teas (1% extract) 0.378–3.55 Schenk et al. 1989 

Herbal teas (1% extract) 0.14–1.065 Schenk et al. 1989 

Instant coffee (1% solution) 0.02–0.581 Schenk et al. 1989 

Whole coffee (3% extract) 0.235–1.163 Schenk et al. 1989 

Beverages 1.3a MAFF 1999 

Animal products (mg/kg) 

Beef, cookeda 0.2 Greger et al. 1985 

Cheese (e.g., Swiss, cheddar, bleu) 3.83–14.1 Schenk et al. 1989 

Cheese, (e.g., cottage, cheddar, Swiss) 0.12–19 Pennington 1987 

Cheese, American 411–695 Pennington 1987 

Cheese, processed 297 Greger et al. 1985 

Chicken, with skin, cookeda 0.7 Greger et al. 1985 

Egg, chicken 0.107 Schenk et al. 1989 

Eggs, scrambled 2.865 Schenk et al. 1989 

Eggs, cookeda 0.1 Greger et al. 1985 

Eggs 0.14 MAFF 1999 

Fish (cod), cookeda 0.4 Greger et al. 1985 

Fish, salmon 5.44 Schenk et al. 1989 

Fish, herring 0.127 Schenk et al. 1989 

Fish 6.1 MAFF 1999 

Ham, cookeda 1.2 Greger et al. 1985 

Meat products 1.9 MAFF 1999 

Milk, whole 0.06–2 Pennington 1987 

Milk (skim, whole, and powdered) 0.028–7.9 Schenk et al. 1989 

Milk 0.07 MAFF 1999 

Poultry 0.3 MAFF 1999 

Salami 1.12 Pennington 1987 

Yoghurt, plain low-fat 1.12 Pennington 1987 

Yoghurt, strawberry, sweetened 0.63 Pennington 1987 

Fruits (mg/kg) 

Apple, fresh 0.14 Pennington 1987 
ALUMINUM 201 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Estimated Aluminum Concentrations of Selected Foods 

Aluminum 

Foods concentration Reference 

Banana, fresh 0.05 Pennington 1987 

Grapes, fresh 1.81 Pennington 1987 

Peaches, fresh 0.51 Pennington 1987 

Raisins, dried 3.08 Pennington 1987 

Strawberries, fresh 2.25 Pennington 1987 

Fresh fruit 0.29 MAFF 1999 

Fruit products 0.82 MAFF 1999 

Grains (mg/kg) 

Biscuits, baking powder, refrigerated 16.3 Pennington 1987 

type 

Bread, white 0.351 Schenk et al. 1989 

Bread, white 2.33 Pennington 1987 

Bread, whole wheat 2.91 Pennington 1987 

Bread, pumpernickel 13.2 Schenk et al. 1989 

Bread 6.6 MAFF 1999 

Cereal (e.g., Post Raisin Bran®, Malt-o- 0.040–29.33 Schenk et al. 1989 

Meal Wheat Cereal®) 

Miscellaneous cereals 5.2 MAFF 1999 

Corn chips 1.23 Pennington 1987 

Cornbread, homemade 400 Pennington 1987 

Muffin, blueberry 128 Pennington 1987 

Oatmeal, cooked 0.68 Pennington 1987 

Oats 2.21–4.18 Schenk et al. 1989 

Rice, cookeda 1.7 Greger et al. 1985 

Rice, yellow, Rice-a-Roni® 1.97 Schenk et al. 1989 

Spaghetti, cookeda 0.4 Greger et al. 1985 

Vegetables and legumes (mg/kg) 

Asparagus 4.4 Greger et al. 1985 

Beans, green, cookeda 3.4 Greger et al. 1985 

Beans, navy, boiled 2.06 Pennington 1987 

Cabbage, raw 0.1 Greger et al. 1985 

Cauliflower, cookeda 0.2 Greger et al. 1985 

Corn, boiled 0.1 Pennington 1987 

Cucumber, fresh, pared 0.11 Pennington 1987 

Green vegetables 3.1 MAFF 1999 

Lettuce 0.6 Greger et al. 1985 

Lettuce 0.08 Schenk et al. 1989 

Peanut butter 2.0 Greger et al. 1985 

Peanut butter, natural 6.29 Schenk et al. 1989 

Peas, cookeda 1.9 Greger et al. 1985 
 

ALUMINUM 202 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Estimated Aluminum Concentrations of Selected Foods 

Aluminum 

Foods concentration Reference 

Potatoes, unpeeled, boileda 0.1 Greger et al. 1985 

Potatoes, unpeeled, baked 2.4 Greger et al. 1985 

Potato, red 3.63 Schenk et al. 1989 

Potato, sweet 1.01 Schenk et al. 1989 

Potatoes 0.9 MAFF 1999 

Spinach, cookeda 25.2 Greger et al. 1985 

Tomatoes, cookeda 0.1 Greger et al. 1985 

Other vegetables 2.7 MAFF 1999 

Canned vegetables 0.97 MAFF 1999 

Herbs and spices (mg/kg dry weight) 

Basil 24.80–27.30 López et al. 2000 

Cinnamon 18.54–56.50 López et al. 2000 

Garlic 13.60–15.25 López et al. 2000 

Mustard 30.40–38.56 López et al. 2000 

Nutmeg 22.81–24.80 López et al. 2000 

Oregano 3.74–40.41 López et al. 2000 

Pepper, black 5.79–24.41 López et al. 2000 

Thyme 6.35–7.90 López et al. 2000 

Other food products (mg/kg) 

Baking powder, commercial (Na Al 20,000–26,000 Sorenson et al. 1974 

sulfate containing) 

Candy, milk chocolate 6.84 Pennington 1987 

Chocolate cookie, Oreo 12.7 Schenk et al. 1989 

Cocoa 45 Greger et al. 1985 

Nondairy creamer 25.7–94.3 Schenk et al. 1989 

Nuts 4.0 MAFF 1999 

Oils and fats 1.1 MAFF 1999 

Pickles with aluminum additives 39.2b Greger et al. 1985 

Pickles 0.126–9.97 Schenk et al. 1989 

Salad dressing, Kraft Miracle Whip® 3.7 Schenk et al. 1989 

Salt with aluminum additives 164 Greger et al. 1985 

Salt 31.3–36.6 Schenk et al. 1989 

Soup 0.032–3.6 Schenk et al. 1989 

Sugars and preserves 2.7 MAFF 1999 

a

Food not cooked or stored in aluminum pans, trays, or foil. 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 203 

6. POTENTIAL FOR HUMAN EXPOSURE 

Commercially available teas contain high concentrations of aluminum; 30–45% of this aluminum may be 

dissolved into an infusion of tea (Dong et al. 1999). Aluminum concentrations ranging from 0.2 to 

9.5 mg/L have been reported in tea (Baxter et al. 1989; Flaten and Odegard 1988; Koch et al. 1989; 

Schenk et al. 1989; Müller et al. 1998; Pennington 1987; Pennington and Jones 1989; Kralj et al. 2005; 

Mehra et al. 2007). Fairweather-Tait et al. (1987) reported that approximately one-third of the aluminum 

in commercially available tea leaves was extracted into the tea (1.0 g tea/100 mL water); aluminum 

concentrations ranged from 2.7 to 4.9 mg/L in the tea after 5 minutes. Fimreite et al. (1997) reported 

aluminum concentrations of 4–5 mg/L in tea after 10 minutes. Schenk et al. (1989) reported that herbal 

teas contain lower concentrations of aluminum than ordinary tea (0.140–1.065 mg/L). Total aluminum 

concentrations in black, green, and red tea infusions ranging from 0.5 to 4.0 mg/L, with 10–35% of the 

total aluminum from an anion-exchange column as aluminum citrate. The remaining aluminum, which 

was strongly retained by the column, likely corresponds to aluminum species bound to penolic 

compounds. Addition of lemon or milk was found to change the distribution of the aluminum species in 

the tea infusions (Kralj et al. 2005). 

Brewed coffee (3% extract) and instant coffee (1% solution) contain aluminum concentrations of 0.235– 

1.163 and 0.02–0.581 mg/L, respectively (Schenk et al. 1989). Aluminum concentrations ranging from 

0.1 to 0.34 mg/L have been reported in coffee (Koch et al. 1989; Müller et al. 1998). Another report 

provided aluminum concentration in coffee beans ranging from 11 to 21 mg/kg (Koch et al. 1989). The 

aluminum content of ground coffee beans has been measured at 51.8 mg/kg (Lione et al. 1984). López et 

al. (2000) reported aluminum concentrations in coffee ranging from 25.60 to 29.08 mg/kg dry weight. 

Müller et al. (1998) reported an aluminum concentration of 19 mg/kg dry weight in ground coffee. Lione 

et al. (1984) estimated that brewing coffee in a new aluminum pot can add from 0.88 mg (immediately 

after brewing) to 1.18 mg aluminum (after 12-hour storage in the pot and subsequent reheating) to each 

cup. 

Aluminum concentrations in wines and spirits were 0.388–3.2 and 0.148–0.635 mg/L, respectively 

(Schenk et al. 1989). Lopez et al. (1998) reported mean aluminum concentrations in alcoholic beverages 

consumed in Spain; concentrations were 94.8–1,682.6, 36.5–795.2, and 15.7–739.6 μg/L in wine, beer, 

and other alcoholic beverages (cider, brandy, rum, whisky, gin, anisette, and liquor), respectively. 

In fiscal years 1985/1986, the FDA conducted a survey of elements in fresh clams and oysters collected 

from U.S. coastal areas in use for shellfish production (Capar and Yess 1996). The average concentration 

(wet weight basis) of aluminum found in the four shellfish categories surveyed were: clams (hardshell), 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 204 

6. POTENTIAL FOR HUMAN EXPOSURE 

23±23 mg/kg (n=74); clams (softshell), 115±110 mg/kg (n=59); Eastern oyster, 33±26 mg/kg (n=104); 

and Pacific oyster, 30±28 mg/kg (n=46). Cod and bluefin tuna from the Northwest Atlantic Ocean 

contained an average of 1 and 0.4 mg/kg of aluminum, respectively, in muscle tissue (Hellou et al. 1992a, 

1992b). 

Cooking foods in aluminum pots and pans or storing foods in aluminum foil or cans may increase the 

aluminum content in some foods since aluminum may dissolve when in contact with a salty, acidic, or 

alkaline food (Abercrombie and Fowler 1997; Greger et al. 1985; King et al. 1981; Muller et al. 1993b; 

Nagy and Nikdel 1986). Aluminum concentrations in precooked foods (e.g., applesauce, green beans, 

beef, eggs, ham, pudding, rice, and tomato sauce) ranged from <0.1 to 21.6 mg/kg, while concentrations 

in the foods after cooking in conditioned aluminum pans and stainless steel pans ranged from 0.24 to 

125 mg/kg and from <0.1 to 3.4 mg/kg, respectively (Greger et al. 1985). Acidic foods, such as tomatoes, 

tomato sauce, and applesauce, especially when cooked for >15 minutes, tended to accumulate more 

aluminum than other foods (Greger et al. 1985). Greger et al. (1985) also reported that foods cooked in 

new aluminum cookware had higher aluminum concentrations than foods cooked in old aluminum 

cookware or aluminum cookware that had been treated to simulate use. In addition, the aluminum 

concentrations in the foods prepared in any aluminum cookware (old, new, or treated to simulate use) had 

higher aluminum concentrations than the same foods cooked in stainless steel cookware. A study by Lin 

et al. (1997) noted that cooking with aluminum utensils may be an important aluminum exposure source 

for patients with chronic renal disease. 

Abercrombie and Fowler (1997) reported in a small sampling of canned drinks stored at 15–20 °C, the 

aluminum content ranged from <0.1 to 74 mg/kg depending on the product and storage time. This study 

concluded that there appeared to be little basis for concern about the ingestion of aluminum when the 

internal protective coating of cans remains intact, the cans are stored properly, and the contents are 

consumed in a reasonable period of time. Fairweather-Tait et al. (1987) reported mean aluminum 

concentrations in Coca-Cola® and Pepsi-Cola® of 0.09 and 0.05 μg/g, respectively. Average aluminum

concentrations in various beverages purchased in Australia, New Zealand, and Thailand were 0.90 and 

0.15 in non-cola soft drinks in aluminum cans and glass bottles, respectively, and 0.66 and 0.24 in cola 

drinks in aluminum cans and glass bottles, respectively. Aluminum concentrations averaged 0.16 mg/L in 

beer in either aluminum cans or glass bottles (Duggan et al. 1992). Muller et al. (1993b) reported 

migration of aluminum from aluminum cans (unlacquered) into Coca-Cola® (pH 2.5) and diet CocaCola® (pH 3.0), and that the concentration of aluminum increased as the storage period increased. 

Concentrations of aluminum ranged from 46 to 170 μg/L in Coca-Cola® (storage for 40–101 days) and 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 205 

6. POTENTIAL FOR HUMAN EXPOSURE 

from 14 to 250 μg/L in diet Coca-Cola® (storage for 44–173 days), respectively. Vela et al. (1998) 

examined the change in aluminum concentration in beer packaged in aluminum cans over time. Two 

brands of beer stored at 5 °C showed little change in aluminum concentration over 5 months. However, 

when stored at 23 °C, the concentrations increased from 50.0 to 546.5 μg/L and from 108.0 to 414.0 μg/L

for the two brands of beer after 5 months. Joshi et al. (2003) studied the potential for the migration of 

aluminum into commercial sauces packaged in aluminum pouches. The results of this study indicated 

that after 45 days at 22 and 50 °C samples showed only minor changes in aluminum content as compared 

to fresh samples. 

Aluminum concentrations of 0.6–3.7 and 0.1–0.4 mg/g were reported in four different types of tobacco 

and two samples of cannabis, respectively (Exley et al. 2006). Various elements were determined in 

tobacco used in the manufacture of 12 brands of cigarettes in the United States; aluminum concentrations 

ranged from 0.699 to 1.2 mg/g (Iskander et al. 1986). 

Aluminum compounds are also used extensively in the manufacture of cosmetics (e.g., aluminum 

hexahydrate in deodorants) and in medical treatments (e.g., aluminum hydroxide in antacids to control 

gastric hyperacidity or aluminum oxide in dental ceramic implants) (Brusewitz 1984; FDA 2002; NIH 

2004; NRC 1982). Many antacids contain 300–600 mg aluminum hydroxide (approximately 104–208 mg 

of aluminum) per tablet/capsule/5 mL dose (Zhou and Yokel 2005). Lione (1985a) reported aluminum 

content/dose (single tablet or 5 mL liquid) for antacids, internal analgesics (buffered aspirins), 

antidiarrheals, and anti-ulcerative drugs. The aluminum content per dose (single tablet or 5 mL liquid) 

ranged from 35 to 208 mg for antacids, 9–52 mg for buffered aspirins, 36–1,450 mg for antidiarrheal 

drugs, and 207 mg for an anti-ulcerative drug. Potential daily aluminum dosage ranged from 126 to 

5,000 mg for these medications (Lione 1985a). Aluminum hydroxide (1–5%) is found in car polishes and 

paints and aluminum chlorohydrate (>1–20%) is found in antiperspirants and deodorants (NIH 2004). 

Fernandez-Lorenzo et al. (1999) reported mean aluminum concentrations of 225.9 (8–1,149), 69.0 (20– 

204), and 152.5 (104–201) μg/L in infant formulas, whole cow’s milk, and soy milk, respectively, in a

study in Spain. Ikem et al. (2002) reported mean aluminum concentrations of 58, 92, and 150 μg/L in 

milk-based powdered formulas from Nigeria, the United Kingdom, and the United States, respectively. 

Mean aluminum concentrations of 101 and 460 μg/L were reported for milk-based liquid formulas from 

the United Kingdom and soy-based powder formulas from the United States, respectively. Daily intakes 

of aluminum for infants in the United States were estimated to be 97, 573, and 361 μg/day for milk-based 

powder formulas, soy-based powder formulas, and hypoallergenic powder formulas from the United 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 206 

6. POTENTIAL FOR HUMAN EXPOSURE 

States (Ikem et al. 2002). Navarro-Blasco and Alvarez-Galindo (2003) reported aluminum concentrations 

in soy-based infant formulas from Spain that ranged from 313 to 3,479 μg/L, with a mean of 930 μg/L. 

Mean aluminum concentrations in other types of Spanish infant formula were 499, 237, 252, 292, 574, 

687, and 453 μg/L for preterm formula, non-adapted starter formula, adapted starter formula, follow-up 

formula, lactose-free formula, hypoallergenic formula, and inform error diet formula, respectively. 

Aluminum concentrations were determined in infant formulas and food in Turkey (Sipahi et al. 2006). 

Aluminum concentrations in cereal-, milk-, cereal plus milk-based baby food were reported to be 6.43, 

8.02, and 7.43, 3.33 and 13.15 μg/g, respectively. Aluminum concentrations in starches and rice flours, 

traditionally used in baby foods, were also reported as 3.33 and 13.15 μg/g, respectively (Sipahi et al. 

2006). 

Older reports on aluminum concentrations in infant formulas are also available; however, it is not known 

if these values would be necessarily representative of aluminum levels in infant formulas currently on the 

market and available to consumers. Aluminum concentrations in cow’s milk-based infant formulas 

generally ranged from 4 to 700 μg/L and from 5 to 2,500 μg/L in soy-based infant formulas (Baxter et al. 

1989, 1990, 1991; Bloodworth et al. 1991; Simmer et al. 1990). Average aluminum concentrations in 

infant formula from Canada were 0.129, 0.217, and 0.717 μg/g in ready-to-use, concentrated, and powder 

milk-based infant formulas, respectively. Aluminum concentrations in Canadian soy-based formulas 

were 1.98, 1.41, and 9.44 μg/g in ready-to-use, concentrated, and powder milk-based infant formulas, 

respectively (Dabeka and McKenzie 1990). 

The median aluminum level in breast milk collected from 12 Canadian women was reported to be 

14 μg/L (range <5–45 μg/L) (Koo et al. 1988). In an Australian study, Weintraub et al. (1986) reported 

human breast milk concentrations of 30 μg/L. Simmer et al. (1990) reported a mean aluminum 

concentration of 49 μg/L in breast milk collected from Australian women. Hawkins et al. (1994) reported 

a mean breast milk aluminum concentrations of 9.2 μg/L collected from 15 nursing mothers in the United 

Kingdom. In a study of Croatia women, an average aluminum concentration in breast milk was 380 μg/L, 

with a range of 4 to 2,670 μg/L (Mandić et al. 1995). Fernandez-Lorenzo et al. (1999) reported mean 

aluminum concentrations of 23.9 μg/L (range 7–42 μg/L) in human milk in a study in Spain. Baxter et al. 

(1991) reported a mean aluminum concentration of 27 μg/L (range 3–79 μg/L) in a study in the United 

Kingdom. 

Concentrations of aluminum in whole blood and plasma have been reported to range from 0.14 to 

6.24 mg/L and from 0.13 to 0.16 mg/L, respectively (Sorenson et al. 1974). Aluminum concentrations in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 207 

6. POTENTIAL FOR HUMAN EXPOSURE 

serum have been reported as 1.46 and 0.24 mg/L, using neutron activation and atomic absorption analysis, 

respectively (Berlyne et al. 1970). An aluminum concentration in serum of 0.037 mg/L was reported 

using flameless atomic absorption analysis (Fuchs et al. 1974). Versieck and Cornelis (1980) discussed 

the possibility of aluminum contamination in blood and plasma samples from some of these early studies. 

This may question the reliability of aluminum levels reported in some older reports. House (1992) 

reported a geometric mean aluminum concentration of 0.0267 mg/L in serum and plasma for 71 office 

employees who were not occupationally exposed to aluminum. Mean plasma or serum aluminum 

concentrations were reported from various studies ranging from 0.0016 to 0.035 mg/L (House 1992). 

Drablos et al. (1992) analyzed aluminum serum concentrations in 230 nonexposed workers (controls) and 

reported a mean aluminum serum concentration of 0.005 mg/L. Nieboer et al. (1995) reviewed 34 studies 

on aluminum concentrations in serum or plasma, and also reported that aluminum serum concentrations in 

the general population were typically <0.01 mg/L. In an investigation of workers at an open bauxite mine 

in Surinam, serum aluminum concentrations of 24 men working in the mine for an average of 24 years 

were low and not statistically different from controls (de Kom et al. 1997). Razniewska and TrzcinkaOchocka (2003) reported mean aluminum concentrations of 0.99 and 9.75 μg/L in serum and urine,

respectively, in 18 healthy subjects not using medications containing aluminum. 

A mean aluminum concentration of 23.21 μg/L (range 5.98–206.93 μg/L) was reported in serum samples

collected form 533 female children (6–8 years old) living in Riyadh City, Saudi Arabia (Al-Saleh and 

Shinwari 1996). Hawkins et al. (1994) reported plasma aluminum concentrations in infants fed various 

formulas and breast milk. A mean plasma aluminum concentration of 8.6 μg/L was reported in breast fed 

infants; mean aluminum concentrations in plasma of infants fed various formulas ranged from 9.2 to 

15.2 μg/L. Mean aluminum plasma concentrations of 9.9, 8.4, and 13.4 μg/L in breastfed infants at birth, 

1 month, and 3 months of age, respectively. Infants on soy-based infant formulas, containing 1,600– 

1,700 μg/L of aluminum, were reported to have mean aluminum plasma concentrations of 8.2–12.4, 7.6– 

8.5, and 10.8–12.4 μg/L at birth, 1 month, and 3 months of age, respectively (Litov et al. 1989). 

Aluminum concentrations in the urine can serve as an indicator of increased exposure to aluminum 

because a large proportion of ingested aluminum passes quickly through the body. Drablos et al. (1992) 

analyzed aluminum urine concentrations in 230 nonexposed workers (controls) and reported a mean 

aluminum urine level of 0.005 mg/L (range, 0.001–0.037 mg/L). Nieboer et al. (1995) reviewed eight 

studies on aluminum concentrations in urine and reported that aluminum urine concentrations in healthy 

individuals typically ranged from 0.0027 to 0.0081 mg/L. In a Finnish study of aluminum in urine from 

3,212 occupationally exposed workers, mostly aluminum welders, between 1993 and 1996, the average 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 208 

6. POTENTIAL FOR HUMAN EXPOSURE 

annual urinary aluminum level was 1.4 μmol/L (0.038 mg/L) and the range was 1.08–2.04 μmol/L

(0.029–0.055 mg/L) (Valkonen and Aitio 1997). The samples, collected as part of a routine occupational 

health program, were collected after the weekend as a morning specimen. The mean urinary aluminum 

concentration in 44 nonexposed persons, who did not use antacid preparations, was 0.33 μmol/L

(0.0089 mg/L), and the range and standard deviation were 0.07–0.82 μmol/L (0.002–0.022 mg/L) and 

0.18 μmol/L (0.0022 mg/L), respectively. The mean serum aluminum concentration of 21 of these 

nonexposed individuals was 0.06 μmol/L (0.0016 mg/L), and the range and standard deviation were 0.02– 

0.13 μmol/L (0.0005–0.0035 mg/L) and 0.03 μmol/L (0.0008 mg/L), respectively. Drablos et al. (1992) 

studied aluminum concentrations in workers at an aluminum fluoride plant. Mean aluminum 

concentrations in urine were 0.011 mg/L (range, 0.002–0.046 mg/L) for 15 plant workers, 0.032 mg/L 

(range, 0.006–0.136 mg/L) for 7 foundry workers, and 0.054 mg/L (range, 0.005–0.492 mg/L) for 

12 potroom workers as compared to 0.005 mg/L (range, 0.001–0.037 mg/L) for 230 unexposed controls. 

Mean aluminum concentrations were 5.06 and 3.74 μg/L in blood, and 6.56 and 6.35 μg/L in urine of

103 workers in the optoelectronic industry and 67 controls, respectively (Liao et al. 2004). Pre- and 

postshift average aluminum concentrations in urine ranging from 0.13 to 0.153 mg/L were reported in 

welders from the construction industry (Buchta et al. 2005). Aluminum concentrations in human breast 

tissue and breast tissue fat of 4–437 nmol/g (0.1–12 μg/g) dry weight and 3–192 nmol/g oil (0.08– 

5.18 μg/g oil), respectively, have been reported (Exley et al. 2007). 

Nieboer et al. (1995) reported background concentrations of aluminum in bone of 1–3 μg/g dry weight. 

Background aluminum concentrations in brain tissues (primarily grey matter) of healthy individuals 

typically ranges from 1 to 3 μg/g dry weight or <0.5 μg/g wet weight (Nieboer et al. 1995). Markesbery 

et al. (1984) determined trace element concentrations in various human brain regions in infants through 

adults. Aluminum concentrations were shown to increase with increasing age. Mean aluminum 

concentrations in adults were 0.467 μg/g wet weight, as compared to 0.298 μg/g wet weight in infants. 

Overall aluminum concentrations ranged from ≤0.050 to 3.05 μg/g, with the highest mean aluminum

concentrations in the globus pallius (0.893 μg/g) and the lowest in the superior parietal lobule 

(0.282 μg/g). 

Metal concentrations were determined in spermatozoa and seminal plasma from men working in two 

industrial companies, a refinery and a polyolefin factory, 40 km east of Helsinki, Finland, and from sperm 

bank donor candidates from Helsinki, Finland in 1994. Aluminum concentrations in the factory 

employees were 0.93 and 0.54 mg/kg in spermatozoa and seminal plasma, respectively, and were 

2.52 and 0.87 mg/kg in spermatozoa and seminal plasma, respectively, in the donor candidates. The 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 209 

6. POTENTIAL FOR HUMAN EXPOSURE 

authors attributed the lower concentrations in the factory workers to good quality of occupational 

protection in the factories. In addition, the factory employees lived in the countryside as compared to the 

donor candidates, who lived in a more urban area (Hovatta et al. 1998). Mean aluminum concentrations 

in seminal plasma of 2,200, 1,530, and 270 μg/L were reported in samples collected from men working in 

smelter, refinery, and chemical industries respectively. A mean concentration of 460 μg/L was reported 

in hospital workers (control group) (Dawson et al. 2000). Mean aluminum concentrations ranged from 

18.0 to 101.0 μg/L in seminal plasma collected from 64 apparently healthy men (21–35 years of age) 

recruited from the University of Texas (Dawson et al. 1998). A mean aluminum concentration of 

15.0 μg/L was reported in sweat collected from the arms of 15 normal, healthy subjects while exercising 

(Omokhodion and Howard 1994). Sighinolfi et al. (1989) reported aluminum concentration ranging from 

25 to 102 μg/L in human saliva. 

Aluminum concentrations in hair ranging from 0.1 to 36 μg/g have been reported (Alder et al. 1976;

Caroli et al. 1994). Imahori et al. (1979) measured various elements in 202 human hair samples collected 

from a local population in the Tokyo metropolitan area. Aluminum was detected in 95 and 99 of the male 

and female hair samples, respectively. Mean aluminum concentrations were 13.7 mg/kg (range <0.24– 

65.0 mg/kg) and 13.6 mg/kg (<1.93–67.1 mg/kg) in male and female hair samples, respectively. 

Kobayashi et al. (1989) reported mean hair aluminum concentrations of 3.9 and 6.2 μg/g in patients with 

senile dementia of Alzheimer type and a control group, respectively. Shore and Wyatt (1983) reported 

aluminum concentrations of 7.5 and 6.2 ppm (μg/g) in hair from patients with Alzheimer’s disease and 

age-matched (nondemented) controls, respectively. Elemental concentrations were determined in hair 

from children (6–15 years old) living in environmentally degraded districts of the East Aral Sea region 

(Kazakhstan and Uzbekistan). Mean aluminum concentrations were 89.5 and 113.6 mg/kg in samples 

collected from two regions, Kazalinsk and Zhanakorgan, respectively (Chiba et al. 2004). Wilhelm et al. 

(1989) reported that use of hair analysis as an indicator of systematically incorporated metals may not be 

reliable, since endogenous metal concentrations in hair may be masked by the uptake of metals, including 

aluminum, from exogenous sources. 

Human albumin solutions and other biological products intended for human use may contain aluminum 

because aluminum compounds are used in their manufacture or as a result of contamination. In albumin 

products, aluminum is generally introduced as a contaminant from filters, filter aides, buffer solutions, 

and anticoagulants, as well as the container itself. The aluminum level in a 5% pooled human albumin 

solution was 0.507 μg/mL (Progar et al. 1996).
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 210 

6. POTENTIAL FOR HUMAN EXPOSURE 

Metal concentrations were measured in two lichen species (Parmelic conspersa and Xanthoria calcicola) 

from the island of Vulcano and around Mt. Etna, Sicily. Aluminum concentrations were 14,619 and 

17,964 mg/kg dry weight in lichens collected near Mt. Etna and Vulcano, respectively (Varrica et al. 

2000). 

Mean aluminum concentrations in the soft tissues of zebra mussels (Dreissena polymorpha) collected in 

1993 and 1994 from Lake Erie, Lake Ontario, and the Niagara River ranged from 232 to 5,030 mg/kg dry 

weight (Lowe and Day 2002). Whole fish composites were analyzed for various metals as part of a 

survey of 167 lakes in the northeastern United States as part of the Environmental Monitoring and 

Assessment Program (1992–1994); a mean aluminum concentration of 8.26 mg/kg wet weight (range 

0.26–114.5 mg/kg wet weight) was reported (Yeardley et al. 1998). Aluminum concentrations ranged 

from 2 to 4 mg/kg dry weight in the livers of various seabirds collected from the northern Pacific Ocean 

in 1992 (Elliott 2005). Mean aluminum concentrations in the feathers of nestling black-crowned nightherons in the Chesapeake and Delaware Bays ranged from 9.18 to 78.85 mg/kg dry weight (Golden et al. 

2003). 

An aluminum concentration of 25,948 mg/kg was reported in house dust from residences in Ottawa, 

Canada (Butte and Heinzow 2002). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

Since aluminum is ubiquitous in the environment, the general population will be exposed to aluminum by 

inhalation of ambient air and the ingestion of food and water. Pennington and Schoen (1995) reported 

average daily intakes of 8–9 and 7 mg/day for adult men and woman, respectively, based on an FDA 

Total Diet Study. According to the 1997 total diet study conducted by the Food Standards Agency, the 

average U.K. population dietary exposure to aluminum was estimated to be 3.4 mg/day (MAFF 1999). 

Greger (1992) estimated that most adults consume 1–10 mg aluminum per day from natural sources. 

Biego et al. (1998) reported a daily average intake for aluminum of 4.2 mg in a study in France. Food 

additives containing aluminum, including preservatives, coloring agents, anticaking agents, and leavening 

agents are major dietary sources of aluminum in the United States (Saiyed and Yokel 2005; Soni et al. 

2001). 

In a report on FDA's Total Diet Study, the foods highest in aluminum were those suspected of containing 

aluminum additives (e.g., processed cheese, grain products, and grain-based desserts) (Pennington 1987). 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 211 

6. POTENTIAL FOR HUMAN EXPOSURE 

Measured daily dietary intakes of aluminum were reported to range from 2 to 14 mg/day. The major 

contributors to aluminum in the diet are grain products (24–49%), dairy products (17–36%), desserts (9– 

26%), and beverages (5–10%) (Pennington 1987). FDA revised their Total Diet Study in 1991 to reflect 

current food consumption patterns and to include additional sex-age groups (Pennington and Schoen 

1995). Dietary intakes ranged from 0.7 mg/day for infants to 11.5 mg/day for 14–16-year-old males. The 

aluminum intake of adult males ranged from 8 to 9 mg/day and that for adult females was about 

7 mg/day. Dietary intakes for 2-, 6-, and 10-year-old children were 4.6, 6.5, and 6.8 mg/day, respectively. 

Aluminum intakes per kilogram of body weight were 0.10 mg/kg for infants, 0.35 mg/kg for 2-year-old 

children, and 0.30 mg/kg for 10-year-old children. The other sex age groups had aluminum intakes of 

0.10–0.15 mg/kg, except for 14–16-year-old males who had an aluminum intake of 0.18 mg/kg. Principal 

sources for aluminum were milk and diary products (36%), fish and crustaceans (29%), cereals (16%), 

and vegetables (8%). 

Saiyed and Yokel (2005) reported the aluminum content in various foods in the United States with 

aluminum food additives. Cheese from a frozen pizza was reported to contain up to 14 mg of aluminum 

from basic sodium aluminum phosphate. An equivalent amount of cheese from a ready-to-eat restaurant 

pizza contained 0.03–0.09 mg of aluminum. Up to 1.5 mg of aluminum were found in single serving 

packets of nondairy creamer containing sodium aluminosilicate. Products such as baking powder, 

pancake and waffle mixes, and ready-to-eat pancakes contained up to 180 mg of aluminum per serving 

(Saiyed and Yokel 2005). 

Cooking in aluminum containers often results in statistically significant, but not biologically important, 

increases in the aluminum content of some foods. In one study, increases in the aluminum content of 

foods after contact with aluminum utensils were <1 mg/kg for 47% of the food examined and <10 mg/kg 

for 85% of the food examined (Pennington and Schoen 1995). The migration of aluminum from 

cookware into food will increase with the acidity of the food and the duration of exposure. For example, 

red current juice was prepared by boiling berries for 3 hours in either an aluminum or stainless steel pot. 

The aluminum concentrations of the juice prepared in the aluminum pot was 89.1 mg/L, whereas the juice 

prepared in the stainless steel pot was 1.83 mg/L (Valkonen and Aitio 1997). Aluminum was also shown 

to migrate into fish baked on aluminum foil. Increases in aluminum concentration ranged from a factor of 

2 for saithe fillets baked on aluminum foil without added ingredients (0.10–0.21 mg/kg) to a factor of 

about 70 for mackerel fillets grilled on aluminum foil with onion rings and mixed spices (0.07– 

5.04 mg/kg). The migration of aluminum into foods appeared to be dependent on factors such as 

temperature, duration of cooking, the composition and pH of the food, and the presence of other 
 

 

 

 

 

 

 

 

 

ALUMINUM 212 

6. POTENTIAL FOR HUMAN EXPOSURE 

substances (e.g., organic acids and salt) (Ranau et al. 2001). A study by Lin et al. (1997) noted that 

cooking with aluminum utensils may be an important aluminum exposure source for patients with chronic 

renal disease. 

The intake of aluminum in foods is low compared with the amount of aluminum consumed when taking 

aluminum-containing medication, such as antacids, buffered aspirins, antidiarrheal agents, and certain 

anti-ulcer drugs at their recommended dosages (Lione 1983, 1985a; Pennington and Schoen 1995; Soni et 

al. 2001; Zhou and Yokel 2005). Antacids and buffered aspirin, which are often taken in multiple daily 

doses for prolonged periods, contain 4–562 mg/kg of aluminum (Lione 1983; Schenk et al. 1989; Shore 

and Wyatt 1983). For example, according to Pennington and Schoen (1995), buffered aspirin may 

contain 10–20 mg of aluminum per tablet. Many antacids contain 300–600 mg aluminum hydroxide 

(approximately 104–208 mg of aluminum) per tablet/capsule/5 mL dose (Zhou and Yokel 2005). Other 

exposures to aluminum can occur through the use of cosmetics and other consumer products containing 

aluminum compounds (Lewis 2001; NIH 2004; O’Neil et al. 2001). 

Pennington and Schoen (1995) reported average daily intakes of 8–9 and 7 mg/day for adult men and 

woman, respectively, based on an FDA Total Diet Study. According to the 1997 total diet study 

conducted by the Food Standards Agency, the average U.K. population dietary exposure to aluminum was 

estimated to be 3.4 mg/day (MAFF 1999). Biego et al. (1998) reported a daily average intake for 

aluminum of 4.2 mg in a study in France. 

Lione (1985a) estimated that 126–728 and 840–5,000 mg were possible daily doses of aluminum 

consumed in buffered aspirins and antacids products, respectively. These doses are from 6 to almost 

40 times and 42–250 times greater, respectively, than aluminum doses obtained from consumption of 

food. When large oral loads of aluminum (1,000–4,000 mg/day) in the form of antacids are ingested, 

some of this excess aluminum is absorbed, usually <1% of the intake amount in healthy individuals 

(Gorsky et al. 1979; Kaehny et al. 1977; Reiber et al. 1995). 

Median concentrations of aluminum in drinking water not receiving coagulation treatment and that 

receiving coagulation treatment have been reported as 0.043 and 0.112 mg/L, respectively (Miller et al. 

1984a). If the total dose of aluminum obtained from water is calculated based on an estimated 

consumption of 1.4 L/day, the amount of aluminum ingested would respectively be 0.06 and 0.16 mg/day 

or roughly 1% of the 7–9 mg/day for adults from dietary sources. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 213 

6. POTENTIAL FOR HUMAN EXPOSURE 

While the intake of aluminum is mainly through the ingestion of food and drinking water, inhalation of 

ambient air represents a small contribution to an individual’s exposure to aluminum (Browning 1969). 

Background concentrations of aluminum in the atmosphere generally range from 0.005 to 0.18 μg/m3 in 

the United States (Hoffman et al. 1969; Sorenson et al. 1974). If the inhalation rate is taken to be 

20 m3

/day, then the total amount of aluminum obtained from inhalation of 0.18 μg/m3 would be 

3.6 μg/day, suggesting that ambient air is not normally a major exposure pathway for aluminum. This is

negligible compared with the estimated dietary intake for adults of 7–9 mg/day. However, the aluminum 

content of air in urban and industrial areas has been reported to be considerable higher, ranging from 

0.4 to 8.0 μg/m3 (Cooper et al. 1979; Dzubay 1980; Kowalczyk et al. 1982; Lewis and Macias 1980; 

Moyers et al. 1977; Ondov et al. 1982; Pillay and Thomas 1971; Sorenson et al. 1974; Stevens et al. 

1978). If the inhalation rate is taken to be 20 m3

/day, then the total amount of aluminum inhaled would 

range from 8 to 160 μg/day, which is still negligible compared with the aluminum intake from dietary 

sources. Dusts arising from soil, especially in industrial or agricultural areas (Eisenreich 1980), and from 

the metal surfaces of air conditioners can contain large amounts of aluminum (Crapper McLachlan 1989), 

resulting in high localized concentrations and, subsequently, in higher exposures. Typically, however, for 

the general population, inhalation is likely to be less important as an exposure pathway than is dietary 

exposure to aluminum, but may represent a source of greater exposure in some urban environments. 

Occupational exposure to aluminum occurs not only in the refining of the primary metal, but also in 

secondary industries that use aluminum products (e.g., aircraft, automotive, and metal products), and 

aluminum welding (Nieboer et al. 1995). Three major steps are involved in primary aluminum 

production. Aluminum is first extracted with caustic soda from bauxite ore, precipitated as aluminum 

hydroxide, and subsequently converted to aluminum oxide in a calcination process. In the second step, 

the oxide is dissolved in molten cryolite (Na3AlF6) and electrolyzed to yield the pure molten metal. The 

electrolytic cells are called pots and the work area is called the potroom. Casting is the final step in the 

process where molten aluminum is poured into ingots in the foundry. Exposure is primarily to aluminum 

hydroxide and oxide in the initial extraction and purification process, to aluminum oxide and aluminum 

fluoride in the potroom (as well as to tar-pitch volatiles including PAHs), and to partially oxidized 

aluminum metal fumes in the foundry (Drablos et al. 1992; IARC 1984; Nieboer et al. 1995). 

Most of the studies of occupational exposure (aluminum refining and metal industry workers) to 

aluminum have dealt with inhalation of aluminum-containing dust particles. Rarely is a worker exposed 

solely to aluminum-containing dust; exposure to mixtures of aluminum with fine respirable particles or 

other toxic chemicals is more prevalent. For example, it had been observed that the incidence of bladder 
 

 

 

 

 

 

 

 

ALUMINUM 214 

6. POTENTIAL FOR HUMAN EXPOSURE 

cancer was unusually high among aluminum reduction workers. An epidemiological study showed that 

volatile PAHs in coal tar pitch, however, were the actual causative agents (Theriault et al. 1984a). 

Synergism among metal dusts, fine particles, toxic chemicals including PAHs, and cigarette smoke is a 

highly plausible cause of skin irritation and cancers appearing in workers for many industrial processes 

involving aluminum. 

According to the National Occupational Exposure Study (NOES) conducted by NIOSH from 1981 to 

1983, the industries with the largest numbers of workers potentially exposed to aluminum and aluminum 

compounds include: plumbing, heating, and air conditioning; masonry and other stonework; electrical 

work; machinery except electrical; certified air transportation equipment; electrical components; 

fabricated wire products; general medical and surgical hospitals; industrial buildings and warehouses; and 

special dies, tools, jigs, and fixtures (NIOSH 1991). 

A group of 44 aluminum welders in the train body and truck trailer construction industry were monitored 

for aluminum exposure (Buchta et al. 2005). Median aluminum concentrations of 5.6 mg/m3 (range: 0– 

31.5 mg/m3

) and 4.5 mg/m3 (range: 1.3–15.6 mg/m3) in respirable dust in air were reported in welding 

fumes in 1999 and 2001, respectively. Median aluminum concentrations in aluminum welders were 

152.7 μg/L (range: 2.9–656.3 μg/L) and 145.5 μg/L (range: 5.0–656.3 μg/L) in urine in pre- and 

post-shift samples in 2001, respectively. Median aluminum concentrations in aluminum welders were 

10.6 μg/L (range: 3.3–40.3 μg/L) and 14.3 μg/L (range: 3.8–51.0 μg/L) in plasma in pre- and post-shift 

samples in 2001, respectively (Buchta et al. 2005). 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7, Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 
 

 

 

 

 

 

 

 

 

ALUMINUM 215 

6. POTENTIAL FOR HUMAN EXPOSURE 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

As with adults, exposures of children to aluminum from breathing air, drinking water, and eating food is 

generally low. As aluminum is part of the natural environment and found widely in soils, rocks, and 

foods, exposure to low levels of aluminum is unavoidable. Children are likely to ingest dirt from their 

unwashed hands or when playing with soils and may be exposed to aluminum in this manner. Children 

living in proximity to hazardous waste sites or industries that release aluminum to the environment may 

be exposed to higher levels of aluminum than are found in the natural environment via ingestion of 

aluminum contained in soil, or via inhalation of aluminum from soil that is entrained in air. While 

aluminum contained in dirt may be in many forms, some of these forms may be embedded in minerals not 

bioavailable even in the acid environment of the stomach. 

When FDA revised their Total Diet Study in 1991, several sex-age groups relating to children were 

included (Pennington and Schoen 1995). Average dietary intakes of aluminum in children are shown in 

Table 6-5. Dietary intakes of aluminum for children ranged from 0.7 mg/day for infants to 11.5 mg/day 

for 14–16-year-old males. Aluminum intakes per kilogram of body weight for children ranged from 

0.10 mg/kg for infants to 0.35 mg/kg for 2-year-old children. The major sources of aluminum in food by 

age-sex group are shown in Table 6-6. Processed foods containing aluminum additives such as processed 

cheese and grain-based products constitute the foods with the largest quantities of aluminum and the 

largest components of the dietary intake of children. Soy-based formula may contain high quantities of 

aluminum and infants on such formula would have much higher dietary intakes of aluminum than other 

infants. Pennington and Schoen (1995) reported that soy-based infant formula was a major contributor to 

aluminum for infants, contributing 0.161 mg/day. 

As with adults, aluminum intake from aluminum-containing medication, such as antacids, buffered 

aspirins, and antidiarrheal agents would overwhelm ordinary dietary intakes (Pennington and Schoen 

1995). Children may be exposed to aluminum from aluminum-containing medications, vaccinations, 

parenteral feeding, dialysis fluids, and treatment for hyperphosphatemia (Advenier et al. 2003; Andreoli 

et al. 1984; Baylor et al. 2002; Bougle et al. 1991; Bozynski et al. 1989; Chedid et al. 1991; Goyens and 

Brasseur 1990; Griswold et al. 1983; Klein et al. 1989; Koo et al. 1986, 1992; Malakoff 2000; Milliner et 

al. 1987; Moreno et al. 1994; Naylor et al. 1999; Offit and Jew 2003; Randall 1983; Robinson et al. 1987; 

Salusky et al. 1990; von Stockhausen et al. 1990; Warady et al. 1986). Advenier et al. (2003) reported a 

mean aluminum concentration of 1.6 μmol/L (0.043 mg/L) in parenteral nutrition solutions, resulting 
ALUMINUM 216 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Dietary Intakes of Aluminum in Children 

Aluminum intake 

Age-sex group (mg/day) (mg/kg) 

6–11-Months 0.7 0.10 

2-Years 4.6 0.35 

6-Years 6.5 0.30 

10-Years 6.8 0.11 

14–16-Years (females) 7.7 0.15 

14–16-Years (males) 11.5 0.18 

Source: Pennington and Schoen 1995 
ALUMINUM 217 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Major Sources of Aluminum in Food by Age-Sex Group 

Aluminum/day 

Foods by age-sex group (Al/day) mg Percent of total intake 

6–11-month-old infants (0.7 mg) 

Soy-based formula 

American processed cheese 

Yellow cake with icing 

Green beans, strained 

0.161 

0.122 

0.088 

0.038 

23.0 

17.4 

12.6 

5.4 

Pancakes 0.029 4.1 

Total 0.438 62.6 

2-year-old children (4.6 mg) 

Cornbread 1.580 34.3 

American processed cheese 

Yellow cake with icing 

Fish sticks 

1.037 

0.384 

0.173 

22.5 

8.3 

5.4 

Pancakes 0.113 2.5 

Tortillas 0.093 2.0 

Muffins 0.093 2.0 

Fruit drink from powder 

Taco/tostada 

Tea 

0.079 

0.071 

0.061 

1.7 

1.5 

1.3 

Total 3.684 80.1 

6-year-old children (6.5 mg) 

American processed cheese 

Yellow cake with icing 

Pancakes 

1.382 

1.091 

0.752 

21.3 

16.8 

11.6 

Fish sticks 0.529 8.1 

Cornbread 0.450 6.9 

Tortillas 0.297 4.6 

Taco/tostada 

Muffins 

0.209 

0.202 

3.2 

3.1 

Hamburger 

Fruit drink from powder 

Total 

0.104 

0.105 

5.121 

1.6 

1.6 

78.8 

10-year-old children (6.8 mg) 

American processed cheese 

Cornbread 

1.498 

1.105 

22.0 

16.3 

Pancakes 0.858 12.6 

Tortillas 0.344 5.1 

Yellow cake with icing 

Fish sticks 

0.350 

0.280 

5.1 

4.1 

Taco/tostada 0.259 3.8 
ALUMINUM 218 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Major Sources of Aluminum in Food by Age-Sex Group 

Aluminum/day 

Foods by age-sex group (Al/day) mg Percent of total intake 

Muffins 0.207 3.0 

Chocolate cake with icing 0.141 2.1 

Chocolate snack cake 0.144 2.1 

Total 5.186 76.3 

14–16-year-old females (7.7 mg) 

American processed cheese 2.139 27.8 

Yellow cake with icing 0.906 11.8 

Cornbread 0.781 10.1 

Taco/tostada 0.682 8.9 

Pancakes 0.668 8.7 

Tortillas 0.325 4.2 

Muffins 0.219 2.8 

Cheeseburger 0.183 2.4 

Tea 0.159 2.1 

Fish sticks 0.125 1.6 

Total 6.187 80.4 

14–16-year-old males (11.5 mg) 

Cornbread 4.209 36.6 

American processed cheese 1.978 17.2 

Pancakes 1.038 9.0 

Yellow cake with icing 0.925 8.0 

Taco/tostada 0.398 3.5 

Tortillas 0.398 3.5 

Cheeseburger 0.310 2.7 

Tea 0.225 2.0 

Hamburger 0.211 1.8 

Fish sticks 0.170 1.5 

Total 9.862 85.8 

Source: Pennington and Schoen 1995 
 

 

 

 

 

 

 

ALUMINUM 219 

6. POTENTIAL FOR HUMAN EXPOSURE 

in a mean aluminum daily intake of 0.08 μmol/kg/day (0.002 mg/kg/day). An upper limit of 0.90 μg/L 

for aluminum in all large-volume parenteral solutions used in total parenteral nutrition therapy was set by 

the FDA (Advenier et al. 2003). Aluminum compounds such as aluminum hydroxide, aluminum 

phosphate, or aluminum sulfate (alum) are commonly used as an adjuvant in many vaccines licensed by 

the FDA; the amount of aluminum in vaccines is limited to no more than 0.85 mg/dose (Baylor et al. 

2002). 

Elevated levels of aluminum may be found in the tissues and fluids of children undergoing treatments, 

such as parenteral feeding or dialysis, or if they are receiving aluminum-containing medications 

(Advenier et al. 2003; Andreoli 1990; Andreoli et al. 1984; Bougle et al. 1991; Bozynski et al. 1989; 

Chedid et al. 1991; Goyens and Brasseur 1990; Griswold et al. 1983; Klein et al. 1989; Koo et al. 1986, 

1992; Milliner et al. 1987; Moreno et al. 1994; Naylor et al. 1999; Robinson et al. 1987; Roodhooft et al. 

1987; Salusky et al. 1986, 1990; von Stockhausen et al. 1990); however, these levels are atypical of the 

general population. 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

In addition to individuals who are occupationally exposed to aluminum (see Section 6.5), there are several 

groups within the general population that have potentially higher exposures (higher than background) 

than the general population. These populations include members of the general population living in the 

vicinity of industrial emission sources and hazardous waste sites, individuals with chronic kidney failure 

requiring long-term hemodialysis treatment, infants fed a formula diet containing high levels of 

aluminum, and individuals consuming large quantities of antacid formulations for gastric disorders, antiulcerative medications, buffered analgesics for arthritis, or antidiarrheal medications. Furthermore, the 

elderly are at risk because of multiple chronic diseases including ulcers and other gastrointestinal 

diseases, rheumatoid arthritis, and renal disorders. Aluminum has been detected in virtually all food 

products (especially plant-derived and processed foods), ambient air, drinking water, and soils. 

Substantially higher concentrations of aluminum have been detected in localized areas around some 

industrial and hazardous waste disposal sites. 

Individuals living or working in proximity to aluminum production facilities may be exposed to higher 

concentrations of aluminum in the ambient air than members of the general population. In addition, 

individuals living in proximity to hazardous waste sites may be exposed to aluminum via ingestion of 

aluminum contained in soil from their unwashed hands when working or playing with contaminated soils 
 

 

 

 

 

 

 

 

 

ALUMINUM 220 

6. POTENTIAL FOR HUMAN EXPOSURE 

and sediments. Children in particular are likely to ingest dirt from their unwashed hands, or inhale 

resuspended dust during near-ground activities. If residential wells are the primary source of drinking 

water, this may also pose a risk to human health via consumption of contaminated drinking water. 

Individuals with chronic renal failure requiring long-term hemodialysis treatment are another group 

within the general population that may be exposed to greater than background levels of aluminum (Alfrey 

1987; Chappuis et al. 1988, 1989; Chedid et al. 1991; Fernández-Martin et al. 1998; Griswold et al. 1983; 

Lione 1985a; Marumo et al. 1984; Muller et al. 1993b; Salusky et al. 1990; Winterberg et al. 1987). 

Elevated levels of aluminum may be found in the tissues and fluids of individuals undergoing treatments, 

such as hemodialysis, or if they are receiving aluminum-containing medications (Chappuis et al. 1988, 

1989; Chedid et al. 1991; Griswold et al. 1983; Marumo et al. 1984; Salusky et al. 1990; Tsukamoto et al. 

1979; Winterberg et al. 1987); however, these levels are atypical of the general population. Aluminum 

levels in virtually every body tissue are significantly higher in this group of patients if aluminum is 

present in the dialysate (Alfrey et al. 1980; Cooke and Gould 1991). In addition, Main and Ward (1992) 

reported a 10-fold increased serum aluminum concentration in a hemodialysis patient after she was 

prescribed effervescent analgesic tablets containing citrate. This patient was already taking aluminum 

hydroxide capsules. Once the effervescent analgesic tablets were discontinued, the patient’s serum 

aluminum levels fell to acceptable levels within 3 weeks. Since citrate appeared to enhanced aluminum 

absorption, these authors stated that patients with renal failure taking aluminum compounds should not be 

prescribed citrate-containing preparations. In a study by Fernández-Martin et al. (1998), a decrease in 

serum aluminum concentrations in patients on hemodialysis over the past 10 years was observed, from 

61.8 μg/L in 1988 to 25.7 μg/L in 1996. These reductions have been achieved due to the restriction of the 

use of oral aluminum hydroxide, as well as to the use of adequate water treatment systems. 

The oral intake of aluminum tends to be higher for children than for adults (Greger 1992). Calculations 

based on the FDA’s Total Diet Study suggest that 2-year-old children (13 kg body weight) consumed 

almost 3 times as much aluminum per kg body weight as adult males (75 kg body weight) or adult 

females (60 kg body weight), respectively (0.48 versus 0.18 and 0.15 mg aluminum/kg body weight, 

respectively) (Greger 1992). Infants fed milk-based or soy-based infant formulas can be exposed to 

higher concentrations of aluminum than infants fed breast milk or cows’ milk (see Section 6.4.4). Within 

this group, the infants believed to be most at risk would be preterm infants with impaired renal function 

because they would be less able to excrete the absorbed aluminum (Bishop 1992; Greger 1992; Koo et al. 

1988, 1992; Weintraub et al. 1986). 
 

 

 

 

 

 

 

 

ALUMINUM 221 

6. POTENTIAL FOR HUMAN EXPOSURE 

As discussed in Section 6.4.4, individuals consuming large quantities of antacid formulations, antiulcerative medications, buffered analgesics, or antidiarrheal medications are exposed to higher than 

background doses of aluminum in their diet. Lione (1985a) estimated that 126–728 and 840–5,000 mg 

were possible daily doses of aluminum consumed in buffered aspirins for rheumatoid arthritis and antacid 

products, respectively. These doses are 6–40 and 42–250 times greater, respectively, than aluminum 

doses obtained from consumption of foods (3.4–9 mg/day) (Biego et al. 1998; MAFF 1999; Pennington 

and Schoen 1995). 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of aluminum is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of aluminum. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of aluminum and 

various aluminum-containing compounds are sufficiently well defined to allow an assessment of the 

environmental fate of these compounds (HSDB 2008; Lewis 2001; Lide 2005; O’Neil et al. 2001). No 

additional data are needed at this time. 

Production, Import/Export, Use, Release, and Disposal. According to the Emergency 

Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required 

to submit substance release and off-site transfer information to the EPA. The TRI, which contains this 

information for 2005, became available in May of 2007. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 
 

 

 

 

 

 

 

 

 

ALUMINUM 222 

6. POTENTIAL FOR HUMAN EXPOSURE 

Because aluminum compounds occur naturally (Browning 1969; Dinman 1983; IARC 1984; NRC 1982) 

and are widely used in industry, in the manufacture of household products, and in processing, packaging, 

and preserving food (Browning 1969; Lewis 2001; O’Neil et al. 2001; Stokinger 1981; Venugopal and 

Luckey 1978), the potential for human exposure to these compounds through ingestion of food and water 

and inhalation of airborne particulates is substantial. Recent data on production, import/export, and use 

are available (Lewis 2001; O’Neil et al. 2001; USGS 2007a, 2007c). Information on disposal of 

aluminum compounds is limited. In the United States, about 3 million metric tons of aluminum was 

recovered from purchased scrap in 2005 (USGS 2007b, 2007c). TRI data are available for releases of 

aluminum, as fume or dust and as aluminum oxide (fibrous forms) (TRI05 2007). Additional information 

on disposal would be useful in assessing the potential for the release of and exposure to aluminum 

compounds. 

Environmental Fate. Aluminum partitions to air, water, soil, and plant material. As an element, 

aluminum cannot be degraded in the environment; it can undergo various precipitation or ligand exchange 

reactions in the environment. Its partitioning to various media is determined by the physical and chemical 

properties of the aluminum compound and the characteristics of the environmental matrix that affects its 

solubility (Brusewitz 1984; Dahlgren and Ugolini 1989; Filipek et al. 1987; Goenaga and Williams 1988; 

James and Riha 1989; Litaor 1987; Mulder et al. 1989; Wangen and Jones 1984). Aluminum is 

transported through the atmosphere primarily as a constituent of soil and other particulate matter 

(Eisenreich 1980). Transformations are not expected to occur during transport of aluminum through the 

atmosphere. Aluminum partitions between solid and liquid phases by reacting and complexing with 

water molecules, anions, and negatively charged functional groups on humic materials and clay (Bodek et 

al. 1988). Information on the environmental fate of aluminum is sufficient to permit a general 

understanding of transport and transformation in all environmental media. No additional information is 

needed at this time. 

Bioavailability from Environmental Media. Aluminum compounds are deposited in the lungs 

following inhalation (Christie et al. 1963; Steinhagen et al. 1978; Stone et al. 1979; Thomson et al. 1986) 

and are poorly absorbed following ingestion (Hohl et al. 1994; Priest et al. 1998; Stauber et al. 1999; 

Steinhausen et al. 2004). A fractional absorption of 1.5–2% was estimated based on the relationship 

between urinary aluminum excretion and the airborne soluble aluminum to which workers were exposed 

(Yokel and McNamara 2001). Very limited information is available regarding absorption following 

dermal contact; however, this pathway of exposure is not expected to be significant. Additional 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 223 

6. POTENTIAL FOR HUMAN EXPOSURE 

information on absorption following ingestion of soils contaminated with aluminum compounds and 

dermal contact would be useful in assessing bioavailability following exposure via these routes, 

particularly at hazardous waste sites. 

Food Chain Bioaccumulation. Little information is available on the uptake of aluminum into food 

crops. Uptake into root crops is of particular importance, since many plant species concentrate aluminum 

in their roots (DOE 1984; Kabata-Pendias and Pendias 1984; Vogt et al. 1987). The limited information 

available on bioconcentration in animals appears to indicate that aluminum is not significantly taken up 

by livestock (DOE 1984). The fact that in studies dealing with aluminum in food, aluminum is generally 

present in low concentrations in fruit, vegetables, and meat products that do not contain aluminum 

additives or have other contact with aluminum (e.g., cooked in aluminum pots) (Greger et al. 1985; 

MAFF 1999; Pennington 1987; Pennington and Schoen 1995; Schenk et al. 1989; Sorenson et al. 1974), 

would support a conclusion that aluminum does not bioaccumulate in the food chain. Because of its 

toxicity to many aquatic species, aluminum does not bioconcentrate appreciably in fish and shellfish and 

therefore, it would not be a significant component of the diet of animals that feed upon them (Rosseland 

et al. 1990). Further studies on the uptake of aluminum by plants, especially those grown on acid soils, 

would be useful in expanding a limited database and characterizing the importance of food chain 

bioaccumulation of aluminum as a source of exposure for particular population groups. 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of aluminum 

in contaminated media at hazardous waste sites are needed so that the information obtained on levels of 

aluminum in the environment can be used in combination with the known body burden of aluminum to 

assess the potential risk of adverse health effects in populations living in the vicinity of hazardous waste 

sites. 

Estimates of human exposure to aluminum from food (Biego et al. 1998; Greger 1992; MAFF 1999; 

Pennington 1987; Pennington and Schoen 1995; Saiyed and Yokel 2005; Schenk et al. 1989; Sorenson et 

al. 1974), drinking water (Cech and Montera 2000; DOI 1970; Letterman and Driscoll 1988; Miller et al. 

1984a; Schenk et al. 1989), and air (Browning 1969; Crapper McLachlan 1989; Sorenson et al. 1974) are 

available, as are estimates from exposure from antacids, buffered analgesics, antidiarrheal and antiulcerative compounds (Lione 1983, 1985a; Schenk et al. 1989; Shore and Wyatt 1983; Zhou and Yokel 

2005). Information on the intake of aluminum from vitamins and other dietary supplements is lacking 

and would be useful in estimating human exposure. Additional information on the occurrence of 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 224 

6. POTENTIAL FOR HUMAN EXPOSURE 

aluminum in the atmosphere, surface water, groundwater, and soils surrounding hazardous waste sites 

would be helpful in updating estimates of human intake. 

Exposure Levels in Humans. Measurements of the aluminum content in human tissues, especially 

in blood (Berlyne et al. 1970; de Kom et al. 1997; Drablos et al. 1992; Fuchs et al. 1974; House 1992; 

Liao et al. 2004; Nieboer et al. 1995; Razniewska and Trzcinka-Ochocka 2003; Sorenson et al. 1974), 

urine (Buchta et al. 2005; Drablos et al. 1992; Liao et al. 2004; Nieboer et al. 1995; Razniewska and 

Trzcinka-Ochocka 2003; Valkonen and Aitio 1997), and breast milk (Baxter et al. 1991; FernandezLorenzo et al. 1999; Hawkins et al. 1994; Koo et al. 1988; Mandić et al. 1995; Simmer et al. 1990;

Weintraub et al. 1986), are available. However, Versieck and Cornelis (1980) discussed the possibility of 

aluminum contamination in blood and plasma samples from some of early studies. This may question the 

reliability of aluminum levels reported in some older reports. 

Measurements of aluminum in other human tissues and fluids, such as bone, brain, saliva, spermatozoa, 

and seminal fluid are also available (Dawson et al. 1998, 2000; Hovatta et al. 1998; Markesbery et al. 

1984; Nieboer et al. 1995; Sighinolfi et al. 1989). However, recent biological monitoring data, 

particularly for aluminum in blood and urine, are limited. More recent information would be useful in 

assessing current exposure levels. Additional biological monitoring data for populations surrounding 

hazardous waste sites would be useful in helping to better characterize human exposure levels. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Measurements of the aluminum content in tissues, blood, and urine of 

children who have been exposed to aluminum, as well as unexposed children, are limited. Chiba et al. 

(2004) reported aluminum concentrations in hair of children. Al-Saleh and Shinwari (1996) reported 

aluminum concentrations in serum samples of girls aged 6–8 years. Hawkins et al. (1994) and Litov et al. 

(1989) reported plasma aluminum concentrations in infants fed various formulas and breast milk. Studies 

measuring aluminum concentrations in tissues, blood, and urine of specialized groups of children (e.g., 

infants with renal failure or on parenteral nutrition) have also been reported (Advenier et al. 2003; 

Andreoli 1990; Andreoli et al. 1984; Bougle et al. 1991; Bozynski et al. 1989; Chedid et al. 1991; Goyens 

and Brasseur 1990; Griswold et al. 1983; Klein et al. 1989; Koo et al. 1986, 1992; Milliner et al. 1987; 

Moreno et al. 1994; Naylor et al. 1999; Robinson et al. 1987; Roodhooft et al. 1987; Salusky et al. 1986, 

1990; von Stockhausen et al. 1990). 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 225 

6. POTENTIAL FOR HUMAN EXPOSURE 

Additional information monitoring aluminum concentrations in children would be useful in assessing 

both the normal aluminum content of children and the effect of exposure on aluminum concentrations in 

children. This information would also be useful in assessing differences in the effect of aluminum 

exposure on children to that of adults. While the largest source of aluminum exposure in adults is from 

aluminum-containing medications and cosmetics, we do not know the amount of such products that may 

be given to children. Additional information on the intake of available aluminum from soil during 

childhood activities, or the placental transfer to fetal blood, especially among pregnant women taking 

antacids as a result of abdominal upsets, would be useful in assessing exposure levels in children. 

Data are available on the intake of aluminum in food eaten by children and from their diet (Dabeka and 

McKenzie 1990; Koo et al. 1988; Pennington and Schoen 1995; Pennington 1987; Simmer et al. 1990; 

Weintraub et al. 1986). Aluminum concentrations in human breast milk, infant formula, and cow’s milk 

have been reported. The aluminum content of human breast milk generally ranged from 9.2 to 49 μg/L, 

lower than that reported in infant formulas (Fernandez-Lorenzo et al. 1999; Hawkins et al. 1994; Koo et 

al. 1988; Simmer et al. 1990; Weintraub et al. 1986). Soy-based infant formulas contain higher 

concentrations of aluminum, as compared to milk-based infant formulas or breast milk. Recent reports 

provide average aluminum concentrations ranging from 460 to 930 μg/L for soy-based infant formulas 

and from 58 to 150 μg/L for milk-based formulas (Fernandez-Lorenzo et al. 1999; Ikem et al. 2002; 

Navarro-Blasco and Alvarez-Galindo 2003). Infant formulas are much higher in aluminum than human 

breast milk. Daily intakes of aluminum for infants in the United States were estimated to be 97, 573, and 

361 μg/day from milk-based powder formulas, soy-based powder formulas, and hypoallergenic powder 

formulas, respectively (Ikem et al. 2002). 

Child health data needs relating to susceptibility are discussed in Section 3.12.2, Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for aluminum were located. This substance is not 

currently one of the compounds for which a sub-registry has been established in the National Exposure 

Registry. The substance will be considered in the future when chemical selection is made for subregistries to be established. The information that is amassed in the National Exposure Registry facilitates 

the epidemiological research needed to assess adverse health outcomes that may be related to exposure to 

this substance. 
 

 

 

ALUMINUM 226 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2006) database provides additional information obtainable 

from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1. These 

studies are summarized in Table 6-7. 
 

 

ALUMINUM 227 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-7. Ongoing Studies on Aluminum 

Investigator Affiliation Research description Sponsor 

Longnecker, M Not provided This research proposes to study elemental 

concentrations in toenails, which may provide 

a good measure of exposure for various 

elements, including aluminum. 

NIH 

Yokel, RA University of 

Kentucky, 

Lexington, 

Kentucky 

The overall objective of the proposed 

research is to test the null hypothesis that the 

bioavailability of aluminum is comparable 

from foods and from drinking water. 

NIH 

NIH = National Institutes of Health 

Source: FEDRIP 2006 
ALUMINUM 228
 

6. POTENTIAL FOR HUMAN EXPOSURE 

This page is intentionally blank. 
 

 

 

 

 

 

 

ALUMINUM 229 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring aluminum, its metabolites, and other biomarkers of exposure and effect to 

aluminum. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is 

to identify well-established methods that are used as the standard methods of analysis. Many of the 

analytical methods used for environmental samples are the methods approved by federal agencies and 

organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other 

methods presented in this chapter are those that are approved by groups such as the Association of 

Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). 

Additionally, analytical methods are included that modify previously used methods to obtain lower 

detection limits and/or to improve accuracy and precision. 

7.1 BIOLOGICAL MATERIALS 

Because of the ubiquitous nature of aluminum, contamination is a major problem encountered in the 

analysis of aluminum by all methods except accelerator mass spectroscopy (AMS) using radioactive 26Al. 

When using the other methods, all items used during collection, preparation, and assay should be checked 

for aluminum contribution to the procedure. Only by taking these stringent precautions will one be able 

to produce accurate results. A variety of analytical methods have been used to measure aluminum levels 

in biological materials, including AMS, graphite furnace atomic absorption spectrometry (GFAAS), flame 

atomic absorption spectrometry (FAAS), eletrothermal atomic absorption spectrometry (ETAAS), 

neutron activation analysis (NAA), inductively coupled plasma-atomic emission spectrometry (ICPAES), inductively coupled plasma-mass spectrometry (ICP-MS), and laser microprobe mass spectrometry 

(LAMMA) (Roggli et al. 1999; Maitani et al. 1994; Owen et al. 1994; Razniewska and Trzcinka-Ochocka 

2003; Van Landeghem et al. 1994) (see Table 7-1). Front-end separation techniques such as 

chromatography are frequently coupled with analytical methods. 

AMS is a technique that can now be used to accurately determine the atomic content in as little as a few 

milligrams of biological material. AMS has been used in the past for measuring long-lived radionuclides 

that occur naturally in our environment, but it is suitable for analyzing the ratio of the concentrations of 

radioactive 26Al to stable 27Al in biological samples. AMS combines a particle accelerator with ion 

sources, large magnets, and detectors, and is capable of a detection limit of one atom in 1015 (1 part per 

quadrillion [ppq]). This method has biomedical applications regarding the uptake and distribution of 

aluminum in the body, but is dependent upon the availability of the radioactive 26Al tracer, which is 
 

 

 

 

 

ALUMINUM	 230 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Aluminum in Biological Materials 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

GFAAS Low μg/L 

levels 

GFAAS 2 μg/L

GFAAS 14.3 μg/L

HPLC/ICP-AES No data 

No data	 King et al. 

1981 

No data	 Alderman 

and 

Gitelman 

1980 

97–102%	 Bettinelli et 

al. 1985 

No data	 Maitani et al. 

1994 

98–100% in Wrobel et al. 

spiked and 1995 

synthetic 

serum 

99.2±12.4% Van 

Landeghem 

et al. 1994 

97–105%	 Wawschinek 

et al. 1982 

No data	 Gardiner et 

al. 1981 

No data	 Gorsky and 

Dietz 1978 

No data	 Van der 

Voet et al. 

1985 

No data	 Blotcky et al. 

1976 

No data	 Sanz-Medel 

et al. 1987 

No data	 Razniewska 

and 

TrzcinkaOchocka 

(2003) 

No data	 Gorsky and 

Dietz 1978 

No data	 Gorsky and 

Dietz 1978 

Serum 

Serum 

Serum 

Serum (Alorganic acid 

species) 

Serum (Alorganic acid 

species) 

Serum (Alorganic acid 

species) 

Plasma 

Whole blood, 

plasma, or 

serum 

Whole blood 

Whole blood 

Urine 

Urine and blood 

Direct injection into atomizer 

Dilution with water; addition of 

EDTA 

Centrifugation and injection of 

supernatant 

Addition of sodium 

bicarbonate; direct injection 

into chromatography column 

Dilution with mobile phase; 

fractions collected for ETAAS 

analysis 

Addition of citrate buffer; 

direct injection into 

chromatography column 

Dilution 

Dilution with water 

Addition of sodium citrate; 

centrifugation; injection of 

supernatant 

Dilution with Triton X-100 

Digestion; ion-exchange 

clean-up 

Dilution with water 

Urine and serum Dilution with 0.2% nitric acid 

and water 

Urine Direct injection 

Urine Direct injection 

HPLC/ETAAS 

HPLC/ETAAS 

GFAAS 

GFAAS 

GFAAS 

GFAAS 

NAA 

GFAAS or ICPAES 

ETAAS 

GFAAS 

GFAAS 

No data 

0.12 μg/L

3–39 μg/L

24 μg/L

Low μg/L 

levels 

1.9 μg/L 

(serum); 

1.8 μg/L 

(plasma); 

2.3 μg/L 

(whole 

blood) 

50 μg/L

Low μg/L 

levels 

0.6 μg/L 

(serum and 

urine) 

Low μg/L 

levels 

Low μg/L 

levels 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 231 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Aluminum in Biological Materials 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Urine and blood Dilution with water ICP-AES 1 μg/L No data Allain and 

(urine); Mauras 

4 μg/L 1979 

(blood) 

Biological Homogenization with EDTA GFAAS 0.002– 95–106% LeGendre 

tissues 10.057 μg/g and Alfrey 

1976 

Biological Freeze-drying; grinding for NAA 8 μg/g No Wood et al. 

tissues homogenization recovery; 1990 

RSD <10% 

Biological Drying; nitric acid digestion; GFAAS 0.5 μg/g 80–117% Bouman et 

tissues dilution with water al. 1986 

Biological Mounting of paraffin sections SEM/EDXA 0.1% by NA Abraham 

tissues of formalin fixed tissue on weight in a and Burnett 

carbon discs; deparaffin detected 1985 

sample particle 

Kidney, liver, Acid digestion; dilution with ICP-AES No data 98.8±8.6% Maitani et al. 

urine water in liver 1994 

Kidney, liver, Microwave nitric acid SEC/ICP-MS 0.04 μg/g 100±14% of Owen et al. 

femur digestion; addition of internal spiked Al in 1994 

standard, dilution with eluent reference 

material 

Brain Freeze drying; acid digestion; GFAAS 0.03 μ/g No data Xu et al. 

dilution with potassium 1992a 

dichromate matrix modifier 

Brain Fixing and embedding in LAMMA Low μg/g No data Lovell et al. 

polymer matrix; sectioning range 1993 

and staining to visualize Al 

deposits; laser vaporization of 

selected sample surface into 

mass spectrometer 

Hair Isopropanol wash; nitric acid GFAAS 0.65 μg/g 84–105% Chappuis et 

digestion; dilution with water al. 1988 

Human blood, Acid digestion, Parr bomb ICP-AES 1 μg/L >75% Que Hee 

urine, serum, technique, microwave, or hot and Boyle 

feces plate method 1988 

Human Homogenization; microwave ICP-MS 4.8–11 ng/g No data de la Flor St. 

milk/infant digestion with boiling nitric Remy et al. 

formula acid/hydrogen peroxide 2004 
 

 

 

 

 

ALUMINUM 232 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Aluminum in Biological Materials 

Sample 

Analytical detection Percent 

Sample matrix Preparation method method limit recovery Reference 

Human milk/cow Dilution with ultrapure water ICP-MS 3 μg/L No data Martino et 

milk/infant al. 2000 

formula 

All None AMS 1 ppq NA Flarend and 

Elmore 1997 

AMS = accelerated mass spectroscopy; EDTA = ethylene diamine tetra acetic acid; EDXA = dispersive x-ray 

analysis; ETAAS = electrothermal atomic absorption spectrometry; GFAAS = graphite furnace atomic absorption 

spectrometry; HLPC/ICP-AES = high-performance liquid chromatography/ICP-AES; ICP-AES = inductively coupled 

plasma - atomic emission spectroscopy; ICP-MS = inductively coupled plasma-mass spectrometry; LAMMA = laser 

ablution microprobe mass spectrometry; NA = not applicable; NAA = neutron activation analysis; ppq = parts per 

quadrillion; SEC/ICP-MS = size-exclusion chromatography/ICP-AES/mass spectrometry; SEM = scanning electron 

microscopy 
 

 

 

 

 

 

 

 

 

ALUMINUM 233 

7. ANALYTICAL METHODS 

produced using a cyclotron. The first step in the analysis process is the chemical extraction of aluminum 

(both stable and radioactive) from the biological sample using a method which is free of aluminum 

contamination. The extractant is loaded into a holder and inserted through a vacuum lock into the ion 

source, which then employs ion bombardment to ionize the sample atoms. These are removed from the 

sample using magnets, and are separated by mass and charge by accelerators, bending magnets, and 

electron stripper screens. An electrostatic analyzer selects particles based on their energy, and a gas 

ionization detector counts the ions one at a time using a rate of energy loss assessment that distinguishes 

between any competing isobars. The amount of 26Al can be calculated from the measured ratio of 26Al to 

27Al and the amount of carrier added during the chemical preparation of the sample (Elmore and Phillips 

1987; Flarend and Elmore 1997). 

GFAAS is the most common technique used for the determination of low-ppb (μg/L) levels of aluminum

in serum, plasma, whole blood, urine, and biological tissues (Alder et al. 1977; Alderman and Gitelman 

1980; Bettinelli et al. 1985; Bouman et al. 1986; Chappuis et al. 1988; Couri et al. 1980; Gardiner and 

Stoeppler 1987; Gorsky and Dietz 1978; Guillard et al. 1984; Keirsse et al. 1987; Rahman et al. 1985; 

Savory and Wills 1986; CEC 1984; van der Voet et al. 1985; Wrobel et al. 1995; Xu et al. 1992a). This is 

because GFAAS offers the best combination of sensitivity, simplicity, and low cost. When used as a 

detector for high-performance liquid chromatography (HPLC), GFAAS can analyze for species of 

complexed or bound aluminum which have been separated into fractions on the chromatography column 

(Van Landeghem et al. 1994). 

NAA has been used to determine low levels of aluminum in biological tissues and urine (Blotcky et al. 

1976; Savory and Wills 1986; Wood et al. 1990; Yukawa et al. 1980). NAA involves the bombardment 

of a sample with neutrons, which transforms some of the stable 27Al atoms into several radioactive 

aluminum isotopes beginning with 28Al, and measurement of the induced radioactivity. Advantages of 

NAA include good sensitivity and relative independence from matrix (or media) effects and interferences. 

Moreover, this technique can be used to detect almost all elements of environmental concern in the same 

sample (Sheldon et al. 1986). One major problem with using NAA with aluminum is the need to correct 

for interfering reactions with phosphorus and silicon, which produce the same radioisotope (28Al) of 

aluminum. Other disadvantages of this technique include its high cost, the limited availability of nuclear 

reactors for NAA analysis, the short 2.25-minute half-life of 28Al that requires prompt analysis of the 

sample following bombardment with neutrons, and disposal problems of radioactive waste. 

The ICP-AES technique, also referred to as ICP-optical emission spectroscopy (ICP-OES), has been 

reported for the measurement of aluminum in biological materials and is an excellent alternative to 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 234 

7. ANALYTICAL METHODS 

GFAAS for those laboratories possessing the appropriate instrumentation (Allain and Mauras 1979; 

Lichte et al. 1980; Maitani et al. 1994; Que Hee and Boyle 1988; Que Hee et al. 1988; Sanz-Medel et al. 

1987). ICP-AES is a multi-elemental technique that is relatively free of chemical interferences. The 

matrix problems that can exist in atomic absorption spectrometry (AAS) are minimized in ICP-AES due 

to the very high excitation temperature of the sample (Savory and Wills 1986). The limits of detection for 

the ICP-AES method have been reported to be about 1 and 4 μg aluminum/L of urine and blood, 

respectively (Allain and Mauras 1979). A major problem with using the ICP-AES technique is the 

intense and broad emission of calcium, which increases the aluminum background and can raise the 

detection limit for this element (Allain and Mauras 1979; Que Hee and Boyle 1988; Savory and Wills 

1986). Titanium also interferes with aluminum analysis (Que Hee and Boyle 1988). Also, the relatively 

high cost and complexity of this technique can limit its routine use in many laboratories. However, ICPAES, especially ICP-MS, technologies have advanced recently largely through the efforts of the 

Department of Energy, and the cost of analysis has declined considerably. 

Inductively coupled plasma-mass spectrometry (ICP-MS) is a powerful technique that uses an inductively 

coupled plasma as an ion source and a mass spectrometer as an ion analyzer. It can measure the presence 

of >75 elements in a single scan, and can achieve detection limits down to parts per trillion (ppt) levels 

for many elements—levels that are two or three orders of magnitude lower than those obtained by ICPAES (Keeler 1991). It is more expensive than ICP-AES and requires more highly skilled technical 

operation. Aluminum levels in urine and saliva were detected down to 0.02 μg/mL and in blood serum to 

0.001 μg/mL using ICP-MS (Ward 1989). Speciation studies have employed ICP-MS as a detector for 

aluminum in tissue fractions separated by size-exclusion chromatography (SEC) with detection limits of 

0.04 μg/g in femur, kidney, and brain (Owen et al. 1994). ICP-MS has been used to determine metal 

concentrations, including aluminum, in human milk, cow milk, and infant formulas (de la Flor St. Remy 

et al. 2004; Martino et al. 2000). 

LAMMA has been utilized for the analysis of aluminum in brain tissue affected with Alzheimer’s disease 

(Lovell et al. 1993). This analytical technique of nuclear microscopy can simultaneously image and 

analyze features in unstained and untreated tissue sections, and therefore avoids contamination problems 

associated with tissue prepared using conventional chemical techniques. Lovell et al. (1993) reported 

aluminum concentrations in neurofibrillary tangle (NFT)-bearing neurons and in NFT-free neurons in 

brain tissue from seven autopsy-confirmed Alzheimer’s disease patients. LAMMA was also used in a 

study that did not detect aluminum in pyramidal neurons in brain tissue from Alzheimer’s disease patients 

(Makjanic et al. 1998). However, in tissue that had been subject to conventional procedures such as 
 

 

 

 

 

 

 

 

ALUMINUM 235 

7. ANALYTICAL METHODS 

fixation and osmication, aluminum was observed in both neurons and surrounding tissue. The method, 

however, requires rigorous histological sectioning and preparation prior to analysis, specialized analytical 

equipment, and highly trained personnel. 

Secondary ion mass spectrometry (SIMS) is an analytical method that can be used for the imaging of 

aluminum and other metals in a variety of materials or biological specimins (Goldsmith et al. 1999; 

Linton and Goldsmith 1992). This technique uses a primary ion beam to generate secondary ions from 

the specimen, which are analyzed by mass spectrometry. Spatial resolution is reported to be comparable 

to that attainable with electron microscopy. 

Adequate digestion methods are important in the determination of all metals, including aluminum. Que 

Hee and Boyle (1988) showed that Parr bomb digestions were always superior to hot plate digestions for 

many elements, including aluminum, in feces, liver, and testes. Microwaving in closed vessels produced 

lower aluminum recoveries in liver than Parr bomb digestions. The Parr bomb values for citrus leaves 

were within 5% of the NBS certified values. 

Abraham and Burnett (1983) described a method for quantitative analysis of inorganic particulate burden 

in situ in tissue sections using scanning election microscopy (SEM) with backscattered election (BSE) 

imaging and energy dispersive x-ray analysis (EDXA). This method can compliment bulk tissue analysis 

since the analyst can observe the association of certain elements within a particle and the particle size. 

This information can be correlated to cellular or tissue changes with the types, locations, and 

concentrations of particles within the tissue. In addition, small samples (<1 μg) can be analyzed. EDXA, 

which is used to identify the chemical composition of the mineral, allows for separation of particulates 

into two major classes, endogenous and exogenous. Endogenous particles contain calcium or iron in 

combination with phosphorus as major constituents along with smaller amounts of sodium, magnesium, 

and potassium. The remaining particles are considered exogenous, and are divided into three major 

classes: silica, silicates, and metals. This method has been used to identify aluminum particulates in 

various human tissues, including lung, kidney, brain, and bone (Baxter et al. 1985; Hull and Abraham 

2002; Jederlinic et al. 1990; Perl and Brody 1980; Perl et al. 1982). 

Razniewska and Trzcinka-Ochocka (2003) reported a method for the determination of aluminum 

concentrations in blood serum and urine using ETAAS. Serum and urine samples were analyzed directly 

following dilution with 0.2% nitric acid and water. The detection limit was reported to be 0.6 μg/L for 
 

 

 

 

 

 

 

 

ALUMINUM 236 

7. ANALYTICAL METHODS 

serum and urine, with a quantification limit of 1.2 μg/L. This method provided reliable aluminum levels 

at concentrations observed among non-exposed, healthy individuals. 

7.2 ENVIRONMENTAL SAMPLES 

A number of analytical techniques have been used for measuring aluminum concentrations in 

environmental samples. These include GFAAS, FAAS, NAA, ICP-AES, ICP-MS, spectrophotometry 

using absorbance and fluorescence detection, phosphorimetry, chromatography, and gas chromatography 

equipped with an electron capture detector (GC/ECD) (Andersen 1987, 1988; AOAC 1990; APHA 

1998a, 1998b, 1998c, 1998d; Dean 1989; Fernandez de la Campa et al. 1988; EPA 1983a, 1983b, 1994a, 

1994b, 1994c, 2000; Fleming and Lindstrom 1987; Gardiner et al. 1987; NIOSH 1994, 2003a, 2003b, 

2003c; OSHA 2001, 2002; USGS 1996). They are summarized in Table 7-2. 

There are three NIOSH methods (7300, 7301, and 7303) that analyze elements, including aluminum, in 

air by ICP-AES; these methods differ only in the digestion method. NIOSH method 7013 analyzes 

aluminum in air using FAAS. In all of these NIOSH methods, particulate from the air is collected over a 

filter, either a 0.8-μm cellulose ester membrane or a 5.0-μm polyvinyl chloride membrane. The 

applicable working ranges are 0.5–10 mg/m3 for a 100-L air sample by Method 7013, 0.005–2.0 mg/m3 

for a 500-L air sample by Methods 7300 and 7301, and up to 100 mg/m3 in a 500-L sample for Method 

7303. The digestion procedures in Method 7013 (nitric acid) will not dissolve alumina (Al2O3); lithium 

borate fusion is needed. The digestion procedure in Method 7300 (nitric/perchloric acid) may not 

completely solubilize some species of aluminum; alternative producers are cited in the method (NIOSH 

1994, 2003a, 2003b, 2003c). 

Method ID-121 (OSHA 2002) can be used to determine the amount of aluminum particulates in the 

workplace atmosphere. Airborne particulates are collected on filters using calibrated sampling pumps and 

the samples are analyzed using flame atomic absorption or emission spectrometry. This method can also 

determine aluminum contained in wipe and bulk samples. Method ID-109-SG (OSHA 2001) determines 

aluminum oxide in workplace atmospheres. In this method sample filters are fused with a flux containing 

lithium borate, ammonium nitrate, and sodium bromide in platinum crucibles in order to solubilize the 

aluminum oxide. 

Method 990.08 (AOAC 1990) determines metals, including aluminum, in solid wastes (coal fly ash, 

industrial and electroplating sludges, mine tailings, river sediment, and soils). 
 

 

 

 

ALUMINUM 237 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Aluminum in Environmental
 

Samples
 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Air Collect sample on MCE 

filter, followed by digestion 

by HNO3 

Method 

7013 

(FAAS) 

2 μg/sample No data NIOSH 1994 

Air Collect sample on MCE or 

PVC filter, followed by 

nitric/perchloric acid 

ashing 

Method 

7300 (ICPAES) 

0.115 μg/filter 101.5– 

105.4% 

(MCE) 

77.4–92.9% 

(PVC) 

NIOSH 2003a 

Air Collect sample on MCE 

filter, followed by hot 

block/HCl/HNO3 digestion 

Method 

7303 (ICPAES) 

0.111 μg/mL No data NIOSH 2003b 

Air Collect sample on MCE or 

PVC filter, followed by 

aqua regia ashing 

Method 

7301 (ICPAES) 

0.115 μg/filter 99.6– 

208.1% 

(MCE) 

-1.9–112.1% 

NIOSH 2003c 

(PVC) 

Air Collect sample on MCE or 

PVC filter, followed by 

HNO3 digestion or 

extraction with deionized 

Method ID121 (FAAS 

or AES) 

0.02 μg/mL 94.5% 

(average) 

OSHA 2002 

water 

Air (Al2O3) Collect sample on LAPVC 

filter, followed by fusion 

with LiBO2/NH4NO3/NaBr 

Method ID109-SG 

(FAAS) 

0.5 μg/mL 96% 

(average) 

OSHA 2001 

Water Filter and acidify filtrate 

with HNO3 and analyze 

Method 

3113 B 

(GFAAS) 

3 μg/L No data APHA 1998a 

Water Digest sample with 

HNO3/HCl and analyze 

Method 

3120 B 

(ICP-AES) 

40 μg/L No data APHA 1998b 

Water Filter and acidify filtrate 

with HNO3 and analyze 

Method 

3125 (ICPMS) 

0.03 μg/L 98.42% 

(mean) 

APHA 1998c 

Water Acidify with H2SO4, add 

ascorbic acid, buffer and 

dye (Erichrome cyanine 

R); measure absorbance 

at 535 nm 

Method 

3500-Al B 

(Spectrophotometer) 

6 μg/L No data APHA 1998d 

Water, 

waste water, 

and solid 

wastes 

For dissolved 

constituents: filter, acidify 

filtrate, and analyze; for 

samples containing solids: 

digestion with HNO3/HCl 

prior to analysis 

Method 

200.7 

(ICP-AES) 

45 μg/L 88–113% EPA 1994a 
 

 

 

 

 

 

 

 

ALUMINUM	 238 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Aluminum in Environmental
 

Samples
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Water, For dissolved Method 1.0 μg/L 100.4% EPA 1994b
 

waste water, constituents: filter, acidify 200.8(ICP- (aqueous) (average)
 

sludges, and filtrate, and analyze; for MS) 0.4 mg/kg (solids)
 

soils samples containing solids:
 

digestion with HNO3/HCl 

prior to analysis 

Water, For dissolved Method 7.8 μg/L 97.1– EPA 1994c 

waste water, constituents: filter, acidify 200.9 111.7% 

sludges, and filtrate, and analyze; for (GFAAS) 

soils samples containing solids: 

digestion with HNO3/HCl 

prior to analysis 

Water	 For dissolved Method 30 μg/L No data EPA 2000 

constituents: filter, acidify 6010C 

filtrate, and analyze; for (ICP-AES) 

samples containing solids: 

digestion with HNO3/HCl 

prior to analysis 

Water Filter, acidify filtrate, and 

analyze 

Method I1472-95 

(ICP-AES) 

5 μg/L 86.1–99.9% USGS 1996 

Water and 

waste water 

For dissolved 

constituents, filter, acidify 

filtrate, and analyze; for 

suspended metals digest 

with HNO3 and analyze 

Method 

202.1 

(FAAS) 

100 μg/L No data EPA 1983a 

Water and 

waste water 

For dissolved 

constituents, filter, acidify 

filtrate, and analyze; for 

suspended metals digest 

with HNO3 and analyze 

Method 

202.2 

(GFAAS) 

3 μg/L No data EPA 1983b 

Solid wastes Digest sample in 

HNO3/H2O2 /HCl, dilute 

with water; remove 

particulate matter 

Method 

990.08 

(ICP-AES) 

45 μg/L No data AOAC 1990 

Soil Filter sample and cleanup on chromatography 

column 

GFAAS No data No data Gardiner et al. 

1987 

Fly ash Dry sample in vacuum 

and irradiate 

NAA No data Not 

applicable 

Fleming and 

Lindstrom 1987 

Plants Digest sample with nitric 

acid and analyze 

Spectrophoto7 μg/L Not 

applicable 

Dean 1989 

meter 
 

 

 

 

ALUMINUM 239 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Aluminum in Environmental
 

Samples
 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Rock, Acid digest sample using ICP-AES 0.001 μg/L 90% Que Hee and 

magma, soil, Parr bomb or microwave Boyle 1988 

paint, citrus 

leaves 

Dialysis Dilute sample with acidic Phosphor­ 3 μg/L No data Andersen 1987 

fluids Triton X-100 imetry 

Dialysis Add Ferron and cetyl- Phosphor­ 5.4 μg/L No data Fernandez de la 

fluids trimethylammonium imetry Campa et al. 1988 

bromide solution to 

sample and measure 

phosphorescence at 

586 nm 

Rock, soil Digest with acid AMS 10-15 g/g sample Not Flarend and 

applicable Elmore 1997 

AMS = accelerated mass spectroscopy; FAAS = flame atomic absorption spectrometry; GC/ED = gas 

chromatography/electron capture detector; GFAAS : graphite furnace atomic absorption spectrometry; ICPAES = inductively couples plasma-atomic absorption spectrometry; ICP-MS = inductively couples plasma-mass 

spectrometry LAPVC = Low Ash Polyvinyl Chloride; MCE = mixed cellulose ester; NAA = neutron activation analysis; 

PVC = polyvinyl chloride 
 

 

 

 

 

ALUMINUM 240 

7. ANALYTICAL METHODS 

Method 200.7 (EPA 1994a) provides procedures for determination of metals, including aluminum, in 

solution in water, wastewater, and solid wastes. Method 200.8 (EPA 1994b) provides procedures for 

determination of dissolved elements, including aluminum in groundwater, surface water, and drinking 

water, as well as determination of total recoverable element concentrations in these waters as well as 

waste waters, sludges and soils samples. Method 200.9 (EPA 1994c) provides procedures for the 

determination of dissolved and total recoverable elements, including aluminum, by graphite furnace 

atomic absorption (GFAA) in groundwater, surface water, drinking water, storm runoff, industrial and 

domestic wastewater, as well as determination of total recoverable elements in sediment, sludges, and 

soil. 

GFAAS and FAAS are the techniques (Methods 202.1 and 202.2) recommended by EPA for measuring 

low levels of aluminum in water and waste water. Detection limits of 100 and 3 μg of aluminum/L of

sample were obtained using the FAAS and GFAAS techniques, respectively (EPA 1983a, 1983b). 

Spectrophotometry and GC/ECD have also been employed to measure low-ppb (μg/L) levels of

aluminum in water (Dean 1989; Ermolenko and Dedkov 1988; Gosink 1975). Flow-injection systems 

using absorbance (Benson et al. 1990) and fluorescence detection (Carrillo et al. 1992) have been used to 

monitor aqueous aluminum levels in the field and in the laboratory setting, with detection limits as low as 

0.3 μg/L. Ion chromatography using spectrophoto-metric detection and on-line preconcentration gives an 

effective detection limit <1 μg/L in aqueous samples. GFAAS is the method of choice for measuring

low-ppb levels of aluminum in dialysis fluids (Andersen 1987, 1988; Woolfson and Gracey 1988). 

The GFAAS and NAA techniques have been employed for measuring aluminum levels in soil and fly ash, 

respectively (Fleming and Lindstrom 1987; Gardiner et al. 1987). Que Hee and Boyle (1988) employed 

ICP/AES to measure aluminum in rocks, soils, volcano magma, and print. Aluminum silicate matrices 

require disruption by hydrofluoric acid/nitric acid digestion in Parr bombs to achieve >90% recoveries of 

aluminum and other elements in preparation for ICP-AES analysis using wet ashing (Que Hee and Boyle 

1988). Aluminum in air particulates and filters has been determined by pressurized digestion and ICPAES detection (Dreetz and Lund 1992). Microwave digestions in closed polypropylene bottles gave the 

same concentrations of aluminum for rocks and soils. 
 

 

 

 

 

 

 

 

 

 

ALUMINUM 241 

7. ANALYTICAL METHODS 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of aluminum is available. Where adequate information is not 

available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research 

designed to determine the health effects (and techniques for developing methods to determine such health 

effects) of aluminum. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. GFAAS is the method of 

choice for measuring low-ppb levels of aluminum in whole blood, serum, plasma, urine, and various 

biological tissues (Alder et al. 1977; Alderman and Gitelman 1980; Bettinelli et al. 1985; Bouman et al. 

1986; Chappuis et al. 1988; Couri et al. 1980; Gardiner and Stoeppler 1987; Gorsky and Dietz 1978; 

Guillard et al. 1984; Keirsse et al. 1987; Rahman et al. 1985; Savory and Wills 1986; CEC 1984; van der 

Voet et al. 1985). Chromatographic techniques coupled with GFAAS detection have been used to 

separate various metal species and determine aluminum content in serum (Maitani et al. 1994; Van 

Landeghem et al. 1994). The NAA and ICP-AES methods have also been used to measure ppb levels of 

aluminum in biological tissues and fluids (Blotcky et al. 1976; Savory and Wills 1986; Yukawa et al. 

1980). ICP-MS has the requisite sensitivity to detect low-ppb levels of aluminum (Ward 1989) in 

biological and environmental media though it is more expensive than GFAAS. However, the cost of ICPMS, as well as ICP-AES, analyses has decreased significantly over the last few years. LAMMA can 

detect aluminum deposits in specific structures of the brain and might be used to correlate the effects of 

aluminum accumulation (Lovell et al. 1993). 

SEM/EDXA allows for quantitative analysis of inorganic particulate burden in situ in tissue sections. 

This method can compliment bulk tissue analysis since the analyst can observe the association of certain 

elements within a particle and the particle size. This information can be correlated to cellular or tissue 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 242 

7. ANALYTICAL METHODS 

changes with the types, locations, and concentrations of particles within the tissue (Abraham and Burnett 

1983). 

Although sensitive analytical methods are available for measuring the presence of aluminum in biological 

tissues and fluids, it is not known whether data collected using these techniques have been used to 

correlate the levels of aluminum in biological materials to exposure and effect levels. The problem of 

contamination during tissue preparation (Makjanic et al. 1998) makes this task more challenging. 

Razniewska and Trzcinka-Ochocka (2003) noted that there was a need for a simple and sensitive method 

for the routine measurement of aluminum concentrations in serum and urine. These authors reported a 

method measuring aluminum concentrations in serum and urine using ETAAS. This method provided 

reliable results at concentrations observed among non-exposed, healthy individuals. There is a need for 

additional methods that can measure aluminum concentrations in blood and urine at low concentrations, 

approximately 1–10 μg/L. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. FAAS and ICP-AES have been used to measure aluminum in air (Dreetz and Lund 1992; 

NIOSH 1994, 2003a, 2003b, 2003c; OSHA 2001, 2002). For measuring aluminum in water and waste 

water, spectrophotometry (Benson et al. 1990; Carrillo et al. 1992; Ermolenko and Dedkov 1988), 

GC/ECD (Gosink 1975), and FAAS and GFAAS (EPA 1983a, 1983b) have been employed. GFAAS has 

been used to analyze aluminum in the soil (Gardiner et al. 1987), and GFAAS (Andersen 1987) as well as 

phosphorimetry (Fernandez de la Campa et al. 1988) have been useful in determining aluminum levels in 

dialysis fluids. The method used to measure aluminum levels in flyash is NAA (Fleming and Lindstrom 

1987). The media of most concern for potential exposure to aluminum are water and dialysis fluids. 

GFAAS technique is sensitive for measuring background levels of aluminum in water (EPA 1983b) and 

dialysis fluids (Andersen 1987; Woolfson and Gracey 1988) and levels of aluminum at which health 

effects might begin to occur. GFAAS and FAAS are the techniques (Methods 202.1 and 202.2) 

recommended by EPA for detecting aluminum levels in water and waste water (EPA 1983a, 1983b). 

GFAAS is the method of choice for measuring low-ppb levels of aluminum in dialysis fluids (Andersen 

1987; Woolfson and Gracey 1988). ICP-AES has been utilized to detect aluminum in biological media 

(leaves, feces, serum, blood, liver, spleen, kidney, urine, and testes) and environmental matrices (rocks, 

soils, water, volcano magma, paint) in addition to other elements (Que Hee and Boyle 1988) and, more 

recently, ICP-MS has been shown to be useful for even more sensitive analyses of such media. No 

additional methods for detecting elemental aluminum in environmental media appear to be necessary at 
 

 

ALUMINUM 243 

7. ANALYTICAL METHODS 

this time. A need exists for developing a range of NIST analytical standards for calibrating instruments 

and assessing the accuracy and precision of the various analytical methods. 

7.3.2 Ongoing Studies 

The information in Table 7-3 was found as a result of a search of the Federal Research in Progress 

database (FEDRIP 2006). 
 

 

 

ALUMINUM 244 

7. ANALYTICAL METHODS 

Table 7-3. Ongoing Studies on Aluminum 

Investigator Affiliation Research description Sponsor 

Mutti, A. University of The present research project is aimed at NIH 

Parma, Parma, applying the most sensitive, selective and 

Italy specific reference analytical techniques to the 

study of the composition of exhaled breath 

condensate in chronic obstructive pulmonary 

disease patients using ETAAS and ICP-MS. 

Progar, J Not provided The goal of the research program is directed NIH 

toward the development of analytical 

methodology to determine the quantitative, 

qualitative, and/or structural identification of 

inorganic chemical constituents and 

impurities in drug and biological products 

through spectrometric means, including 

FAAS, GFAAS, FES, ICP-AES, and ICP-MS. 

May, JC Not provided The research goal is to ensure the safety, NIH 

purity and potency of vaccines and other 

biological products through research relating 

to the development of new or improved 

accurate, validated, qualitative and/or 

quantitative methods for the determination 

and/or characterization of the chemical 

preservatives, stabilizers, inactivators, 

adjuvants, residual moisture, protein and 

other chemical constituents of vaccines and 

biological products. 

ETAAS = Electro-thermal atomic absorption spectroscopy; FAAS = flame atomic absorption spectrometry;
 

FES = flame emission spectrometry; GFAAS = graphite furnace atomic absorption spectrometry; ;
 

ICP-AES = inductively coupled argon plasma-emission spectrometry ICP-MS = Inductively coupled plasma - mass 

spectrometry; NIH = National Institutes of Health
 

Source: FEDRIP 2006
 
 

 

 

 

 

 

 

 

 

ALUMINUM 245 

8. REGULATIONS AND ADVISORIES
 

The international and national regulations and guidelines regarding aluminum and aluminum compounds 

in air, water, and other media are summarized in Table 8-1. 

ATSDR has derived an intermediate-duration oral minimal risk level (MRL) of 1 mg Al/kg/day for 

aluminum. This MRL is based on a NOAEL of 26 mg Al/kg/day and a LOAEL of 130 mg Al/kg/day for 

neurodevelopmental effects in the offspring of mice exposed to aluminum lactate in the diet on gestation 

day 1 through lactation day 21 followed by pup exposure until postnatal day 35 (Golub and Germann 

2001). The MRL was derived by dividing the NOAEL by an uncertainty factor of 100 (10 for animal to 

human extrapolation and 10 for human variability) and a modifying factor of 0.3 to account for the higher 

bioavailability of the aluminum lactate used in the principal study, as compared to the bioavailability of 

aluminum in the human diet and drinking water. 

ATSDR has derived a chronic-duration oral MRL of 1 mg Al/kg/day for aluminum. This MRL is based 

on a LOAEL of 100 mg Al/kg/day for neurological effects in mice exposed to aluminum lactate in the 

diet during gestation, lactation, and postnatally until 2 years of age (Golub et al. 2000). The MRL was 

derived by dividing the LOAEL by an uncertainty factor of 300 (3 for the use of a minimal LOAEL, 

10 for animal to human extrapolation, and 10 for human variability) and a modifying factor of 0.3 to 

account for the higher bioavailability of the aluminum lactate used in the principal study, as compared to 

the bioavailability of aluminum in the human diet and drinking water. 

EPA has not derived a reference dose (RfD) or reference concentration (RfC) for aluminum, but has 

derived an RfD for aluminum phosphide of 4x10-4 mg/kg/day based on a NOAEL of 0.51 mg/kg of food 

or 0.025 mg/kg/day (phosphine) converted to 0.043 mg/kg/day of aluminum phosphide for body weight 

and clinical parameters observed in a rats during a chronic oral study (IRIS 2008). 
 

 

ALUMINUM 246 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Aluminum and Compounds 

Agency Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification for 

aluminum production 

Group 1a IARC 1987 

WHO Air quality guidelines No data WHO 2000 

Drinking water quality guidelines for 

aluminumb 

≤0.1 mg/L in large water 

treatment facilities 

WHO 2004 

≤0.2 mg/L in small water 

treatment facilities 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) for aluminum 

and compounds (as Al) 

Metal dust 

Pyro powders 

Soluble salts 

Alkyls (NOS) 

TLV (8-hour TWA) for aluminum 

oxidec 

10 mg/m3 

5 mg/m3 

2 mg/m3 

2 mg/m3 

10 mg/m3 

ACGIH 2005 

EPA AEGL-1 for aluminum phosphided Not recommended due to 

insufficient data 

EPA 2006a 

AEGL-2 for aluminum phosphided 

10 minutes 4.0 ppm 

30 minutes 4.0 ppm 

60 minutes 2.0 ppm 

4 hours 0.50 ppm 

8 hours 

AEGL-3 for aluminum phosphided 

0.25 ppm 

10 minutes 7.2 ppm 

30 minutes 7.2 ppm 

60 minutes 3.6 ppm 

4 hours 0.90 ppm 

8 hours 0.45 ppm 

Hazardous air pollutant No data EPA 2006c 

42 USC 7412 
 

 

 

 

 

 

ALUMINUM 247 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Aluminum and Compounds 

Agency Description Information Reference 

NATIONAL (cont.) 

NIOSH 

OSHA 

REL (10-hour TWA) 

Aluminum 

Aluminum oxide 

PEL (8-hour TWA) for general 

industry for aluminum metal (as Al) 

and aluminum oxide 

10 mg/m3 (total dust) 

5 mg/m3 (respirable fraction) 

15 mg/m3 (total dust) 

5 mg/m3 (respirable fraction) 

15 mg/m3 (total dust) 

5 mg/m3 (respirable fraction) 

NIOSH 2005 

OSHA 2007b 

29 CFR 1910.1000 

PEL (8-hour TWA) for shipyard 

industry for aluminum metal (as Al) 

and aluminum oxide 

15 mg/m3 (total dust) 

5 mg/m3 (respirable fraction) 

OSHA 2007a 

29 CFR 1915.1000 

b. Water 

EPA Designated as hazardous 

substances in accordance with 

Yes EPA 2006b 

40 CFR 116.4 

Section 311(b)(2)(A) of the Clean 

Water Act for aluminum sulfate 

Drinking water standards and 

health advisories 

0.05–0.2 mg/L EPA 2006f 

National primary drinking water 

standards 

No data EPA 2003 

National secondary drinking water 

standards for aluminum 

0.05–0.2 mg/L EPA 2008 

40 CFR 143.3 

Reportable quantities of hazardous 

substances designated pursuant to 

Section 311 of the Clean Water Act 

5,000 pounds EPA 2006h 

40 CFR 117.3 

for aluminum sulfate 

Water quality criteria for human 

health for aluminum 

EPA 2006e 

Freshwater CMC 750 μg/L 

Freshwater CCC 87 μg/L 

c. Food 

FDA Bottled drinking water for aluminum 0.2 mg/L FDA 2005 

21 CFR 165.110 

d. Other 

ACGIH Carcinogenicity classification for 

aluminum oxide 

A4e ACGIH 2005 

EPA Carcinogenicity classification for 

aluminum phosphide 

No data IRIS 2008 

RfC for aluminum phosphide 

RfD for aluminum phosphide 

No data 

4x10-4 mg/kg/day 
 

 

 

 

 

 

 

ALUMINUM 248 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Aluminum and Compounds 

Agency Description Information Reference 

NATIONAL (cont.) 

EPA Identification and listing of 

hazardous substances; hazardous 

waste number for aluminum 

phosphide 

Pesticide classified as restricted 

use for aluminum phophide 

Pesticide exemptions from the 

requirement of a tolerance 

Aluminum hydroxide (for use as 

a diluent and carrier) 

Aluminum oxide (for use as a 

diluent) 

Aluminum sulfate (for use as a 

safener adjuvant) 

Superfund, emergency planning, 

and community right-to-know 

Designated CERCLA hazardous 

substance 

Reportable quantity 

Aluminum phosphide 

Aluminum sulfate 

Effective date of toxic chemical 

release reporting 

Aluminum (fume or dust) 

Aluminum oxide (fibrous 

forms) 

Aluminum phosphide 

Extremely hazardous substances 

and their threshold planning 

quantities for aluminum 

phosphide 

P006 EPA 2006d 

40 CFR 261, 

Appendix VIII 

Yesf EPA 2006g 

40 CFR 152.175 

EPA 2006l 

40 CFR 180.910 

Yesg 

Yesg 

Yesg EPA 2006m 

40 CFR 180.920 

EPA 2006i 

40 CFR 302.4 

Yes 

100 pounds 

5,000 pounds 

EPA 2006k 

40 CFR 372.65 

01/01/87 

01/01/87 

01/01/95 

500 pounds EPA 2006j 

40 CFR 355, 

Appendix A 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 249 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Aluminum and Compounds 

Agency Description Information Reference 

NATIONAL (cont.) 

NTP Carcinogenicity classification No data NTP 2004 

a

Group 1: carcinogenic to humans

b

Reason for not establishing a guideline value: owing to limitations in the animal data as a model for humans and 

the uncertainty surrounding the human data, a health-based guideline value cannot be derived; however, practicable 

levels based on optimization of the coagulation process in drinking-water plants using aluminium-based coagulants 

are derived: ≤0.1 mg/L in large water treatment facilities, and ≤0.2 mg/L in small facilities. c

TWA: the value is for particulate matter containing no asbestos and <1% crystalline silica. 

d

AEGL-1 is the airborne concentration of a substance above which it is predicted that the general population, 

including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic nonsensory 

effects. AEGL-2 is the airborne concentration of a substance above which it is predicted that the general population, 

including susceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or 

an impaired ability to escape. AEGL-3 is the airborne concentration of a substance above which it is predicted that 

the general population, including susceptible individuals, could experience life-threatening health effects or death. e

A4: not classifiable as a human carcinogen. 

f

Pesticide classified as restricted use: limited to use by or under the direct supervision of a certified applicator for 

agricultural crop uses. Criteria influencing restriction includes inhalation hazard to humans. 

g

Pesticide exemptions from the requirement of a tolerance: residues of the following materials are exempted from 

the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally 

active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest. 

ACGIH = American Conference of Governmental Industrial Hygienists; AEGL = Acute Exposure Guideline Level; 

Al = aluminum; CERCLA = Comprehensive Environmetnal Response, Compensation, and Liability Act; CFR = Code 

of Federal Regulations; CCC = Criterion Continuous Concentration; CMC = Criteria Maximum Concentration; 

EPA = Environmental Protection Agency; FDA = Food and Drug Administration; IARC = International Agency for 

Research on Cancer; IRIS = Integrated Risk Information System; NIOSH = National Institute for Occupational Safety 

and Health; NOS = not otherwise specified; NTP = National Toxicology Program; OSHA = Occupational Safety and 

Health Administration; PEL = permissible exposure limit; REL = recommended exposure limit; RfC = inhalation 

reference concentration; RfD = oral reference dose; TLV = threshold limit values; TWA = time-weighted average; 

USC = United States Code; WHO = World Health Organization 
ALUMINUM 250
 

8. REGULATIONS AND ADVISORIES 

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ALUMINUM 304 

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ALUMINUM 305 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 
 

 

 

 

 

 

 

 

 

ALUMINUM 306 

10. GLOSSARY 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 
 

 

 

 

 

 

 

ALUMINUM 307 

10. GLOSSARY 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical 

is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 
 

 

 

 

 

 

ALUMINUM 308 

10. GLOSSARY 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An OR of greater than 1 is considered to indicate greater risk of disease in the 

exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate 

(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides 

the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM 309 

10. GLOSSARY 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical 

information, such as air/blood partition coefficients, and metabolic parameters. PBPK models are also 

called biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL, from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 
 

 

 

 

 

ALUMINUM 310 

10. GLOSSARY 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed group. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value-Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The absorption, distribution, and elimination of toxic compounds in the living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowestobserved-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 
 

 

 

 

ALUMINUM A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 
 

 

ALUMINUM A-2 

APPENDIX A 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology and Environmental Medicine, expert panel peer reviews, and agency-wide MRL 

Workgroup reviews, with participation from other federal agencies and comments from the public. They 

are subject to change as new information becomes available concomitant with updating the toxicological 

profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. 

For additional information regarding MRLs, please contact the Division of Toxicology and 

Environmental Medicine, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, 

Mailstop F-32, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Aluminum 

CAS Numbers: 7429-90-5 

Date: June 2008 

Profile Status: Final 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Graph Key: 46 

Species: Mouse 

Minimal Risk Level: 1 [X] mg/kg/day [ ] ppm 

Reference: Golub MS, Germann SL. 2001. Long-term consequences of developmental exposure to 

aluminum in a suboptimal diet for growth and behavior in Swiss Webster mice. Neurotoxicol Teratol 

23:365-372. 

Experimental design: Groups of pregnant Swiss Webster mice were exposed to 0, 100, 500, or 1,000 mg 

Al/kg diet on gestational days 0–21 and during lactation until day 21. On PND 21, one male and one 

female pup from each litter were placed on the same diet as the dam. The offspring were exposed until 

PND 35. The composition of the diet was modified from the National Research Council's 

recommendations; the investigators noted that the nutrients were reduced to correspond to the usual intake 

of these nutrients by young women. The average daily intakes of phosphorus, calcium, magnesium, iron, 

and zinc in women aged 18–24 years are 83, 56, 71, 69, and 67% of the RDA; these percents were used to 

modify the recommended dietary intake for the mice used in this study. Doses of 26, 130, and 260 mg 

Al/kg/day are calculated by averaging reported estimated doses of 10, 50, and 100 mg Al/kg/day for 

adults (i.e., at beginning of pregnancy) and 42, 210, and 420 mg Al/kg/day maximal intake during 

lactation. The doses at lactation were calculated using doses estimated in previous studies with similar 

exposure protocols performed by the same group of investigators (Golub et al. 1995). At 3 months of 

age, the females were tested for neurotoxicity using the Morris water maze. At 5 months of age, males 

were tested for motor activity and function using rotarod, grip strength, wire suspension, mesh pole 

descent, and beam traversal tests. 

Effect noted in study and corresponding doses: No alterations in pregnancy weight gain or pup birth 

weights were observed. At PND 21, significant decreases in pup body weights were observed at 130 and 

260 mg/kg/day. No information on maternal weight gain during lactation was reported; however, the 

investigators noted that the decrease in pup weight was not associated with reduced maternal food intake. 

At PND 35, the decrease in body weight was only significant at 260 mg/kg/day. On PND 90, female 

mice in the 260 mg/kg/day group weighed 15% less than controls. Decreases in heart and kidney weights 

were observed at 260 mg/kg/day in the females. Also, decreases in absolute brain weight were observed 

in females at 260 mg/kg/day and relative brain weights were observed at 26 or 260 mg/kg/day. In the 

males, significant decreases in body weight were observed at 130 (10%) and 260 (18%) mg/kg/day at 

5 months; an increase in food intake was also observed these doses. In the Morris maze (tested at 

3 months in females), fewer animals in the 260 mg/kg/day group had escape latencies of <60 seconds 

during sessions 1–3 (learning phase) and a relocation of the visible cues resulted in increased latencies at 

130 and 260 mg/kg/day. Body weight did not correlate with latency to find the platform or with the 

distribution of quadrant times. The investigators concluded that controls used salient and/or nonsalient 

cues, 26 and 130 mg/kg/day animals used both cues, but had difficulty using only one cue, and 

260 mg/kg/day animals only used the salient cues. In the males tested at 5 months, a significant decrease 

in hindlimb grip strength was observed at 260 mg/kg/day, an increase in the number of rotations on the 

rotorod as observed at 260 mg/kg/day, and a shorter latency to fall in the wire suspension test as was 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM	 A-4 

APPENDIX A 

observed at 130 and 260 mg/kg/day. The investigators noted that there were significant correlations 

between body weight and grip strength and number of rotations. When hindlimb grip strength was 

statistically adjusted for body weight, the aluminum-exposed mice were no longer significantly different 

from controls. 

Reference: Colomina MT, Roig JL, Torrente M, et al. 2005. Concurrent exposure to aluminum and 

stress during pregnancy in rats: effects on postnatal development and behavior of the offspring. 

Neurotoxicol Teratol 27:565-574. 

Experimental design: Groups of female Sprague-Dawley rats were exposed to 0, 50, or 100 mg Al/kg/day 

aluminum nitrate nonahydrate in drinking water; citric acid (710, 355, and 710 mg/kg/day in the control, 

50, and 100 ppm groups, respectively) was added to the drinking water to increase aluminum absorption. 

The adult rats were exposed to aluminum for 15 days prior to mating and the during gestation and 

lactation periods; after weaning, the pups were exposed to the same aluminum concentration as the 

mothers from postnatal day 21 through 68. The basal diet (Panlab rodent chow) contained 41.85 μg Al/g

diet. Aluminum doses were calculated by adding the basal dietary aluminum doses (calculated using 

reference values for mature Sprague-Dawley rats) to reported aluminum doses from water; the total 

aluminum doses were 3, 53, and 103 mg Al/kg/day. In addition to aluminum exposure, some animals in 

each group underwent restraint stress for 2 hours/day on gestation days 6–20; the restraint consisted of 

placing the rats in cylindrical holders. The following neurobehavioral tests were performed on the 

offspring: righting reflex (PNDs 4, 5, 6), negative geotaxis (PNDs 7, 8, 9), forelimb grip strength 

(PNDs 10–13), open field activity (PND 30), passive avoidance (PND 35), and water maze (only tested at 

53 mg/kg/day on PND 60). On PND 68, rats were killed and aluminum levels were measured in the 

cortex, hippocampus, striatum, cerebellum, and brainstem. 

Effect noted in study and corresponding doses: No significant alterations in body weight, food 

consumption, or water consumption were observed during gestation in the dams exposed to aluminum. 

The investigators noted that decreases in water and food consumption were observed during the lactation 

period in the rats exposed to 103 mg Al/kg/day, but the data were not shown, and maternal body weight 

during lactation was not mentioned. No significant alterations in the number of litters, number of fetuses 

per litter, viability index, or lactation index were observed. Additionally, no differences in days at pinna 

detachment or eye opening were observed. Age at incisor eruption was significantly higher in males 

exposed to 53 mg/kg/day, but not in males exposed to 103 mg/kg/day or in females. A significant delay 

in age at testes descent was observed at 103 mg/kg/day and vagina opening was delayed at 53 and 

103 mg/kg/day. A decrease in forelimb grip strength was observed at 103 mg/kg/day; no alterations in 

other neuromotor tests were observed. Additionally, no alterations in open field behavior or passive 

avoidance test were observed. In the water maze test, latency to find the hidden platform was decreased 

in the 53 mg/kg/day group on test day 2, but not on days 1 or 3; no significant alteration in time in the 

target quadrant was found. 

Dose and end point used for MRL derivation: The Golub and Germann (2001) and Colomina et al. 

(2005) studies identify four end points that could be used as the point of departure for derivation of the 

intermediate-duration oral MRL: 

(1)	 latency to fall off wire in wire suspension test; adverse effect level of 130 mg Al/kg/day, no 

effect level of 26 mg Al/kg/day (Golub and Germann 2001); 

(2)	 latency to locate the platform following cue relocation in the water maze test; adverse effect 

level of 130 mg Al/kg/day, no effect level of 26 mg Al/kg/day (Golub and Germann 2001); 

(3)	 decreased forelimb grip strength; adverse effect level of 103 mg Al/kg/day, no effect level of 

53 mg Al/kg/day (Colomina et al. 2005); and 
 

 

 

 

 

 

 

 

 

 

 

ALUMINUM	 A-5 

APPENDIX A 

(4)	 delay in vagina opening; adverse effect level of 53 mg Al/kg/day, no effect level not 

identified (Colomina et al. 2005). 

Benchmark dose modeling was considered for each of these end points. Continuous variable models in 

the EPA Benchmark Dose Software (BMDS version 1.3.2) were fit to the data. A change of 1 standard 

deviation from control was selected as the BMR. Benchmark dose modeling was not conducted for 

latency to fall from the wire and forelimb grip strength because it is unclear whether the data reported in 

Table 5 (Golub and Germann 2001) and Figure 2 (Colomina et al. 2005), respectively, was for the mean 

±SEM or the mean ± standard deviation. For delay in maturation, none of the available models provided 

an adequate fit (as assessed by the p-values for variance); therefore, the data set is unsuitable for BMD 

modeling. For the change in the latency to find the platform, the constant variance linear model provided 

an adequate fit. However, the BMD (419 mg Al/kg/day) and BMDL (186 mg Al/kg/day) were higher 

than the dose at which the change in latency was statistically significant (130 mg Al/kg/day), suggesting 

that using the change of 1 standard deviation from controls may not be an appropriate BMR for these 

data. 

Using a NOAEL/LOAEL approach, the NOAEL of 26 mg Al/kg/day identified in the Golub and 

Germann (2001) study was selected as the point of departure for the MRL. 

[X] NOAEL [ ] LOAEL 

Uncertainty Factors used in MRL derivation: 

[ ] 10 for use of a LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Modifying Factors used in MRL derivation: 

[X] 0.3 to account for possible differences in the bioavailability of the aluminum lactate used in 

the Golub and Germann (2001) study and the bioavailability of aluminum from drinking water 

and a typical U.S. diet. 

No studies were identified that estimated the bioavailability of aluminum lactate following long-term 

dietary exposure; however, a bioavailability of 0.63% was estimated in rabbits receiving a single dose of 

aluminum lactate (Yokel and McNamara 1988). Yokel and McNamara (2001) and Powell and Thompson 

(1993) suggested that the bioavailability of aluminum from the typical U.S. diet was 0.1%; the 

bioavailability of aluminum from drinking water ranges from 0.07 to 0.39% (Hohl et al. 1994; Priest et al. 

1998; Stauber et al. 1999; Steinhausen et al. 2004). These data suggest that aluminum lactate has a higher 

bioavailability than aluminum compounds typically found in drinking water or the diet. 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? Golub and Germann 

(2001): Doses of 26, 130, and 260 mg Al/kg/day are calculated by averaging reported estimated doses of 

10, 50 and 100 mg Al/kg/day for adults (i.e., at beginning of pregnancy), and 42, 210, and 420 mg 

Al/kg/day maximal intake during lactation. The doses at lactation were calculated using doses were 

estimated in previous studies with similar exposure protocols performed by the same group of 

investigators (e.g., Golub et al. 1995). 

Colomina et al. (2005): Doses of 3, 53, and 103 mg Al/kg/day were calculated by adding the basal 

dietary aluminum doses (calculated using reference values for mature Sprague-Dawley rats) to reported 

aluminum doses from water. 
 

 

 

 

 

 

 

 

 

ALUMINUM A-6 

APPENDIX A 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

Not applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: The neurotoxicity and 

neurodevelopmental toxicity of aluminum are well-documented effects of aluminum in orally-exposed in 

mice and rats. A wide variety of behavioral tests were conducted in rats and mice; alterations in motor 

function were the most consistently observed effects. Decreases in forelimb and/or hindlimb grip strength 

have been observed in adult mice exposed to 195 mg Al/kg/day as aluminum lactate in the diet for 

90 days (Golub et al. 1992b), mice (6 weeks of age at study beginning) exposed to 195 mg Al/kg/day as 

aluminum lactate in the diet for 5–7 weeks (Oteiza et al. 1993), the offspring of mice exposed on 

gestation day 1 through lactation day 21 to 155 mg Al/kg/day (Donald et al. 1989; Golub et al. 1995) or 

250 mg Al/kg/day (Golub et al. 1995) as aluminum lactate, and the offspring of rats exposed to 103 mg 

Al/kg/day as aluminum nitrate in drinking water (with added citric acid) for 15 days prior to mating and 

on gestation day 1 through lactation day 21 (Colomina et al. 2005). Decreases in spontaneous motor 

activity were observed in mice exposed to 130 mg Al/kg/day for 6 weeks (Golub et al. 1989) or 195 mg 

Al/kg/day for 90 days (Golub et al. 1992b). Motor impairments have also been detected in mice in the 

wire suspension test in which offspring exposed to 130 mg Al/kg/day had a shorter latency to fall from 

the wire and in the rotorod test in which offspring exposed to 260 mg Al/kg/day had a higher number of 

rotations (which occur when the animals lost its footing, clung to the rod, and rotated with it for a full 

turn) (Golub and Germann 2001). Neurobehavioral alterations that have occurred at similar dose levels 

include decreased responsiveness to auditory or air-puff startle (Golub et al. 1992b, 1995), decreased 

thermal sensitivity (Golub et al. 1992a), increased negative geotaxis latency (Golub et al. 1992a), and 

increased foot splay (Donald et al. 1989). Additionally, one study found significant impairment in 

performance of the water maze test in offspring of mice exposed to 130 mg Al/kg/day on gestation day 1 

through lactation day 21 (Golub and Germann 2001). Colomina et al. (2005) did not find alterations in 

this test in rats exposed to 53 mg Al/kg/day; however, this study did not run probe tests, which showed 

significant alterations in the Golub and Germann (2001) study. Other studies have utilized passive 

avoidance tests or operant training tests to evaluate potential impairment of cognitive function. However, 

the interpretation of the results of these tests is complicated by an increase in food motivation in 

aluminum exposed mice (Golub and Germann 1998). 

In addition to the neurodevelopmental effects, there is also strong evidence that gestational and/or 

lactational exposure can cause other developmental effects. Aluminum does not appear to result in an 

increase in the occurrence of malformations and anomalies and does not typically affect birth weight. 

Gestation and/or lactation exposure can result in significant decreases in pup body weight gain in rats and 

mice (Colomina et al. 2005; Golub and Germann 2001; Golub et al. 1992a). The decreases in pup body 

weight are often associated with decreases in maternal body weight during the lactation phase of the 

study; however, decreases in body weight have also been observed in a cross-fostering study when 

gestation-exposed pups were nursed by control mice (Golub et al. 1992a). Other studies involving 

gestation and lactation exposure to aluminum did not find changes in pup growth in mice (Donald et al. 

1989; Golub and Germann 1998; Golub et al. 1995). In rats, a delay in physical maturation, particularly 

delays in vagina opening, testes descent, and incisor eruption, has been reported at 53 mg Al/kg/day 

(Colomina et al. 2005). 

Agency Contacts (Chemical Managers): Sam Keith, Dennis Jones, Zemoria Rosemond 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM A-7 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Aluminum 

CAS Numbers: 7429-90-5 

Date: June 2008 

Profile Status: Final 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Graph Key: 56 

Species: Mouse 

Minimal Risk Level: 1 [X] mg/kg/day [ ] ppm 

Reference: Golub MS, Germann SL, Han B, et al. 2000. Lifelong feeding of a high aluminum diet to 

mice. Toxicology 150:107-117. 

Experimental design: Groups of 8 male and 10 female Swiss Webster mice were exposed to 7 or 

1,000 μg Al/g diet as aluminum lactate in a purified diet. The investigators estimated adult doses of 

<1 and 100 mg/kg/day. The mice were exposed to aluminum from conception (via feeding the dams) 

through 24 months of age. Body weight, food intake, and clinical signs were determined during the last 

6 months of the study. Neurobehavioral test battery (foot splay, temperature sensitivity, negative 

geotaxis, and grip strength), 1 hour spontaneous activity, and auditory startle tests were conducted at 

18 and 24 months. 

In a companion study, groups of 6–9 male and female Swiss Webster mice or 7 male and female 

C57BL/6J mice (number per sex were not reported) were exposed to 7 or 1,000 μg Al/g diet as aluminum

lactate in a purified diet (<1 and 100 mg/kg/day) from conception (via feeding the dams) through 

24 months of age. Body weight, food intake, and clinical signs were determined during the last 6 months 

of the study. Neurobehavioral test battery (foot splay, temperature sensitivity, negative geotaxis, and grip 

strength) and Morris maze testing were at 22–23 months of age. 

Effect noted in study and corresponding doses: In the principal study, no significant alterations in 

mortality were observed. A significant decrease in body weight was observed in the female mice 

(approximately 20%). In the males, there was a significant increase in body weight (approximately 10%). 

No significant alterations in food intake were observed in either sex. However, food intake/g body weight 

was significantly higher in the aluminum exposed mice. No significant alterations in the occurrence of 

clinical signs or indications of neurodegenerative syndromes were found. Significant increases in relative 

spinal cord, heart, and kidney weights were found. Significant alterations in negative geotaxis and tail 

withdrawal time in the temperature sensitivity test (males only) were observed at 18 months. At 

24 months, significant alterations in forelimb and hindlimb grip strength and temperature sensitivity were 

found in male and female mice. Forelimb and hindlimb grip strength was decreased and thermal 

sensitivity was decreased, as evidenced by an increase in tail withdrawal times. Auditory startle response 

tests could not be completed in the older mice. Similarly, vertical spontaneous movement could not be 

measured; no effect on horizontal movement was found. 

In the companion study, no alterations in neurobehavioral battery test performance were observed; the 

investigators note that this may be due to the small number of animals per group. In general, aluminumexposed mice performed better on the water maze test than controls. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM A-8 

APPENDIX A 

Dose and end point used for MRL derivation: A LOAEL of 100 mg Al/kg/day for decreased forelimb 

and hindlimb grip strength and decreased thermal sensitivity. A benchmark dose approach for deriving an 

MRL was not utilized because the Golub et al. (2000) study only tested one aluminum group. 

[ ] NOAEL [X] LOAEL 

Uncertainty Factors used in MRL derivation: 

[X] 3 for use of a minimal LOAEL 

[X] 10 for extrapolation from animals to humans 

[X] 10 for human variability 

Modifying Factors used in MRL derivation: 

[X] 0.3 to account for possible differences in the bioavailability of the aluminum lactate used in 

the Golub and Germann (2001) study and the bioavailability of aluminum from drinking water 

and a typical U.S. diet. 

No studies were identified that estimated the bioavailability of aluminum lactate following long-term 

dietary exposure; however, a bioavailability of 0.63% was estimated in rabbits receiving a single dose of 

aluminum lactate (Yokel and McNamara 1988). Yokel and McNamara (2001) and Powell and Thompson 

(1993) suggested that the bioavailability of aluminum from the typical U.S. diet was 0.1%; the 

bioavailability of aluminum from drinking water ranges from 0.07 to 0.39% (Hohl et al. 1994; Priest et al. 

1998; Stauber et al. 1999; Steinhausen et al. 2004). These data suggest that aluminum lactate has a higher 

bioavailability than aluminum compounds typically found in drinking water or the diet. 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No (doses 

corresponding to food ppm levels were reported by investigators). 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

Not applicable. 

Was a conversion used from intermittent to continuous exposure? Not applicable. 

Other additional studies or pertinent information that lend support to this MRL: A small number of 

animal studies examined the chronic toxicity of aluminum. Schroeder and Mitchener (1975a, 1975b) 

examined the systemic toxicity of aluminum following lifetime exposure of rats and mice to very low 

doses of aluminum sulfate in the drinking water. Although the levels of aluminum in diet were not 

reported, they are assumed to be low because the animals were fed a low-metal diet in metal-free 

environmental conditions. Studies conducted by Roig et al. (2006) and Golub et al. (2000) primarily 

focused on the neurotoxicity of aluminum following lifetime exposure (gestation day 1 through 

24 months of age). In the Golub et al. (2000) study, significant decreases in forelimb and hindlimb grip 

strength, and a decrease in thermal sensitivity were observed in mice exposed to 100 mg Al/kg/day; 

negative geotaxis was significantly altered at 18 months, but not at 24 months. No effect on horizontal 

activity was observed. A 10% increase in body weight and a 20% decrease in body weight were observed 

in the males and females, respectively. In a companion study by this group, no significant cognitive 

impairments were found in the Morris water maze test; in fact, aluminum-exposed mice performed better 

than controls in the learning tasks. Roig et al. (2006) also found no significant alterations in performance 

on the Morris water maze in rats exposed to 100 mg Al/kg/day as aluminum nitrate in the drinking water 

(with added citric acid). Although significant differences were found between the two aluminum groups 
 

 

 

 

ALUMINUM A-9 

APPENDIX A 

(50 and 100 mg Al/kg/day), this was primarily due to the improved performance (as compared to controls, 

no significant differences) in the 50 mg Al/kg/day group. Roig et al. (2006) also found no significant 

alterations in open field activity. 

Additional support for the selection of these end points, and neurotoxicity in general, comes from a 

number of intermediate-duration studies that indicate that this is one of most sensitive targets of 

aluminum toxicity (Colomina et al. 2005; Donald et al. 1989; Golub and Germann 2001; Golub et al. 

1992a, 1995). 

Agency Contacts (Chemical Managers): Sam Keith, Dennis Jones, Zemoria Rosemond 
ALUMINUM A-10 

APPENDIX A 

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ALUMINUM	 B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions: 

1.	 What effects are known to occur in humans? 

2.	 What effects observed in animals are likely to be of concern to humans? 

3.	 What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 
 

 

 

 

 

 

 

 

 

ALUMINUM B-2 

APPENDIX B 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 
 

 

 

 

ALUMINUM	 B-3 

APPENDIX B 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1)	 Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically 

when sufficient data exist, three LSE tables and two LSE figures are presented in the document. 

The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, 

and dermal (LSE Tables 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation 

(LSE Figure 3-1) and oral (LSE Figure 3-2) routes. Not all substances will have data on each 

route of exposure and will not, therefore, have all five of the tables and figures. 

(2)	 Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. 

In this example, an inhalation study of intermediate exposure duration is reported. For quick 

reference to health effects occurring from a known length of exposure, locate the applicable 

exposure period within the LSE table and figure. 

(3)	 Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. 

NOAELs and LOAELs can be reported in the tables and figures for all effects but cancer. 

Systemic effects are further defined in the "System" column of the LSE table (see key number 

18). 

(4)	 Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL 

(also see the two "18r" data points in sample Figure 3-1). 

(5)	 Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and 

Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. 

Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent 

human doses to derive an MRL. 

(6)	 Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimens are provided in this column. This permits comparison of NOAELs and LOAELs from 

different studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation 

for 6 hours/day, 5 days/week, for 13 weeks. For a more complete review of the dosing regimen, 

refer to the appropriate sections of the text or the original reference paper (i.e., Nitschke et al. 

1981). 

(7)	 System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and 

dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered 

in these systems. In the example of key number 18, one systemic effect (respiratory) was 

investigated. 

(8)	 NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "b"). 
 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM	 B-4 

APPENDIX B 

(9)	 LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help 

readers identify the levels of exposure at which adverse health effects first appear and the 

gradation of effects with increasing dose. A brief description of the specific end point used to 

quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key 

number 18 (hyperplasia) is a Less Serious LOAEL of 10 ppm. MRLs are not derived from 

Serious LOAELs. 

(10)	 Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11)	 CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE 

tables and figures do not contain NOAELs for cancer, but the text may report doses not causing 

measurable cancer increases. 

(12)	 Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to 

derive an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13)	 Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14)	 Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15)	 Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log 

scale "y" axis. Inhalation exposure is reported in mg/m3 or ppm and oral exposure is reported in 

mg/kg/day. 

(16)	 NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 

corresponds to the entry in the LSE table. The dashed descending arrow indicates the 

extrapolation from the exposure level of 3 ppm (see entry 18 in the table) to the MRL of 

0.005 ppm (see footnote "b" in the LSE table). 

(17)	 CEL. Key number 38m is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the 

LSE table. 
 

ALUMINUM	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived 

from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the 

cancer dose response curve at low dose levels (q1*). 

(19)	 Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
SAMPLE

1 → Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

LOAEL (effect) Exposure 

Key to frequency/ NOAEL Less serious Serious (ppm) figurea Species duration System (ppm) (ppm) Re

2 3 4 

→ INTERMEDIATE EXPOSURE 

5 6 7 8 9 10 

→ Systemic ↓ ↓ ↓ ↓ ↓ ↓

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

→ 5 d/wk Nit

6 hr/d 

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wo

5 d/wk organs) 7 hr/d 

39 Rat 89–104 wk 10 (CEL, lung tumors, NT

5 d/wk nasal tumors) 6 hr/d 

40 Mouse 79–103 wk 10 (CEL, lung tumors, NT

5 d/wk hemangiosarcomas) 6 hr/d 

12 → a The number corresponds to entries in Figure 3-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent ex

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 

ALUMINUM B-8
 

APPENDIX B 

This page is intentionally blank. 
 

ALUMINUM C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS
 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD benchmark dose 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMDG North America/Intergovernmental Maritime Dangerous Goods Code 
 

 

ALUMINUM C-2 

APPENDIX C 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton Koc organic carbon partition coefficient Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 

MF modifying factor 
ALUMINUM C-3 

APPENDIX C 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 
 

 

ALUMINUM C-4 

APPENDIX C 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
 

ALUMINUM C-5 

APPENDIX C 

> greater than ≥ greater than or equal to 

= equal to 

< less than ≤ less than or equal to 

% percent α alpha β beta γ gamma δ delta 

μm micrometer 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 
ALUMINUM C-6
 

APPENDIX C 

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ALUMINUM D-1 

APPENDIX D. INDEX
 

absorbed dose............................................................................................................................................125
 

adrenal gland..................................................................................................................................... 104, 107
 

adrenals .....................................................................................................................................................104
 

adsorbed....................................................................................................................................................187
 

adsorption.......................................................................................................................................... 175, 187
 

ambient air .................................................................................................................. 11, 177, 210, 213, 219
 

anemia.......................................................................................................................................................127
 

bioaccumulation........................................................................................................................................223
 

bioavailability ................. 24, 26, 27, 66, 78, 84, 97, 101, 102, 105, 116, 126, 136, 140, 143, 223, 227, 245
 

bioconcentration factor .............................................................................................................................189
 

biokinetic ..................................................................................................................................................113
 

biomarker .......................................................................................................... 124, 125, 126, 139, 143, 229
 

body weight effects................................................................................................................. 29, 44, 74, 131
 

breast milk............................................................................. 6, 106, 123, 177, 206, 207, 214, 220, 224, 225
 

cancer................................................................................................................ 15, 48, 49, 89, 121, 129, 214
 

carcinogen......................................................................................................................................... 134, 249
 

carcinogenic .................................................................................................................... 15, 27, 49, 134, 249
 

carcinogenicity.................................................................................................................................... 90, 134
 

carcinoma....................................................................................................................................................90
 

cardiovascular ................................................................................................................................. 41, 68, 90
 

cardiovascular effects............................................................................................................................ 41, 68
 

clearance ..................................................................................................................... 16, 100, 105, 122, 132
 

cognitive function ................................................................................................... 13, 14, 20, 21, 47, 82, 89
 

crustaceans........................................................................................................................................ 189, 211
 

death........................................................................................................ 27, 28, 29, 66, 67, 76, 90, 129, 249
 

deoxyribonucleic acid (see DNA)...............................................................................................................97
 

dermal effects.................................................................................................................. 44, 73, 91, 131, 133
 

developmental effects ................................................................. 20, 47, 85, 89, 97, 117, 134, 136, 140, 141
 

DNA (see deoxyribonucleic acid)................................................................................................. 97, 98, 125
 

elimination rate ...........................................................................................................................................99
 

endocrine................................................................................................................... 43, 44, 73, 90, 119, 120
 

endocrine effects ............................................................................................................................. 43, 44, 73
 

fetal tissue .................................................................................................................................................108
 

fetus........................................................................................................... 106, 107, 109, 120, 123, 128, 136
 

fractional absorption ......................................................................................................................... 100, 222
 

gastrointestinal effects .......................................................................................................................... 42, 69
 

general population......................................................... 11, 13, 124, 138, 177, 207, 210, 213, 219, 220, 249
 

genotoxic.....................................................................................................................................................27
 

genotoxicity...............................................................................................................................................134
 

groundwater ...................................................................................... 177, 184, 185, 186, 195, 197, 224, 240
 

half-life.............................................................................................................. 105, 107, 108, 112, 124, 233
 

hematological effects ............................................................................................................................ 42, 69
 

hematopoietic...................................................................................................................... 49, 127, 128, 133
 

hepatic effects ......................................................................................................................... 43, 71, 72, 126
 

hydrolysis..................................................................................................................................................191
 

immune system ........................................................................................................................... 75, 135, 137
 

immunological .......................................................................................................... 27, 45, 75, 96, 132, 136
 

immunological effect ..................................................................................................................................75
 

Kow ............................................................................................................................ 151, 152, 153, 154, 155
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ALUMINUM D-2 

APPENDIX D 

LD50.............................................................................................................................................................66
 

leukemia......................................................................................................................................................90
 

lymphatic ....................................................................................................................................................49
 

lymphoreticular............................................................................................................................. 45, 96, 136
 

mass spectroscopy..................................................................................................................... 229, 232, 239
 

metabolic effects ............................................................................................................................. 29, 45, 90
 

micronuclei ......................................................................................................................................... 97, 134
 

milk ............................3, 6, 106, 108, 123, 175, 177, 188, 202, 203, 205, 206, 211, 220, 225, 231, 232, 234
 

mucociliary ...............................................................................................................................................100
 

musculoskeletal effects ............................................................................................................. 42, 43, 71, 91
 

neonatal..................................................................................................................................... 122, 123, 124
 

neurobehavioral................................................... 12, 14, 16, 21, 23, 25, 46, 77, 79, 117, 118, 120, 135, 137
 

neurochemical...........................................................................................................................................118
 

neurodevelopmental.............................................. 14, 19, 20, 24, 87, 88, 117, 119, 132, 135, 136, 138, 245
 

neurological effects....... 12, 14, 16, 24, 45, 47, 76, 77, 83, 96, 119, 123, 126, 131, 133, 137, 138, 140, 245
 

nuclear......................................................................................................................................... 83, 233, 234
 

ocular effects................................................................................................................................... 44, 73, 74
 

odds ratio............................................................................................................................................... 77, 96
 

pharmacodynamic.....................................................................................................................................112
 

pharmacokinetic................................................................................................................ 112, 113, 114, 121
 

placenta ..................................................................................................................... 106, 108, 123, 128, 140
 

pulmonary fibrosis .................................................................................................................. 16, 39, 41, 133
 

renal effects........................................................................................................................................... 43, 72
 

reproductive effects............................................................................................... 18, 47, 83, 84, 85, 97, 134
 

respiratory effects............................................................................................................................ 16, 29, 67
 

retention ...................................................................................................... 82, 100, 105, 112, 126, 139, 141
 

solubility ....................................................................................... 11, 99, 102, 116, 186, 187, 191, 194, 222
 

spermatozoa ...................................................................................................................................... 208, 224
 

systemic effects......................................................................................................................... 29, 67, 90, 91
 

thyroid........................................................................................................................................... 44, 73, 107
 

toxicokinetic.................................................................................................................. 27, 99, 100, 140, 141
 

tremors ........................................................................................................................................................46
 

tumors ............................................................................................................................................. 15, 48, 90
 

weanling...................................................................................................................................... 14, 123, 135