TOXICOLOGICAL PROFILE FOR 

ZINC 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

August 2005 
ZINC 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. 
ZINC iii 

UPDATE STATEMENT 

A Toxicological Profile for Zinc, Draft for Public Comment was released in September 2003. 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/Toxicology Information Branch 

1600 Clifton Road NE 

Mailstop F-32 

Atlanta, Georgia 30333 


ZINC vi 

*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 November 17, 1997 (62 FR 61332). For prior 

versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 FR 18744); 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); and February 

28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the Administrator of ATSDR 

to prepare a toxicological profile for each substance on the list. 
 

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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: 1-888-42-ATSDR or (404) 498-0110 Fax: (770) 488-4178 

E-mail: atsdric@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 
ZINC viii 

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

Toxicity; and numerous chemical-specific case studies. 

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, 55 West Seegers Road, Arlington Heights, 

IL 60005 • Phone: 847-818-1800 • FAX: 847-818-9266. 
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CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Nickolette Roney, M.S. 

Cassandra V. Smith, M.S. 

Malcolm Williams, D.V.M., Ph.D. 

Agency for Toxic Substances and Disease Registry, Atlanta, GA 

Mark Osier, Ph.D., D.A.B.T. 

Sari J. Paikoff, Ph.D. 

Syracuse Research Corporation, North Syracuse, NY 

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 Research Implementation 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. 

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PEER REVIEW 

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

1. Olen Brown, Ph.D., University of Missouri-Columbia, Columbia, Missouri; 

2. Robert Michael, Ph.D., RAM TRAC Corporation, Schenectady, New York; and 

3. Gary Pascoe, Ph.D., DABT, Pascoe Environmental Consulting, Port Townsend, Washington. 

These experts collectively have knowledge of zinc'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. 

 

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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 ZINC? ........................................................................................................................1 

1.2 WHAT HAPPENS TO ZINC WHEN IT ENTERS THE ENVIRONMENT? ...........................2 

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

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

1.5 HOW CAN ZINC AFFECT MY HEALTH?..............................................................................4 

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

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

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

 TO ZINC?....................................................................................................................................7 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

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

1.10 WHERE CAN I GET MORE INFORMATION? .......................................................................9 

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

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ZINC IN THE UNITED 

STATES ....................................................................................................................................11 

2.2 SUMMARY OF HEALTH EFFECTS......................................................................................11 

2.3 MINIMAL RISK LEVELS (MRLs) .........................................................................................16 

3. HEALTH EFFECTS..............................................................................................................................21 

3.1 INTRODUCTION.....................................................................................................................21 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................22 

3.2.1 Inhalation Exposure ..............................................................................................................23 

3.2.1.1 Death ............................................................................................................................23 

3.2.1.2 Systemic Effects...........................................................................................................24 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................36 

3.2.1.4 Neurological Effects.....................................................................................................36 

3.2.1.5 Reproductive Effects....................................................................................................37 

3.2.1.6 Developmental Effects .................................................................................................37 

3.2.1.7 Cancer...........................................................................................................................37 

3.2.2 Oral Exposure........................................................................................................................38 

3.2.2.1 Death ............................................................................................................................38 

3.2.2.2 Systemic Effects...........................................................................................................39 

3.2.2.3 Immunological and Lymphoreticular Effects...............................................................63 

3.2.2.4 Neurological Effects.....................................................................................................64 

3.2.2.5 Reproductive Effects....................................................................................................65 
 

 

 

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3.2.2.6 Developmental Effects .................................................................................................66 

3.2.2.7 Cancer...........................................................................................................................67 

3.2.3 Dermal Exposure...................................................................................................................69 

3.2.3.1 Death ............................................................................................................................69 

3.2.3.2 Systemic Effects...........................................................................................................69 

3.2.3.3 Immunological and Lymphoreticular Effects...............................................................73 

3.2.3.4 Neurological Effects.....................................................................................................73 

3.2.3.5 Reproductive Effects....................................................................................................73 

3.2.3.6 Developmental Effects .................................................................................................73 

3.2.3.7 Cancer...........................................................................................................................73 

3.3 GENOTOXICITY .....................................................................................................................73 

3.4 TOXICOKINETICS..................................................................................................................75 

3.4.1 Absorption.............................................................................................................................75 

3.4.1.1 Inhalation Exposure......................................................................................................75 

3.4.1.2 Oral Exposure...............................................................................................................77 

3.4.1.3 Dermal Exposure ..........................................................................................................79 

3.4.2 Distribution ...........................................................................................................................80 

3.4.2.1 Inhalation Exposure......................................................................................................81 

3.4.2.2 Oral Exposure...............................................................................................................82 

3.4.2.3 Dermal Exposure ..........................................................................................................82 

3.4.3 Metabolism............................................................................................................................82 

3.4.4 Elimination and Excretion.....................................................................................................83 

3.4.4.1 Inhalation Exposure......................................................................................................83 

3.4.4.2 Oral Exposure...............................................................................................................83 

3.4.4.3 Dermal Exposure ..........................................................................................................84 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models .............84 

3.5 MECHANISMS OF ACTION ..................................................................................................87 

3.5.1 Pharmacokinetic Mechanisms...............................................................................................87 

3.5.2 Mechanisms of Toxicity........................................................................................................88 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ..........................89 

3.7 CHILDREN’S SUSCEPTIBILITY...........................................................................................91 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ....................................................................93 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Zinc .................................................94 

3.8.2 Biomarkers Used to Characterize Effects Caused by Zinc ...................................................95 

3.9 INTERACTIONS WITH OTHER CHEMICALS ....................................................................96 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE.............................................100 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................101 

3.11.1 Reducing Peak Absorption Following Exposure ............................................................101 

3.11.2 Reducing Body Burden...................................................................................................102 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .........................................102 

3.12 ADEQUACY OF THE DATABASE......................................................................................103 

3.12.1 Existing Information on Health Effects of Zinc..............................................................104 

3.12.2 Identification of Data Needs ...........................................................................................106 

3.12.3 Ongoing Studies..............................................................................................................114 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................119 

4.1 CHEMICAL IDENTITY.........................................................................................................119 

4.2 PHYSICAL AND CHEMICAL PROPERTIES......................................................................119 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................129 

5.1 PRODUCTION .......................................................................................................................129 
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5.2 IMPORT/EXPORT .................................................................................................................130 

5.3 USE..........................................................................................................................................130 

5.4 DISPOSAL..............................................................................................................................137 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................139 

6.1 OVERVIEW............................................................................................................................139 

6.2 RELEASES TO THE ENVIRONMENT................................................................................142 

6.2.1 Air .......................................................................................................................................142 

6.2.2 Water...................................................................................................................................148 

6.2.3 Soil ......................................................................................................................................151 

6.3 ENVIRONMENTAL FATE....................................................................................................152
 

6.3.1 Transport and Partitioning...................................................................................................153 

6.3.2 Transformation and Degradation ........................................................................................159 

6.3.2.1 Air...............................................................................................................................159 

6.3.2.2 Water ..........................................................................................................................160 

6.3.2.3 Sediment and Soil.......................................................................................................160 

6.3.2.4 Other Media................................................................................................................161 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT...............................161 

6.4.1 Air .......................................................................................................................................162 

6.4.2 Water...................................................................................................................................163 

6.4.3 Sediment and Soil ...............................................................................................................168 

6.4.4 Other Environmental Media................................................................................................173 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .....................................175 

6.6 EXPOSURES OF CHILDREN...............................................................................................179 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...........................................181 

6.8 ADEQUACY OF THE DATABASE......................................................................................181 

6.8.1 Identification of Data Needs ...............................................................................................182 

6.8.2 Ongoing Studies ..................................................................................................................186 

7. ANALYTICAL METHODS ...............................................................................................................191 

7.1 BIOLOGICAL MATERIALS.................................................................................................192 

7.2 ENVIRONMENTAL SAMPLES............................................................................................197 

7.3 ADEQUACY OF THE DATABASE......................................................................................201 

7.3.1 Identification of Data Needs ...............................................................................................202 

7.3.2 Ongoing Studies ..................................................................................................................203 

8. REGULATIONS AND ADVISORIES ...............................................................................................205 

9. REFERENCES ....................................................................................................................................211 

10. GLOSSARY ......................................................................................................................................301 

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 

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LIST OF FIGURES 

3-1. Levels of Significant Exposure to Zinc—Inhalation .......................................................................... 28 

3-2. Levels of Significant Exposure to Zinc—Oral ................................................................................... 53 

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

Hypothetical Chemical Substance .......................................................................................................86
 

3-4. Existing Information on Health Effects of Zinc ...............................................................................105
 

6-1. Frequency of NPL Sites with Zinc Contamination...........................................................................140
 

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LIST OF TABLES 

3-1. Levels of Significant Exposure to Zinc—Inhalation .......................................................................... 25 

3-2. Levels of Significant Exposure to Zinc—Oral ................................................................................... 40 

3-3. Levels of Significant Exposure to Zinc—Dermal .............................................................................. 70 

3-4. Genotoxicity of Zinc In Vivo ..............................................................................................................74
 

3-5. Genotoxicity of Zinc In Vitro .............................................................................................................76
 

3-6. Ongoing Studies on Zinc Health Effects ..........................................................................................115
 

4-1. Chemical Identity of Zinc and Selected Compounds .......................................................................120
 

4-2. Physical and Chemical Properties of Zinc and Selected Compounds ..............................................125
 

5-1. Facilities that Produce, Process, or Use Zinc....................................................................................131
 

5-2. Facilities that Produce, Process, or Use Zinc Compounds...............................................................133
 

5-3. Distribution of U.S. Zinc Consumption in 2002...............................................................................136
 

6-1. Releases to the Environment from Facilities that Produce, Process, or Use Zinc ............................143
 

6-2. Releases to the Environment from Facilities that Produce, Process, or Use Zinc Compounds........146
 

6-3. Zinc Loadings in Urban Storm Water Runoff ..................................................................................149
 

6-4. Dissolved Zinc in Rivers of the United States..................................................................................164
 

6-5. Median Zinc Levels in Bed Sediment from River Basins of the United States................................170
 

6-6. Ongoing Studies on the Environmental Effects of Zinc ...................................................................187
 

7-1. Analytical Methods for Determining Zinc in Biological Materials..................................................193
 

7-2. Analytical Methods for Determining Zinc in Environmental Samples............................................198
 

7-3. Ongoing Studies on Analytical Methods for Zinc ............................................................................204
 

8-1. Regulations and Guidelines Applicable to Zinc and Zinc Compounds............................................206
 

ZINC 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about zinc and the effects of exposure to it. Zinc is an 

essential element needed by your body and is commonly found in nutritional supplements. 

However, taking too much zinc into the body can affect your health. 

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. Zinc has been found in at least 985 of the 1,662 current or 

former NPL sites. Although the total number of NPL sites evaluated for zinc is not known, the 

possibility exists that the number of sites at which zinc 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 zinc may harm you. 

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. 

If you are exposed to zinc, 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. 

1.1 WHAT IS ZINC? 

Zinc is one of the most common elements in the Earth's crust. Zinc is found in the air, soil, and 

water and is present in all foods. In its pure elemental (or metallic) form, zinc is a bluish-white, 

shiny metal. Powdered zinc is explosive and may burst into flames if stored in damp places. 

Metallic zinc has many uses in industry. A common use for zinc is to coat steel and iron as well 
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1. PUBLIC HEALTH STATEMENT 

as other metals to prevent rust and corrosion; this process is called galvanization. Metallic zinc 

is also mixed with other metals to form alloys such as brass and bronze. A zinc and copper alloy 

is used to make pennies in the United States. Metallic zinc is also used to make dry cell 

batteries. 

Zinc can also combine with other elements, such as chlorine, oxygen, and sulfur, to form zinc 

compounds. Zinc compounds that may be found at hazardous waste sites are zinc chloride, zinc 

oxide, zinc sulfate, and zinc sulfide. Most zinc ore found naturally in the environment is in the 

form of zinc sulfide. Zinc compounds are widely used in industry. Zinc sulfide and zinc oxide 

are used to make white paints, ceramics, and other products. Zinc oxide is also used in 

producing rubber. Zinc compounds, such as zinc acetate, zinc chloride, and zinc sulfate, are used 

in preserving wood and in manufacturing and dyeing fabrics. Zinc chloride is also the major 

ingredient in smoke from smoke bombs. Zinc compounds are used by the drug industry as 

ingredients in some common products, such as vitamin supplements, sun blocks, diaper rash 

ointments, deodorants, athlete's foot preparations, acne and poison ivy preparations, and 

antidandruff shampoos. Information can be found on the chemical and physical properties of 

zinc in Chapter 4 and on its occurrence and fate in the environment in Chapter 6. 

1.2 WHAT HAPPENS TO ZINC WHEN IT ENTERS THE ENVIRONMENT? 

Zinc enters the air, water, and soil as a result of both natural processes and human activities. 

Most zinc enters the environment as the result of mining, purifying of zinc, lead, and cadmium 

ores, steel production, coal burning, and burning of wastes. These activities can increase zinc 

levels in the atmosphere. Waste streams from zinc and other metal manufacturing and zinc 

chemical industries, domestic waste water, and run-off from soil containing zinc can discharge 

zinc into waterways. The level of zinc in soil increases mainly from disposal of zinc wastes from 

metal manufacturing industries and coal ash from electric utilities. Sludge and fertilizer also 

contribute to increased levels of zinc in the soil. In air, zinc is present mostly as fine dust 

particles. This dust eventually settles over land and water. Rain and snow aid in removing zinc 

from air. Most of the zinc in lakes or rivers settles on the bottom. However, a small amount 

may remain either dissolved in water or as fine suspended particles. The level of dissolved zinc 
ZINC 3 

1. PUBLIC HEALTH STATEMENT 

in water may increase as the acidity of water increases. Fish can collect zinc in their bodies from 

the water they swim in and from the food they eat. Most of the zinc in soil is bound to the soil 

and does not dissolve in water. However, depending on the type of soil, some zinc may reach 

groundwater, and contamination of groundwater has occurred from hazardous waste sites. Zinc 

may be taken up by animals eating soil or drinking water containing zinc. Zinc is also a trace 

mineral nutrient and as such, small amounts of zinc are needed in all animals. For more 

information about what happens to zinc in the environment, see Chapter 6. 

1.3 HOW MIGHT I BE EXPOSED TO ZINC? 

Zinc is an essential element needed by your body in small amounts. We are exposed to zinc 

compounds in food. The average daily zinc intake through the diet in this country ranges from 

5.2 to 16.2 milligrams (milligram=0.001 gram). Food may contain levels of zinc ranging from 

approximately 2 parts of zinc per million (2 ppm) parts of foods (e.g., leafy vegetables) to 

29 ppm (meats, fish, poultry). Zinc is also present in most drinking water. Drinking water or 

other beverages may contain high levels of zinc if they are stored in metal containers or flow 

through pipes that have been coated with zinc to resist rust. If you take more than the 

recommended daily amount of supplements containing zinc, you may have higher levels of zinc 

exposure. 

In general, levels of zinc in air are relatively low and fairly constant. Average levels of zinc in 

the air throughout the United States are less than 1 microgram of zinc per cubic meter (μg/m3

) of 

air, but range from 0.1 to 1.7 μg/m3

 in areas near cities. Air near industrial areas may have 

higher levels of zinc. The average zinc concentration for a 1-year period was 5 μg/m3 in one 

area near an industrial source. 

In addition to background exposure that all of us experience, about 150,000 people also have a 

source of occupational exposure to zinc that might elevate their total exposure significantly 

above the average background exposure. Jobs where people are exposed to zinc include zinc 

mining, smelting, and welding; manufacture of brass, bronze, or other zinc-containing alloys; 

manufacture of galvanized metals; and manufacture of machine parts, rubber, paint, linoleum, 
ZINC 4 

1. PUBLIC HEALTH STATEMENT 

oilcloths, batteries, some kinds of glass and ceramics, and dyes. People at construction jobs, 

automobile mechanics, and painters are also exposed to zinc. For more information on exposure 

to zinc, see Chapter 6. 

1.4 HOW CAN ZINC ENTER AND LEAVE MY BODY? 

Zinc can enter the body through the digestive tract when you eat food or drink water containing 

it. Zinc can also enter through your lungs if you inhale zinc dust or fumes from zinc-smelting or 

zinc-welding operations on your job. The amount of zinc that passes directly through the skin is 

relatively small. The most likely route of exposure near NPL waste sites is through drinking 

water containing a high amount of zinc. Zinc is stored throughout the body. Zinc increases in 

blood and bone most rapidly after exposure. Zinc may stay in the bone for many days after 

exposure. Normally, zinc leaves the body in urine and feces. More information on how zinc 

enters and leaves your body can be found in Chapter 3. 

1.5 HOW CAN ZINC AFFECT MY HEALTH? 

Scientists use many tests to protect the public from harmful effects of toxic chemicals and to find 

ways for treating persons who have been harmed. 

One way to learn whether a chemical will harm people is to determine how the body absorbs, 

uses, and releases the chemical. For some chemicals, animal testing may be necessary. Animal 

testing may also help identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method for getting information needed to make wise 

decisions that protect public health. Scientists have the responsibility to treat research animals 

with care and compassion. Scientists must comply with strict animal care guidelines because 

laws today protect the welfare of research animals. 

Inhaling large amounts of zinc (as zinc dust or fumes from smelting or welding) can cause a 

specific short-term disease called metal fume fever, which is generally reversible once exposure 
ZINC 5 

1. PUBLIC HEALTH STATEMENT 

to zinc ceases. However, very little is known about the long-term effects of breathing zinc dust 

or fumes. 

Taking too much zinc into the body through food, water, or dietary supplements can also affect 

health. The levels of zinc that produce adverse health effects are much higher than the 

Recommended Dietary Allowances (RDAs) for zinc of 11 mg/day for men and 8 mg/day for 

women. If large doses of zinc (10–15 times higher than the RDA) are taken by mouth even for a 

short time, stomach cramps, nausea, and vomiting may occur. Ingesting high levels of zinc for 

several months may cause anemia, damage the pancreas, and decrease levels of high-density 

lipoprotein (HDL) cholesterol. 

Eating food containing very large amounts of zinc (1,000 times higher than the RDA) for several 

months caused many health effects in rats, mice, and ferrets, including anemia and injury to the 

pancreas and kidney. Rats that ate very large amounts of zinc became infertile. Rats that ate 

very large amounts of zinc after becoming pregnant had smaller babies. Putting low levels of 

certain zinc compounds, such as zinc acetate and zinc chloride, on the skin of rabbits, guinea 

pigs, and mice caused skin irritation. Skin irritation from exposure to these chemicals would 

probably occur in humans. EPA has determined that because of lack of information, zinc is not 

classifiable as to its human carcinogenicity. 

Consuming too little zinc is at least as important a health problem as consuming too much zinc. 

Without enough zinc in the diet, people may experience loss of appetite, decreased sense of taste 

and smell, decreased immune function, slow wound healing, and skin sores. Too little zinc in the 

diet may also cause poorly developed sex organs and retarded growth in young men. If a 

pregnant woman does not get enough zinc, her babies may have birth defects. 

More information on the health effects linked with exposure to higher-than-normal levels of zinc 

is presented in Chapter 3. 
ZINC 6 

1. PUBLIC HEALTH STATEMENT 

1.6 HOW CAN ZINC AFFECT CHILDREN? 

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

conception to maturity at 18 years of age. 

Zinc is essential for proper growth and development of young children. Mothers who did not eat 

enough zinc during pregnancy had a higher frequency of birth defects and gave birth to smaller 

children (lower birth weight) than mothers whose zinc levels were sufficient. Very young 

children who did not receive enough zinc in the diet were smaller, both in length and in body 

weight, than children who ate enough zinc. Some foods, such as soy-based formulas, contain 

high levels of phytate, which can result in a decreased absorption of zinc in the diet. Too much 

of these foods may result in effects similar to those that occur when children receive too little 

zinc in the diet. 

Little is known about whether children who eat too much zinc will react differently from adults 

who have ingested large amounts of zinc. A child who accidentally drank a large amount of a 

caustic zinc solution was found to have damage to his mouth and stomach, and later to his 

pancreas, but similar effects have been seen in adults who accidentally drank the same solution. 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ZINC 

If your doctor finds that you have been exposed to substantial amounts of zinc, ask whether your 

children might also have been exposed. Your doctor might need to ask your state health 

department to investigate. 

Children living near waste sites containing zinc are likely to be exposed to higher environmental 

levels of zinc through breathing, drinking contaminated drinking water, touching soil, and eating 

contaminated soil. It is unlikely that a child would ingest enough zinc from eating soil to cause 

harmful effects. However, parents should supervise to see that children avoid eating soil and 

wash their hands frequently, especially before eating. Parents should consult their family 
ZINC 7 

1. PUBLIC HEALTH STATEMENT 

physicians about whether (and how) hand-to-mouth behaviors in their children might be 

discouraged. A more complete discussion can be found in Section 3.11 of the profile. 

Children and adults require a certain amount of zinc in the diet in order to remain healthy. 

However, overuse of some medicines or vitamin supplements containing zinc might be harmful; 

these medicines should always be used appropriately. If you are accidentally exposed to large 

amounts of zinc, consult a physician immediately. 

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

EXPOSED TO ZINC? 

Medical tests can determine whether your body fluids contain high levels of zinc. Samples of 

blood or feces can be collected in a doctor's office and sent to a laboratory that can measure zinc 

levels. It is easier for most laboratories to measure zinc in blood than in feces. The presence of 

high levels of zinc in the feces can mean recent high zinc exposure. High levels of zinc in the 

blood can mean high zinc consumption and/or high exposure. High zinc levels in blood or feces 

reflect the level of exposure to zinc. Measuring zinc levels in urine and saliva also may provide 

information about zinc exposure. Tests to measure zinc in hair may provide information on 

long-term zinc exposure; however, no useful correlation has been found between hair zinc levels 

and zinc exposure and these tests are not routinely used. Since zinc levels can be affected by 

dietary deficiency and cell stress, these results may not be directly related to current zinc 

exposure. More information on tests to measure zinc in the body can be found in Chapter 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 
ZINC 8 

1. PUBLIC HEALTH STATEMENT 

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-to-exceed 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. 

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 zinc include the following: 

The federal government has set standards and guidelines to protect individuals from the potential 

health effects of excessive zinc. EPA has stated that drinking water should contain no more than 

5 mg of zinc per liter of water (5 mg/L or 5 ppm) because of taste. Furthermore, any release of 

more than 1,000 pounds (or in some cases 5,000 pounds) of zinc or its compounds into the 

environment (i.e., water, soil, or air) must be reported to EPA. 

The National Academy of Sciences (NAS) estimates an RDA for zinc of 11 mg/day (men). 

Eleven mg/day is the same as 0.16 mg per kilogram (kg) of body weight per day for an average 

adult male (70 kg). An RDA of 8 mg/day, or 0.13 mg per kg of body weight for an average adult 

female (60 kg), was established for women because they usually weigh less than men. Lower 

zinc intake was recommended for infants (2–3 mg/day) and children (5–9 mg/day) because of 

their lower average body weights. The RDA provides a level of adequate nutritional status for 

most of the population. Extra dietary levels of zinc are recommended for women during 

pregnancy and lactation. An RDA of 11–12 mg/day was set for pregnant women. Women who 

nurse their babies need 12–13 mg/day. 
 

 

 

ZINC 9 

1. PUBLIC HEALTH STATEMENT 

To protect workers, OSHA has set an average legal limit of 1 mg/m3 for zinc chloride fumes and 

5 mg/m3 for zinc oxide (dusts and fumes) in workplace air during an 8-hour workday, 40-hour 

work week. This regulation means that the workroom air should contain no more than an 

average of 1 mg/m3

 of zinc chloride over an 8-hour working shift of a 40-hour work week. 

NIOSH similarly recommends that the level of zinc oxide in workplace air should not exceed an 

average of 1 mg/m3 over a 10-hour period of a 40-hour work week. For more information on 

recommendations and standards for zinc exposure, 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 1-888-42ATSDR (1-888-422-8737), by e-mail at 

atsdric@cdc.gov, or by writing to: 

Agency for Toxic Substances and Disease Registry 

 Division of Toxicology 

1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 
 

 

 

ZINC 10 

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/ 
ZINC	 11 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ZINC IN THE UNITED 

STATES 

Zinc is ubiquitous in the environment, constituting 20–200 ppm (by weight) of the Earth's crust. It is not 

found as elemental zinc in nature, instead being found mainly as zinc oxide or sphalerite (ZnS). Zinc is 

released into the environment as the result of mining, smelting of zinc, lead, and cadmium ores, steel 

production, coal burning, and burning of wastes. Ambient background air concentrations of zinc are 

generally <1 μg/m3

. Zinc is found in soils and surficial materials of the contiguous United States at 

concentrations between <5 and 2,900 mg/kg, with a mean of 60 mg/kg. The zinc background 

concentrations in surface waters are usually <0.05 mg/L, but can range from 0.002 to 50 mg/L. 

Zinc metal is used most commonly as a protective coating of other metals, such as iron and steel. Zinc is 

also a component of various alloys including those used for die casting as well as brass and bronze. Many 

zinc alloys may be found in electrical components of household goods. Alloys containing zinc and 

copper are used to make U.S. one-cent coins. Zinc metal dust is widely used in paint coatings, as a 

catalyst, and as a reducing and precipitating agent in organic and analytical chemistry. 

Exposure of the general population to zinc is primarily by ingestion. The average daily intake of zinc 

from food in humans is 5.2–16.2 mg zinc/day; assuming a 70-kg average body weight, this corresponds to 

0.07–0.23 mg zinc/kg/day. Zinc is widespread in commonly consumed foods, but tends to be higher in 

those of animal origin, particularly some sea foods. Meat products contain relatively high concentrations 

of zinc, whereas fruits and vegetables have relatively low concentrations. Other possible pathways for 

zinc exposure are water and air. Individuals involved in galvanizing, smelting, welding, or brass foundry 

operations are exposed to metallic zinc and zinc compounds. 

2.2 SUMMARY OF HEALTH EFFECTS 

Zinc is an essential nutrient for humans and animals that is necessary for the function of a large number of 

metalloenzymes, including alcohol dehydrogenase, alkaline phosphatase, carbonic anhydrase, leucine 

aminopeptidase, and superoxide dismutase. Zinc deficiency has been associated with dermatitis, 

anorexia, growth retardation, poor wound healing, hypogonadism with impaired reproductive capacity, 
ZINC 12 

2. RELEVANCE TO PUBLIC HEALTH 

impaired immune function, and depressed mental function; an increased incidence of congenital 

malformations in infants has also been associated with zinc deficiency in the mothers. Zinc deficiency 

may also have an impact on the carcinogenesis of other chemicals, although the direction of the influence 

seems to vary with the carcinogenic agent. The recommended dietary allowance (RDA) for zinc is 

11 mg/day in men and 8 mg/day in women; these correspond to approximately 0.16 mg/kg/day for men 

and 0.13 mg/kg/day for women. Higher RDAs are recommended for women during pregnancy and 

lactation (12 mg/day). 

The effects of inhalation exposure to zinc and zinc compounds vary somewhat with the chemical form of 

the zinc compound, but the majority of the effects seen will occur within the respiratory tract. Following 

inhalation of zinc oxide, and to a lesser extent zinc metal and many other zinc compounds, the most 

commonly reported effect is the development of “metal fume fever.” Metal fume fever is characterized 

by chest pain, cough, dyspnea, reduced lung volumes, nausea, chills, malaise, and leukocytosis. 

Symptoms generally appear a few hours after exposure, and are reversible 1–4 days following cessation 

of exposure. Exposure levels associated with the development of metal fume fever have not been 

identified, though are generally in the range of 77–600 mg zinc/m3

. Acute experimental exposures of 

humans to lower concentrations of zinc oxide (14 mg/m3

 for 8 hours or 45 mg zinc/m3 for 20 minutes) 

and occupational exposures to low concentrations of zinc (8–12 mg zinc/m3

 for 1–3 hours and 0.034 mg 

zinc/m3

 for 6–8 hours) did not produce symptoms of metal fume fever. 

In contrast, inhalation of high levels of zinc chloride, which is corrosive, generally results in more 

pronounced damage to the mucous membranes of the respiratory tract without the effects normally seen 

in metal fume fever. Symptoms of high-concentration zinc chloride exposure include dyspnea, cough, 

pleuritic chest pain, bilateral diffuse infiltrations, pneumothorax, and acute pneumonitis, resulting from 

respiratory tract irritation. In many cases, exposure levels for these effects have not been reported, as the 

exposures were to zinc chloride-containing smoke and were not quantified and the contribution of other 

components of the smoke cannot be entirely eliminated. However, one study of zinc chloride exposure 

estimated an exposure level of 1,955 mg zinc/m3

. Similar irritant effects of zinc chloride have been seen 

in animal studies of lower exposure levels (13–121 mg/m3

) and longer duration (5–100 daily exposures). 

The effects observed after zinc chloride inhalation are likely due to the caustic nature of zinc chloride, 

rather than a direct action of the zinc ion. 

Nausea has been reported by humans exposed to high concentrations of zinc oxide fumes (300– 

600 mg/m3

) and zinc chloride (~120 mg/m3) smoke, as well as following oral exposure to zinc chloride 
 

 

ZINC 13 

2. RELEVANCE TO PUBLIC HEALTH 

and zinc sulfate. Other gastrointestinal symptoms reported in cases of excess zinc exposure include 

vomiting, abdominal cramps, and diarrhea, in several cases with blood. In general, oral exposure levels 

associated with gastrointestinal effects of zinc have not been reliably reported, but the limited available 

data suggest that oral concentrations of 910 mg zinc/L or single-dose exposures of ~140–560 mg zinc 

(acute oral doses of 2–8 mg/kg/day) are sufficient to cause these effects. The noted effects are consistent 

with gastrointestinal irritation. It is unclear in the majority of human studies whether the gastrointestinal 

effects seen following zinc inhalation were due to systemic zinc or were the result of direct contact with 

the gastrointestinal tract following mucociliary clearance of inhaled zinc particles and subsequent 

swallowing. 

Following longer-term exposure to lower doses (~0.5–2 mg zinc/kg/day) of zinc compounds, the 

observed symptoms generally result from a decreased absorption of copper from the diet, leading to early 

symptoms of copper deficiency. The most noticeable manifestation of the decreased copper levels is 

anemia, manifesting as decreased erythrocyte number or decreased hematocrit. High-dose zinc 

administration has also resulted in reductions in leukocyte number and function. Some studies have also 

found decreases in high-density lipoprotein (HDL) levels in humans exposed to increased levels of zinc; 

however, not all studies have confirmed this observation. Long-term consumption of excess zinc may 

also result in decreased iron stores, although the mechanism behind this effect is not presently clear. 

In most cases, dermal exposure to zinc or zinc compounds does not result in any noticeable toxic effects. 

Zinc oxide is used routinely in topical applications including sunscreens and creams designed to assist in 

wound healing. However, dermal exposure to zinc chloride, and to a lesser extent other zinc salts, can 

result in severe skin irritancy, characterized by parakeratosis, hyperkeratosis, inflammatory changes in the 

epidermis and superficial dermis, and acanthosis of the follicular epithelia. 

Available studies have not presented evidence of reproductive or developmental effects in humans or 

animals following inhalation of zinc compounds. Effects on reproductive or developmental end points 

have been noted in oral-exposure animal studies, but generally only at very high doses (>200 mg/kg/day). 

Available studies of zinc-induced carcinogenic effects in humans and animals following both oral or 

inhalation exposure have not adequately demonstrated an increase in cancer incidence following longterm exposure to zinc compounds. The EPA currently classifies zinc and compounds as carcinogenicity 

group D (not classifiable as to human carcinogenicity). 
ZINC 14 

2. RELEVANCE TO PUBLIC HEALTH 

The primary effects of zinc are the development of metal fume fever and effects of zinc on copper status; 

a more detailed discussion of these end points follows. The reader is referred to Section 3.2, Discussion 

of Health Effects by Route of Exposure, for additional information on other health effects. 

Metal Fume Fever. Metal fume fever, a well-documented acute disease induced by inhalation of metal 

oxides, especially zinc, impairs pulmonary function but does not usually progress to chronic lung disease. 

Symptoms generally appear within a few hours after acute exposure, usually with dryness of the throat 

and coughing. The most prominent respiratory effects of metal fume fever are substernal chest pain, 

cough, and dyspnea. The impairment of pulmonary function is characterized by reduced lung volumes 

and a decreased diffusing capacity of carbon monoxide. Leukocytosis persisting for approximately 

12 hours after the fever dissipates is also a common manifestation of metal fume fever. In general, the 

symptoms of metal fume fever resolve within 1–4 days after cessation of exposure and do not lead to 

long-term respiratory effects. Inhalation of “ultrafine” zinc oxide particles may also result in metal fume 

fever, as well as histologic damage and inflammation of the lung periphery. 

Exposure levels leading to the development of metal fume fever have been characterized. Minimal 

changes in forced expiratory flow were observed 1 hour after a 15–30-minute exposure to 77 mg zinc/m3 

as zinc oxide, while at higher levels (300–600 mg/m3

, from 10 minutes to 3 hours), shortness of breath, 

nasal passage irritation, cough, substernal chest pain, persistent rales of the lung base, and a decreased 

vital capacity have been reported. Exposure to lower levels of zinc oxide, either for acute (14 mg zinc/m3 

for 8 hours or 45 mg zinc/m3

 for 20 minutes) or chronic (8–12 mg zinc/m3 for 1–3 hours and 0.034 mg 

zinc/m3

 for 6–8 hours) duration did not result in the symptoms of metal fume fever. However, analysis by 

bronchoalveolar lavage of volunteers exposed to zinc oxide for up to 2 hours (mean concentration 

16.4 mg zinc/m3

) revealed an increase in levels of the cytokines TNF, IL-6 and IL-8, and increases in the 

number of polymorphonuclear leukocytes and lymphocytes in the BAL fluid. Thus, it appears that while 

the precursor events for the development of metal fume fever begin to occur even at very low zinc 

concentrations, the condition itself does not appear to fully manifest until exposure levels reach much 

higher (>75 mg/m3

) levels. Similar effects, including decreased ventilation, an inflammatory response, 

and changes in cytokine levels, have also been seen in animal studies of zinc oxide inhalation. 

The exact mechanism behind the development of metal fume fever is not known, but it is believed to 

involve an immune response to the inhaled zinc oxide. It has been suggested that the zinc oxide causes 

inflammation of the respiratory tract and the release of histamine or histamine-like substances. In 

response, an allergen-antibody complex is formed that may elicit an allergic reaction upon subsequent 
ZINC 15 

2. RELEVANCE TO PUBLIC HEALTH 

exposure to the allergen. In response to the allergen-antibody complex, an anti-antibody is formed. The 

anti-antibody dominates with continued exposure to the zinc oxide, thereby producing a tolerance. When 

the exposure is interrupted and re-exposure occurs, the allergen-antibody complex dominates, producing 

an allergic reaction and symptoms of metal fume fever. 

Effects on Copper Status. When ingested zinc levels are very high, zinc is believed to inhibit copper 

absorption through interaction with metallothionein at the brush border of the intestinal lumen. Both 

copper and zinc appear to bind to the same metallothionein protein; however, copper has a higher affinity 

for metallothionein than zinc and displaces zinc from metallothionein protein. Copper complexed with 

metallothionein is retained in the mucosal cell, relatively unavailable for transfer to plasma, and is 

excreted in the feces when the mucosal cells are sloughed off. Thus, an excess of zinc can result in a 

decreased availability of dietary copper, and the development of copper deficiency. This fact has been 

used therapeutically in the treatment of Wilson’s Disease. Zinc supplementation is used to substantially 

decrease the absorption of copper from the diet, which can aggravate the disease. 

Copper is incorporated into metalloenzymes involved in hemoglobin formation, carbohydrate 

metabolism, catecholamine biosynthesis, and cross-linking of collagen, elastin, and hair keratin. The 

copper-dependent enzymes, which include cytochrome c oxidase, superoxide dismutase, ferroxidases, 

monoamine oxidase, and dopamine β-monooxygenase, function mainly to reduce molecular oxygen. 

Excess zinc may alter the levels or activity of these enzymes before the more severe symptoms of copper 

deficiency, which include anemia and leucopenia, begin to manifest. Numerous studies in humans 

receiving 40–50 mg supplemental zinc/day (0.68–0.83 mg zinc/kg/day) have reported decreases in 

erythrocyte superoxide dismutase, mononuclear white cell 5'-nucleotidase, and plasma 5'-nucleotidase 

activities. While the results from study to study are not always consistent, the available studies of 

volunteers identify 40–50 mg supplemental zinc/day as the level at which subtle changes in coppercontaining enzymes begin to be seen. This effect level is supported by other studies that collectively 

identify a no-observed-adverse-effect level (NOAEL) of 30 mg supplemental zinc/day for changes in 

copper-containing enzyme levels in adult men. 

Long-term administration (1–8 years) of high zinc levels (2–11.6 mg/kg/day) has caused anemia in 

humans. However, adequate studies of the chronic effects of lower levels of zinc on copper status in 

humans are not available. Decreased hemoglobin and hematocrit and the development of anemia have 

also been observed in animals orally exposed to high zinc doses. 
ZINC 16 

2. RELEVANCE TO PUBLIC HEALTH 

2.3 MINIMAL RISK LEVELS (MRLs) 

Estimates of exposure levels posing minimal risk to humans (MRLs) have been made for zinc. 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 inhalation MRLs have been derived for zinc. A number of acute-duration studies of exposed workers 

have identified metal fume fever as an end point of concern, with effects generally noted at airborne zinc 

oxide levels of 77–600 mg zinc/m3

 (Blanc et al. 1991; Hammond 1944; Sturgis et al. 1927). However, 

these occupational studies were not able to adequately control or correct for possible exposure to other 

compounds, and were therefore not suitable for use in MRL derivation. Animal studies (Amdur et al. 

1982; Drinker and Drinker 1928) corroborate the effects observed in humans; however, the studies are 

generally limited in the methods utilized, and other possible targets of toxicity were not examined. Only 

one chronic-duration inhalation study in humans was located (Ameille et al. 1992). In this study, 

exposure levels were not reported; thus, the study could not be used as the basis for the derivation of a 

chronic-duration MRL. Thus, no chronic-duration inhalation MRL could be derived. 
ZINC	 17 

2. RELEVANCE TO PUBLIC HEALTH 

Oral MRLs 

An oral acute MRL was not derived for zinc. A number of case reports involving high-dose acute 

exposure were located (Brandao-Neto et al. 1990a; Callender and Gentzkow 1937; Lewis and Kokan 

1998; Murphy 1970); nausea, vomiting, and other signs of gastrointestinal distress were the primary 

effects noted. However, a great deal of uncertainty exists for these studies, including a lack of accurate 

assessment of exposure levels and a minimal evaluation of end points. Animal studies of acute-duration 

oral exposure to zinc are generally limited to studies of mortality (Domingo et al. 1988a; Straube et al. 

1980), with the exception of a study in rats that only evaluated effects on the central nervous system 

(Kozik et al. 1980). As no studies sufficient for derivation of an acute oral MRL were available, no value 

was derived. 

•	 An MRL of 0.3 mg zinc/kg/day has been derived for intermediate-duration oral exposure (15– 

364 days) to zinc. 

Prolonged oral exposure to zinc has been shown to decrease the absorption of copper from the diet, 

resulting in the development of copper deficiency. At low doses (~0.7–0.9 mg zinc/kg/day) and 

intermediate exposure durations (6–13 weeks), the effect is minor and manifests as subclinical changes in 

copper-sensitive enzymes, such superoxide dismutase (Davis et al. 2000; Fischer et al. 1984; Milne et al. 

2001; Yadrick et al. 1989). At higher exposure levels (~2 mg zinc/kg/day) for chronic duration, more 

severe symptoms of copper deficiency, including anemia, have been reported (Broun et al. 1990; Gyorffy 

and Chan 1992; Hale et al. 1988; Hoffman et al. 1988; Patterson et al. 1985; Porter et al. 1977; Prasad et 

al. 1978; Ramadurai et al. 1993; Stroud 1991; Summerfield et al. 1992). 

Available intermediate-duration studies have examined the effect of zinc supplementation on sensitive 

biological indices in humans. A series of two studies (Bonham et al. 2003a, 2003b) evaluated a large 

number of hematological and immunological parameters as well as several copper-sensitive enzymes 

(e.g., superoxide dismutase) in healthy men exposed to 0.43 mg supplemental zinc/kg/day, and reported 

no significant changes resulting from zinc exposure. Studies by three other groups have evaluated 

exposures in the 0.6–0.8 mg zinc/kg/day range and identified slight but measurable effects. A study in 

postmenopausal women receiving a total of 53 mg zinc/day (44 mg supplemental zinc/day, or 0.68 mg 

supplemental zinc/kg/day) (Davis et al. 2000; Milne et al. 2001) reported increases in bone-specific 

alkaline phosphatase (~25%) and extracellular superoxide dismutase (~15%) levels and decreases in 

mononuclear white cell 5'-nucleotidase (~30%) and plasma 5'-nucleotidase (~36%) activity. Another 

study (Fischer et al. 1984) exposed groups of male volunteers to 0.71 mg supplemental zinc/kg/day for 
ZINC 18 

2. RELEVANCE TO PUBLIC HEALTH 

6 weeks; erythrocyte superoxide dismutase (ESOD) activity decreased after 4 weeks in the supplement 

group and was significantly lower than controls by 6 weeks. In women exposed to 0.83 mg supplemental 

zinc/kg/day for 10 weeks, ESOD activity declined over the supplementation period and was significantly 

(p<0.05) lower (47% decrease) than pretreatment values at 10 weeks (Yadrick et al. 1989). 

While the decrease in ESOD activity reported in the available human studies is noteworthy, it is important 

to note that other enzymes, including catalase and other forms of superoxide dismutase, also serve to 

detoxify superoxide within the body. The overall effect of reducing the levels of an isoform of 

superoxide dismutase on the body’s ability to detoxify superoxide radical is therefore uncertain. The 

subjects in the zinc supplementation studies did not report increased frequencies of clinical signs or 

symptoms. The other changes in copper status across the studies evaluating zinc supplementation in the 

50 mg/day range, such as changes in alkaline phosphatase, mononuclear white cell 5'–nucleotidase, and 

plasma 5'–nucleotidase activities (Davis et al. 2000; Milne et al. 2001), are generally slight and of 

questionable clinical and biological significance. The subclinical changes in copper status observed in the 

intermediate-duration studies of zinc supplementation (Davis et al. 2000; Fischer et al. 1984; Milne et al. 

2001; Yadrick et al. 1989) are considered nonadverse effects. 

Yadrick et al. (1989) also reported decreased serum ferritin in zinc-supplemented (0.86 mg supplemental 

zinc/kg/day) premenopausal women. A statistically significant decrease in serum ferritin levels from 

36.6 to 28.2 μg/L (23% decrease), was observed. According to the most recent NHANES data (cited in 

IOM 2000), the median range for serum ferritin levels in menstruating women is 36–40 μg/L, while a 

value of <12 μg/L represents depleted iron stores. Thus, the subjects in the Yadrick study dropped below 

the median range for women of their age group, but were still considerably above the level that would 

represent a depletion of iron stores. This is supported by a lack of reported changes in hemoglobin or 

hematocrit levels in the study population (Yadrick et al. 1989). In a 90-day study of postmenopausal 

women exposed to 0.68 mg supplemental zinc/kg/day while living in a metabolic ward (Milne et al. 

2001), no changes were reported in serum iron, hematocrit, or percentage of transferrin saturation were 

observed. However, the study did not evaluate ferritin levels, which are the most sensitive indicator of 

body iron stores. Other studies that evaluated similar zinc dose levels (Black et al. 1988; Fischer et al. 

1984) have not evaluated ferritin levels or other indices of iron status. ATSDR considers the subclinical 

change in iron stores as indicated by a decrease in serum ferritin levels to be nonadverse. 

As it identified the highest NOAEL for effects of zinc exposure, the Yadrick et al. (1989) study was 

selected as the principal study for MRL derivation. The study identified subclinical changes in copper 
 

 

 

ZINC	 19 

2. RELEVANCE TO PUBLIC HEALTH 

status (decreased ESOD levels) and iron status (decreased ferritin levels) in women exposed to 0.83 mg 

supplemental zinc/kg/day. This exposure level was designated a NOAEL and selected as the point of 

departure for the derivation of the MRL. The uncertainty factor for MRL derivation was 3, representing 

uncertainties involving intrahuman variability; a larger factor for sensitive populations was not believed 

necessary, as women already represent a sensitive population with regards to changes in iron status. The 

resulting intermediate-duration MRL is 0.3 mg/kg/day. 

It should be noted that the MRL is calculated based on the assumption of healthy dietary levels of zinc 

(and copper), and represents the level of exposure above and beyond the normal diet that is believed to be 

without an appreciable risk of toxic response. The MRL is based on soluble zinc salts; it is less likely that 

nonsoluble zinc compounds would have these effects at similar exposure levels. 

•	 The intermediate-duration oral MRL of 0.3 mg zinc/kg/day has been accepted as the chronic oral 

MRL. 

The chronic oral MRL is expected to be without adverse effects when consumed on a daily basis over a 

long period of time; neither inducing nutritional deficiency in healthy, nonpregnant, adult humans 

ingesting the average American diet nor resulting in adverse effects from excess consumption. The MRL 

was not based on a chronic-duration oral study due to a lack of adequate long-term studies in humans and 

animals. Several studies have reported copper deficiency-induced anemia resulting from longer-term 

exposure to zinc, either via supplements or other sources (Broun et al. 1990; Gyorffy and Chan 1992; 

Hale et al. 1988; Hoffman et al. 1988; Patterson et al. 1985; Porter et al. 1977; Prasad et al. 1978; 

Ramadurai et al. 1993; Stroud 1991; Summerfield et al. 1992); effects generally occurred at estimated 

exposure levels of approximately 2–10 mg zinc/kg/day. However, the available studies are limited by 

small numbers of subjects evaluated (often a single individual), limited evaluation of end points, and 

limited reporting of study results, making them unsuitable for use in the derivation of a chronic-duration 

MRL. 

ZINC 21 

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 zinc. 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. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

Zinc is an essential nutrient in humans and animals that is necessary for the function of a large number of 

metalloenzymes. These enzymes include alcohol dehydrogenase, alkaline phosphatase, carbonic 

anhydrase, leucine aminopeptidase, superoxide dismutase, and deoxyribonucleic acid (DNA) and 

ribonucleic acid (RNA) polymerase. As such, zinc is required for normal nucleic acid, protein, and 

membrane metabolism, as well as cell growth and division. Zinc also plays an essential role in the 

maintenance of nucleic acid structure of genes (zinc finger phenomenon). Zinc deficiency has been 

associated with dermatitis, anorexia, growth retardation, poor wound healing, hypogonadism with 

impaired reproductive capacity, impaired immune function, and depressed mental function; increased 

incidence of congenital malformations in infants has also been associated with zinc deficiency in the 

mothers (Cotran et al. 1989; Elinder 1986; Sandstead 1981). Zinc deficiency may also have an impact on 

carcinogenesis, though the direction of the influence seems to vary with the agent (Fong et al. 1978; 

Mathur 1979; Wallenius et al. 1979). Therefore, certain levels of zinc intake are recommended. The 

RDA for zinc is 11 mg/day in men and 8 mg/day in women (IOM 2002). Higher RDAs are 

recommended for women during pregnancy and lactation (12 mg/day for pregnant women and nursing 

women). While a detailed discussion of zinc deficiency is beyond the scope of this toxicological profile, 

the subject has been thoroughly reviewed by other agencies (IOM 2002; WHO 1996). 

Just as zinc deficiency has been associated with adverse effects in humans and animals, overexposures to 

zinc also have been associated with toxic effects. This chapter contains a description of the toxic effects 

that have been associated with exposures to high levels of zinc and selected zinc compounds by the 

inhalation, oral, and dermal routes. Specifically, zinc chloride, zinc oxide, zinc sulfate, and zinc sulfide 

will be discussed. Other zinc compounds are discussed in this chapter whenever data regarding these 
ZINC 22 

3. HEALTH EFFECTS 

compounds add relevant information to the discussion on zinc. Any general comments regarding the lack 

of data on zinc refer to both zinc and its compounds. 

Because there are differences in toxicity between the various zinc compounds following inhalation 

exposure, these compounds will be discussed under separate subheadings in Section 3.2.1 (Inhalation 

Exposure). After oral or dermal exposure, the toxicities are comparable for all zinc compounds. 

Therefore, in Section 3.2.2 (Oral Exposure) and Section 3.2.3 (Dermal Exposure), the discussion will not 

be subdivided, but the specific zinc compounds will be identified in each case. 

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 

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. 
ZINC 23 

3. HEALTH EFFECTS 

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 

In humans, death has resulted from acute exposure to zinc compounds. When a high concentration 

(estimated at 33,000 mg zinc/m3

) of zinc chloride smoke resulted from the explosion of many generators 

in a tunnel following a bombing raid in World War II, 10 of the 70 exposed people in the tunnel died 

within 4 days (Evans 1945). The smoke generated contained mainly highly caustic zinc chloride, but 

exposure to other constituents, namely zinc oxide, hexachloroethane, calcium silicate, and an igniter, was 

also possible. Therefore, the deaths resulting from the explosion cannot be conclusively attributed to only 

exposure to zinc chloride. This is the only human study reporting an estimated exposure level that caused 

death. Another study reported the death of a fireman exposed to the contents of a smoke bomb in a closed 

environment (Milliken et al. 1963). The man died 18 days after exposure because of respiratory 

difficulty. Again, exposure to zinc chloride was simultaneous with exposure to other substances in the 

smoke. Two soldiers exposed without gas masks to zinc chloride smoke during military training 

developed severe adult respiratory distress syndrome (ARDS) and died 25–32 days after the incident 

(Hjortso et al. 1988). Diffuse microvascular obliteration, widespread occlusion of the pulmonary arteries, 

and extensive interstitial and intra-alveolar fibrosis were observed at autopsy. Zinc levels in major organs 

and tissues obtained during autopsy were within the normal range, and no zinc particles were observed by 

scanning electron microscopy. According to the authors, the fumes from the smoke bombs consisted 

mainly of zinc chloride. However, no exposure levels were estimated, and other substances were also 

present in the smoke. Because of the caustic nature of zinc chloride, it is likely that these effects were the 

result of severe irritation from the compound, rather than direct actions of the zinc ion. 
ZINC 24 

3. HEALTH EFFECTS 

A case study presented by Murray (1926) reported on an infant death due to bronchopneumonia resulting 

from inhalation, and possibly ingestion, of an unspecified amount of zinc stearate powder spilled from a 

container. However, it is unclear whether the death was due to the zinc content or whether aspiration 

bronchopneumonia would result from inhalation of similar powders that do not contain zinc. 

In mice, the reported LCT50 (product of lethal concentration and time to kill 50% of animals) of zinc 

chloride is 11,800 mg/minute/m3

 (Schenker et al. 1981). However, Schenker et al. (1981) did not provide 

information on how this value was determined. Following exposure to zinc chloride smoke for 3– 

20 weeks, mortality was 50% in mice exposed to 121.7 mg zinc/m3 (compared to 20% in controls) and 

22% in guinea pigs exposed to 119.3 mg zinc/m3

 (compared to 8% in controls) (Marrs et al. 1988). The 

smoke was similar to that described by Evans (1945) and also contained zinc oxide, hexachloroethane, 

and other compounds. 

3.2.1.2 Systemic Effects 

The highest NOAEL values and all LOAEL values from each reliable study for systemic effects in each 

species and duration category are recorded in Table 3-1 and plotted in Figure 3-1. 

No studies were located regarding musculoskeletal, endocrine, dermal, or body weight effects in humans 

or animals after inhalation exposure to zinc or zinc compounds. The systemic effects observed after 

inhalation exposure are discussed below. In most cases, the effects of zinc are discussed without 

separating effects caused by the individual zinc compounds. However, the respiratory effects of the 

individual zinc compounds are discussed separately because the nature of the respiratory toxicity differs 

depending on the particular compound to which one is exposed. 

Respiratory Effects. 

Zinc Oxide. Metal fume fever, a well-documented acute disease induced by intense inhalation of metal 

oxides, especially zinc, impairs pulmonary function but does not progress to chronic lung disease (Brown 

1988; Drinker and Drinker 1928; Malo et al. 1990). Symptoms generally appear within a few hours after 

acute exposure, usually with dryness of the throat and coughing (Drinker et al. 1927b). The most 
105

77

103

3.93.9

545

16.4

544

33

98

0.0036

110

0.034

Table 3-1 Levels of Significant Exposure to Zinc - Inhalation 

a

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE Systemic 

1 Human 15-30 min 

System 

Resp 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

77 (minimal change in 

pulmonary function) 

LOAEL 

Serious 

(mg/m3) 

Reference Chemical Form 

Blanc et al. 1991 Zinc oxide 

2 Human 1 d 

2hr/d Resp 3.9 (dry or sore throat, chest tightness) Gordon et al. 1992 Zinc oxide 

Other 3.9 (fever/chills and 

headache) 

3 Human 1x 

15-120 minutes 1x 

Resp 16.4 (Increased indices of 

pulmonary inflammation) 

Kuschner et al. 1995 Zinc oxide 

4 Human 1x 

10-30 minutes 1x 

Resp 33 (Altered levels of 

inflammatory cytokines in bronchoalveolar lavage fluid) 

Kuschner et al. 1997 Zinc oxide 

5 Human 2 hr Resp 0.0036 Linn et al. 1981 

Zinc amm sulfate 

6 Human 6-8 hr 

(Occup) Resp 0.034 M Marquart et al. 1989 Zinc oxide 
112

600600600

116

2.2

121

0.73

119

1.8

4.7

123

2.2

Table 3-1 Levels of Significant Exposure to Zinc - Inhalation (continued) 

a

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/m3) 

Less Serious 

(mg/m3) 

LOAEL 

Serious 

(mg/m3) 

Reference Chemical Form 

7 Human 10.5-12 min Resp 

Gastro Hemato 

600 M (decreased vital capacity) 600 M (nausea) 600 M (increased leukocytes) 

Sturgis et al. 1927 Zinc oxide 

8 Rat 

(Fischer- 344) 

1 d 3hr/d Resp 2.2 (increased LDH protein in bronchoalveolar lavage 

fluid) 

Gordon et al. 1992 Zinc oxide 

9 Gn Pig 1 hr Resp 0.73 M (decrease in lung 

compliance) 

Amdur et al. 1982 Zinc oxide 

10 Gn Pig 1-3 d 

3hr/d Resp 1.8 M 4.7 M (increased neutrophils, LDH, and protein in 

bronchoalveolar lavage fluid) 

Conner et al. 1988 Zinc oxide 

11 Gn Pig 

(Hartley) 

1 d 3hr/d Resp 2.2 (increased LDH and protein in 

bronchoalveolar lavage fluid) 

Gordon et al. 1992 Zinc oxide 
122

6.3

124

3.7

120

2.2

5.6

118

4.6

127

77

Table 3-1 Levels of Significant Exposure to Zinc - Inhalation (continued) 

Exposure/ LOAEL 

Duration/ 

a Frequency Key to Species NOAEL Less Serious Serious (Route) Figure (Strain) Reference Chemical Form 

Lam et al. 1982 Zinc oxide Lam et al. 1985 Zinc oxide Lam et al. 1988 Zinc oxide Gordon et al. 1992 Zinc oxide Blanc et al. 1991 Zinc oxide 

12 Gn Pig 

(Hartley) 

13 Gn Pig 

(Hartley) 

14 Gn Pig 

(Hartley) 

15 Rabbit 

(New Zealand) 

Immuno/ Lymphoret 

16 Human 

System (mg/m3) (mg/m3) (mg/m3) 

3 hr Resp 6.3 M (decreased functional 

residual capacity) 

6d 3hr/d Resp 3.7 M (impaired lung function; inflammation; increased 

pulmonary resistance; increased lung weight) 

5 d 3hr/d Resp 2.2 M 5.6 M (impaired lung function; increased lung weight) 

1 d 2hr/d Resp 4.6 15-30 min 77 (increased number of 

leukocytes, T cells, T suppressor cells, and natural killer cells in bronchoalveolar lavage fluid) 

a The numbers corresponds to entries in Figure 3-1. amm sulfate = ammonium sulfate; d = day(s); Gastro = gastrointestinal; Gn pig = guinea pig; Hemato = hematological; hr = hour(s); LDH = lactate dehydrogenase; lowest-observed-adverse-effect level; min = minute(s); NOAEL = no-observed-adverse-effect level; (occup) = occupational; Resp = respiratory 
1000 

Respiratory Gastrointestinal Hematological Other Immuno/Lymphor 

Figure 3-1 Levels of Significant Exposure to Zinc - Inhalation

Acute (≤14 days)

Systemic 

mg/m3 

7 7 7

100

1 16

43

10

12g 14g 10g 15h 13g 2 2

11g 14g 8r 10g

1

9g 

0.1 

6

0.01 

5

0.001 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
 

 

 

 

 

ZINC 29 

3. HEALTH EFFECTS 

prominent respiratory effects of metal fume fever are substernal chest pain, cough, and dyspnea (Rohrs 

1957). The impairment of pulmonary function is characterized by reduced lung volumes and a decreased 

diffusing capacity of carbon monoxide (Malo et al. 1990; Vogelmeier et al. 1987). The respiratory effects 

have been shown to be accompanied by an increase in bronchiolar leukocytes (Vogelmeier et al. 1987). 

The respiratory symptoms generally disappear in the exposed individual within 1–4 days (Brown 1988; 

Drinker et al. 1927b; Sturgis et al. 1927). Inhalation of zinc oxide is most likely to occur in occupational 

situations where zinc smelting or welding take place. Ultrafine zinc oxide particles (0.2–1.0 μm) 

originate from heating zinc beyond its boiling point in an oxidizing atmosphere. Upon inhalation, these 

small particles (<1 μm) reach the alveoli and cause inflammation and tissue damage in the lung periphery 

(Brown 1988; Drinker et al. 1927b; Vogelmeier et al. 1987). 

A number of studies have measured exposure levels associated with metal fume fever. Workers involved 

in pouring molten zinc reported shortness of breath and chest pains 2–12 hours following exposure to 

320–580 mg zinc/m3

 as zinc oxide for 1–3 hours (Hammond 1944); the number of workers was not 

reported. Two volunteers had nasal passage irritation, cough, substernal chest pain, persistent rales of the 

lung base, and a decreased vital capacity for approximately 3–49 hours following acute inhalation (10– 

12 minutes) of 600 mg zinc/m3

 as zinc oxide (Sturgis et al. 1927). This study is limited due to an 

inadequate number of subjects, a lack of controls, and a lack of analysis of the final aerosol product. A 

subject experimentally exposed to zinc oxide fumes reported mild pain when breathing deeply the next 

day after a 5-hour exposure to 430 mg zinc/m3

 (Drinker et al. 1927a). Minimal changes in forced 

expiratory flow were observed 1 hour after a 15–30-minute exposure to 77 mg zinc/m3 as zinc oxide 

(Blanc et al. 1991). 

Acute experimental exposures to lower concentrations of zinc oxide (14 mg/m3 for 8 hours or 45 mg 

zinc/m3 for 20 minutes) and occupational exposures to similar concentrations (8–12 mg zinc/m3

 for 1– 

3 hours and 0.034 mg zinc/m3

 for 6–8 hours) did not produce symptoms of metal fume fever (Drinker et 

al. 1927b; Hammond 1944; Marquart et al. 1989). In a single-blind experiment, exposure of subjects to 

3.9 mg zinc/m3

 as zinc oxide resulted in sore throat and chest tightness but no impairment of pulmonary 

function (Gordon et al. 1992). It is speculated that subjects in other studies may have been less 

susceptible because of the development of tolerance to zinc (Gordon et al. 1992). Kuschner et al. (1995) 

exposed a group of 14 volunteers to a single exposure of varying levels of zinc oxide fume (mean 

concentration 16.4±12.5 mg/m3

) for 15–120 minutes (mean duration 45±28 minutes) and evaluated the 

response by bronchoalveolar lavage (BAL). Significant increases were reported in the number of polymorphonuclear leukocytes and lymphocytes in the BAL fluid, but not in the number of macrophages or in 
 

 

ZINC 30 

3. HEALTH EFFECTS 

lymphocyte subpopulations; aside from a decrease in FEV1, no changes were reported in pulmonary 

function tests. In a follow-up study by the same group (Kuschner et al. 1997), single-exposed volunteers 

showed an increase in levels of the cytokines TNF, IL-6, and IL-8 as a result of zinc oxide inhalation. 

Recurrent episodes of cough and dyspnea were reported in a former mild smoker 3 years after beginning 

work in a metal foundry where exposure to zinc oxide presumably occurred (Ameille et al. 1992). This 

case was distinguishable from metal fume fever because of the lack of tolerance to zinc (as shown by the 

late emergence of symptoms). 

Several animal studies have been conducted to quantify specific effects after acute zinc oxide inhalation. 

As in human exposure, the respiratory system is the primary site of injury following inhalation exposure. 

Acute administration of 88–482 mg zinc/m3

 as zinc oxide to rats and rabbits resulted in the following 

pulmonary changes: grayish areas with pulmonary congestion, various degrees of peribronchial 

leukocytic infiltration, and bronchial exudate composed almost entirely of polymorphonuclear leukocytes 

(Drinker and Drinker 1928). Cats similarly exposed exhibited more severe effects including 

bronchopneumonia, leukocyte infiltration into alveoli, and grayish areas with congestion. During the 

exposure period, the cats demonstrated labored breathing and evidence of upper respiratory tract 

obstruction. A minimum effect level could not be determined for any species because the concentration 

varied widely (88–482 mg zinc/m3

) during exposure. 

Guinea pigs administered 0.73 mg zinc/m3

 as zinc oxide for 1 hour had a progressive decrease in lung 

compliance but no change in air flow resistance. These observations reflect a response in the lung 

periphery where submicrometer aerosols are likely to deposit (Amdur et al. 1982). The authors postulated 

that reduced compliance may be associated with human metal fume fever. 

In contrast to the results of Amdur et al. (1982), no effects on ventilation, lung mechanics (respiratory 

frequency, tidal volume, pulmonary resistance, and pulmonary compliance), diffusing capacity of carbon 

monoxide, or most lung volume parameters were observed by Lam et al. (1982) following the exposure of 

guinea pigs to 6.3 mg zinc/m3

 as zinc oxide for 3 hours. However, functional residual capacity was 

significantly decreased. The discrepancy between the results of Amdur et al. (1982) and Lam et al. 

(1982) may be attributable to the use of anesthetized animals by Lam et al. (1982). In a later study, 

exposures of guinea pigs to 3.7 or 4.3 mg zinc/m3

 as zinc oxide for 3 hours/day, for 6 days, resulted in 

transient functional, morphological, and biochemical changes (Lam et al. 1985). Functional changes 

included increased flow resistance, decreased lung compliance, and decreased diffusing capacity, all of 

which returned to normal within 24–72 hours following exposure. The morphological changes (increased 
ZINC 31 

3. HEALTH EFFECTS 

lung weight, inflammation involving the proximal portion of alveolar ducts and adjacent alveoli, 

interstitial thickening, and increased pulmonary macrophages and neutrophils in adjacent air spaces) 

were, however, still present at 72 hours. In guinea pigs with evidence of an inflammatory reaction 

involving the peripheral airways, DNA synthesis increased in bronchiolar cells. Similarly, exposure of 

guinea pigs to 5.6 mg zinc/m3

 as zinc oxide for 3 hours/day, for 5 days, resulted in gradual decreases in 

total lung capacity, vital capacity, and decreased carbon monoxide diffusing capacity (Lam et al. 1988); 

however, no effects were observed in guinea pigs exposed to 2.2 mg zinc/m3

. The reason that effects 

have been seen in the guinea pig at exposure levels lower than humans may have to do with the structural 

features of the guinea pig lung. The bronchi and peripheral airways of guinea pigs have a thicker smooth 

muscle layer and only a small surface area covered by alveolar sacs compared to the bronchi and 

peripheral airways of other laboratory animals and humans. This makes the guinea pig more susceptible 

than other laboratory animals to functional impairment of the peripheral airways and should be noted in 

toxicity comparisons (Lam et al. 1982). 

The bronchoalveolar lavage fluid of rats or guinea pigs exposed to 1.8 mg zinc/m3

 as zinc oxide for 

3 hours contained increased levels of lactate dehydrogenase and total protein, suggesting effects on cell 

viability or membrane permeability (Gordon et al. 1992). Rabbits were not affected following a similar 

exposure to 4.6 mg zinc/m3

 for 2 hours. Guinea pigs had foci of inflammation after exposure to 4.7 mg 

zinc/m3

 for 3 days, and the bronchoalveolar lavage fluid contained increased levels of protein, angiotensin 

converting enzyme, and neutrophils (Conner et al. 1988). No significant changes in respiratory effects 

were observed in this study following exposure to 1.8 mg zinc/m3 for 3 days. 

Zinc Chloride. Zinc chloride, a corrosive inorganic salt, is more damaging than zinc oxide to the mucous 

membranes of the nasopharynx and respiratory tract upon contact. Zinc chloride is a primary ingredient 

in smoke bombs used by the military for screening purposes, crowd dispersal, and occasionally in military 

and civilian fire-fighting exercises. Reports of serious respiratory injury have been reported to result from 

accidental inhalation of smoke from these bombs. These reports are of limited use in assessing the 

toxicity of zinc chloride because exposure to other compounds, usually hexachloroethane, zinc oxide, and 

calcium silicides, also occur. Furthermore, the specific concentrations inhaled are usually unknown. 

Despite these limitations, several case studies have described similar respiratory effects in humans 

following acute inhalation exposures. These effects include dyspnea, cough, pleuritic chest pain, bilateral 

diffuse infiltrations, pneumothorax, and acute pneumonitis from respiratory tract irritation (Johnson and 

Stonehill 1961; Matarese and Matthews 1966; Schenker et al. 1981; Zerahn et al. 1999). In the study by 

Johnson and Stonehill (1961), cough, dyspnea, burning throat, diffuse infiltrates throughout the lung, 
ZINC 32 

3. HEALTH EFFECTS 

chemical pneumonitis, and decreased vital capacity were observed at an estimated zinc chloride exposure 

level of 4,075 mg/m3

 (1,955 mg zinc/m3). In other studies, more severe effects have occurred, including 

ulcerative and edematous changes in mucous membranes, fibrosis, subpleural hemorrhage, advanced 

pulmonary fibrosis, and fatal respiratory distress syndrome (Evans 1945; Hjortso et al. 1988; Homma et 

al. 1992; Milliken et al. 1963). 

Focal alveolitis, consolidation, emphysema, infiltration with macrophages, and fibrosis were observed in 

guinea pigs that died following exposure to 119 mg zinc/m3

 as zinc chloride smoke for 1 hour/day, 

5 days/week, for 3–20 weeks (Marrs et al. 1988); no changes were seen in guinea pigs that survived 

13 months after the 20-week exposure. Thirteen months after a 20-week exposure, rats similarly exposed 

to 12.8 mg zinc/m3

 showed an increase in peribronchial inflammatory cell (lymphocytes and macrophage) 

infiltration. Mice exposed to 121.7 mg zinc/m3

 as zinc chloride smoke, but not to lower doses, for 

1 hour/day, 5 days/week, showed increased macrophages and lymphocytes in the lungs (Marrs et al. 

1988). The smoke also contained zinc oxide, hexachloroethane, and other compounds. 

Zinc Ammonium Sulfate. Zinc ammonium sulfate is a compound emitted during combustion of fossil 

fuels and is, therefore, found in the ambient air. Humans acutely exposed to a concentration of 0.0036 mg 

zinc/m3

 as zinc ammonium sulfate for 2 hours (Linn et al. 1981) exhibited minimal or no short-term 

respiratory effects (including minimal substernal irritation, throat irritation, and coughing in asthmatic 

subjects). However, most human exposures to an ambient air pollutant such as zinc ammonium sulfate 

are chronic, and this study provides little information about the health effects associated with typical 

exposures. 

No studies were located regarding respiratory effects in animals after inhalation exposure to zinc 

ammonium sulfate. 

Zinc Stearate. Inhalation of zinc stearate powder resulted in aspiration bronchopneumonia in an infant 

(Murray 1926). However, it is unclear whether the bronchopneumonia resulted from the inhalation of 

zinc stearate powder specifically or from a nonspecific effect of the inhalation of powders. 

No studies were located regarding respiratory effects in animals after inhalation exposure to zinc stearate. 

Cardiovascular Effects. No atypical heart sounds or blood pressure abnormalities were observed in 

24 employees occupationally exposed to concentrations as high as 130 mg zinc/m3

 of metallic zinc dust, 
ZINC 33 

3. HEALTH EFFECTS 

zinc oxide dust, zinc sulfide dust, or lithophone dust (a combination of barium sulphate and ≈30% zinc 

sulphide) for 2–35.5 years (Batchelor et al. 1926). However, this study is limited because only selected 

employees were examined. 

Only limited information was located regarding cardiovascular effects in animals following inhalation 

exposure to zinc. Routine gross and microscopic examination of the hearts of rats and mice revealed no 

adverse effects 13 months after exposure to 121.7 mg zinc/m3

 as zinc chloride smoke (also containing 

other compounds) for 1 hour/day, 5 days/week, for 20 weeks (Marrs et al. 1988). Similarly, no changes 

were observed in the hearts of guinea pigs exposed to 119.3 mg zinc/m3 as zinc chloride smoke for 

1 hour/day, 5 days/week, for 20 weeks, and then observed for an additional 17 months (Marrs et al. 1988). 

Gastrointestinal Effects. Nausea was reported by humans exposed to high concentrations of zinc 

oxide fumes (Hammond 1944; Rohrs 1957; Sturgis et al. 1927) and zinc chloride smoke (Evans 1945; 

Johnson and Stonehill 1961; Schenker et al. 1981). The zinc chloride smoke also contained zinc oxide, 

hexachloroethane, and other compounds. In general, exposure levels associated with nausea have not 

been reported. However, exposures to 320 mg zinc/m3

 as zinc oxide for 1–3 hours (Hammond 1944) or 

600 mg zinc/m3

 as zinc oxide for 10–12 minutes (Sturgis et al. 1927) were reported to have resulted in 

nausea; it should be noted, however, that the zinc used in these studies contained slight impurities (i.e., 

lead, magnesium). Autopsies of victims who died following exposure to very high concentrations of zinc 

chloride smoke revealed irritation of the stomach and intestines (Evans 1945). The smoke also contained 

zinc oxide, hexachloroethane, and other compounds. Workers in the galvanizing industry were found by 

McCord et al. (1926) to have a higher than expected incidence of gastrointestinal problems; however, 

these individuals may have been exposed to other chemicals (arsenic, hydrogen sulfide). Of 15 workers 

examined with 7–20 years of experience, 12 had frequent episodes of epigastric or abdominal pain, 

nausea, vomiting, ulcers, constipation, tarry stools, and/or gas. It is unclear whether these effects were 

due to systemic zinc or were the result of direct contact with the gastrointestinal tract following 

mucociliary clearance of inhaled zinc particles and subsequent swallowing. In contrast, 24 workers with 

2–35.5 years of exposure to ≤130 mg zinc/m3 as metallic zinc dust, zinc sulfide dust, zinc oxide, or 

lithophone dust reported no nausea or vomiting and only occasional mild abdominal discomfort that could 

not be attributed with certainty to zinc exposure (Batchelor et al. 1926). A study examining the acidity of 

the stomach contents after stimulation in controls and workers employed in the production of brass alloys 

showed that stomach acidity was similar in the two groups prior to stimulation but remained elevated for 

longer periods after stimulation in the exposed workers (Hamdi 1969). This was proposed to account for 
ZINC 34 

3. HEALTH EFFECTS 

the gastric complaints of workers exposed to zinc fumes. Despite these findings, x-rays showed no 

lesions in the stomachs or duodenums of exposed workers. 

The only information available regarding gastrointestinal effects in animals was found in a study by 

Marrs et al. (1988) in which rats and mice were exposed to 121.7 mg zinc/m3 as zinc chloride smoke 

(which also contains zinc oxide, hexachlorophene, and other compounds) for 1 hour/day, 5 days/week, for 

20 weeks, and then observed for an additional 13 months. In the same study, guinea pigs were exposed to 

119.3 mg zinc/m3 as zinc chloride smoke for 1 hour/day, 5 days/week, for 3 weeks. All animals were 

sacrificed at the end of 18 months. Routine gross and microscopic evaluation of the stomach and 

intestines at 18 months revealed no persistent adverse effects. 

Hematological Effects. Leukocytosis persisting for approximately 12 hours after fever dissipates is 

one of the hallmarks of metal fume fever (Mueller and Seger 1985). Such effects have been observed in a 

number of case reports of occupational and experimental exposure of humans to zinc oxide fumes (Brown 

1988; Drinker et al. 1927a; Malo et al. 1990; Rohrs 1957; Sturgis et al. 1927). Increased leukocyte counts 

were observed following experimental exposures to 430 mg zinc/m3 as zinc oxide for 3 hours (Drinker et 

al. 1927a) or 600 mg zinc/m3 as zinc oxide for 10–12 minutes (Sturgis et al. 1927). These studies are 

limited in that they used an inadequate number of subjects, lacked controls, and used impure zinc oxide. 

Decreased numbers of red blood cells and hemoglobin were found in several workers with 7–20 years of 

experience in the galvanizing industry (McCord et al. 1926). However, there were excess tobacco use 

and alcohol consumption by workers and possible concurrent exposure to other chemicals (chloride, 

sulfide), which confound the study results. No anemia was detected among 12 workers exposed for 4– 

21 years to zinc oxide fumes in the production of brass alloys (Hamdi 1969). These workers may have 

also been exposed to magnesium, copper, and aluminum. 

No studies were located regarding hematological effects in animals after inhalation exposure to zinc. 

Hepatic Effects. Routine blood chemistries and examinations revealed no liver disease among 

12 workers with 4–21 years of exposure to zinc oxide fumes in the production of brass alloys (Hamdi 

1969). 

No adverse effects were observed during gross and microscopic examination of livers of rats and guinea 

pigs exposed to 121.7 mg zinc/m3 or 119.3 mg zinc/m3

, respectively, as zinc chloride smoke for 
 

 

ZINC 35 

3. HEALTH EFFECTS 

1 hour/day, 5 days/week, for 20 weeks, and sacrificed at the end of 18 months (Marrs et al. 1988). 

Significant increases in the incidence of fatty liver were observed in mice exposed to 12.8 or 121.7 mg 

zinc/m3 as zinc chloride smoke using the same exposure paradigm; however, the incidence did not 

increase with dose (Marrs et al. 1988). The smoke contained other compounds in addition to zinc 

chloride. 

Renal Effects. Urinalyses and histories of urinary function revealed no adverse effects in 24 workers 

exposed for 2–35.5 years to ≤130 mg zinc/m3 as metallic zinc dust, zinc sulfide dust, zinc oxide, or 

lithophone dust (Batchelor et al. 1926). 

No adverse effects were observed following gross and microscopic examination of kidneys from rats, 

mice, and guinea pigs exposed for 1 hour/day, 5 days/week, for 20 weeks, to concentrations as high as 

121.7 or 119.3 mg zinc/m3 as zinc chloride smoke (which also contained other compounds) and then 

sacrificed 13 months later (Marrs et al. 1988). 

Ocular Effects. Reddened conjunctiva and corneal burns occurred in individuals exposed to high 

concentrations of zinc chloride smoke (estimated at 33,000 mg zinc/m3

) when several smoke generators 

exploded in a tunnel during World War II (Evans 1945). The ocular effects may have been due to direct 

contact with the smoke. 

Homeostatic Effects. A fever appearing 3–10 hours after exposure to zinc oxide fumes and lasting 

approximately 24–48 hours is characteristic of metal fume fever caused by zinc (Mueller and Seger 

1985). Elevated body temperature has been observed in a number of experimental and occupational zinc 

oxide exposures (Brown 1988; Drinker et al. 1927a; Hammond 1944; Malo et al. 1990; Rohrs 1957; 

Sturgis et al. 1927; Vogelmeier et al. 1987). Using a number of exposure concentrations for various 

durations, Drinker et al. (1927b) found that the increase in body temperature was dependent on the 

exposure duration and concentration. Based on their data, they calculated that the threshold for pyrogenic 

effects was 45 mg zinc/m3 for 20 minutes. This study is limited in that impurities were present in the zinc 

used and no statistical analysis was performed. Exposure to zinc chloride smoke (which also contains 

other compounds) has also been associated with fever (Hjortso et al. 1988; Matarese and Matthews 1966). 

No studies were located regarding other systemic effects in animals following inhalation exposure to zinc. 
ZINC 36 

3. HEALTH EFFECTS 

3.2.1.3 Immunological and Lymphoreticular Effects 

One report described hives and angioedema in a man exposed to zinc fumes at a zinc smelting plant 

(Farrell 1987). The author suggested that the patient had an immediate or delayed immunoglobulin E 

(IgE) response (or both) after a low dose of zinc fumes. Metal fume fever also resulted when the 

exposure increased. The signs and symptoms of toxicity were repeated in a challenge test conducted at 

the patient's home. 

In a group of 14 welders acutely exposed to 77–153 mg zinc/m3 as zinc oxide, significant correlations 

between the concentration of airborne zinc and the proportion of activated T cells, T helper cells, 

T inducer cells, T suppressor cells, and activated killer T cells were observed 20 hours after exposure 

(Blanc et al. 1991). In addition, significant increases in levels of polymorphonuclear leukocytes, 

macrophages, and all types of lymphocytes were observed in the bronchoalveolar lavage fluid 20 hours 

after exposure. Increased levels of lymphocytes, with a predominance of CD8 cells, in the 

bronchoalveolar lavage fluid were reported in a case study of a smelter exposed to unspecified levels of 

zinc fumes (Ameille et al. 1992). 

The bronchoalveolar lavage fluid of rats or guinea pigs exposed to 2.2 mg zinc/m3 for 3 hours contained 

increased levels of β-glucuronidase, suggesting a change in macrophage function (Gordon et al. 1992). 

Rabbits were not affected following a similar exposure to 4.6 mg zinc/m3

 for 2 hours. Rats, mice, and 

guinea pigs were exposed to concentrations as high as 119.3 or 121.7 mg zinc/m3

 as zinc chloride smoke 

for 1 hour/day, 5 days/week, for 20 weeks (Marrs et al. 1988). Routine gross and histopathologic 

examination of the lymph nodes, thymus, and spleen at the end of 18 months revealed no adverse effects. 

The smoke also contained zinc oxide, hexachlorophene, and other compounds. 

3.2.1.4 Neurological Effects 

Humans have reported nonspecific neurological effects such as headaches and malaise in association with 

other symptoms following inhalation of zinc oxide and in metal fume fever (Rohrs 1957; Sturgis et al. 

1927). Staggering gait, hallucinations, and hilarity were observed in an individual who intentionally 

inhaled aerosols of metallic paint containing copper and zinc (Wilde 1975). However, it is most likely 

that these effects were due to exposure to hydrocarbon propellant rather than zinc. Amr et al. (1997) 

reported an increase in neuropsychiatric symptoms, including fear of poisoning, headache, nervousness, 

insomnia, and changes in EEG, in workers who were occupationally-exposed to zinc phosphide for a 
ZINC 37 

3. HEALTH EFFECTS 

period of many years; however, exposure levels were not reported, and no tests of statistical significance 

were performed. 

No studies were located regarding neurological effects in animals after inhalation exposure to zinc. 

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after inhalation exposure to zinc. 

Following an initial exposure of rats, mice, and guinea pigs to concentrations as high as 119.3 or 

121.7 mg zinc/m3 as zinc chloride smoke (which also contained other compounds) for 1 hour/day, 

5 days/week, for 20 weeks; histological evaluation revealed no adverse effects on the mammary glands, 

ovaries, fallopian tubes, or uteri were observed at 18 months (Marrs et al. 1988). 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure 

to zinc. 

3.2.1.7 Cancer 

In two epidemiological studies, workers did not have an increased incidence of cancers associated with 

occupational exposure (primarily inhalation exposure) to zinc (Logue et al. 1982; Neuberger and 

Hollowell 1982). 

Workers in nine electrolytic zinc and copper refining plants were studied by Logue et al. (1982). The 

workers at two of these plants were exposed to zinc or zinc and copper; the other workers were exposed 

to copper. An association between cancer mortality and zinc exposure was not found. 

Excess lung cancer mortality associated with residence in an old lead/zinc mining and smelting area of the 

midwestern United States was studied by Neuberger and Hollowell (1982). The age- and sex-adjusted 

mortality rates were compared to state and national rates. The analysis determined that lung cancer 

mortality was elevated in the region but was not found to be associated with exposure to environmental 
ZINC 38 

3. HEALTH EFFECTS 

levels of lead or zinc. Many confounding factors were not considered in the analysis, such as smoking, 

occupation, and duration of residence in the area in question. 

Female Porton strain mice (98–100/group) exposed to 121.7 mg zinc/m3 of a zinc oxide/hexachloroethane 

smoke mixture (which produces zinc chloride), 1 hour/day, 5 days/week, for 20 weeks had a statistically 

significant increase in the incidence of alveologenic carcinoma (30 versus 8% in control) thirteen months 

after the end of exposure (Marrs et al. 1988). No increased tumor incidences were seen in mice exposed 

to 1, 1.3, or 12.8 mg zinc/m3

. Guinea pigs and rats were also tested with similar dose levels, and no 

significant carcinogenic response was observed. A number of factors limit the usefulness of this study, 

including the presence of several compounds in the smoke that may have carcinogenic potential, the use 

of only female animals, and the short duration of the exposure (20 weeks). 

3.2.2 Oral Exposure 

Zinc has been orally administered in a variety of forms, such as zinc chloride, zinc sulfate, zinc oxide, 

powdered zinc, and others. Some of these compounds, such as zinc sulfate, have been administered in 

both hydrated and anhydrous forms. Study authors often do not state definitely which form was used in a 

particular study. Knowledge of the form used and its molecular weight is necessary to calculate the 

amount of elemental zinc administered under a given set of circumstances, and is similarly important in 

that different chemical forms of zinc may be absorbed to differing degrees depending on their in vivo 

solubility, resulting in differing levels of toxicity. If adequate information was not reported by the study 

authors, it was assumed that an anhydrous, soluble compound was used. 

3.2.2.1 Death 

In a case report presented by Murray (1926), an infant died from bronchopneumonia resulting from 

inhalation and ingestion of an unspecified amount of zinc stearate powder spilled from a container. 

However, the cause of death (bronchopneumonia) suggests that it resulted from the inhalation exposure, 

rather than the oral exposure, and it is unclear whether the lung damage resulted from the inhalation of 

zinc stearate powder specifically or from a general effect of the inhalation of powders. 

The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been 

determined in rats and mice (Domingo et al. 1988a). In general, mice appear to be more sensitive than 
 

 

ZINC 39 

3. HEALTH EFFECTS 

rats to the lethal effects of zinc. In rats, zinc acetate was the most lethal compound tested; zinc nitrate, 

zinc chloride, and zinc sulfate (in order of decreasing toxicity) were less lethal. In mice, the most lethal 

compound was zinc acetate followed by zinc nitrate, zinc sulfate, and zinc chloride. Ingestion of 390 mg 

zinc/kg/day as zinc oxide in the diet for 3–13 days was lethal to 3 of 3 ferrets (Straube et al. 1980). An 

equivalent dose in humans would be approximately 27 g zinc/day (which would probably be intolerable 

to humans because of gastric discomfort). Death was reported in mice that consumed 1,110 mg 

zinc/kg/day as zinc sulfate in their diet for 13 weeks (Maita et al. 1981). Mortality was also observed in 

20% of rats ingesting 191 mg zinc/kg/day as zinc acetate in drinking water for 3 months (Llobet et al. 

1988a). 

The LD50 values and all LOAEL values from each reliable study 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 from each reliable study for systemic effects in each 

species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Ingestion of zinc or zinc-containing compounds has resulted in a variety of systemic effects in the 

gastrointestinal and hematological systems and alterations in the blood lipid profile in humans and 

animals. In addition, lesions have been observed in the liver, pancreas, and kidneys of animals. No 

studies were located regarding respiratory, ocular, or metabolic effects in humans or animals after oral 

exposure to zinc. 

Observed systemic effects after oral exposure are discussed below. The effects discussed in case reports 

are not included in Table 3-2 or Figure 3-2 because of the small sample size and lack of control data. 

Cardiovascular Effects. A number of studies in humans and animals have examined the effects of 

zinc on serum cholesterol and triglycerides. However, no studies regarding the direct relationship 

between excessive zinc intake and cardiac mortality were located. No effects on electrocardiographic 

results were found in a group of elderly subjects (>65 years of age) taking zinc supplements of up to 2 mg 

zinc/kg/day (Hale et al. 1988) or 0.71 mg zinc/kg/day (Czerwinski et al. 1974). There was also no effect 

on the frequency of cardiovascular disease (heart attack, heart failure, hypertension, or angina) in elderly 

subjects (>67 years of age) taking up to 2 mg zinc/kg/day for a mean of 8 years (Hale et al. 1988). 
409

237

410

623

411

528

412

293

413

337

414

86

417

605

418

204

Table 3-2 Levels of Significant Exposure to Zinc - 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) 

237 M (LD50) 

Reference Chemical Form 

Domingo et al. 1988a Zinc acetate 

2 Rat 

(SpragueDawley) 

once (G) 623 M (LD50) Domingo et al. 1988a Zinc sulfate 

3 Rat 

(SpragueDawley) 

once (G) 528 M (LD50) Domingo et al. 1988a Zinc chloride 

4 Rat 

(SpragueDawley) 

once (G) 293 M (LD50) Domingo et al. 1988a Zinc nitrate 

5 Mouse 

(SwissWebster) 

once (G) 337 M (LD50) Domingo et al. 1988a Zinc sulfate 

6 Mouse 

(SwissWebster) 

once (G) 86 M (LD50) Domingo et al. 1988a Zinc acetate 

7 Mouse 

(SwissWebster) 

once (G) 605 M (LD50) Domingo et al. 1988a Zinc chloride 

8 Mouse 

(SwissWebster) 

once (G) 204 M (LD50) Domingo et al. 1988a Zinc nitrate 
419

390

425

0.5

427

6.7

540

6.8

429

86

86

438

487

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to Species 

Figure (Strain) 

9 Ferret 

Systemic 

10 Human 11 Human 12 Human 13 Human 

Neurological 

14 Rat 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

<2 wk (F) 390 (3/3 died) Straube et al. 1980 Zinc oxide 

once (W) Endocr 0.5 (decreased serum cortisol levels) Brandao-Neto et al. 199

Zinc sulfate 

once (W) Gastro 6.7 (gastrointestinal distress; diarrhea) Callender and Gentzkow 

Zinc oxide 

Single oral exposure (IN) 

Gastro 6.8 M (Transient nausea, 

lasting approximately 6 hours) 

Lewis and Kokan 1998 Zinc gluconate 

2 d (F) Gastro 

Endocr 

86 M 

86 M (increased serum 

amylase, lipase) 

Murphy 1970 Zinc elemental 

10 d 1x/d (G) 

487 (minor neuronal 

degeneration; decreased acid phosphatase and acetylchonlinesterase; increased thiamine pyrophosphatase) 

Kozik et al. 1980 Zinc oxide 
440

191

441

1110

451

1.5

549

0.43

454

4.3

450

0.71

550

0.680.68

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to 

Figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

INTERMEDIATE EXPOSURE Death 

15 Rat 3 mo 

ad lib (W) 

System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

191 F (2/10 died) 

Reference Chemical Form 

Llobet et al. 1988a Zinc acetate 

16 Mouse 

Systemic 

17 Human 

13 wk ad lib (F) 3 mo 7d/wk 1x/d (C) 

Other 1.5 

1110 (5/24 died) Maita et al. 1981 

Zinc sulfate Bogden et al. 1988 Zinc acetate 

18 Human 14 wk 

7 d/wk 1x/day 

Hemato 0.43 M Bonham et al. 2003b 

Zinc glycine chelate 

19 Human 6 wk 

2x/d (C) 

Other 4.3 M (increased serum 

LDL-cholesterol; decreased serum HDL-cholesterol) 

Chandra 1984 Zinc sulfate 

20 Human 24 wk 

7d/wk 3x/d (C) 

Cardio 0.71 Czerwinski et al. 1974 

Zinc sulfate 

21 Human 90 d 

1x/d Hemato 

Endocr 

0.68 F 0.68 F 

Davis et al. 2000 Zinc gluconate 
449

0.71

443

2.3

552

0.68

445

2

447

2.4

444

0.83

536

7

Table 3-2 Levels of Significant Exposure to Zinc - 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 

22 Human 6 wk 

7d/wk 2x/d (C) 

Hemato 0.71 Fischer et al. 1984 

Zinc gluconate 

23 Human 5 wk 

2x/d (C) 

Other 2.3 M (decreased serum 

HDL-cholesterol) 

Hooper et al. 1980 Zinc sulfate 

24 Human 90 d 

1x/d Hemato 0.68 F Milne et al. 2001 

Zinc gluconate 

25 Human 6 wk 

3x/d (F) 

Gastro 2 (abdominal cramps; 

vomiting; nausea) 

Samman and Roberts 1Zinc sulfate 

26 Human 6 wk 

7d/wk 3x/d (C) 

Other 2.4 Samman and Roberts 1

Zinc sulfate 

27 Human 10 wk 

7d/wk 2x/d (C) 

Hemato 

b

0.83 F Yadrick et al. 1989 

Zinc gluconate 

28 Rat 14 wk (males) 

or 20 wk (females) 7 d/wk 1x/d (GW) 

Bd Wt 7 M (decreased postpartum 

body weights in F0 animals) 

Khan et al. 2001b Zinc chloride 
460

6

468

19119195

191

191

458

56553

565

56556553

565

Table 3-2 Levels of Significant Exposure to Zinc - 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 

29 Rat 6 wk 

7d/wk ad lib (F) 

Hemato 6 M (ceroplasmin reduced by 

28%) 

L'Abbe and Fischer 198Zinc sulfate 

30 Rat 

(SpragueDawley) 

3 mo ad lib (W) 

Hemato 191 F Llobet et al. 1988a 

Zinc acetate 

Hepatic 191 F Renal 95 F 191 F (increased plasma 

creatine and urea levels; desquamation of epithelial cells of proximal tubules) 

Bd Wt 191 F 

31 Rat 13 wk 

ad lib (F) 

Gastro 565 F Maita et al. 1981 

Zinc sulfate 

Hemato 53 F 565 F (decreased hematocrit 

and WBC) 

Musc/skel 565 F Renal 565 F Other 53 M 565 F (acinar cell necrosis and 

metaplasia in pancreas) 
464

500

469

350

461

12

529

70

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to Species 

Figure (Strain) 

32 Rat 

(SpragueDawley) 

33 Rat 

(SpragueDawley) 

34 Rat 

(Wistar) 

35 Mouse 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

5 wk ad lib (F) 

Hemato 500 (decreased Hb, 

hematocrit, MCH, MCHC; slightly increased WBC) 

Smith and Larson 1946 Zinc carbonate 

6 wk ad lib (F) 

Hemato 350 (decreased Hb) Smith and Larson 1946 

Zinc carbonate 

4 wk 7d/wk ad lib (W) 

Hemato 12 (decreased Hb and 

erythrocytes) 

Zaporowska and Wasile1992 Zinc chloride 

5-14 mo ad lib (W) 

Other 70 (hypertrophy and 

vacuolation of pancreas islet cells; hypertrophy and vacuolation of fasciculata cells in adrenal cortex) 

Aughey et al. 1977 Zinc sulfate 
471

104 1110104

1110

104

1110

104

1110

472

68

473

4

470

174

174

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to 

Figure 

36 37 38 39 

Species 

(Strain) 

Mouse (ICR) Mouse Dog Rabbit (New Zealand) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

13 wk ad lib (F) 9 mo ad lib (F) 9 mo ad lib (W) 22 wk daily (F) 

System 

Gastro Hemato Renal Endocr Hemato Musc/skel Hemato Bd Wt 

NOAEL 

(mg/kg/day) 

104 M 104 M 104 M 104 M 

4 M 

174 M 

Less Serious 

(mg/kg/day) 

1110 F (decreased WBC; 

anemia) 

1110 F (unspecified regressive 

lesions) 

174 M (slight decrease in Hb 

levels) 

LOAEL 

Serious

(mg/kg/day)

1110 F (forestomach ulcers) 1110 F (acinar cell necrosis and 

metaplasia in pancreas) 

68 (severe anemia) 

Reference Chemical Form 

Maita et al. 1981 Zinc sulfate Walters and Roe 1965 Zinc oleate 

Anderson and DanylchuZinc oxide Bentley and Grubb 199Zinc carbonate 
481

323.6323.6323.6323.6

483

64

64

91

478

195 39065 19565 195195 390

485

1.5

547

0.43

40 42 

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

Exposure/ 

Duration/ 

a Frequency Key to Species (Route) Figure (Strain) 

Mink 144 d 

ppd70-214 (F) 

41 Cow 5 wk 

2x/d ppd3-40 (F) 

Ferret 7-97 d 

ad lib (F) 

Immuno/ Lymphoret 

43 Human 3 mo 

7d/wk 1x/d (C) 

44 Human 14 wk 

7 d/wk ns 

System 

Hemato Hepatic Renal Bd Wt Hemato Bd Wt Gastro Hemato Renal Endocr 

NOAEL 

(mg/kg/day) 

323.6 323.6 323.6 

323.6 

64 M 

195 

65 65 

195 

1.5 

0.43 M 

Less Serious

(mg/kg/day)

64 M (decreased hematocrit 

levels) 

195 (anemia) 195 (nephrosis) 390 (pancreatitis) 

LOAEL 

Serious

(mg/kg/day)

91 M (body weight gain

decreased by 46%)

390 (intestinal hemorrhages) 

Reference Chemical Form 

Aulerich et al. 1991 Zinc sulfate Jenkins and Hidiroglou Zinc oxide Straube et al. 1980 Zinc oxide Bogden et al. 1988 Zinc acetate Bonham et al. 2003a Zinc glycine chelate 
548

0.43

484

4.3

486

2.5

488

6.5

542

136

487

76.9

Table 3-2 Levels of Significant Exposure to Zinc - 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 

45 Human 14 wk 

7 d/wk 1x/day 

0.43 M Bonham et al. 2003b 

Zinc glycine chelate 

46 Human 6 wk 

2x/d (C) 

4.3 M (impaired lymphocyte 

and polymorphonuclear leukocyte function) 

Chandra 1984 Zinc sulfate 

47 Human 1 mo 

2x/d (C) 

2.5 Duchateau et al. 1981 

Zinc sulfate 

48 Mouse 8 wk 

7d/wk ad lib (F) 

6.5 Fernandes et al. 1979 

ns 

49 Mouse 

(BALB/c) 

continuously for 42 days (W) 

136 (Increases in direct 

plaque-forming activity of spleen cells and in lymphyocyte proliferation in response to mitogen stimulation) 

Lastra et al. 1997 ns 

50 Mouse 4 wk 

7d/wk ad lib (F) 

76.9 F Schiffer et al. 1991 

Zinc sulfate 
543

0.5

508

0.3

510

25

537

3.5

7

513

200

509

50

250

541

273

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to Species 

Figure (Strain) 

Neurological 

51 Mouse 

(SwissWebster) 

Reproductive 

52 Human 53 Rat 54 Rat 55 Rat 56 Rat 57 Mouse 

(BALB/c) 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

drinking water for 60 days (W) 

0.5 (Increase in latency in 

inhibitory avoidance test) 

Oliveira et al. 2001 Zinc acetate 

Gwk 20 through parturition (C) 

0.3 F Mahomed et al. 1989 

Zinc sulfate 

8 wk 7d/wk ad lib (F) 

25 M (altered sperm chromatin 

structure) 

Evenson et al. 1993 Zinc chloride 

14 wk (males) or 20 wk (females) 7 d/wk 1x/d (GW) 

3.5 F 7 F (Decreased live pups per 

litter in all groups of treated rats) 

Khan et al. 2001b Zinc chloride 

18 d Gd0-18 ad lib (F) 

200 F (increased 

pre-implantation loss) 

Pal and Pal 1987 Zinc sulfate 

150 d ad lib (F) 

50 250 (no reproduction in 

females) 

Sutton and Nelson 1937 Zinc carbonate 

continuously for 42 days (W) 

273 F Lastra et al. 1997 

ns 
514

1110

515

20.8

493

0.06

490

0.3

492

0.3

503

250

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to Species 

Figure (Strain) 

58 Mouse 

(ICR) 

59 Mink 

Developmental 

60 Human 61 Human 62 Human 63 Rat 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

13 wk ad lib (F) 

1110 Maita et al. 1981 

Zinc sulfate 

approx 25 wk ad lib (F) 

20.8 Bleavins et al. 1983 

Zinc sulfate 

11 wk 1x/d (C) 

0.06 F Kynast and Saling 1986 

Zinc aspartate 

Gwk 20 through parturition (C) 

0.3 F Mahomed et al. 1989 

Zinc sulfate 

last 15-25 wk of pregnancy 1x/d (C) 

0.3 F Simmer et al. 1991 

Zinc citrate 

7 wk Gd0-17 ad lib (F) 

250 F Kinnamon 1963 

Zinc carbonate 
498

200

501

100

504

200

502

50 250

497

25

506

260

Table 3-2 Levels of Significant Exposure to Zinc - Oral (continued) 

a

Key to Species 

Figure (Strain) 

64 Rat 

(SpragueDawley) 

65 Rat 66 Rat 

(SpragueDawley) 

67 Rat 68 Rat 

(SpragueDawley) 

69 Mouse 

Exposure/ 

Duration/ 

Frequency 

(Route) System 

NOAEL 

(mg/kg/day) 

Less Serious 

(mg/kg/day) 

LOAEL 

Serious 

(mg/kg/day) 

Reference Chemical Form 

15 d Gd1-15 ad lib (F) 

200 F (29% fetal resorption; 

decreased fetal weight) 

Schlicker and Cox 1968 Zinc oxide 

36 d Gd1-15 ad lib (F) 

100 F Schlicker and Cox 1968 

Zinc oxide 

36 d Gd1-21 ad lib (F) 

200 F (100% fetal resorption) Schlicker and Cox 1968 

Zinc oxide 

150 d ad lib (F) 

50 250 (increased stillbirths) Sutton and Nelson 1937 

Zinc carbonate 

20 d Gd0-20 ad lib (F) 

25 F Uriu-Hare et al. 1989 

Zinc carbonate 

2 gen (F) 260 (alopecia; decreased hematocrit) Mulhern et al. 1986 Zinc carbonate 
507

20.8

546

1.43

Table 3-2 Levels of Significant Exposure to Zinc - 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 

70 Mink approx 

25 wk ad lib (F) 

CHRONIC EXPOSURE Cancer 

71 Human 1x/day 

1 or more years ns 

20.8 

1.43 M (Increased probability of 

advanced prostate cancer) 

Bleavins et al. 1983 Zinc sulfate Leitzmann et al. 2003 ns 

a The number corresponds to entries in Figure 3-2. b Used to derive an intermediate-duration oral minimal risk level (MRL) of 0.3 mg/kg/day; The MRL was calculated by applying an uncertainty factor of 3 (for uncerhuman variability) to the no-observed-adverse-effect level (NOAEL) of 0.83 mg/kg/day. The intermediate oral MRL was adopted as the chronic oral MRL. ad lib = ad libitum; approx = approximately; (C) = capsule; Cardio = cardiovascular; d - day(s); (F) = feed; (G) = gavage; Gastro = gastrointestinal; Gd = gestation dageneration; Gwk = gestation week; Hb = hemoglobin; HDL = high density lipoprotein; Hemato = hematological; LD50 = lethal dose, 50% kill; LDL = low density lipoplowest-observed-adverse-effect level; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; mo = month(s); Musc/skel = mNOAEL = no-observed-adverse-effect level; ns = not specificied; ppd - post partum day; RBC = red blood cell; (W) = drinking water; WBC = white blood cell; wk = wtime(s); yr = year(s) 
Death Gastrointestinal Endocrine Neurological 

Figure 3-2 Levels of Significant Exposure to Zinc - Oral 

Acute (≤14 days) 

Systemic 

mg/kg/day 

1000 

7m 2r 3r 14r 

9f 5m 4r 

1r 8m

100 6m 13 13 

10 

11 12 

1 

10 

0.1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Death Cardiovascular Gastrointestinal Hematological Musculoskeletal Hepatic Re

Figure 3-2 Levels of Significant Exposure to Zinc - Oral 

Intermediate (15-364 days) 

Systemic 

mg/kg/day

10000

1000 16m 36m 36m 

31r 31r 31r 

32r

42f 40n 33r 40n 

15r 42f 30r 42f 30r 

39h 

100 36m 36m 36m 

37m 41q 42f 

31r 

34r 10

29r 

38d 

25

1 27 20 21 22 24

18

0.1 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
10000 

Endocrine Body Weight Other Immuno/Lymphor Neurological Reproductive 

Figure 3-2 Levels of Significant Exposure to Zinc - Oral 

Intermediate (15-364 days) 

Systemic 

mg/kg/day 

1000 36m 58m

31r 

42f 40n 57m 56r 69m 

42f 30r 55r 

39h 

49m 

100 36m 

41q 35m 50m 41q 31r 56r 

53r 

59n 

10 

28r 54r 48m 

19 46 54r 

23 26 47

17 43 

1 

21 

51m 44 45 

52 

0.1 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Cancer * 

Figure 3-2 Levels of Significant Exposure to Zinc - Oral 

Chronic (≥365 days) 

mg/kg/day 

10 

71 

*Doses represent the lowest dose tested per study that produced a tumorigenic

response and do not imply the existence of a threshold for the cancer endpoin

1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
ZINC 57 

3. HEALTH EFFECTS 

In one study, patients having inoperable severe occlusive vascular disease were administered 3.8 mg 

zinc/kg/day as zinc sulfate for at least 1 year (Henzel et al. 1971). Eighteen of the 24 patients experienced 

improvement in lower extremity blood flow and unchanged or decreased arterial pressure. Zinc's role in 

these improvements was not completely understood by the study authors. They hypothesized that when 

optimal zinc levels are provided to the ischemic limb, the activity of certain zinc enzymes promotes the 

reversal of tissue-dependent hypoxia and/or lactic acidemia in the muscles. It is also not known if this 

high dose of zinc was associated with any toxic effects. 

No studies were located regarding cardiovascular effects in animals after oral exposure to zinc. 

Gastrointestinal Effects. Several studies have suggested that zinc ingestion may cause symptoms of 

gastrointestinal distress or alterations in gastrointestinal tissues. For example, one individual who 

ingested about 3 ounces of a zinc chloride solution described acute symptoms that occurred almost 

immediately following contact with the compound, including burning and pain in the mouth and throat 

and vomiting (Chobanian 1981). Later, the patient exhibited pharyngitis, esophagitis, hypocalcemia, and 

elevated levels of amylase; the latter two alterations are suggestive of acute pancreatitis. The patient 

received intravenous hydration and calcium supplementation and recovered within 5 days. The material 

ingested was described as a "zinc chloride solution," and its concentration was not reported. Therefore, a 

dose level could not be established in this case. 

Several cases of gastrointestinal disturbances have been reported after ingestion of zinc sulfate 

(Anonymous 1983; Brown et al. 1964; Moore 1978; Samman and Roberts 1987). Vomiting, abdominal 

cramps, and diarrhea, in several cases with blood, have been observed after ingestion of zinc sulfate. In 

one report, an English school girl ingested 440 mg zinc sulfate/day (2.6 mg zinc/kg/day) in capsules as a 

medically prescribed treatment for acne (Moore 1978). After taking each capsule, she experienced 

epigastric discomfort. A week later, she was admitted to the hospital after a fainting spell. She was 

diagnosed as anemic and subsequently passed melanic stools, indicative of gastrointestinal bleeding. 

Gastrointestinal upset (abdominal cramps, vomiting, nausea) occurred in 26 of 47 healthy volunteers 

following ingestion of zinc sulfate tablets (150 mg as zinc ion in three divided doses per day, 2 mg 

zinc/kg/day) for 6 weeks (Samman and Roberts 1987). A 17-year-old boy who ingested approximately 

6.8 mg zinc/kg as zinc gluconate showed severe nausea and vomiting, but displayed no other symptoms, 

and recovered within 7 hours of ingestion (Lewis and Kokan 1998). Ingestion of zinc oxide has also been 

associated with gastrointestinal distress (Anonymous 1983; Callender and Gentzkow 1937). In one case, 

80% of the personnel of two army companies became ill with gastrointestinal distress and diarrhea after 
ZINC 58 

3. HEALTH EFFECTS 

consuming limeade prepared in galvanized trash cans (Callender and Gentzkow 1937). The average dose 

was estimated to be 6.7–7.1 mg/kg. A second example was presented in a case involving school children 

in New Mexico who experienced nausea and vomiting after accidental excessive zinc intake (Anonymous 

1983). These children had consumed punch containing high levels of zinc dissolved from galvanized 

hinges attached to tanks in which the punch was stored. A 16-year-old boy who ingested 12 g elemental 

zinc over a 2-day period (86 mg zinc/kg/day) experienced light-headedness, lethargy, staggering gait, and 

difficulty writing legibly, but no apparent gastrointestinal disturbances (Murphy 1970). 

Gastrointestinal effects have also been observed in animals. Intestinal hemorrhages were observed in 

ferrets that ingested 390 mg zinc/kg/day as zinc oxide for 2 weeks (Straube et al. 1980). These ferrets 

exhibited a 75% reduction in food intake. No intestinal hemorrhaging was observed in ferrets fed 

195 mg/kg/day for up to 21 days. Oral zinc sulfate exposures of intermediate duration in other 

experimental animals have also resulted in gastrointestinal effects. Mice fed a diet providing 1,110 mg 

zinc/kg/day for 13 weeks developed ulcers in the forestomach, but gastrointestinal effects were not 

observed in rats fed 565 mg zinc/kg/day for 13 weeks (Maita et al. 1981). 

Hematological Effects. In a case report, acute exposure to 2.6 mg zinc/kg/day as zinc sulfate for 

1 week resulted in anemia (Moore 1978). The authors of the report noted that the anemia may have been 

secondary to the gastrointestinal hemorrhages. 

Treatment-related changes in hematological parameters have been observed in humans and animals after 

intermediate or chronic exposure to zinc or zinc-containing compounds. Long-term administration (1– 

8 years) of zinc supplements has caused anemia in humans (Broun et al. 1990; Gyorffy and Chan 1992; 

Hale et al. 1988; Hoffman et al. 1988; Patterson et al. 1985; Porter et al. 1977; Prasad et al. 1978; 

Ramadurai et al. 1993; Salzman et al. 2002; Stroud 1991; Summerfield et al. 1992). Exposure of one 

patient to 2 mg zinc/kg/day as zinc sulfate for 10 months resulted in anemia (Hoffman et al. 1988). A 

significant reduction in erythrocyte superoxide dismutase activity (47% decrease), hematocrit, and serum 

ferritin, compared to pretreatment levels, occurred in female subjects who received supplements (as 

capsules) of 50 mg zinc/day as zinc gluconate for 10 weeks (Yadrick et al. 1989); this study was selected 

as the basis for the intermediate-duration oral MRL. A 15% decrease in erythrocyte superoxide dismutase 

activity was reported in male volunteers receiving 50 mg zinc/day as zinc gluconate for 6 weeks (Fischer 

et al. 1984). A more recent study by Davis et al. (2000; Milne et al. 2001) reported increases in bonespecific alkaline phosphatase levels (~25%) and extracellular superoxide dismutase (~15%), while 

significant decreases were seen in mononuclear white cell 5'-nucleotidase (~30%) and plasma 
 

 

 

ZINC 59 

3. HEALTH EFFECTS 

5'-nucleotidase activity (~36%) following exposure of postmenopausal women to a combined 

(dietary+supplemental) 53 mg zinc/day as zinc glycine chelate. Healthy men given 200 mg zinc/day as 

elemental zinc for 6 weeks showed a reduction in lymphocyte stimulation response to phytohemagglutinin as well as chemotaxis and phagocytosis of bacteria by polymorphonuclear leukocytes (Chandra et 

al. 1984); however, no changes in lymphocyte cell number or in the proportion of lymphocyte populations 

were noted. Exposure of male volunteers to 0.48 mg zinc/kg/day, as zinc glycine chelate, had no effect 

on markers of coagulation (Bonham et al. 2003b) relative to unexposed subjects. While the changes in 

hematological end points following long-term zinc exposure in humans are noteworthy, they were 

subclinical in nature, and therefore, are generally considered to be non-adverse. 

In animals, following oral administration of zinc compounds, decreased hemoglobin, hematocrit, 

erythrocyte, and/or leukocyte levels were observed in rats (Maita et al. 1981; Smith and Larson 1946), 

mice (Maita et al. 1981; Walters and Roe 1965), rabbits (Bentley and Grubb 1991), dogs (Drinker et al. 

1927d; Meurs et al. 1991; Robinson et al. 1991), ferrets (Straube et al. 1980), and preruminant calves 

(Jenkins and Hidiroglou 1991). In rats, the lowest LOAEL for hematological effects was 4 mg/kg/day 

(8 mg/kg every other day) for an increased frequency of basophilic-stippled erythrocytes in rats exposed 

every other day for 14 days (Piao et al. 2003). The second lowest LOAEL is 12 mg zinc/kg/day as zinc 

chloride in a 4-week drinking water study with 2-month-old rats (Zaporowska and Wasilewski 1992) that 

reported decreased hemoglobin (85% of control values) and erythrocytes (90% of control values). The 

highest NOAEL in rats is 191 mg zinc/kg/day as zinc acetate in a 3-month drinking water study (age of 

rats not specified) (Llobet et al. 1988a). The reason that the lowest LOAEL is less than the highest 

NOAEL in rats is unclear, but it may be because of the use of different zinc compounds or different rat 

strains or age. For mice, NOAEL and LOAEL values of 104 and 1,110 mg zinc/kg/day as zinc sulfate, 

respectively, were identified by Maita et al. (1981) in a 13-week feeding study. A serious LOAEL of 

68 mg zinc/kg/day as zinc oleate was identified for severe anemia in a 9-month feeding study in mice 

(Walters and Roe 1965). It is not known if the difference in the LOAELs identified in the Maita et al. 

(1981) and Walters and Roe (1965) studies is due to the use of different zinc compounds, different basic 

diet formulations, different mouse strains, or different exposure durations. Slight decreases in 

hemoglobin levels were observed in rabbits fed 174 mg zinc/kg/day as zinc carbonate (Bentley and Grubb 

1991). Zinc oxide consumption caused anemia in dogs (76.5 mg zinc/kg/day) (Drinker et al. 1927d), 

ferrets (195 mg zinc/kg/day) (Straube et al. 1980), and preruminant calves (64 mg zinc/kg/day) (Jenkins 

and Hidiroglou 1991). Hematological alterations were not observed in cats exposed to up to 83.2 mg 

zinc/kg/day as zinc oxide (Drinker et al. 1927d) or in adult mink exposed to zinc at up to 297.4 mg 

zinc/kg/day as zinc oxide (Aulerich et al. 1991; Bleavins et al. 1983) or to rats exposed to 53 mg 
ZINC 60 

3. HEALTH EFFECTS 

zinc/kg/day as zinc sulfate (Maita et al. 1981). However, decreases in hematocrit and lymphocytes were 

observed in the offspring of mink females that ingested a time-weighted-average dose of 20.8 mg 

zinc/kg/day as zinc sulfate for 10 weeks prior to conception and throughout gestation and lactation 

(Bleavins et al. 1983) indicating that very young mink may be more sensitive to the hematologic effects 

of zinc than adults. An increased number of weanling rats had low levels of ceruloplasmin, a copper 

serum protein, after administration of zinc sulfate for 6 weeks (L'Abbe and Fischer 1984a). 

Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans after 

oral exposure to zinc. 

Rib biopsies revealed no treatment-related effects in dogs given 4 mg zinc/kg/day as zinc oxide in the diet 

for 9 months (Anderson and Danylchuk 1979). No lesions of the bones were observed in rats exposed to 

565 mg zinc/kg/day as zinc sulfate during 13 weeks of exposure in the food (Maita et al. 1981). 

Hepatic Effects. Ingestion of 3.5 mg/kg/day zinc sulfate for 18 weeks by 13 patients being treated for 

chronic venous leg ulcers was reported to have no effect on the results of liver function tests (Hallbook 

and Lanner 1972). However, the type of liver function tests was not specified and results were not 

presented to support this conclusion. 

Several reports described changes in the serum lipid profile of humans exposed to zinc sulfate or 

gluconate for 3–12 months; however, the results are mixed. Ingestion of 2.3–4.3 mg zinc/kg/day for 5– 

6 weeks (Chandra 1984; Hooper et al. 1980) or 0.71 mg zinc/kg/day for 12 weeks (Black et al. 1988) 

reduced levels of high-density lipoprotein (HDL) cholesterol. In the study by Chandra (1984), a slight 

increase in low-density lipoprotein (LDL) cholesterol was observed in subjects who served as their own 

controls; measurements were taken prior to zinc supplementation and after a 10-week postexposure 

period. Serum cholesterol, triglyceride, and LDL cholesterol levels were not affected by zinc 

supplementation in the study by Black et al. (1988). However, in another study, zinc supplements 

depressed HDL cholesterol levels and raised LDL cholesterol levels in elderly subjects (>60 years of 

age), especially in those who exercised. This study was not well controlled, and the wide variation in 

doses of the supplemented group prevented the determination of a LOAEL (Goodwin et al. 1985). Young 

women with a total daily intake of 1.6 mg zinc/kg/day in a 2-month study had a transient decrease in HDL 

cholesterol (Freeland-Graves et al. 1980). In a double-blind crossover study of young men and women 

receiving 2.0 (men) or 2.4 (women) mg zinc/kg/day for 6 weeks, total HDL cholesterol was not affected, 

and LDL cholesterol was significantly decreased in the women (Samman and Roberts 1988). No effect 
ZINC 61 

3. HEALTH EFFECTS 

on HDL cholesterol was seen in elderly men and women (60–89 years old) with a total daily intake 

(dietary zinc plus a zinc acetate supplement) of 1.5 mg/kg/day for 3 months (Bogden et al. 1988), but the 

subjects also received copper supplements (about 0.03 mg/kg). Bonham et al. (2003b) reported that 

supplementation of male subjects with 0.43 mg zinc/kg/day (30 mg/day, assuming a reference body 

weight of 70 kg), as zinc glycine chelate, had no effect on LDL, HDL, or triglyceride levels. Another 

study (Hale et al. 1988) reported no differences in triglycerides and cholesterol levels in subjects 

(≥68 years old) given zinc supplements of up to 2 mg/kg/day for an average of 8 years. 

No histopathology or changes in serum enzyme levels (serum glutamic oxaloacetic transaminase, serum 

glutamic pyruvic transaminase, or alkaline phosphatase) were observed in rats receiving 191 mg 

zinc/kg/day as zinc acetate (Llobet et al. 1988a). Similarly, no histopathology was observed in rats 

administered 98.3 mg zinc/kg/day as zinc oxide, but an insufficient number of animals were tested 

(Drinker et al. 1927c). Sheep fed time-weighted-average doses of 19 mg zinc/kg/day as zinc oxide for 

49–72 days developed hepatic effects, including necrotic hepatocytes and large quantities of hemosiderin 

in Kupffer cells (Allen et al. 1983). Because sheep are ruminants, it is not known if they are a good 

model for predicting human toxicity. No histological damage was observed in adult or young mink fed 

327 or 324 mg zinc/kg/day, respectively, as zinc sulfate for 144 days (Aulerich et al. 1991). 

Decreased hexobarbital sleeping times were reported by Kadiiska et al. (1985) in rats receiving 40 mg 

zinc/kg/day as zinc sulfate. This physiological response suggested an induction of microsomal enzymes. 

Increases in serum cholesterol levels were observed in two studies where rats were fed either 2.8 or 10 mg 

zinc/kg/day as zinc acetate for 2–7 months (Katya-Katya et al. 1984; Klevay and Hyg 1973). Other 

studies have shown no effect on total cholesterol, HDL cholesterol, or serum triglyceride levels in rats 

ingesting 3 or 25 mg zinc/kg/day of unspecified zinc compounds (Fischer et al. 1980; Woo et al. 1983). 

Renal Effects. Thirteen patients treated with zinc sulfate at 3.5 mg zinc/kg/day for 18 weeks for 

chronic venous leg ulcers had normal urinalyses (Hallbook and Lanner 1972). However, neither the 

specific parameters measured for the urinalysis nor the results were presented to support this conclusion. 

Furthermore, urinalysis may not be a sensitive indicator of renal function. 

A number of intermediate-duration studies have demonstrated renal effects in animals exposed to zinc 

oxide, zinc sulfate, and zinc acetate. Zinc sulfate caused an increase in the absolute and relative kidney 

weights and regressive kidney lesions (not specified) in female mice that consumed 1,110 mg zinc/kg/day 
ZINC 62 

3. HEALTH EFFECTS 

in the diet for 13 weeks, but no effects occurred in rats that consumed 565 mg zinc/kg/day or in mice that 

consumed 104 mg zinc/kg/day under similar conditions (Maita et al. 1981). Severe diffuse nephrosis was 

observed in ferrets exposed to 195 mg zinc/kg/day as zinc oxide in the diet (Straube et al. 1980). In rats 

exposed to 191 mg zinc/kg/day as zinc acetate for 3 months, epithelial cell damage in the glomerulus and 

proximal convoluted tubules and increased plasma creatinine and urea levels were observed (Llobet et al. 

1988a). The NOAEL for the effects on creatinine and urea was 95 mg zinc/kg/day. It is unclear whether 

the microscopic changes were observed at lower doses. No histopathological changes in the kidneys were 

observed in three rats that drank water containing 98.3 mg zinc/kg/day as zinc oxide for 35–36 weeks 

(Drinker et al. 1927c); however, interpretation of the results of this study is severely limited by the small 

number of rats used. Renal tubular dilation, with proteinaceous casts and hemosiderin deposits, was 

observed in the kidneys of sheep that ingested 18 mg zinc/kg/day as zinc oxide for 49–72 days (Allen et 

al. 1983). It is not known if sheep are a good model for human toxicity because they are ruminants. No 

renal effects were observed in either adult mink consuming 326.7 mg zinc/kg/day as zinc sulfate or in 

young mink consuming 323.6 mg zinc/kg/day as zinc sulfate for 144 days (Aulerich et al. 1991). Minks 

exposed to 195 mg zinc/kg/day as zinc oxide for 7–97 days in the food developed a diffuse nephrosis, 

though it did not increase with increasing dose (Straube et al. 1980). 

Dermal Effects. No studies were located regarding dermal/ocular effects in humans after oral 

exposure to zinc. 

No dermal effects were seen in adult female minks given a time-weighted dose of 20.8 mg zinc/kg/day as 

zinc sulfate for 10 weeks prior to mating and then throughout gestation and lactation (Bleavins et al. 

1983). However, the offspring of these animals showed graying of the fur around the eyes, ears, jaws, 

and genitals with a concomitant loss of hair and dermatosis in these areas during the weaning period. 

These conditions were reversible upon removal of treatment. 

Endocrine Effects. Only one human exposure study has evaluated endocrine effects of oral zinc 

exposure. Davis et al. (2000; Milne et al. 2001) reported a slight (<10%) decrease in serum T4 levels in 

postmenopausal women exposed to 0.68 mg zinc/kg/day as zinc gluconate; the difference did not attain 

statistical significance, and no changes in free T3 or thyroid stimulating hormone (TSH) levels were 

reported. 

Piao et al. (2003) exposed groups of Wistar rats to 0, 4, or 8 mg zinc/kg as zinc acetate every other day 

for a 14-day period. Levels of T3 were decreased in both groups of exposed rats, relative to controls, but 
ZINC 63 

3. HEALTH EFFECTS 

levels of T4 and TSH were not significantly altered. Zinc exposure resulted in increased levels of serum 

cortisol, which was significant from controls at the 8 mg zinc/kg exposure level. 

Body Weight Effects. No effects on body weight have been reported in humans following oral 

exposure to zinc. However, a 46% decrease in body weight gain was seen in preruminant calves that 

consumed 91 mg zinc/kg/day as zinc oxide for 5 weeks; there was no effect at 64 mg zinc/kg/day (Jenkins 

and Hidiroglou 1991). The relevance of this effect to humans is unclear. Body weights of rabbits 

(Bentley and Grubb 1991), rats (Llobet et al. 1988a), and minks (Aulerich et al. 1991) were unaffected by 

dosing with 174, 191, and 326.7 mg zinc/kg/day, respectively, for 3–12 months. Decreased postpartum 

body weights in F0 animals were observed in rats exposed to 7 mg zinc/kg/day as zinc chloride for 

20 weeks (Khan et al. 2001b). 

3.2.2.3 Immunological and Lymphoreticular Effects 

The highest NOAEL values and all LOAEL values from each reliable study for immunological and 

lymphoreticular effects in each species and duration category are recorded in Table 3-2 and plotted in 

Figure 3-2. 

Zinc plays a role in the normal development and maintenance of the immune system, such as in the 

lymphocyte response to mitogens and as a cofactor for the thymic hormone thymulin (Delafuente 1991; 

Fraker et al. 1986). Oral exposure to zinc at levels much higher than the RDA has impaired immune and 

inflammatory responses. This was observed in in vivo investigations of the immune competence of blood 

components taken from 11 healthy adult men after ingestion of 4.3 mg zinc/kg/day as zinc sulfate for 

6 weeks. The mitogenic response elicited from peripheral blood lymphocytes and the chemotactic and 

phagocytic responses of polymorphonuclear leukocytes were impaired after zinc ingestion. No effects 

were seen on total numbers of lymphocytes or relative numbers of T cells, T cell subsets, or B cells 

(Chandra 1984). The relationship between these observations and decreased levels of immune 

competence that might lead to increased susceptibility to disease is unknown. Zinc supplements 

administered to elderly populations at doses up to 1.5 mg zinc/kg/day (Bogden et al. 1988) or 2.5 mg 

zinc/kg/day (Duchateau et al. 1981) resulted in either no effect or a beneficial effect on immune cell titers 

or delayed cutaneous hypersensitivity responses to specific antigens. A later study (Bonham et al. 2003) 

reported no effects of supplementation of male volunteers with 30 mg zinc/day (0.43 mg zinc/kg/day 

assuming a reference male body weight of 70 kg) as zinc glycine chelate for 14 weeks on levels of 

peripheral blood leucocytes or on the frequency of lymphocyte subsets. 
 

 

ZINC 64 

3. HEALTH EFFECTS 

Decreased lymphocyte activity (incorporation of 3

H-thymidine in response to concanavalin A) was 

reported in mink kits from dams that had ingested a time-weighted-average dose of 20.8 mg zinc/kg/day 

as zinc sulfate for 10 weeks prior to conception and throughout gestation and lactation (Bleavins et al. 

1983). The dose to the kits is unknown. In contrast, no effect was observed on antibody titre 

(immunoglobulin G [IgG] and immunoglobulin M [IgM]) or the mitogenic response of splenic B cells 

isolated from mice fed 76.9 mg zinc/kg/day as zinc sulfate for 4 weeks and challenged with B cell 

antigens either in vivo or in vitro (Schiffer et al. 1991). The in vitro mitogenic response of T cells isolated 

from these mice was increased. There was no effect of the zinc supplement in the plaque forming cell 

assay or on cytotoxic T killer cell activity in mice exposed to 6.5 mg zinc/kg/day in the diet for 8 weeks 

(Fernandes et al. 1979). In mice exposed in utero to 136 mg zinc/kg/day, with exposure continuing 

postnatally, there were increases in direct plaque-forming activity of spleen cells and in lymphocyte 

proliferation in response to mitogen stimulation (Lastra et al. 1997). 

3.2.2.4 Neurological Effects 

Zinc appears to be necessary for normal brain function (Sandstead et al. 1983), but excess zinc is toxic. A 

16-year-old boy who ingested ≈86 mg zinc/kg/day of metallic zinc over a 2-day period in an attempt to 

promote wound healing, developed signs and symptoms of lethargy, light-headedness, staggering, and 

difficulty in writing clearly (Murphy 1970). Lethargy was also observed in a 2-year-old child who 

ingested a zinc chloride solution (≈1,000 mg zinc/kg) (Potter 1981). It is not known whether these 

observations represent direct effects on the nervous system. 

Very limited data were located regarding neurological effects in animals. Minor neuron degeneration and 

proliferation of oligodendroglia occurred in rats dosed with 487 mg zinc/kg/day as zinc oxide for 10 days 

(Kozik et al. 1980). Rats receiving 472 mg zinc/kg/day for 10 days had increased levels of secretory 

material in the neurosecretory nuclei of the hypothalamus (Kozik et al. 1981). Mice exposed postnatally 

to 0.5 mg zinc/kg/day as zinc acetate for 28 days showed no changes in memory formation, but showed a 

gradual decrease in learning extinction throughout the study (de Oliveira et al. 2001). 
 

 

ZINC 65 

3. HEALTH EFFECTS 

3.2.2.5 Reproductive Effects 

The highest NOAEL values and all LOAEL values from each reliable study for reproductive effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Pregnant women receiving capsules containing 0.3 mg zinc/kg/day as zinc sulfate during the last two 

trimesters did not exhibit any reproductive effects (no changes in maternal body weight gain, blood 

pressure, postpartum hemorrhage, or infection) (Mahomed et al. 1989). No other studies were located 

regarding reproductive effects in humans after oral exposure to zinc. 

No measurable effect on gestational length or litter size was observed when female mink ingested a timeweighted average dose of 20.8 mg zinc/kg/day as zinc sulfate (Bleavins et al. 1983). No histological 

alterations in the testes or ovaries were noted in mice fed zinc sulfate (1,110 mg zinc/kg/day) for 

13 weeks (Maita et al. 1981). Male and female rats exposed by gavage to up to 14 mg zinc/kg/day as zinc 

chloride resulted in a nonsignificant decrease in fertility index in all groups that was not related to 

administered dose; in the two highest groups (7 and 14 mg zinc/kg/day), decreases in live pups per litter 

and pup weight at day 21 were also reported (Khan et al. 2001b). Similarly, exposure to up to 8 mg 

zinc/kg/day every other day for 14 days showed no effects on the levels of abnormal sperm in Wistar rats 

(Piao et al. 2003). Male and female rats receiving 50 mg zinc/kg/day as zinc carbonate in the diet were 

reported to reproduce normally for several generations in a poorly documented study by Sutton and 

Nelson (1937). Rats fed 250 mg zinc/kg/day for 14–17 weeks mated successfully but had a higher than 

normal percentage of stillborn pups. A subsequent mating of the parental generation fed 250 mg 

zinc/kg/day for 5 months was unsuccessful. No reproduction occurred in rats fed 500 mg zinc/kg/day for 

5 months (Sutton and Nelson 1937). The frequency of sperm with an altered chromatin structure was 

increased in rats fed 25 mg zinc/kg/day as zinc chloride for 8 weeks (Evenson et al. 1993). Preimplantation loss increased in rats fed diets containing 200 mg zinc/kg/day as zinc sulfate on gestational 

days 0–18 (Pal and Pal 1987). When the rats received 200 mg zinc/kg/day 21 days prior to mating, no 

effects on implantation or other adverse reproductive effects were observed (Pal and Pal 1987). 

Similarly, exposure of up to 372 mg zinc/kg/day in mice prior to and throughout pregnancy did not result 

in changes in reproductive index (Lastra et al. 1997). 
 

 

 

 

ZINC 66 

3. HEALTH EFFECTS 

3.2.2.6 Developmental Effects 

The highest NOAEL values and all LOAEL values from each reliable study for developmental effects in 

each species and duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Zinc is necessary for normal fetal growth and development. Fetal damage may result from zinc 

deficiency. Only one report in the literature suggested adverse developmental effects in humans due to 

exposure to excessive levels of zinc (Kumar 1976). Four women were given zinc supplements of 0.6 mg 

zinc/kg/day as zinc sulfate during the third trimester of pregnancy. Three of the women had premature 

deliveries, and one delivered a stillborn infant. However, the significance of these results cannot be 

determined because very few details were given regarding the study protocol, reproductive histories, and 

the nutritional status of the women. Other human studies have found no developmental effects in the 

newborns of mothers consuming 0.3 mg zinc/kg/day as zinc sulfate (Mahomed et al. 1989) or zinc citrate 

(Simmer et al. 1991) or 0.06 mg zinc/kg/day as zinc aspartate (Kynast and Saling 1986) during the last 

two trimesters. There has been a suggestion that increased serum zinc levels in pregnant women may be 

associated with an increase in neural tube defects (McMichael et al. 1994), but others have failed to 

confirm this association (Hambidge et al. 1993). 

The developmental toxicity of zinc in experimental animals has been evaluated in a number of 

investigations. Exposure to high levels of zinc in the diet prior to and/or during gestation has been 

associated with increased fetal resorptions, reduced fetal weights, altered tissue concentrations of fetal 

iron and copper, and reduced growth in the offspring. 

Administration of zinc in rats at 200 mg zinc/kg/day as zinc oxide in the diet for 21 days prior to mating 

and then throughout gestation resulted in resorption of all fetuses (Schlicker and Cox 1968). Fetal 

resorptions ranged from 4 to 29% when 200 mg zinc/kg/day was administered only during gestation 

(controls had no resorptions). When the dose was reduced to 100 mg zinc/kg/day starting 21 days prior to 

mating, there were no fetal resorptions, malformations, or growth reduction. In contrast, Kinnamon 

(1963) reported no resorptions, no difference in the number of offspring per litter, and no change in 

average wet weight of the fetuses from female rats fed 250 mg zinc/kg/day as zinc carbonate in the diet 

for 53 days before mating and during gestation. The reason for the differences in the results of these 

studies is unknown. No effect on fetal viability, size, or malformations was seen in fetuses from female 

rats fed 25 mg zinc/kg/day as zinc carbonate during gestational days 1–18 (Uriu-Hare et al. 1989). 
ZINC 67 

3. HEALTH EFFECTS 

Administration of 200 mg zinc/kg/day to dams throughout gestation resulted in decreased growth and 

tissue levels of copper and iron in fetal rats (Cox et al. 1969; Schlicker and Cox 1968). In rats, at both 

100 and 200 mg/kg/day during gestational days 1–18, maternal zinc levels increased. However, zinc 

tissue levels in the 22-day-old fetuses were not elevated at 100 mg/kg/day to dams, suggesting that the 

placenta was able to act as a barrier to zinc at the lower dietary level. In contrast, Ketcheson et al. (1969) 

showed that newborn and 14-day-old rats from mothers that had consumed 100 mg/kg/day throughout 

gestation had elevated levels of total zinc and decreased levels of iron. It is unclear whether the longer 

exposure to zinc during gestation or the suckling of newborn rats prior to sacrifice may have accounted 

for these differences. 

Animal studies suggest that exposure to very high levels of dietary zinc is associated with reduced fetal 

weight, alopecia, decreased hematocrit, and copper deficiency in offspring. For example, second 

generation mice exposed to zinc carbonate during gestation and lactation (260 mg/kg/day in the maternal 

diet), and then continued on that diet for 8 weeks, had reduced body weight, alopecia, and signs of copper 

deficiency (e.g., lowered hematocrit and occasional achromotrichia [loss of hair color]) (Mulhern et al. 

1986). Similarly, mink kits from dams that ingested a time-weighted-average dose of 20.8 mg 

zinc/kg/day as zinc sulfate also had alopecia and achromotrichia (Bleavins et al. 1983). It is likely that 

the alopecia resulted from zinc-induced copper deficiency, which is known to cause alopecia in monkeys 

(Obeck 1978). However, no adverse effects were observed in parental mice or mink. No effects on 

reproduction were reported in rats exposed to 50 mg zinc/kg/day as zinc carbonate; however, increased 

stillbirths were observed in rats exposed to 250 mg zinc/kg/day (Sutton and Nelson 1937). 

3.2.2.7 Cancer 

Leitzmann et al. (2003) reported on the occurrence of prostate cancer within a cohort of 46,974 men 

within the United States evaluated between 1986 and 2000. Within the cohort, 2,901 cases of prostate 

cancer were identified, 434 of which were classified as advanced cancer. Zinc supplementation did not 

appear to have an effect on the frequency of developing prostate cancer. However, men within the cohort 

who had taken supplements of ≥100 mg zinc/day had a greater probability of developing advanced 

cancer, if a tumor occurred. 

Other studies evaluating the possible carcinogenic effects of zinc in humans are extremely limited. One 

study reported an association between an excess rate of gastric cancer in the people of North Wales (Great 

Britain) and the high zinc-to-copper ratio (≈30:1) in the soil of household gardens (Stocks and Davies 
ZINC 68 

3. HEALTH EFFECTS 

1964). However, the inference that this excess in gastric cancer is causally associated with soil levels of 

zinc and copper is not consistent with another study. In a survey of cancer registry data (1954–1978) in 

Shipham, Somerset (Great Britain), an area that also has a high soil zinc-to-copper ratio (≈17:1), the 

gastric cancer incidence rate was significantly lower than the regional rate (Philipp et al. 1982). It is 

probable that other factors, not considered by Stocks and Davies (1964), are associated with or 

coincidental to the high soil zinc-to-copper ratio confounded the results. 

The carcinogenicity of zinc in experimental animals following oral exposure was evaluated by Walters 

and Roe (1965). The incidence of tumors was not increased in mice exposed to 951 mg zinc/kg/day as 

zinc sulfate in drinking water for 1 year compared to controls. However, important details regarding the 

study protocol were lacking including the age and sex of the mice, the number of mice at the beginning of 

the study, the purity of the test material, and a complete list of the organs and tissues examined at 

necropsy. The control mice developed intercurrent disease (ectromelia), which resulted in a number of 

deaths; supplementary control mice were added to the study, but they were not concurrent controls. The 

number of animals in treated and control groups surviving at 1 year (study termination) was small (22– 

28 mice/group). The exposure period (1 year) was less than the standard bioassay period (18–24 months). 

There were no data in the study (e.g., survival or body weight data) to indicate that a maximum tolerated 

dose was achieved. These limitations reduce the sensitivity of the study by Walters and Roe (1965) to 

detect a carcinogenic response. 

Halme (1961) exposed tumor-resistant and tumor-susceptible strains of mice to zinc in drinking water. In 

a 5-generation study, groups of tumor-resistant mice (strain not specified) received 0, 10, 20, 50, 100, or 

200 mg zinc/L as zinc chloride in the drinking water. The spontaneous tumor frequency for this strain of 

mice was 0.0004%. The tumor frequencies were reported as: F0=0.8%; F1=3.5%; F1 and F2=7.6%; and 

F3 and F4=25.7%. The majority of the tumors were seen in the 10- and 20-mg zinc dose groups. No 

individual or group tumor incidence data were reported, and a discussion of statistical analysis was not 

included. In the tumor-susceptible mice, strains C3H and A/Sn received 10–29 mg zinc/L in their 

drinking water for 2 years; 33/76 tumors were observed in the C3H strain (31 in females) and 

24/74 tumors were observed in the A/Sn strain (20 in females). Most of the tumors were reported to be 

adenocarcinomas, but the tissues in which they occurred were not reported. The numbers of specific 

tumor types were not reported. The overall tumor frequencies (43.4% for C3H and 32.4% for A/Sn) were 

higher than the spontaneous frequency (15% for each strain), but statistical analyses were not reported. 
ZINC 69 

3. HEALTH EFFECTS 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to zinc. 

3.2.3.2 Systemic Effects 

The dermal toxicity of zinc compounds, particularly effects on the skin, can vary widely with the 

chemical form of zinc. For example, zinc chloride is caustic and can cause severe irritation at levels 

<0.5 mg/cm2 (Lansdown 1991), while zinc sulfate is irritating but not as caustic as zinc chloride, and zinc 

oxide does not appear to be a dermal irritant. Zinc oxide is commonly used in topical applications 

(including sunblock products) without adverse effects. 

Zinc has been reported to promote the healing of burns and wounds when topically applied as zinc oxide 

or calamine lotion (Gordon et al. 1981). The mechanism by which this occurs was not discussed by the 

authors. Zinc oxide contained in an occlusive zinc tape dressing reduced the inflammatory reactions in 

the granulation tissue of wounded rats (Wetter et al. 1986). The authors speculated that zinc acted either 

by a continuous release of zinc ions or by modifying components involved in the tape's adhesive 

properties. 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, musculoskeletal, hepatic, 

renal, or other systemic effects in humans or animals after dermal exposure to zinc. The systemic effects 

observed after dermal exposure are discussed below. The NOAEL values and all LOAEL values from 

each reliable study for dermal effects in each species and duration category are recorded in Table 3-3. 

Hematological Effects. A worker who had been employed making up zinc chloride solutions 

(concentrations not specified) with his hands was found to have microcytic anemia and decreased 

numbers of platelets (DuBray 1937). 

No studies were located regarding hematological effects in animals after dermal exposure to zinc. 
1

mg/cm2

10

mg/cm2

11

mg/cm2

12

mg/cm2

13

mg/cm2

6

mg/cm2

7

mg/cm2

8

mg/cm2

Table 3-3 Levels of Significant Exposure to Zinc - Dermal 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Route) 

ACUTE EXPOSURE 

Systemic 

Human 48 hr 

System 

Dermal 

NOAEL 

2.9 

mg/cm2 

Less Serious 

LOAEL 

Serious 

Reference Chemical Form 

Agren 1990 Zinc Oxide 

Mouse 5 d Dermal 0.48 M 

mg/cm2 

(severe skin irritation) Lansdown 1991 

Zinc chloride 

Mouse 5 d Dermal 0.4 M 

mg/cm2 

(Slight skin irritancy) Lansdown 1991 Zinc sulfate 

Mouse 5 d Dermal 16 M 

mg/cm2 

Lansdown 1991 Zinc Oxide 

Mouse 5 d Dermal 7.2 M 

mg/cm2 

(moderate skin irritation) Lansdown 1991 

Zinc Acetate 

Gn Pig 5 d Dermal 0.4 M 

mg/cm2 

Lansdown 1991 Zinc sulfate 

Gn Pig 5 d Dermal 0.48 M 

mg/cm2 

(moderate skin irritation) Lansdown 1991 

Zinc chloride 

Gn Pig 5 d Dermal 16 M 

mg/cm2 

Lansdown 1991 Zinc Oxide 
9

mg/cm2

2

mg/cm2

3

mg/cm2

4

mg/cm2

5

mg/cm2

Table 3-3 Levels of Significant Exposure to Zinc - Dermal (continued) 

Exposure/ LOAEL 

Duration/ 

Species Frequency Reference 

(Strain) (Route) System NOAEL Less Serious Serious Chemical Form 

Gn Pig 5 d Dermal 7.2 M 

mg/cm2 

Lansdown 1991 Zinc Acetate 

Rabbit 5 d Dermal 0.4 M 

mg/cm2 

Lansdown 1991 Zinc sulfate 

Rabbit 5 d Dermal 16 M 

mg/cm2 

Lansdown 1991 Zinc Oxide 

Rabbit 5 d Dermal 7.2 M 

mg/cm2 

(slight skin irritation ­open patch test;severe skin irritaiton - occluded patch test) 

Lansdown 1991 Zinc Acetate 

Rabbit 5 d Dermal 0.48 M 

mg/cm2 

(severe skin irritation) Lansdown 1991 

Zinc chloride 

d = day(s); Derm = dermal; Gn pig = Guinea pig; hr = hour(s); LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level 
ZINC 72 

3. HEALTH EFFECTS 

Dermal Effects. No signs of dermal irritation were observed in humans after a 25% zinc oxide patch 

(2.9 mg/cm2

) was placed on the skin for 48 hours (Agren 1990). However, 14 out of 17 men who were 

employed in the bagging or packing of zinc oxide and whose skin was frequently covered with zinc oxide 

dust reported having experienced zinc oxide pox at least once (Turner 1921). The pox appeared as itchy 

papular-pustular eruptions in the pubic region, scrotum, inner surface of the thigh, and occasionally on the 

axilla and inner surface of the arms. The study author suggested that these lesions were due to clogging 

of glands by dust, perspiration, and bacteria when skin surfaces coated with these substances were rubbed 

together. In contrast, a case study of 24 workers exposed to dusts of either zinc oxide, zinc sulfide, or 

metallic zinc revealed only 1 worker with papular pustular lesions on the axilla and inner thighs 

(Batchelor et al. 1926). The difference in the results was attributed to differences in the personal hygiene 

of the workers in the two studies. 

The dermal irritancy of several zinc compounds was compared in mice, rabbits, and guinea pigs 

(Lansdown 1991). Of the six zinc compounds tested, zinc chloride had the greatest irritancy potential 

(severe irritation at 0.48 mg/cm2

), followed by zinc acetate (moderate irritation at 7.2 mg/cm2) and zinc 

sulfate (slight irritation at 0.48 mg/cm2

); no signs of irritation were observed following exposure to zinc 

oxide. Although zinc chloride is clearly the most irritating, the relative irritancy of zinc sulfate and zinc 

acetate was not determined because only one dose was tested and a different dose was used for each 

compound. The severe skin irritancy observed following application of zinc chloride was characterized 

by parakeratosis, hyperkeratosis, inflammatory changes in the epidermis and superficial dermis, and 

acanthosis of the follicular epithelia (Lansdown 1991). 

Ocular Effects. In a case report, accidental splashing of a soldering paste containing 30% zinc 

chloride into the eye of a plumber produced an immediate reduction in visual acuity, hyperemia, 

hemorrhaging, conjunctival swelling, corneal opacity, bullous keratopathy, and spotting of the lens 

(Houle and Grant 1973). Most symptoms disappeared after 6 weeks, but residual lens opacities persisted 

for over a year after the exposure. Reddened conjunctivae and lacrimation were observed in 34 persons 

who were exposed to extremely high concentrations of zinc chloride smoke when several smoke 

generators exploded in a tunnel during World War II (Evans 1945). Two of the exposed persons had 

corneal burns and four had small vesicular burns on the forehead or wrist. Zinc chloride was the major 

component of the smoke. However, other components such as zinc oxide, hexachloroethane, calcium 

silicide, the igniter, or the heat of the explosion may have contributed to the injuries that were observed. 
ZINC 73 

3. HEALTH EFFECTS 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to zinc: 

3.2.3.3 Immunological and Lymphoreticular Effects 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.3 GENOTOXICITY 

Genotoxicity studies conducted in a variety of test systems have failed to provide evidence for 

mutagenicity of zinc. However, there are indications of weak clastogenic effects following zinc exposure. 

Chromosome aberrations were observed in the lymphocytes of 24 workers in a zinc smelting plant 

(Bauchinger et al. 1976). However, the workers had increased blood levels of lead and cadmium, and the 

clastogenic effect was attributed to cadmium exposure. 

Results of in vivo studies are shown in Table 3-4. A dominant lethal study in mice failed to show a 

mutagenic potential for zinc. However, chromosomal aberrations have been observed in bone marrow 

cells following in vivo exposure to zinc (Vilkina et al. 1978). This effect was observed in rats exposed to 

14.8 mg zinc/kg/day as zinc chlorate in drinking water (Kowalska-Wochna et al. 1988), mice given 

intraperitoneal injections of 3.6 mg zinc/kg/day as zinc chloride (Gupta et al. 1991), and mice exposed to 

zinc oxide by inhalation (Voroshilin et al. 1978). Chromosomal aberrations caused by zinc were 

observed in the bone marrow cells of mice maintained on a low-calcium diet (Deknudt and Gerber 1979). 

Calcium may be displaced by zinc in calcium-depleted conditions, leading to chromosome breaks and/or 

interfering in the repair process (Deknudt and Gerber 1979). In vivo exposure to zinc may also result in 

single-strand breaks, as measured by the Comet assay in mice (Banu et al. 2001). An increased incidence 

of sister chromatid exchange was observed in bone marrow cells of rats exposed to 17.5 mg zinc/kg/day 

as zinc chlorate in drinking water (Kowalska-Wochna et al. 1988). 
 

 

 

 

 

 

ZINC 74 

3. HEALTH EFFECTS 

Table 3-4. Genotoxicity of Zinc In Vivo 

Species (test system) End point Results Reference 

Mammalian systems: 

Mouse Dominant lethal – Vilkina et al. 1978 

Mouse Single-strand DNA 

breaks 

+ Banu et al. 2001 

Mouse bone marrow Chromosomal + Deknudt and Gerber 

aberrations 1979 

Mouse Chromosomal + Voroshilin et al. 1978 

aberrations 

Rat bone marrow Chromosomal + Kowalska-Wochna 

aberrations 1988 

Mouse bone marrow Chromosomal 

aberrations 

+ Gupta et al. 1991 

Rat bone marrow Sister chromatid + Kowalska-Wochna 

exchange 1988 

Mouse Micronucleus – Gocke et al. 1981 

Drosophilia Sex-linked recessive 

lethal 

– Gocke et al. 1981 

– = negative result; + = positive result; DNA = deoxyribonucleic acid 
 

 

ZINC 75 

3. HEALTH EFFECTS 

Results of in vitro studies are shown in Table 3-5. Exposure to zinc as zinc sulfate or zinc chloride does 

not increase mutation frequencies in bacterial or mammalian cell culture test systems (Amacher and 

Paillet 1980; Gocke et al. 1981; Marzin and Vo Phi 1985; Nishioka 1975; Thompson et al. 1989; Venitt 

and Levy 1974; Wong 1988). Similarly, there was no convincing evidence of a clastogenic effect in 

human lymphocytes exposed to 0.0003–0.00003 M zinc chloride (Deknudt and Deminatti 1978). 

3.4 TOXICOKINETICS 

There is limited information on the toxicokinetic properties of zinc following inhalation or dermal 

exposure. Increased zinc levels in the blood and urine of humans and in the tissue of animals after 

inhalation and dermal exposure to zinc, respectively, indicate that zinc is absorbed by these routes. The 

toxicokinetic properties of ingested zinc have been extensively studied. The absorption of zinc from the 

gastrointestinal tract is homeostatically regulated; under normal physiological conditions, 20–30% of 

ingested zinc is absorbed. Zinc uptake from the intestinal lumen involves passive diffusion and a carriermediated process. A number of factors influence the absorption of zinc; these include the solubility of the 

zinc compound as well as inhibitors, such as calcium, phosphorus, and dietary fiber and phytates 

(components of dietary fiber that may coprecipitate with zinc in the intestines), and enhancers, such as 

amino acids, picolinic acid, and prostaglandin E2. Once absorbed, zinc is widely distributed throughout 

the body. Zinc content is highest in muscle, bone, gastrointestinal tract, kidney, brain, skin, lung, heart, 

and pancreas. In plasma, two-thirds of the zinc is bound to albumin which represents the metabolically 

active pool of zinc. This pool of plasma zinc is frequently referred to as loosely bound zinc because 

albumin has the ability to give up bound zinc to tissues. Zinc is excreted in both urine and feces. 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Quantitative studies regarding absorption of zinc and zinc compounds after inhalation exposure in 

humans are limited. The absorption of inhaled zinc depends on the particle size and solubility, both of 

which may greatly influence the deposition and clearance of zinc aerosols, particularly insoluble zinc 

oxide (a review of the role of particle size in the deposition of particles is found in Witschi and Last 

2001). Elevated levels of zinc have been found in the blood and urine of workers exposed to zinc oxide 

fumes (Hamdi 1969). 
 

 

 

ZINC 76 

3. HEALTH EFFECTS 

Table 3-5. Genotoxicity of Zinc In Vitro 

Results 

Species (test system) End point 

With 

activation 

Without 

activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium 

(TA102) 

Gene mutation Not tested – Marzin and Vo Phi 

1985 

S. typhimurium (TA98, 

TA102, TA1535, TA1537) 

Gene mutation – (S9) – Wong et al. 1988 

S. typhimurium (TA1538, 

TA98, TA100, TA1537) 

Gene mutation – (S9) – Thompson et al. 

1989 

S. typhimurium (TA1535, 

TA1537, TA1538, TA98, 

TA100) 

Gene mutation – (S9) – Gocke et al. 1981 

Escherichia coli Gene mutation Not tested – Nishioka 1975 

E. coli Gene mutation Not tested – Venitt and Levy 

1974 

Mammalian cells: 

Mouse lymphoma Gene mutation Not tested – Amacher and 

Paillet 1980 

Mouse lymphoma Gene mutation + (S9) + Thompson et al. 

1989 

Human lymphocytes Chromosomal 

aberrations 

Not tested + Deknudt and 

Deminatti 1978 

Chinese hamster ovary cells Chromosomal 

aberrations 

+ (S9) + Thompson et al. 

1989 

– = negative result; + = positive result 
ZINC 77 

3. HEALTH EFFECTS 

The rates or percentages of absorption of inhaled zinc in animals are not available; however, studies 

provide data on zinc retention in the lungs. Zinc retention values were 19.8, 11.5, and 4.7% in the lungs 

of guinea pigs, rats, and rabbits, respectively, after inhalation exposure (nose-only) to 3.5–9.1 mg 

zinc/m3 as zinc oxide aerosol for 2–3 hours (Gordon et al. 1992). The aerosol had a mass median 

diameter of 0.17 μm. The retention of zinc in lungs was dose related in male Wistar rats administered a 

single intratracheal instillation of 0.07–3.7 mg zinc/m3 as zinc oxide (Hirano et al. 1989). A half-life of 

14 hours was calculated. 

The absorption of zinc oxide fumes lead to increased levels of zinc measured in the liver, kidney, and 

pancreas of cats exposed to zinc oxide fumes for durations ranging from 15 minutes to 3.25 hours 

(Drinker and Drinker 1928). The usefulness of the study is limited because reporting was inadequate and 

particle size of the zinc oxide aerosol was not determined. Some inhaled particles of zinc oxide are 

subject to ciliary clearance and swallowing. Thus, a portion of the inhaled zinc may ultimately be 

absorbed from the gastrointestinal tract. 

3.4.1.2 Oral Exposure 

Several studies have measured oral absorption rates of zinc in humans. Absorption ranged from 8 to 81% 

following short-term exposures to zinc supplements in the diet; differences in absorption are probably due 

to the type of diet (amount of zinc ingested, amount and kind of food eaten) (Aamodt et al. 1983; Hunt et 

al. 1991; Istfan et al. 1983; Reinhold et al. 1991; Sandstrom and Abrahamson 1989; Sandstrom and 

Cederblad 1980; Sandstrom and Sandberg 1992). For example, dietary protein facilitates zinc absorption; 

fractional zinc absorption ranged from 8% for low-protein rolls to 26% for high-protein rolls 3 days after 

individuals ingested 0.05 mg zinc/kg (Hunt et al. 1991). 

Absorption of labeled zinc was 40.0–48.4% in male Wistar rats fed a diet containing 0.81 mg zinc/kg as 

zinc chloride or zinc carbonate (Galvez-Morros et al. 1992). Fractional absorption in immature organisms 

generally exceeds that in adults. In growing rats, on the basis of indirect calculation from isotope 

experiments, Weigand and Kirchgessner (1992) suggested surprisingly high absorption values of as much 

as 94.7%. It is likely that all these results were influenced by isotope exchange and do not provide 

estimates of net absorption. 

The body's natural homeostatic mechanisms control zinc absorption from the gastrointestinal tract 

(Davies 1980). Persons with adequate nutritional levels of zinc absorb approximately 20–30% of all 
 

 

ZINC 78 

3. HEALTH EFFECTS 

ingested zinc. Those who are zinc-deficient absorb greater proportions of administered zinc (Johnson et 

al. 1988; Spencer et al. 1985). 

Absorption of zinc occurs from all segments of the intestine, although the largest proportion of zinc 

absorption occurs from the duodenum (Methfessel and Spencer 1973). The zinc absorption process 

includes both passive diffusion and a carrier-mediated process (Tacnet et al. 1990). The intestinal 

absorption of zinc appears to be a saturable carrier-mediated process at low zinc dose levels involving a 

cysteine-rich intestinal protein (CRIP) (Davies 1980; Gunshin et al. 1991; Hempe and Cousins 1992; 

Sturniolo et al. 1991). This protein binds zinc entering the intestinal cells from the lumen (Hempe and 

Cousins 1991). CRIP has a limited binding capacity for zinc and becomes saturated when zinc 

concentration in the intestine is high. Metallothionein, a metal-binding protein, may contribute to zinc 

homeostasis at higher zinc absorption. Like several other metals, zinc can induce metallothionein 

production in intestinal mucosal cells (Richards and Cousins 1975). Zinc binds to metallothionein, which 

remains in the mucosal cells lining the gastrointestinal tract, and the bound metal is excreted from the 

body upon sloughing off of these cells. Although the affinity of zinc for metallothionein is relatively low, 

the protein may serve to prevent absorption of excess zinc in the body (Foulkes and McMullen 1987). 

Absorption of zinc in rats is increased when metallothionein levels are lower (Flanagan et al. 1983). It is 

hypothesized that zinc entering luminal cells is associated with CRIP, and a small amount is bound to 

metallothionein; however, as the luminal zinc concentration increases, the proportion of cytosolic zinc 

associated with CRIP is decreased with a concomitant increase in zinc binding to metallothionein (Hempe 

and Cousins 1992). Further details on the influence of CRIP and metallothionein on zinc absorption are 

provided in Section 3.5, Mechanisms of Action. 

Phytate and high phosphorus intakes in animals decrease zinc absorption. In humans, dairy products that 

contain both calcium and phosphorus decrease zinc absorption and plasma zinc concentration (Pecoud et 

al. 1975). Zinc binds to phosphate which results in coprecipitation of zinc with calcium phosphate in the 

intestines (Nelson et al. 1985). Dietary phytate also reduces zinc absorption. The addition of 400 μmol 

phytate to the diet decreased zinc absorption from 43.3±17.9% in females fed bread containing 0.02 mg 

zinc/kg (zinc-65 isotope) to 14.3±3.2% (Sandstrom and Sandberg 1992). Rats given diets supplemented 

with radiolabeled zinc and phytate excreted significantly more zinc in the feces than rats given diets 

supplemented with radiolabeled zinc but without phytate (Davies and Nightingale 1975). The study 

authors suggested that the decrease in absorption was due to the formation of zinc-phytate complexes in 

the intestines. Phytate also reduced reabsorption of zinc secreted into the gastrointestinal tract of humans 

(Sandstrom and Sandberg 1992). 
ZINC 79 

3. HEALTH EFFECTS 

Endogenous substances, such as amino acids, can influence the absorption of zinc. Complexing of zinc 

with amino acids generally enhances its absorption in all segments of the intestine (Wapnir and Stiel 

1986). Although neither zinc nor the amino acid proline are readily absorbed in the colon, complexing of 

zinc with proline during an in vivo intestinal perfusion in rats resulted in increased zinc absorption. 

Acrodermatitis enteropathica is a metabolic disorder that results in the malabsorption of zinc. However, 

when patients afflicted with this disorder were treated with human milk, zinc absorption was enhanced 

(Lombeck et al. 1975). It was reported by Evans (1980) that patients with acrodermatitis enteropathica 

have an impaired tryptophan metabolic pathway. Picolinic acid, a chief metabolite of tryptophan, is also 

a constituent of human milk. Picolinic acid is secreted by the pancreas into the intestinal lumen. A study 

by Boosalis et al. (1983) demonstrated that patients with pancreatic insufficiency had difficulty absorbing 

zinc administered as zinc sulfate. However, when these pancreatic-insufficient patients were given zinc 

as zinc picolinate, the extent of zinc absorption was similar to that of healthy controls. Zinc absorption 

may depend on the bioavailability of picolinic acid. Such a mandatory role of picolinic acid in absorption 

has not been confirmed (Bonewitz et al. 1982). 

The addition of prostaglandin E2 (PGE2) to the mucosal media of everted jejunal sacs from rats 

significantly increased zinc transport (Song and Adham 1979). In contrast, similar addition of 

prostaglandin F2 (PGF2) significantly decreased zinc transport. Addition of PGF2 to the serosal side of the 

jejunal sacs increased the transport of zinc to the mucosal side; PGE2 decreased the serosal to mucosal 

transport of zinc. The mechanism by which prostaglandins regulate zinc transport has not been 

established (Song et al. 1992). The limitation of the in vitro study is the absence of vascular perfusion 

and consequent trapping of metals in the submucosal tissue. Hence, studies of absorption of heavy 

metals, including zinc, in everted sacs have limited physiological relevance (Foulkes 1984) but may 

provide information useful for the design of future in vivo experiments. 

The presence of other trace metals (e.g., mercury, cadmium, copper) may also diminish zinc transport. 

Section 3.9 provides detailed information on the interaction of zinc with other metals. 

3.4.1.3 Dermal Exposure 

Dermal absorption of zinc occurs, but its mechanism is not clearly defined. Studies are very limited 

regarding the absorption of zinc through the skin. Historically, zinc oxide has been used clinically to 
 

 

 

ZINC 80 

3. HEALTH EFFECTS 

promote the healing of burns and wounds (Gordon et al. 1981). Absorption has been observed in burn 

patients treated with gauze dressings containing zinc oxide (Hallmans 1977). The pH of the skin, the 

amount of zinc applied, and the vehicle administered with zinc all affect the absorption of zinc (Agren 

1990, 1991). 

Zinc chloride was also absorbed through the intact skin of the rat (Keen and Hurley 1977). Absorption of 

zinc sulfate was greater than zinc oxide following 4–48-hour dermal application to open wounds in 

Sprague-Dawley rats (Agren et al. 1991). About 12% of zinc oxide (0.25 mg zinc/cm2

) from the dressing 

reached the wound while 65% of zinc sulfate (0.066 mg zinc/cm2

) reached the wound. The data suggest 

that zinc oxide applied to wounds resulted in sustained delivery of zinc ions causing constant woundtissue zinc levels. In contrast, zinc sulfate, being more water soluble than zinc oxide, is rapidly 

transferred into the blood and, therefore, caused decreased wound-tissue zinc levels (Agren et al. 1991). 

3.4.2 Distribution 

Zinc is one of the most abundant trace metals in humans. It is found normally in all tissues and tissue 

fluids and is a cofactor in over 300 enzyme systems. Together, muscle and bone contain approximately 

90% of the total amount of zinc in the body (≈60 and 30%, respectively) (Wastney et al. 1986). Organs 

containing sizable concentrations of zinc are the liver, gastrointestinal tract, kidney, skin, lung, brain, 

heart, and pancreas (Bentley and Grubb 1991; Drinker and Drinker 1928; He et al. 1991; Llobet et al. 

1988a). High concentrations of zinc were also detected in the prostate (Forssen 1972), retina, and sperm 

(Bentley and Grubb 1991). Zinc levels may vary considerably from one individual to another (Forssen 

1972). 

To some degree, the distribution of zinc in some tissues appears to be regulated by age (Schroeder et al. 

1967). Zinc concentrations increase in the liver, pancreas, and prostate and decrease in the uterus and 

aorta with age. Levels in the kidneys and heart peak at approximately 40–50 years of age and then 

decline. 

Zinc is present in blood plasma, erythrocytes, leukocytes, and platelets, but is chiefly localized within 

erythrocytes (of which 87% is in carbonic anhydrase, the major binding site) (Ohno et al. 1985). Zinc 

deficiency has been demonstrated to decrease the ability of erythrocytes to resist hemolysis in vitro. This 

finding suggests that zinc stabilizes the erythrocyte membrane. In plasma, two-thirds of the zinc is bound 

to albumin; the remainder is bound primarily to α2-macroglobulin (Bentley and Grubb 1991; Giroux et al. 
 

 

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1976; Wastney et al. 1986). It appears that the limited number of binding sites for zinc in plasma albumin 

and macroglobulin regulates the amount of zinc retained by the body (Andermann and Dietz 1982). 

Albumin-bound zinc has been correlated with plasma zinc levels, whereas α2-macroglobulin shows no 

correlation with plasma zinc levels. 

Hormones, such as the adrenocorticotrophic hormone (ACTH), appear to regulate the concentration of 

zinc in the liver. ACTH, secreted by the anterior pituitary gland, stimulates the secretion of glucocorticoids. Glucocorticoids, or hormones with glucocorticoid activity, have been shown in vitro to 

stimulate the net zinc uptake in cultured liver cells and at the same time activate the gene that regulates 

metallothionein synthesis (Failla and Cousins 1978). However, there are no in vivo data to support these 

in vitro findings. Metallothionein in the cells of the intestinal mucosa binds zinc, thus regulating its 

release into the blood. 

The transfer of zinc across perfused placentas is slow; only 3% of maternal zinc reached the fetal 

compartment in 2 hours (Beer et al. 1992). The in vitro transfer of zinc between mother and fetus is 

bidirectional, with binding in the placenta (Beer et al. 1992). It is proposed that zinc uptake in the 

placenta involves a potassium/zinc transport system (Aslam and McArdle 1992). Newborns may also be 

exposed to zinc from their mothers by milk transfer of zinc during lactation (Rossowska and Nakamoto 

1992). 

3.4.2.1 Inhalation Exposure 

No studies were located regarding distribution in humans after inhalation exposure to zinc. However, 

occupational studies provided indirect evidence that zinc may distribute to tissues to produce systemic 

effects (Brown 1988; Drinker et al. 1927a; Malo et al. 1990; McCord et al. 1926; Rohrs 1957; Sturgis et 

al. 1927). 

Zinc levels in the lungs of cats peaked immediately after acute exposure to 12–61 mg zinc/kg/day as zinc 

oxide for approximately 3 hours and remained high for 2 days postexposure, then dropped significantly 

thereafter (Drinker and Drinker 1928). Levels in pancreas, liver, and kidneys increased slowly. 
 

 

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3.4.2.2 Oral Exposure 

A single oral dose of 0.7 mg zinc/kg as zinc sulfate given to 11 individuals resulted in peak zinc levels in 

the plasma at 2–3 hours (Statter et al. 1988; Sturniolo et al. 1991). Similarly, Neve et al. (1991) reported 

peak serum zinc concentration at 2.3 hours with 0.7 mg zinc/kg as zinc sulfate. 

Following feeding of 191 mg zinc/kg/day as zinc acetate to rats for 3 months, increased zinc levels were 

significant in the heart, spleen, kidneys, liver, bone, and blood (Llobet et al. 1988a). The greatest 

increases were in bone (258% of the control value) and blood (520% of the control value). Elevated zinc 

levels were found in the kidneys and liver of mice fed 76.9 mg zinc/kg/day as zinc sulfate (Schiffer et al. 

1991) or 38 mg zinc/kg/day as zinc nitrate (Cooke et al. 1990) for approximately 1 month. The kidneys 

and pancreas had higher zinc levels than the liver and carcass of rats fed diets containing 1.1 mg/kg/day 

for an unspecified duration (Weigand and Kirchgessner 1992). Newborn, young, and adult mice 

receiving a single oral dose of 4.6 mg zinc/kg as zinc chloride generally had the highest levels of zinc in 

the liver, kidneys, lungs, bone, muscle, and carcass 1 day after dosing (He et al. 1991). However, the 

amount of zinc in the lungs, muscle, and femur decreased with age. 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution in humans after dermal exposure to zinc. 

Animal data on the distribution of zinc following dermal exposure are limited. Elevated serum zinc levels 

occurred with the application of zinc oxide or zinc sulfate to skin wounds of Sprague-Dawley rats for 4– 

48 hours (Agren et al. 1991). Serum zinc level peaked at 4 hours in rats treated with zinc sulfate, while 

levels were slightly elevated for 48 hours in rats administered zinc oxide. The differences may be 

attributed to the absorbability of the zinc compounds. 

3.4.3 Metabolism 

Plasma provides a metabolically active transport compartment for zinc (Cousins 1985). Zinc is most 

often complexed to organic ligands (existing in loosely or firmly bound fractions) rather than free in 

solution as metallic ion (Gordon et al. 1981). Zinc is found in diffusible or nondiffusible forms in the 

blood (NAS/NRC 1979). In the diffusible form, approximately two-thirds of plasma zinc is freely 
ZINC 83 

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exchangeable and loosely bound to albumin (Cousins 1985); the zinc-albumin complex has an association 

constant of about 106

 (NAS/NRC 1979). The diffusible form of zinc also includes zinc bound to amino 

acids (primarily histidine and cysteine). The zinc-albumin complex is in equilibrium with the zinc-amino 

acid complex (Henkin 1974). The zinc-amino acid complex can be transported passively across tissue 

membranes to bind to proteins. An important binding protein in the kidney and liver is metallothionein, 

although other tissue-binding proteins may be present. 

In the nondiffusible form, a small amount of circulating zinc is tightly bound to α2-macroglobulin in the 

plasma (Cousins 1985). Zinc is incorporated into and dissociated from α2-macroglobulin only in the liver 

(Henkin 1974). This zinc-protein complex has an association constant of >1,010 (Henkin 1974; 

NAS/NRC 1979). The zinc bound to α2-macroglobulin is not freely exchangeable with other zinc ligands 

(i.e., zinc-albumin and zinc-amino acid complexes) in serum. 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

Information was limited regarding zinc excretion following inhalation exposure in humans. Workers 

exposed to zinc oxide fumes had elevated levels of zinc in the urine (Hamdi 1969) indicating that this is a 

route of excretion. 

No studies were located regarding excretion in animals after inhalation exposure to zinc. 

3.4.4.2 Oral Exposure 

The principal route of excretion of ingested zinc in humans is through the intestine (Davies and 

Nightingale 1975; Reinhold et al. 1991; Wastney et al. 1986). Zinc loss in the body is by secretion via the 

gut, and the remainder occurs in the urine (Wastney et al. 1986). Fecal excretion of zinc increases as 

intake increases (Spencer et al. 1985). Excretion of zinc in the urine also reflects zinc intake (Wastney et 

al. 1986). Minor routes of elimination are saliva secretion, hair loss, and sweat (Greger and Sickles 1979; 

Hambidge et al. 1972; Henkin et al. 1975a; Prasad et al. 1963a; Rivlin 1983). 

There was a linear increase in fecal excretion of zinc in proportion to dietary intake in rats fed 

supplementations of 32 mg zinc/kg/day as zinc oxide for 7–42 days (Ansari et al. 1975) or 50– 
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339 mg/kg/day for 21 days (Ansari et al. 1976). No differences in fecal excretion, total excretion, or 

retention of zinc were found among rats given diets containing different forms of zinc (Seal and Heaton 

1983). Rats receiving 2.65 mg zinc/kg/day as zinc chloride, zinc sulfate, zinc phosphate, or zinc citrate, 

over a 4-day period excreted 87–98% of intake. 

A study by Alexander et al. (1981) demonstrated that zinc is excreted in the bile of rats. Analysis of the 

bile indicated that the zinc is primarily complexed with reduced glutathione. Treatment of these rats with 

diethylmaleate, which conjugates with reduced glutathione and restricts its availability, depressed the 

biliary excretion of zinc. This depression confirms a relationship between zinc and glutathione and 

suggests that zinc is transferred from liver to bile by a glutathione-dependent process. 

Other factors may affect zinc excretion. For example, low dietary intake of zinc or malnutrition can 

increase the urinary excretion of zinc. This release of zinc is a result of tissue breakdown and catabolism 

during starvation; and elevated urinary excretion of zinc may persist after intake levels return to normal 

(Spencer et al. 1976). Administration of histidine or high-protein diet may increase urinary zinc 

excretion; however, a corresponding increase in zinc absorption may maintain zinc balance in the body 

(Henkin et al. 1975b; Hunt et al. 1991). 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after dermal exposure to zinc. 

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. 
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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 parametrization, (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 

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. 
 

Inhaled chem ical E xhaled chem ical 

Lungs 

Liver 

Fat 

S low ly 

perfused 

tissues 

Richly 

perfused 

tissues 

K idney 

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 

V ma x K m 

Ingestion 

GI 

Tract 

Fe ces 

Urine

 C hem icals in air 

contacting skin 

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Figure 3-3. Conceptual Representation of a Physiologically Based 

Pharmacokinetic (PBPK) Model for a 

Hypothetical Chemical Substance 

Source: adapted from Krishnan et al. 1994 

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. 
 

 

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If PBPK models for zinc 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. 

Validated PBPK models for zinc in animals or humans are not presently available. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

The absorption of zinc from the intestine is homeostatically controlled. A study by Hempe and Cousins 

(1992) found that CRIP, a diffusible intracellular zinc carrier, binds zinc in the mucosa during absorption; 

this process appears to be saturable (Gunshin et al. 1991; Hempe and Cousins 1992; Sturniolo et al. 

1991). Zinc transport in the intestinal lumen is also influenced by metallothionein which can inhibit zinc 

absorption by competing with CRIP for zinc (Hempe and Cousins 1992). CRIP binds about 40% of 

radiolabeled zinc entering the intestinal cells from the lumen in ligated loops of the small intestine of 

anesthetized rats when the zinc concentration is low (5 μM), but only 14% of the radiolabel when the 

concentration is high (300 μM) (Hempe and Cousins 1991). These findings suggest that CRIP has a 

limited binding capacity for zinc and becomes saturated when zinc concentration in the intestine is high 

(Hempe and Cousins 1992). 

High luminal zinc concentrations may damage the brush border membrane, allowing zinc to enter the cell 

and bind nonspecifically to cell proteins and other ligands (Cousins 1985; Hempe and Cousins 1992). 

Within the intestinal lumen, a number of factors appear to influence the availability of zinc for absorption. 

Methionine, histidine, cysteine, reduced glutathione, citrate, and prostaglandin E2 increase the intestinal 

uptake of zinc (Song et al. 1992), whereas inorganic inhibitors of zinc absorption include cadmium, 

copper, calcium, and ferrous iron (Hamilton et al. 1978; Harford and Sarkar 1991; Ogiso et al. 1979; 

Spencer et al. 1992; Yoshida et al. 1993). The mechanism of inhibition has not been clearly elucidated, 

but it is believed to involve competition for zinc binding sites in the intestinal mucosal cells; an effect on 

charge distribution on the mucosal membrane has also been suggested (Foulkes 1985). The organic 

inhibitors, including phytate and some components of dietary fiber, are believed to complex with zinc and 

decrease its availability. In the mucosal cell, zinc is associated with metalloproteins, including 

metallothionein. The release of zinc from the intracellular protein ligands and its transfer to the blood 

may involve diffusion of complexes with glutathione and similar compounds (Foulkes 1993). 
 

 

ZINC 88 

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In the plasma, albumin is the primary carrier for zinc, with smaller amounts of zinc bound to 

α2-macroglobulin and amino acids (Giroux et al. 1976). The albumin-bound zinc represents the 

metabolically active pool of zinc. Zinc is loosely bound in plasma, and albumin-bound zinc can readily 

be given up to tissues; however, the mechanisms are not fully elucidated. Zinc is initially concentrated in 

the liver after ingestion, and is subsequently distributed throughout the body. The liver, pancreas, bone, 

kidney, and muscle are the major tissue storage sites. When plasma zinc levels are high, liver 

metallothionein synthesis is stimulated, which facilitates the retention of zinc by hepatocytes (Richards 

and Cousins 1975). A storage form of zinc has not been identified in soft tissues, with the possible 

exception of zinc metallothionein. Zinc in bone is relatively unavailable for use by other tissues. 

3.5.2 Mechanisms of Toxicity 

Metal fume fever is the primary effect observed in workers exposed to zinc oxide fumes or dust (Blanc et 

al. 1991; Brown 1988; Drinker et al. 1927b; Vogelmeier et al. 1987). Metal fume fever usually occurs 3– 

10 hours after exposure, and the symptoms persist for 24–48 hours. The exact pathogenesis of metal 

fume fever is not known. It is believed to be an immune response to the inhaled zinc oxide (Mueller and 

Seger 1985). It has been suggested that the zinc oxide causes inflammation of the respiratory tract and 

the release of histamine or histamine-like substances. In response, an allergen-antibody complex is 

formed that may elicit an allergic reaction upon subsequent exposure to the allergen. In response to the 

allergen-antibody complex, an anti-antibody is formed. The anti-antibody dominates with continued 

exposure to the zinc oxide, thereby producing a tolerance. When the exposure is interrupted and 

re-exposure occurs, the allergen-antibody complex dominates, producing an allergic reaction and 

symptoms of metal fume fever (McCord 1960). 

Oral exposure to high levels of zinc has caused anemia, decreased levels of HDL cholesterol, and 

pancreatic damage in humans (Black et al. 1988; Chandra 1984; Chobanian 1981; Hooper et al. 1980; 

Murphy 1970) and animals (Allen et al. 1983; Aughey et al. 1977; Drinker et al. 1927d; Katya-Katya et 

al. 1984; Klevay and Hyg 1973; Maita et al. 1981; Straube et al. 1980). The mechanisms involved in the 

pancreatic damage have not been elucidated. The anemia and possibly the decreased HDL cholesterol 

levels are thought to be caused by a zinc-induced copper deficiency, although the levels at which this 

occur have not been well-characterized. Although it is generally accepted that the anemia is the result of 

copper deficiency, the relationship between zinc and copper levels and HDL cholesterol levels has been 

extensively debated (Fischer et al. 1980; Katya-Katya et al. 1984; Klevay and Hyg 1973; Murthy and 

Petering 1976). 
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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 Colborn and Clement (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 

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 in vitro studies were located regarding endocrine disruption of zinc. 

Pancreas. Increased levels of serum amylase were observed in a man after accidental ingestion of about 

3 ounces of a zinc chloride solution (Chobanian 1981). A 16-year-old boy who ingested an average of 
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approximately 86 mg zinc/kg/day as metallic zinc for 2 days (114 mg/kg on the 1st day and 57 mg/kg on 

the 2nd day) had increased serum amylase and lipase (Murphy 1970). 

In humans receiving a single low dose of zinc sulfate (0.5 mg zinc/kg/day), no changes in blood glucose 

or insulin levels were observed, and there were no differences in response to a glucose load (BrandaoNeto et al. 1990b). 

Pancreatic abnormalities (islet cellular alterations, acinar cell necrosis, metaplasia, fibrosis, pancreatitis) 

resulting from zinc ingestion have been observed in rats (Maita et al. 1981), mice (Aughey et al. 1977; 

Maita et al. 1981), cats (Drinker et al. 1927d), ferrets (Straube et al. 1980), sheep (Allen et al. 1983), and 

birds (Kazacos and Van Vleet 1989; Lu et al. 1990). In dogs (Drinker et al. 1927d) and minks (Aulerich 

et al. 1991), histological changes in the pancreas have not been observed at doses comparable to or higher 

than the dose levels that caused abnormalities in rats, mice, cats, ferrets, and sheep. Degeneration of the 

acinar cells of the pancreas was observed in sheep by Allen et al. (1983) and in rats and mice by Maita et 

al. (1981). Since the pancreatic acinar cells secrete digestive juices into the small intestine, the increase in 

serum amylase and lipase observed in the human case reports (Chobanian 1981; Murphy 1970) would 

correspond to damage in this region of the pancreas. 

In 2-month-old C3H mice exposed to 70 mg zinc/kg/day as zinc sulfate, hypertrophy and vacuolation of 

the β-cells of the pancreatic islets were observed beginning after 3 months of exposure and become more 

severe by 12 months (Aughey et al. 1977). The pancreatic islets secrete the hormones glucagon and 

insulin. No change in plasma levels of insulin and glucose was observed in this study after 6 months of 

exposure. No effect on islet cells was reported in rats exposed up to 565 mg/kg/day or mice exposed to 

1,110 mg/kg/day as zinc sulfate in a 13-week study by Maita et al. (1981), and Allen et al. (1983) 

reported that islet cells in sheep were generally unaffected, although occasional vacuolization occurred. 

Degeneration of acinar cells, but no effects on the islet cells, were found in ducklings (Kazacos and Van 

Vleet 1989); however, the relevance of this to humans is unclear. The data are too limited and 

contradictory to determine whether pancreatic islet cells are a primary target cell of zinc toxicity. 

Adrenal Gland. Decreased levels of serum cortisol (a hormone secreted by the adrenal cortex) were 

observed in humans after a single dose of 0.5 mg zinc/kg/day as zinc sulfate (Brandao-Neto et al. 1990b). 

No effects on the adrenal gland itself have been reported in humans. 
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In mice receiving 70 mg zinc/kg/day as zinc sulfate in the drinking water, hypertrophy and increased lipid 

content of the zona fasciculata cells of the adrenal cortex were observed as early as 3 months after the 

start of zinc supplementation (Aughey et al. 1977). 

Pituitary. No effects on pituitary function have been reported in humans following oral exposure to zinc. 

However, mice receiving 70 mg zinc/kg/day as zinc sulfate in the drinking water for 5–14 months had 

hypertrophy and increased granularity suggesting increased activity of the pituitary (Aughey et al. 1977). 

It is unclear whether the increased activity was a direct effect of the zinc or a reaction to decreased 

secretion from the adrenal cortex. 

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. 

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 
ZINC 92 

3. HEALTH EFFECTS 

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 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

While a detailed discussion of zinc deficiency is beyond the scope of this document, there is considerably 

more information on the effects of zinc deficiency on the developing fetus in pregnant women than exists 

for the effects of excess zinc during pregnancy. Maternal zinc deficiency can result in intrauterine growth 

retardation, teratogenesis, or embryonic or fetal death (for review, see King 2000). Zinc supplementation 

during pregnancy is usually sufficient to prevent these outcomes. Similarly, zinc deficiency during early 

life can result in adverse effects, including skin rash, diarrhea, anorexia, and growth failure, with more 

severe instances resulting in detrimental effects on the immune and nervous systems (Krebs 1999). 

Infants, more than adults, appear to be particularly sensitive to zinc deficiency, possibly the result of their 

higher zinc requirements on a per body weight basis. 

A case study presented by Murray (1926) reported on an infant death due to bronchopneumonia resulting 

from inhalation, and possibly ingestion, of an unspecified amount of zinc stearate powder spilled from a 

container. However, it is unclear whether the death was due to the zinc content or whether aspiration 
ZINC 93 

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bronchopneumonia would result from inhalation of similar powders that do not contain zinc. Other data 

on the effects of zinc inhalation in young children are not available. 

The human data on the effects of excess zinc in children consist mainly of reports of acute ingestion. The 

primary symptoms in these subjects mimic those of adult exposure, consisting mainly of gastrointestinal 

disturbances (nausea, vomiting, epigastric discomfort), with occasional neurologic symptoms 

(Anonymous 1983; Lewis and Kokan 1998; Moore 1978; Murphy 1970). Data are not presently 

sufficient to determine whether children are more sensitive to these effects than adults. 

The most sensitive animal model to zinc toxicity in young animals appears to be the mink. Young minks 

appear to be more sensitive to both the hematologic (decreased hematocrit and lymphocyte number) and 

dermal effects (graying of the fur and dermatosis) of oral zinc than adults (Bleavins et al. 1983). Other 

studies have examined the effects of zinc exposure in young animals (Drinker et al. 1927d; L'Abbe and 

Fischer 1984a; Maita et al. 1981), but have not provided data on adult animals similarly exposed for 

comparison. Additional data will be required to adequately assess the susceptibility of children to zinc 

exposure, relative to adults. 

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 

1989a). 

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 or 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 
ZINC 94 

3. HEALTH EFFECTS 

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 zinc are discussed in Section 3.8.1. 

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 zinc 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 Zinc 

There is no simple measure of zinc body burden. Under normal physiological conditions, the 

plasma/serum zinc level is ≈1 μg/mL (NAS/NRC 1979) and the urinary level is 0.5 mg/g creatinine 

(Elinder 1986). Several studies have reported increased levels of zinc in the serum and urine of humans 

and animals after inhalation, oral, or dermal exposure to zinc (Agren et al. 1991; Bentley and Grubb 1991; 

Brandao-Neto et al. 1990a; Hallmans 1977; Hamdi 1969; Keen and Hurley 1977; Neve et al. 1991; Statter 

et al. 1988; Sturniolo et al. 1991). However, relationships between serum and/or urine levels and zinc 

exposure levels have not been established. 

Hair and nail samples provide a lasting record of long-term metal intake possibly over weeks or months 

(Hayashi et al. 1993; Wilhelm et al. 1991). Mean zinc concentrations of 129–179 μg/g have been 

estimated for nails (Hayashi et al. 1993; Wilhelm et al. 1991) and 102–258 μg/g for hair (Folin et al. 

1991; McBean et al. 1971; Provost et al. 1993; Wilhelm et al. 1991). Most investigators have found a 

poor correlation between hair and plasma zinc levels since the zinc in hair does not exchange with the 
ZINC 95 

3. HEALTH EFFECTS 

body zinc pool (McBean et al. 1971; Rivlin 1983). Furthermore, measurements of zinc in hair can be 

affected by extraneous contamination of hair, contamination by sweat, location of hair sample (distance 

from scalp), hair coloring, and rate of hair growth (McBean et al. 1971; Rivlin 1983). Although the nail 

is considered more resistant to washing procedures than hair, external contamination and uncertainties 

regarding the length and period of exposure reflected by the observed zinc concentration limit this 

measurement as a biomarker of exposure for zinc (Wilhelm et al. 1991). 

3.8.2 Biomarkers Used to Characterize Effects Caused by Zinc 

The respiratory tract is the most sensitive target organ for zinc following inhalation exposure. Inhalation 

of zinc oxide results in a syndrome referred to as metal fume fever. Symptoms include fevers, chills, 

cough, listlessness, and metallic taste. Although oxides of several heavy metals (antimony, aluminum, 

arsenic, cadmium, cobalt, copper, iron, lead, magnesium, manganese, mercury, nickel, selenium, silver, 

and tin) and pyrolysis products of fluorocarbon polymers (polytetrafluoroethylene [Teflon] and 

fluorinated polyethylene propylene) also produce metal fume fever (Ellenhorn and Barceloux 1988), this 

group of symptoms may be used as a nonspecific biomarker to identify inhalation exposure to zinc oxide. 

The target organs associated with oral zinc exposure include the gastrointestinal tract, blood, immune 

system, and pancreas. The toxic effects observed after oral exposure to zinc include nausea, vomiting, 

diarrhea, decreased hemoglobin and hematocrit levels, immune suppression, increased serum amylase and 

lipase, and decreased HDL cholesterol levels (a more detailed discussion of effects associated with 

exposure to zinc is presented in Section 3.2). However, nausea, vomiting, and diarrhea may be observed 

following exposure to any gastrointestinal irritant. Increases in serum amylase and lipase are also 

markers for pancreatic damage; therefore, any condition resulting in pancreatitis (i.e., biliary tract disease 

[gallstones], alcoholism, trauma, inflammation, blood-borne bacterial infections, viral infections, 

ischemia, and drugs such as azathioprine, thiazides, sulfonamides, and oral contraceptives) would result 

in similar increases in these enzymes (Cotran et al. 1989). A hypochromic microcytic anemia that is not 

responsive to iron supplements may indicate exposure to zinc; however, such anemia may also reflect 

copper, pyridoxine, or cobalt deficiency, lead intoxication, poor diet, or chronic blood loss (Suber 1989). 

Thus, none of the above-mentioned effects observed after exposure to zinc is specific to zinc exposure. 

However, the combination of these toxic effects may be indicative of zinc overexposure. Additional 

information on the health effects of zinc may be found in Section 3.2.2. Additional information on 
ZINC 96 

3. HEALTH EFFECTS 

biomarkers for renal, hepatobiliary, immune, and nervous system effects may be found in the 

CDC/ATSDR (1990) and OTA (1990) reports listed in Chapter 9. 

Increased erythrocyte metallothionein may be an index of zinc exposure in humans (Grider et al. 1990). 

Daily supplementation of 50 mg zinc/day to subjects for at least 7 days caused a 7-fold increase in 

metallothionein concentration in erythrocytes. At least 3–4 days are required before an increase in 

metallothionein is observed. This biomarker of exposure is only useful for recent zinc exposure because 

the metallothionein levels decreased approximately a week after discontinuation of a 63-week 

supplementation of zinc (Grider et al. 1990). Fourteen days after discontinuation of zinc supplements, 

metallothionein levels were reduced by 61%. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Zinc is an essential element obtained from the diet. Many different metals and nutrients interact with the 

absorption, distribution, and excretion of zinc. However, information was not found concerning 

interactions that increase the toxicity of zinc or other substances in the presence of zinc (i.e., that cause 

the same amount of zinc to result in a greater toxic response). Zinc administration may increase the 

toxicity of lead; however, the data are conflicting (Cerklewski and Forbes 1976; Hsu et al. 1975). The 

toxicity of zinc is believed to be due to its interaction with copper, as explained below. 

Metallothionein, a sulfhydryl-rich protein inducible by certain divalent cations and a variety of other 

agonists, is involved in the interaction between zinc and other metals such as copper (Wapnir and 

Balkman 1991). Inhibition of intestinal copper absorption by zinc may demonstrate competition between 

the two metals at the brush border of the lumen (Wapnir and Balkman 1991). Dietary intake of copper 

(1, 6, and 36 mg/kg) or zinc (5, 30, and 180 mg/kg) do not significantly alter the absorption of the other 

(Oestreicher and Cousins 1985), but when zinc levels are much higher than copper levels, copper 

absorption is depressed (Fischer et al. 1981). This fact has been used therapeutically in the treatment of 

Wilson’s Disease, in which zinc supplementation is used to prevent the over-absorption of copper caused 

by the disease (for a brief review, see Brewer 2000). High levels of dietary zinc are known to induce de 

novo synthesis of metallothionein in the intestinal mucosal cell. Both copper and zinc appear to bind to 

the same metallothionein protein; however, copper has a higher affinity for metallothionein than zinc and 

displaces the zinc that is attached to the metallothionein (Ogiso et al. 1979). Copper complexed with 

metallothionein is retained in the mucosal cell, relatively unavailable for transfer to plasma, and is 

excreted in the feces when the mucosal cells are sloughed off (Fischer et al. 1981; L'Abbe and Fischer 
ZINC 97 

3. HEALTH EFFECTS 

1984b). A number of factors influence the effect of dietary zinc on copper metabolism, including the 

amount of copper and zinc in the diet, the zinc-to-copper ratio, age of the individual, and the duration of 

exposure to high zinc levels (Johnson and Flagg 1986). 

In a study of zinc-supplemented women, Yadrick et al. (1989) reported decreased levels of serum ferritin, 

a sensitive indicator of iron status. Supplementation of the subjects with iron resulted in a reversal of the 

diminished iron status, although whether this was due to an interaction with zinc or simply due to 

additional iron being provided is not clear. Other studies of zinc-exposed subjects have not reported 

significant changes in copper status (Black et al. 1988; Fischer et al. 1984; Milne et al. 2001); however, 

these studies have either evaluated male subjects, who are not as sensitive to changes in iron status, or 

have not evaluated serum ferritin. 

Physiological interactions of zinc and cadmium have been discussed in a number of reviews (EPA 1980c; 

NAS 1980; Underwood 1977). Exposure to cadmium may cause changes in the distribution of zinc, with 

accumulation of zinc in the liver and kidney. This accumulation in the liver and kidney may result in a 

deficiency in other organs, particularly if the dietary intake of zinc is marginal. In vitro data demonstrate 

that zinc and cadmium enter renal proximal cells by a saturable, carrier-mediated process and a 

nonsaturable pathway (Gachot and Poujeol 1992). At low cadmium doses, cadmium and zinc compete 

for a common transport carrier system in renal proximal cells. It is hypothesized that, at high doses, the 

subcellular microtubule system is disrupted by cadmium, which may interfere with changes in carrier 

configuration that are necessary for transport of the metals (modification of the cytoskeleton), and thereby 

lead to noncompetitive inhibition between cadmium and zinc (Gachot and Poujeol 1992). Combined 

treatment with cadmium and zinc in primary cultures of kidney cells resulted in enhanced toxicity of 

cadmium (Yoshida et al. 1993); however, pretreatment with a nontoxic concentration of zinc caused 

increased induction of metallothionein synthesis and partial protection against cadmium (Yoshida et al. 

1993). 

Cadmium is 10 times more efficient than zinc in metallothionein induction in vitro (Harford and Sarkar 

1991). Induction by either cadmium or zinc alone is saturable; however, simultaneous administration of 

cadmium and zinc results in induction of metallothionein in an additive manner. The additive effect on 

metallothionein induction may involve binding of the metals either to two or more metallothionein 

promoter binding proteins or separate sites on the same promoter binding protein (Harford and Sarkar 

1991). 
 

 

ZINC 98 

3. HEALTH EFFECTS 

Zinc acetate pretreatment in the mouse TRL-1215 cell line reduced single-strand DNA damage associated 

with cadmium exposure (Coogan et al. 1992). Diminished cadmium-induced DNA damage was not due 

to decreased cadmium burden in the zinc-pretreated cells. Instead, cadmium levels were actually greater 

than those in nonpretreated cells (Coogan et al. 1992). Metallothionein levels were elevated in these 

cells, suggesting that zinc pretreatment affects cadmium genotoxicity by inducing metallothionein which 

may sequester cadmium from genetic material. In contrast, simultaneous exposure to cadmium and zinc 

decreased cadmium accumulation in the cells, perhaps because of direct competition for a common 

transport mechanism (Coogan et al. 1992). 

Zinc acetate reduced or prevented cadmium carcinogenesis in the prostate, in the testes, or at the injection 

site in rats (Gunn et al. 1963a, 1964; Waalkes et al. 1989). The effect of zinc on the cadmium-induced 

carcinogenesis appeared to be dependent on dose, route, and target site. Sustained levels of zinc inhibited 

cadmium-induced injection sarcomas but had no effect on the incidence of testicular Leydig cell tumors 

(Waalkes et al. 1989). 

Excessive dietary zinc has been shown to induce a reversible copper deficiency and anemia in 

experimental animals (Magee and Matrone 1960; Murthy and Petering 1976; O'Dell 1969; Underwood 

1977; Wapnir and Balkman 1991). Similar effects have been seen in humans receiving long-term 

treatment with zinc (Porter et al. 1977; Prasad et al. 1978). However, no significant decreases in plasma 

copper levels were observed in humans receiving zinc for 6 weeks or 6 months (Henkin et al. 1976; 

Samman and Roberts 1987) or in mice administered zinc for 1–12 weeks (Sutomo et al. 1992). A 

reduction in erythrocyte superoxide dismutase (an index of metabolically available copper), without a 

decrease in plasma copper levels, was exhibited following exposure to high amounts of ingested zinc 

(Fischer et al. 1984). These findings suggest that superoxide dismutase may be a sensitive indicator of 

zinc-copper interaction. However, as not all studies of zinc supplementation have noted changes in 

superoxide dismutase levels, the association is still not completely clear. 

Cobalt has been demonstrated to induce seminiferous tubule damage and degeneration (vacuole 

formation, sloughing of cells, giant cell formation) in the testes of mice following exposure for 13 weeks 

(Anderson et al. 1993). Coadministration of cobalt and zinc chloride in the drinking water resulted in 

complete or partial protection in 90% of the animals. The sites of competitive interaction between zinc 

and cobalt were not established in the study; however, the authors postulated that the mechanism(s) may 

be similar to those involved in prevention of cadmium toxicity by zinc. 
 

 

 

ZINC 99 

3. HEALTH EFFECTS 

The effect of tin on heme biosynthesis appears to be dependent on the concentration of zinc (Chmielnicka 

et al. 1992). Oral administration of tin can affect the heme synthesis by inhibiting δ-aminolevulinic acid 

dehydratase (ALAD) activity in blood. Zinc is required for ALAD activity and provides a protective role 

in heme synthesis by increasing the activity of ALAD. It is postulated that when the tin and zinc are 

coadministered, these metals are probably attaching to similar binding sites in the ALAD enzyme 

(Chmielnicka et al. 1992). 

Calcium decreases the bioavailability of zinc; the converse is also true (Heth and Hoekstra 1965; Spencer 

et al. 1992). Oral zinc administration is associated with decreased calcium levels in the serum and in the 

bone of rats (Yamaguchi et al. 1983). Zinc inhibited calcium uptake in rat brush border membrane 

vesicles, possibly by competing directly at high-affinity calcium binding sites (Roth-Bassell and 

Clydesdale 1991). The interaction of calcium and zinc is apparently dose related; intestinal absorption of 

calcium at a low calcium intake (230 mg/day) was inhibited at a high zinc intake of 140 mg/day but not at 

a lower zinc intake of 100 mg/day (Spencer et al. 1992). 

Pretreatment with zinc has been shown to reduce hepatotoxicity induced by xenobiotics such as 

acetaminophen, bromobenzene, carbon tetrachloride, D-galactosamine, gentamicin, and salicylate (Cagen 

and Klaassen 1979; Gunther et al. 1991; Hu et al. 1992; Szymanska et al. 1991; Yang et al. 1991). The 

protective effect of zinc against carbon tetrachloride toxicity is dose dependent at high dose levels of zinc, 

probably because of sequestering of toxic metabolites of carbon tetrachloride by metallothionein (Cagen 

and Klaassen 1979). Similarly, the protective action of zinc against bromobenzene and acetaminophen 

appears to be associated with elevated metallothionein levels (Szymanska et al. 1991). Inhibition of lipid 

peroxidation may be the basis for the protective effect of zinc against hepatic damage induced by 

D-galactosamine in rats (Hu et al. 1992). Zinc may be elevating NADPH (nicotinamide adenine 

dinucleotide phosphate) content in the cell, resulting in regeneration of glutathione, which increases the 

antioxidative ability of hepatic cells. Salicylate-induced hepatic alterations (increased lipid droplets and 

iron, reduced glycogen) (Gunther et al. 1991) and gentamicin-induced proximal tubular necrosis (Yang et 

al. 1991) were diminished in rats pretreated with injections of zinc chloride and zinc sulfate, respectively. 

This finding corresponded to a dramatic increase in metallothionein content with combined treatment of 

salicylate and zinc compared to a less significant increase with salicylate alone. 

Animal studies suggest that the administration of zinc may also inhibit tumor growth. Forty weeks after 

exposure, the incidence of injection site sarcomas was 40–60% in rats receiving simultaneous 

intramuscular administration of nickel subsulfide and zinc oxide compared to an incidence of 100% 
 

 

ZINC 100 

3. HEALTH EFFECTS 

following administration of nickel subsulfide alone (Kasprzak et al. 1988). Supplementing drinking water 

with zinc sulfate reduced the incidence of 9,10-dimethyl-1,2-benzanthracene-induced tumors in the cheek 

pouches of mice (Poswillo and Cohen 1971). Zinc decreased DNA synthesis in hepatomas induced by 

3'-methyl-4-dimethylaminoazobenzene (Duncan and Dreosti 1975). The investigators speculated that the 

changes were due to inhibited cell division cycle at the level of DNA replication. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to zinc than will most persons 

exposed to the same level of zinc 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 zinc, or compromised function of organs affected by zinc. 

Populations who are at greater risk due to their unusually high exposure to zinc are discussed in 

Section 6.7, Populations with Potentially High Exposures. 

No specific data regarding human subpopulations that are unusually susceptible to the toxic effects of 

zinc were located. Healthy elderly people have been shown to have greater daily zinc intake than 

housebound elderly people (Bunker et al. 1987; Prasad 1988). Data from animal studies indicate that 

certain human subpopulations may be more susceptible to excess zinc because of zinc's depleting effect 

on copper (Underwood 1977). People who are malnourished or have a marginal copper status may be 

more susceptible to the effects of excessive zinc than people who are adequately nourished (Underwood 

1977). 

Hepatic zinc levels are elevated in patients with hemochromatosis, a genetic disease associated with 

increased iron absorption from the intestine (Adams et al. 1991). The chronic iron loading that occurs 

could result in hepatic metallothionein induction leading to the accumulation of zinc because 

metallothionein has a greater affinity for zinc than iron. These individuals may, therefore, have a greater 

likelihood of developing toxicity with zinc exposure levels that do not normally result in any symptoms in 

the general population. However, available studies, including this one, have not correlated increased 

hepatic zinc with any adverse effects. 
ZINC 101 

3. HEALTH EFFECTS 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to zinc. 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 zinc. When specific 

exposures have occurred, poison control centers and medical toxicologists should be consulted for 

medical advice. The following text provides specific information about treatment following exposures to 

zinc: 

Ellenhorn MJ, Barceloux DG. 1988. Medical toxicology: Diagnosis and treatment of human poisoning. 

New York, NY: Elsevier, 879-880, 1064-1065. 

3.11.1 Reducing Peak Absorption Following Exposure 

General recommendations for the management and treatment of patients following acute exposure to zinc 

include removal of the victim from the contaminated area and removal and isolation of contaminated 

clothing, jewelry, and shoes (Bronstein and Currance 1988; Stutz and Janusz 1988). Excess contaminant 

is gently brushed away and excess liquids blotted with absorbent material. Measures that are appropriate 

to the route of exposure are taken to remove zinc from the body. Exposed eyes are flushed immediately 

with water, followed as soon as possible with irrigation of each eye with normal saline. Exposed skin is 

washed immediately with soapy water. Administration of ipecac to induce emesis, gastric lavage, 

ingestion of activated charcoal, and cathartics have been recommended to decrease the gastrointestinal 

absorption of zinc (Burkhart et al. 1990; Ellenhorn and Barceloux 1988). Because zinc causes nausea and 

vomiting following exposure by the oral route, use of emetic agents may be unnecessary. Ipecac 

administration may be contraindicated following ingestion of caustic zinc compounds such as zinc 

chloride. The large amounts of phosphorus and calcium in milk and cheese, and phytate in brown bread, 

may reduce absorption of zinc from the gastrointestinal tract (Pecoud et al. 1975). Therefore, if vomiting 

and diarrhea are not prohibitive, ingestion of dairy products or brown bread may also reduce 

gastrointestinal absorption of zinc. In a study of intestinal absorption of zinc in iron-deficient mice, the 

uptake of zinc from the gut was inhibited by adding iron to the duodenal loop system. The proposed 

mechanism was that iron and zinc shared a common gut mucosal binding site (Hamilton et al. 1978). 

However, it is unknown whether ingestion of iron supplements would be effective in reducing absorption 

of zinc overdoses. 
ZINC 102 

3. HEALTH EFFECTS 

3.11.2 Reducing Body Burden 

Zinc is an essential trace element that is normally found in tissues and fluids throughout the body and is 

under homeostatic control (NAS/NRC 1989b). Increased levels have been observed in the heart, spleen, 

kidneys, liver, bone, and blood of animals following subchronic oral exposure to zinc (Llobet et al. 

1988a) indicating that some zinc accumulation occurs during excess intakes. The greatest increases were 

observed in bone and blood. 

Administration of the chelating agent, calcium disodium ethylene diaminetetraacetate (CaNa2EDTA), is 

the treatment of choice for reducing the body burden of zinc in humans following exposure to high levels 

(Ellenhorn and Barceloux 1988). Ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic 

acid (DTPA), and dimercaprol (BAL) are the most common antidotes used in the treatment of human zinc 

intoxications (Llobet et al. 1989; Murphy 1970; Spencer and Rosoff 1966). Markedly elevated serum 

zinc levels in a young child who ingested a zinc chloride solution were normalized by intravenously 

administering a single small dose of CaNa2EDTA (11.5 mg/kg) (Potter 1981). Use of chelation therapy 

(administration of BAL) was reported in a case study of a 16-year-old boy who ingested 12 g of metallic 

zinc (Murphy 1970). The boy exhibited lethargy and elevated blood zinc levels that were both reversed 

following intramuscular administration of BAL. Chelation therapy has been demonstrated to increase the 

urinary excretion of zinc 22-fold (Spencer and Rosoff 1966). Intravenous and nebulized N-acetylcysteine 

(another metal chelating agent) have also been observed to increase urinary zinc excretion and decrease 

plasma levels following inhalation of zinc chloride smoke (Hjortso et al. 1988). 

The efficacy of 16 different chelating agents as possible antidotes for acute oral zinc exposure has been 

determined in mice (Llobet et al. 1988b). The most efficient chelators were DTPA, cyclohexanediaminetetraacetic acid (CDTA), and EDTA. Increased urinary levels of zinc and decreased bone and liver zinc 

levels were observed following administration of the chelators. The maximum efficiency of the chelators 

was observed when they were administered from 10 minutes to 12 hours after zinc exposure (Domingo et 

al. 1988a, 1988b). 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

Anemia has been observed in humans and animals after oral exposure to zinc. It has been postulated that 

excess zinc intake may result in copper deficiency (mechanisms of action are discussed in Section 3.5). 

The anemia observed following zinc intake is believed to be caused by the copper deficiency. 
 

 

ZINC 103 

3. HEALTH EFFECTS 

Administration of copper in patients with zinc-related anemia has been shown to be effective in 

increasing the hemoglobin levels (Porter et al. 1977; Smith and Larson 1946). 

The exact mechanism of metal fume fever (a syndrome consisting of a leukocytosis with chills, fever, 

cough, myalgias, headache, weakness, and dyspnea) is unknown (Ellenhorn and Barceloux 1988), but 

respiratory tract inflammation and the development of an immune complex reaction have been proposed 

(McCord 1960). Treatment is supportive (e.g., bed rest, analgesics, and antipyretics) (Mueller and Seger 

1985). 

In severe cases, inhalation of zinc chloride has resulted in advanced pulmonary fibrosis and fatal 

respiratory distress syndrome (Evans 1945; Hjortso et al. 1988; Milliken et al. 1963). L-3,4-Dehydroproline was given to two soldiers after inhaling a high concentration of zinc chloride smoke (also 

contained other chemicals) in an attempt to inhibit collagen deposition in the lungs (Hjortso et al. 1988). 

This therapy did not prevent respiratory failure. 

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 zinc 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 zinc. 

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. 
ZINC 104 

3. HEALTH EFFECTS 

3.12.1 Existing Information on Health Effects of Zinc 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to zinc 

are summarized in Figure 3-4. The purpose of this figure is to illustrate the existing information 

concerning the health effects of zinc. 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. 

Figure 3-4 indicates whether a particular health effect end point has been studied for a specific route and 

duration of exposure. There is little information concerning death in humans after inhalation, oral, or 

dermal exposure to zinc. However, several case studies report death after exposure to extremely high 

levels of zinc chloride and other components of zinc chloride smoke (Evans 1945; Hjortso et al. 1988; 

Milliken et al. 1963). 

Systemic effects of acute inhalation exposure to generally unspecified levels of various zinc compounds 

in humans have been reported in several clinical case studies (Blanc et al. 1991; Brown 1988; Hjortso et 

al. 1988; Matarese and Matthews 1966; Vogelmeier et al. 1987). Case studies and experimental studies 

of systemic effects in humans following acute, intermediate, and chronic oral exposures are available 

(Anonymous 1983; Black et al. 1988; Brandao-Neto et al. 1990a; Chandra 1984; Chobanian 1981; Hale et 

al. 1988; Hallbook and Lanner 1972; Hoffman et al. 1988; Hooper et al. 1980; Malo et al. 1990; Moore 

1978; Patterson et al. 1985; Porter et al. 1977; Potter 1981; Prasad et al. 1978). Experimental studies in 

humans following acute, intermediate, and chronic dermal exposures were located for hematological, 

dermal, and ocular effects (Agren 1990; Evans 1945; Fischer et al. 1984; Turner 1921; Yadrick et al. 

1989). 

Information concerning respiratory effects of acute inhalation exposure to zinc in animals is available 

(Amdur et al. 1982; Drinker and Drinker 1928; Lam et al. 1982, 1988). One study (Marrs et al. 1988) 

was located regarding other systemic effects in animals following inhalation exposure to zinc for an 

intermediate-exposure duration. Information regarding systemic effects of zinc following oral exposure 
 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Human 

Inhalation 

Oral 

Dermal 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Animal 

Inhalation 

Oral 

Dermal 

Existing Studies 

ZINC 105 

3. HEALTH EFFECTS 

Figure 3-4. Existing Information on Health Effects of Zinc 
ZINC 106 

3. HEALTH EFFECTS 

in animals is available for acute, intermediate, and chronic exposure durations (Allen et al. 1983; 

Anderson and Danylchuk 1979; Aughey et al. 1977; Bentley and Grubb 1991; Domingo et al. 1988a; 

Drinker et al. 1927c; Jenkins and Hidiroglou 1991; Katya-Katya et al. 1984; Klevay and Hyg 1973; 

Llobet et al. 1988a; Maita et al. 1981; Straube et al. 1980; Walters and Roe 1965). One acute dermal 

study evaluated dermal irritancy in animals (Lansdown 1991). 

Immunological effects were reported in humans following inhalation exposure to zinc oxide (Blanc et al. 

1991; Farrell 1987). Another study reported potential adverse immunological effects following oral 

exposure of humans (Chandra 1984). Clinical symptoms suggestive of neurological effects have been 

reported by humans following inhalation exposure (Rohrs 1957; Sturgis et al. 1927; Wilde 1975) or oral 

exposure (Anonymous 1983; Murphy 1970; Potter 1981) to zinc. There were studies that examined 

reproductive and developmental effects in women orally exposed to zinc during their pregnancies (Kynast 

and Saling 1986; Mahomed et al. 1989; Simmer et al. 1991). 

One study examined immunological and reproductive effects in animals following inhalation exposure to 

zinc chloride (Marrs et al. 1988). Immunological and neurological end points were evaluated in animals 

following oral exposure to zinc (Bleavins et al. 1983; Kozik et al. 1980, 1981; Schiffer et al. 1991). 

Information regarding developmental and reproductive effects in animals after oral exposure to zinc is 

available (Cox et al. 1969; Ketcheson et al. 1969; Kinnamon 1963; Mulhern et al. 1986; Pal and Pal 1987; 

Schlicker and Cox 1968; Sutton and Nelson 1937). Studies regarding genotoxicity in animals after 

inhalation and oral exposures to zinc are limited (Gupta et al. 1991; Kowalska-Wochna et al. 1988; 

Voroshilin et al. 1978). 

Epidemiological studies regarding carcinogenicity after inhalation and oral exposure to zinc are available 

(Logue et al. 1982; Neuberger and Hollowell 1982; Philipp et al. 1982; Stocks and Davies 1964); 

however, they were not well controlled and the data are of little significance. Studies are available 

regarding carcinogenicity in animals after inhalation and oral exposure to zinc (Marrs et al. 1988; Walters 

and Roe 1965). However, the studies have several deficiencies that limit their usefulness. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. Symptoms of metal fume fever (headache, fever, leukocytosis, 

myalgias) have been observed in humans acutely exposed to airborne zinc oxide (Blanc et al. 1991; 

Brown 1988; Drinker et al. 1927b; Sturgis et al. 1927). Acute oral exposure to zinc has resulted in 
 

 

 

ZINC 107 

3. HEALTH EFFECTS 

gastrointestinal disturbances (abdominal pain, nausea, vomiting, esophageal erosion), evidence of 

pancreatic damage (increased serum amylase and lipase levels), and decreased levels of serum cortisol in 

humans (Anonymous 1983; Brandao-Neto et al. 1990a; Chobanian 1981; Murphy 1970; Potter 1981). 

Acute dermal exposure to zinc oxide has not been shown to be irritating to human skin (Agren 1990). 

Toxic effects similar to those observed for metal fume fever have been observed in guinea pigs (Amdur et 

al. 1982; Lam et al. 1985). In addition to LD50 data, only one reliable study assessed the acute oral 

toxicity of zinc compounds in animals. Pancreatic, gastrointestinal, and liver damage were observed in 

sheep (Allen et al. 1983). It is doubtful that sheep (ruminant animals) are an appropriate model for 

toxicity of orally administered zinc in humans. The dermal toxicity of several zinc compounds has been 

tested in rabbits, guinea pigs, and mice (Lansdown 1991). Zinc acetate, zinc chloride, and zinc sulfate 

have irritating properties. Skin irritation was not observed in rabbits, guinea pigs, or mice after zinc oxide 

paste application (Lansdown 1991). 

The animal data (Amdur et al. 1982; Drinker and Drinker 1928; Lam et al. 1982, 1988) corroborate 

occupational exposure studies that indicate metal fume fever is an end point of concern. However, other 

possible targets of toxicity have not been examined. Thus, an acute inhalation MRL cannot be derived. 

A large amount of the human oral exposure data is in the form of case reports, and a great deal of 

uncertainty exists regarding the dose levels. The uncertainty about whether sheep are a good model for 

humans precludes using these data to derive an oral MRL for acute-duration exposure. Additional studies 

involving acute exposure to zinc compounds by all routes of exposure would be helpful to identify target 

organ and dose-response relationships. There are groups who may be exposed to zinc at hazardous waste 

sites for brief periods; therefore, this information is important. 

Intermediate-Duration Exposure. Metal fume fever was observed in an individual exposed to zinc 

fumes and zinc powder for approximately 1 month (Malo et al. 1990). Anemia and decreased levels of 

HDL cholesterol have been observed in humans taking high doses of zinc supplements (Chandra 1984; 

Hoffman et al. 1988; Hooper et al. 1980). Intermediate-duration dermal exposure to zinc oxide dust has 

resulted in pustular lesions, but these lesions were attributed to clogging of the sebaceous glands resulting 

from poor hygiene (Turner 1921). Rats, mice, and guinea pigs exposed to smoke containing zinc chloride 

and other compounds had evidence of lung irritation (Marrs et al. 1988). No intermediate-duration 

animal dermal studies were located. In animals that ingested zinc for an intermediate duration, anemia 

and kidney and pancreas damage were observed (Bentley and Grubb 1991; Drinker et al. 1927d; Jenkins 

and Hidiroglou 1991; Llobet et al. 1988a; Maita et al. 1981; Straube et al. 1980). 
ZINC 108 

3. HEALTH EFFECTS 

Only one case report regarding human intermediate-duration inhalation exposure was located, and this 

study did not report the exposure level (Malo et al. 1990). Thus, an intermediate-duration inhalation 

MRL could not be derived. There are less serious LOAELs (decreased serum HDL cholesterol) identified 

in the Hooper et al. (1980) and Chandra (1984) human oral exposure studies; however, evidence 

regarding this effect is inconsistent (Bogden et al. 1988; Hale et al. 1988; Samman and Roberts 1988). 

An intermediate-duration oral MRL was derived for zinc based on hematological effects (decreased 

hematocrit, serum ferritin, and erythrocyte superoxide dismutase) in women given 50 mg Zn/day as zinc 

gluconate supplements for 10 weeks (Yadrick et al. 1989); as these effects were subclinical, they were 

considered to be non-adverse, and were identified as a NOAEL. Several other studies of zinc 

supplementation in humans support this NOAEL (Bonham et al. 2003a, 2003b; Davis et al. 2000; Fischer 

et al. 1984; Milne et al. 2001). The toxic effects of intermediate-duration exposure to zinc compounds are 

relatively well characterized for the oral route. There are insufficient toxicokinetic data to determine if 

the toxic effects observed following oral exposure would occur following inhalation or dermal exposure. 

Inhalation and dermal studies would be useful to determine possible target organs and dose-response 

relationships. There are populations surrounding hazardous waste sites that might be exposed to zinc 

compounds for similar durations. 

Chronic-Duration Exposure and Cancer. No exposure-related effects on lung function were 

observed in a group of welders chronically exposed to zinc (Marquart et al. 1989). Anemia has been 

observed in humans following ingestion of high doses of zinc supplements (Broun et al. 1990; Hale et al. 

1988; Porter et al. 1977; Prasad et al. 1978). Chronic-duration dermal exposure to zinc oxide dust has 

resulted in pustular lesions, but these were attributed to clogging of the sebaceous glands resulting from 

poor hygiene (Batchelor et al. 1926). No chronic-duration inhalation or dermal studies in animals were 

located. Pancreatic damage was observed in mice after chronic exposure to zinc sulfate in drinking water 

(Aughey et al. 1977). 

A chronic-duration inhalation MRL could not be derived for zinc because neither of the inhalation studies 

reported the levels of airborne zinc. Due to a lack of adequate chronic-duration oral studies, the 

intermediate-duration oral MRL was adopted as the chronic-duration oral MRL, based on hematological 

effects (decreased hematocrit, serum ferritin, and erythrocyte dismutase) in women given zinc gluconate 

supplements for 10 weeks (Yadrick et al. 1989). Additional studies involving chronic exposure to zinc 

compounds by all routes of exposure would be helpful to identify dose-response relationships. 
ZINC 109 

3. HEALTH EFFECTS 

Although there are several human and animal carcinogenicity studies, the limitations of these studies 

preclude their use in assessing the carcinogenicity of zinc (Logue et al. 1982; Neuberger and Hollowell 

1982; Walters and Roe 1965). Carcinogenicity studies by all routes of exposure would be useful. 

Genotoxicity. Several in vitro microbial gene mutation assays were negative (Marzin and Vo Phi 

1985; Nishioka 1975; Thompson et al. 1989; Venitt and Levy 1974; Wong 1988), but evidence from gene 

mutation assays in mammalian cells is mixed (Amacher and Paillet 1980; Thompson et al. 1989). An 

increase in the occurrence of chromosomal aberrations was observed in vitro in human lymphocytes 

(Deknudt and Deminatti 1978) and in vivo in rats and mice (Deknudt and Gerber 1979; Gupta et al. 1991; 

Kowalska-Wochna et al. 1988; Voroshilin et al. 1978). Increased sister chromatid exchange was 

observed in vivo in rat bone marrow (Kowalska-Wochna et al. 1988). However, while there are sufficient 

in vivo data establishing the clastogenicity of zinc, data regarding the mutagenicity of zinc are conflicting. 

Studies designed to assay different types of genotoxicity (i.e., mutagenicity in mammalian cells, effect of 

excess zinc on DNA replication) would be useful for determining the genotoxic potential of zinc. 

Reproductive Toxicity. No complications occurred in the pregnancies of women exposed to daily 

doses of zinc sulfide during the last two trimesters (Mahomed et al. 1989). No studies were located 

regarding the reproductive toxicity of zinc in humans after inhalation or dermal exposure. Increased preimplantation loss and reproductive dysfunction in rats were observed in oral exposure studies (Pal and Pal 

1987; Sutton and Nelson 1937). No histological changes in reproductive organs were observed in rats, 

mice, or guinea pigs following inhalation exposure to zinc chloride smoke, but reproductive function was 

not assessed (Marrs et al. 1988). No dermal reproductive toxicity studies in animals were located. 

Inhalation and dermal studies assessing reproductive function would be useful to determine whether zinc 

has the potential to cause reproductive effects by these routes. An oral reproductive toxicity study in a 

different animal strain as well as a multigeneration study, including reproductive organ pathology, would 

be useful for determining whether oral zinc exposure is likely to cause reproductive toxicity in humans. 

Developmental Toxicity. No studies were located regarding the potential of zinc to cause 

developmental effects in humans after inhalation or dermal exposure. In a very brief report of a human 

study in which pregnant women received high-doses of zinc supplements during the last trimester of 

pregnancy, an increased incidence of stillbirths and one premature delivery were observed (Kumar 1976). 

This study, however, has many limitations. Increased fetal resorptions were observed in rats after oral 

exposure to zinc (Schlicker and Cox 1968). No studies were located regarding developmental toxicity in 

animals after inhalation or dermal exposure to zinc. Additional inhalation, oral, and dermal exposure 
 

 

ZINC 110 

3. HEALTH EFFECTS 

studies in animals would be useful to predict whether developmental effects should be a concern for 

humans exposed to zinc. 

Immunotoxicity. Metal fume fever is believed to be an immune response to zinc oxide. A correlation 

between the concentration of airborne zinc and the number of all types of T cells (helper, inducer, 

suppressor, and killer) in the bronchoalveolar lavage fluid of humans, possibly related to the onset of 

metal fume fever, was observed in an acute-duration inhalation study (Blanc et al. 1991). Impaired 

immune response in humans has been reported in an intermediate-duration oral study (Chandra 1984). 

No immune effects were observed in mice after oral exposure to zinc (Schiffer et al. 1991). There is 

some limited information to suggest that the immune system is a target of zinc toxicity. A battery of 

immune function tests after inhalation, oral, and dermal exposure to zinc compounds would be useful in 

determining if zinc is immunotoxic. 

Neurotoxicity. Staggering gait and hallucinations were reported in an individual who intentionally 

inhaled metallic paint aerosols (Wilde 1975). Because there was simultaneous exposure to copper and 

hydrocarbons, this study cannot be used to assess the neurotoxic potential of zinc. Nonspecific signs and 

symptoms of neurotoxicity (light-headedness, dizziness, headache, and lethargy) have been reported by 

humans following acute oral exposure to zinc (Murphy 1970; Potter 1981). Very limited data suggest that 

high oral doses of zinc can cause minor neuron degeneration and alteration of secretion of the 

hypothalamus in rats (Kozik et al. 1980, 1981). No studies were located regarding neurotoxic effects in 

animals after inhalation or dermal exposure to zinc. Additional studies by all routes of exposure would be 

useful to determine if exposure to zinc compounds would result in neurotoxicity. 

Epidemiological and Human Dosimetry Studies. Acute high-level exposure to zinc by 

inhalation resulted in respiratory irritation and metal fume fever (Blanc et al. 1991; Hjortso et al. 1988; 

Johnson and Stonehill 1961; Linn et al. 1981; Schenker et al. 1981; Sturgis et al. 1927). Welders are a 

subpopulation of workers who have a high potential for exposure to zinc oxide. Most of the available 

studies did not report exposure levels or used a small number of subjects. Studies that correlate 

occupational exposure to zinc with health effects would be useful. A number of human oral exposure 

studies have shown that excess levels of zinc can result in anemia, pancreatic damage, decreased serum 

HDL cholesterol levels, and immunotoxicity (Black et al. 1988; Chandra 1984; Hooper et al. 1980). 

There are insufficient data for establishing dose-response relationships. Studies designed to establish 

dose-response relationships would be useful for establishing cause/effect relationships and future 

monitoring of individuals living near hazardous waste sites. 
ZINC 111 

3. HEALTH EFFECTS 

Biomarkers of Exposure and Effect. 

Exposure. Increased serum and urine levels of zinc were observed in humans and animals after 

inhalation, oral, or dermal exposure to zinc (Bentley and Grubb 1991; Brandao-Neto et al. 1990b; 

Hallmans 1977; Keen and Hurley 1977). However, the relationships between zinc exposure levels and 

the levels of zinc in biological fluids have not been established. Hair and nail samples may be a potential 

biomarker for long-term zinc exposure (McBean et al. 1971; Rivlin 1983; Wilhelm et al. 1991); however, 

no correlation has been demonstrated between these parameters and zinc exposure levels. Development 

of a biomarker with more exposure and dose data would aid in future medical surveillance that could lead 

to better detection of zinc exposure. 

Effect. Several potential biomarkers for the effects of zinc have been identified. These include increased 

levels of serum amylases and lipase, indicative of pancreatic damage; non-iron responsive anemia; and 

decreased HDL cholesterol levels (Suber 1989). However, these biomarkers of effect are not specific for 

zinc. These biomarkers cannot be used for dosimetry. A potential biomarker of exposure for recent 

exposures to zinc is increased erythrocyte metallothionein concentrations (Grider et al. 1990). Further 

investigation of serum biomarkers of effect, particularly for chronic exposure, in zinc-exposed 

populations would be useful to determine whether exposed populations may be experiencing adverse 

health effects as the result of zinc exposures. 

Absorption, Distribution, Metabolism, and Excretion. Absorption of zinc in humans after oral 

exposure to high levels has been well described (Aamodt et al. 1983; Hunt et al. 1991; Reinhold et al. 

1991; Sandstrom and Abrahamson 1989; Sandstrom and Cederblad 1980; Sandstrom and Sandberg 1992; 

Spencer et al. 1985). However, quantitative evidence of zinc absorption in humans after inhalation or 

dermal exposure is very limited. It is known that workers exposed to zinc oxide fumes who experience 

toxic effects have elevated levels of zinc in plasma and urine (Hamdi 1969). However, it remains to be 

established whether the elevated levels are the result of the pulmonary absorption or of the swallowing of 

particles leading to gastrointestinal absorption. Toxic effects have also been observed in humans after 

dermal exposure (DuBray 1937), indicating dermal absorption. 

Information regarding the absorption of zinc in animals following inhalation exposure was limited to lung 

retention data (Gordon et al. 1992; Hirano et al. 1989). However, there was information to assess the 

extent of absorption following oral exposure (Davies 1980; Galvez-Morros et al. 1992; Johnson et al. 
ZINC 112 

3. HEALTH EFFECTS 

1988; Weigand and Kirchgessner 1992). Evidence is limited regarding dermal absorption in animals, but 

it indicates that zinc sulfate and zinc oxide can penetrate the skin (Agren 1990; Agren et al. 1991; Gordon 

et al. 1981; Hallmans 1977). Mechanistic data on the oral absorption is reported by Hempe and Cousins 

(1992); however, there is a lack of information regarding the mechanism of action of inhalation and 

dermal exposures. 

Information on physiological levels and zinc distribution following subtoxic short-term exposures to zinc 

in humans and animals is abundant (NAS/NRC 1979; Wastney et al. 1986). Blood levels of zinc have 

been determined in humans following oral exposure to zinc sulfate (Neve et al. 1991; Statter et al. 1988; 

Sturniolo et al. 1991). Increased zinc tissue content has been seen after short-term oral exposure in 

humans (Cooke et al. 1990; He et al. 1991; Llobet et al. 1988a; Schiffer et al. 1991; Weigand and 

Kirchgessner 1992). Studies on tissue distribution in humans following high exposure to zinc for 

inhalation, oral, and dermal would be useful. There were no studies regarding blood or tissue distribution 

after acute, high-level exposures to zinc in animals following inhalation or dermal exposure. Additional 

mechanistic data on the transfer of zinc from respiratory and dermal absorption sites to the blood would 

be useful. 

The principal excretion route of ingested zinc is through the intestines (Davies and Nightingale 1975; 

Reinhold et al. 1991; Wastney et al. 1986). There is a lack of information regarding the excretion of zinc 

in both animals and humans following inhalation and dermal exposure. 

Therefore, additional studies designed to assess the toxicokinetic properties of zinc following inhalation 

and dermal exposures would be useful. 

Comparative Toxicokinetics. Data suggest that humans and animals have similar target organs of 

zinc toxicity (Allen et al. 1983; Aughey et al. 1977; Black et al. 1988; Blanc et al. 1991; Brown 1988; 

Chandra 1984; Chobanian 1981; Drinker et al. 1927b, 1927d; Hoffman et al. 1988; Hooper et al. 1980; 

Katya-Katya et al. 1984; Klevay and Hyg 1973; Lam et al. 1982, 1985, 1988; Maita et al. 1981; Moore 

1978; Murphy 1970; Smith and Larson 1946; Straube et al. 1980; Sturgis et al. 1927). Toxicokinetic 

studies have been performed in both humans and animals following oral exposure; however, data are 

limited for inhalation and dermal exposures. The animal model used most often to evaluate the 

toxicokinetics of zinc are rats (Agren et al. 1991; Alexander et al. 1981; Galvez-Morros et al. 1992; 

Hirano et al. 1989; Llobet et al. 1988a; Weigand and Kirchgessner 1992) and may be a good model for 

assessing the kinetics of zinc in humans. 
 

 

ZINC 113 

3. HEALTH EFFECTS 

Methods for Reducing Toxic Effects. No established methods or treatments for reducing the 

absorption of zinc were located. Studies that examined the effectiveness of emetics and cathartics in the 

prevention of zinc absorption would be useful. Once absorbed from the gastrointestinal tract, zinc bound 

to plasma albumin is distributed to the rest of the body. Zinc has a high affinity for proteins, and a 

number of chelating agents are effective in increasing urinary excretion of zinc following acute- and 

intermediate-duration administrations (Domingo et al. 1988a, 1988b; Llobet et al. 1989). Studies 

designed to examine the effectiveness of chelating agents following chronic zinc exposure would be 

useful in determining treatments to reduce the zinc body burden. Very little information is known about 

the absorption and distribution of zinc following inhalation or dermal exposure. Studies to determine the 

mechanisms of absorption and distribution would be useful for developing treatments or methods for 

reducing the toxic effects of zinc after inhalation or dermal exposure. 

Although the exact mechanisms of many of the toxic actions of zinc are not known, the pathogenesis of 

metal fume fever following inhalation exposure (McCord 1960; Mueller and Seger 1985) and anemia 

following oral exposure (Prasad et al. 1978) are known. Studies to more clearly elucidate the mechanisms 

involved in metal fume fever and anemia and to determine the mechanisms involved in pancreatic 

damage and decreased HDL cholesterol levels would be useful. Therapy for metal fume fever is mainly 

supportive (Mueller and Seger 1985). Administration of copper has been shown to be effective in 

alleviating zinc-induced anemia (Porter et al. 1977). Research into methods useful for mitigating metal 

fume fever and other adverse effects of zinc would be helpful. 

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. 

While a considerable amount of data are available on the effects of zinc deficiency on the growth and 

development of children, less is known about the effects of excess zinc on children. Accidental acute oral 

exposures result in mainly gastrointestinal symptoms, including nausea, vomiting, and epigastric 

discomfort (Anonymous 1983; Lewis and Kokan 1998; Moore 1978; Murphy 1970). Data are not 

presently available to determine whether children are more susceptible to these effects than adults. 

Similarly, additional animal studies examining the effects of similar exposure on young and mature 

animals would be useful to further clarify possible mechanisms of childhood susceptibility, if it exists. 
ZINC 114 

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 

A selection of ongoing studies, located in the Federal Research in Progress database (FEDRIP 2003), is 

presented in Table 3-6. 
ZINC 115 

3. HEALTH EFFECTS 

Table 3-6. Ongoing Studies on Zinc Health Effectsa 

Investigator Institute Research area 

Abrams SA Baylor College of Medicine, Zinc metabolism in health and chronic 

Houston, Texas inflammatory bowel disease children 

Black MM University of Maryland, Effect of micronutrient supplementation on 

Baltimore, Maryland children's growth, immune functioning, and 

morbidity 

Blanchard K Department of Veterans Affairs, Efficacy and safety of oral zinc therapy in 

Medical Center, Shreveport, patients with Polycythemia Vera 

Louisiana 

Blumenthal SS Department of Veterans Affairs, Cadmium, zinc, metallothionein, and kidney 

Medical Center, Milwaukee, cytotoxicity 

Wisconsin 

Bobilya DJ University of New Hampshire, Evaluation of zinc transport by using an in vitro 

Durham, New Hampshire model of the blood brain barrier under different 

conditions of zinc status 

Bobilya DJ University of New Hampshire, Testing to determine whether co-transport with 

Durham, New Hampshire albumin is a significant route for zinc transport by 

endothelial cells 

Brewer GJ University of Michigan at Ann Studies on the treatment of Wilson’s disease 

Arbor, Ann Arbor, Michigan with zinc 

Brown KH University of California, Bioavailability of vitamin A and zinc from 

Nutrition, Davis, California selected foods of potential use for intervention 

programs in populations at high risk of deficiency 

Brown KH University of California, Determination of the safety and efficacy of three 

Nutrition, Davis, California levels of zinc supplementation, provided with or 

without supplemental copper 

Brown NM Northwestern University, Combination of fluorescent microscopy studies 

Evanston, Illinois with biophysical and proteomic approaches to 

identify zinc rich cellular compartments and 

isolate the proteins associated with these 

vesicles 

Choi DW Washington University, St. Zinc and ischemic brain injury 

Louis, Missouri 

Choi DW Washington University, St. Study of Zn2+-mediated neurotoxicity 

Louis, Missouri 

Cline TR Purdue University, Animal Measurement of the effects of fasting, diet 

Science, West Lafayette, particle size and elevated levels of zinc on 

Indiana growth and stomach morphology in young pigs 

Disilvestro RA Ohio State University, College of Determine whether stress-induced accumulation 

Human Ecology, Columbus, of certain radicals is affected by copper and zinc 

Ohio consumption in rats 

Disilvestro RA Ohio State University, College of Zinc supplementation in Crohn's disease 

Human Ecology, Columbus, patients 

Ohio 
ZINC 116 

3. HEALTH EFFECTS 

Table 3-6. Ongoing Studies on Zinc Health Effectsa 

Investigator Institute Research area 

Fraker PJ Michigan State University, East 

Lansing, Michigan 

Identification of the underlying mechanisms that 

cause the lymphopenia and reduced host 

defense that accompanies zinc deficiency in 

humans and animals 

Freake HC University of Connecticut, 

Nutritional Sciences, Storrs, 

Effects of zinc on nuclear actions of thyroid 

hormone 

Connecticut 

Griffiths JK Tufts University Boston, Boston, 

Massachusetts 

Examination of how vitamin A and zinc 

supplementation interact in improving immunity, 

fostering growth, and preventing infection, in 

populations at risk for malnutrition and vitamin A 

and zinc deficiency 

Guo MG University of Vermont, 

Nutritional Sciences, Burlington, 

Vermont 

Determination of whether the solubility of 

minerals added as organic salts of Zn, Fe, and 

Cu is greater than that of formulae prepared 

using inorganic ones 

Hennig B University of Kentucky, Animal 

Science, Lexington, Kentucky 

Examination of the antiatherogenic properties of 

zinc 

Hennig B University of Kentucky, Animal 

Science, Lexington, Kentucky 

Interference of zinc with the generation of an 

oxidative environment mediated by fatty acids 

Johnson MA University of Georgia, College of 

Family and Consumer Science, 

Athens, Georgia 

Examination of the influence of supplements of 

copper, zinc, and/or manganese on indices of 

bone formation and bone resorption in 

postmenopausal women 

Keen CL University of California Davis, 

Davis, California 

Examination of potential mechanisms by which 

maternal and embryonic zinc deficiency arise, 

and how this deficiency results in abnormal 

development and growth 

King LM ARS, Germplasm and 

Physiology Lab, Beltsville, 

Maryland 

Mechanisms of zinc and calcium regulation of 

sperm storage in the turkey 

Lee J-M Washington University, St. 

Louis, Missouri 

Role of zinc in focal ischemic brain injury 

Lei DK University of Maryland, Human 

Nutrition and Food Science, 

College Park, Maryland 

Modulation of p53 human tumor suppressor 

gene expression by zinc status 

MacDonald RS University of Missouri, Food 

Science and Engineering, 

Columbia, Missouri 

Examination of the cellular and molecular 

mechanisms that become limiting in humans and 

animals when they are deprived of the essential 

nutrient zinc 

Mody I University of California Los 

Angeles, Los Angeles, California 

Pathological consequence of the plastic 

conversion of zinc (Zn2+)-insensitive synaptic 

GABA/A receptors into Zn2+-sensitive ones 

Moser-Veillon PB University of Maryland, Nutrition 

and Food Science, College 

Park, Maryland 

Zinc needs and homeostasis during lactation 
ZINC 117 

3. HEALTH EFFECTS 

Table 3-6. Ongoing Studies on Zinc Health Effectsa 

Investigator Institute Research area 

Onstad CA Agricultural Research Service, 

Houston, Texas 

Assessment of the effects of low zinc intake 

compared with a zinc intake consistent with the 

RDA on zinc absorption and kinetics in 

9–13-year-old girls 

Onstad CA Agricultural Research Service, 

Houston, Texas 

Measurement of the content of Ca, Mg, Fe, and 

Zn in existing germ-plasm of selected food crops 

to characterize genetic diversity 

Panemangalore M Kentucky State University, 

Human Nutrition Research 

Program, Frankfort, Kentucky 

Evaluation of the use of prophyrin profiles, 

ceruloplasmin, superoxide dismutase in serum 

or blood cells as biomarkers of zinc and copper 

status in humans and animals 

Reeves PG Agricultural Research Service, 

Grand Forks, North Dakota 

Studies to determine the correlation between 

sperm motility and heavy metals in semen, 

blood, urine, plasma, and saliva 

Sazawal S Johns Hopkins University, 

Baltimore, Maryland 

Role of zinc in childhood growth and 

development and the effects of zinc deficiency 

on childhood morbidity 

Spears JW North Carolina State University, 

Animal Science, Raleigh, North 

Carolina 

Determination of the effect of dietary level and 

source of zinc and copper on growth, 

reproduction, mineral status, and mineral 

excretion during the productive life span of 

female swine 

Tankanow RM University of Michigan at Ann 

Arbor, Ann Arbor, Michigan 

Zinc gluconate glycine lozenges and vitamin c 

effects on common cold 

Thompson RB University of Maryland, 

Baltimore, Maryland 

Development of a group of optical probes for 

studying zinc in neural tissue by fluorescence 

microscopy 

Tielsch JM Johns Hopkins University, 

Baltimore, Maryland 

Examination of the role of micronutrient 

deficiency on the health and well-being of 

women and children in underdeveloped areas of 

the world 

Wagner GJ University of Kentucky, 

Agronomy, Lexington, Kentucky 

Study of the mechanisms for vacuolar 

storage/sequestration of Cd, Zn, Mn, and Ni 

Weiss JH University of California Irvine, 

Irvine, California 

Ca2+, Zn2+, and selective excitotoxic 

neurodegeneration 

a

Source: FEDRIP 2003 

FEDRIP = Federal Research in Progress 

ZINC 119 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Information concerning the chemical identity of elemental zinc and zinc compounds is listed in Table 4-1. 

Zinc is a naturally occurring element found in the earth=s surface rocks. Because of its reactivity, zinc 

metal is not found as the free element in nature. There are approximately 55 mineralized forms of zinc. 

The most important zinc minerals in the world are sphalerite (ZnS), smithsonite (ZnCO3), and 

hemimorphite (Zn4Si2O7(OH2)H2O). Zinc appears in Group IIB of the periodic table and has two 

common oxidation states, Zn(0) and Zn(+2). Zinc forms a variety of different compounds, such as zinc 

chloride, zinc oxide, and zinc sulfate (Goodwin 1998; Ohnesorge and Wilhelm 1991; WHO 2001). 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

Information regarding the physical and chemical properties of elemental zinc and zinc compounds is 

located in Table 4-2. 

Zinc is a lustrous, blue-white metal that burns in air with a bluish-green flame. It is stable in dry air, but 

upon exposure to moist air, it becomes covered with a film of zinc oxide or basic carbonate (e.g., 

2ZnCO3·3Zn(OH)2) isolating the underlying metal and retarding further corrosion. Bonding in zinc 

compounds tends to be covalent, as in the sulfide and oxide (Goodwin 1998). In solution, four to six 

ligands can be coordinated with the zinc ion. Zinc has a strong tendency to react with acidic, alkaline, 

and inorganic compounds. Since zinc is amphoteric (i.e., capable of reacting chemically either as an acid 

or a base), it also forms zincates (e.g., [Zn(OH)3H2O]- and [Zn(OH)4]

2-) (Goodwin 1998; Ohnesorge and 

Wilhelm 1991; WHO 2001). 

In humans and animals, zinc is an essential nutrient that plays a role in membrane stability, in over 

300 enzymes, and in the metabolism of proteins and nucleic acids (WHO 2001). 
ZINC 120 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Zinc and Selected Compoundsa 

Characteristic Zinc Zinc acetate Zinc chloride 

Synonyms Zinc dust; zinc powder	 Acetic acid, zinc salt; Butter of zinc; chlorure de zinc 

acetic acid, zinc(II) salt; (French); zinc (Chlorure de) 

dicarbomethoxyzinc; (French); zinc butter; zinc 

octan zinecnaty [Czech]; chloride (ZnCl2); zinc 

zinc diacetate; zinc(II) dichloride; zinco (cloruro di) 

acetate (Italian); zinkchlorid (German); 

zinkchloride (Dutch) 

Registered trade Asarco; L 15; Blue No data Tinning flux (DOT)b

; AI3-0440; 

name(s) powder; CI 77945; CI Zintrace 

pigment Metal 6; 

Emanay zinc dust; 

Granular zinc; JASAD; 

Merrillite; PASCO 

Chemical formula Zn Zn(C2H3O2)2 ZnCl2 

Chemical structure Zn Cl-Zn-Cl O O 

2+

Zn

O O 

Identification numbers: 

CAS registry 7440-66-6 557-34-6 (anhydrous) 7646-85-7 

5970-45-6 (dihydrate) 

 NIOSH RTECS ZG8600000 AK1500000 (anhydrous) ZH1400000 

ZG8750000 (dihydrate) 

 EPA hazardous No data No data No data 

waste 

 OHM/TADS 7216955 No data 7216957 

 DOT/UN/NA/ Zinc, powder or dust, Zinc acetate, Zinc chloride, anhydrous, UN 

IMCO shipping UN 1436; zinc, powder environmental hazardous 2331; zinc chloride, solution, 

or dust, zinc ashes, substance, solid, NOS, UN 1840; zinc chloride, 

IMO4.3; zinc ashes, UN 3077 anhydrous, solution, IMO 8.3 

UN 1435 

HSDB 1344 1043 1050 

NCI No data No data No data 
ZINC 121 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Zinc and Selected Compoundsa 

Characteristic Zinc chromate Zinc cyanide 

Synonyms Basic zinc chromate; chromic acid, Cyanure de zinc (French); zinc 

zinc salt(1:1); chromic acid, zinc salt; dicyanide 

chromium zinc oxide; zinc chrome 

yellow; zinc chromate; zinc chromate 

AM; zinc chromate C; zinc chromate 

O; zinc chromate Z; zinc chromate(VI) 

hydroxide; zinc chrome; zinc chrome 

(anti-corrosion); zinc chromium oxide; 

zinc hydroxychromate; zinc 

tetraoxychromate 

Registered trade Pigment yellow 36; buttercup yellow; No data 

name(s) zinc tetraoxychromate 76A; zinc 

tetraoxychromate 780B; zinc yellow; 

ZTO; zincro ZTO 

Chemical formula ZnCrO4

Chemical structure O O

Zn(CN)2 

Zn 

Cr Zn C C 

O O N N 

Identification numbers: 

 CAS registry 13530-65-9 557-21-1 

 NIOSH RTECS GB3290000 ZH1575000 

EPA hazardous waste No data P121; an acute hazardous waste when 

a discarded commercial chemical 

product or manufacturing chemical 

intermediate or an off-specification 

commercial chemical product or a 

manufacturing chemical intermediate. 

D003; a waste containing zinc cyanide 

may (or may not) be characterized a 

hazardous waste following testing for 

the reactivity characteristics as 

prescribed by RCRA regulations 

OHM/TADS No data No data 

 DOT/UN/NA/IMCO No data Zinc cyanide, UN 1713; Zinc cyanide, 

shipping IMO 6.1 

HSDB 6188 1051 

NCI 77955 No data 
ZINC 122 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Zinc and Selected Compoundsa 

Characteristic Zinc hydroxide Zinc oxide 

Synonyms Zinc dihydroxide Zinc monoxide; zincum oxydatum; zinci oxydum; zinci 

oxicum; cynku tlenek (Polish) 

Registered trade 

name(s) 

No data Actox 14; Actox 16; Actox 216; AI3-00277; Akro-Zinc 

Bar85b

; Amalox; Amaloz; Azo 22; Azodox; Blanc de 

Zinc; Cadox XX 78; Caswell No 920; Chinese White; 

CI 77947; CI Pigment White 4; Electrox 2500; Emanay 

Zinc Oxide; Emar; Felling Zinc Oxide; Flores de Zinci; 

Flowers of Zinc; GIAP 10; Green Seal-8; Hubbuck's 

White; Kadox 15; Kadox-25; Kadox 72; Outmine; 

Ozide; Ozlo; Permanent White; Philosopher's Wool; 

Powder Base 900; Protox 166; Protox 168; Protox 169; 

Protox Type 166; Protox Type 167; Protox Type 168; 

Protox Type 169; Protox Type 267; Protox Type 268; 

Red Seal; Red seal-9; Snow White; Unichem ZO; 

Vandem VAC; Vandem VOC; Vandem VPC; C-Weiss 

8 (German); White Seal-7; XX 78; XX 203; XX 601; 

Zinca 20; Zinc White; Zincoid; Zn 0701T; Calamineb

; 

Zinciteb 

Chemical formula Zn(OH)2 ZnO 

Chemical structure HO Zn OH Zn=O 

Identification numbers: 

 CAS registry 20427-58-1 1314-13-2 

 NIOSH RTECS ZH3853000 ZH4810000 

EPA hazardous waste No data No data 

OHM/TADS No data No data 

 DOT/UN/NA/IMCO 

shipping 

No data No data 

HSDB No data 5024 

NCI No data No data 
 

 

 

 

 

 

 

 

 

 

 

ZINC 123 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Zinc and Selected Compoundsa 

Characteristic Zinc phosphate Zinc sulfate 

Synonyms 

Registered trade 

name(s) 

Chemical formula 

Chemical structure 

Identification numbers: 

 CAS registry 

 NIOSH RTECS 

Zinc ortho-phosphate; neutral zinc 

phosphate; tribasic zinc phosphate; 

trizinc diphosphate; zinc acid 

phosphate; zinc phosphate (3:2) 

Bonderite 181; Bonderite 40; 

Bonderite 880; C.I. Pigment White 

32; Delaphos; Delaphos 2M; 

Fleck’s Extraordinary; Fleck’s 

Extraordinary cement; Granodine 

16NC; Granodine 80; Heucophos 

ZP 10; LF Bowsei PW 2; Man-Gill 

51339; Man-Gill 51355; Microphos 

90; Phoshinox PZ 06; Pigment 

White 32; Sicor ZNP/M; ZPF; Sicor 

ZNP/S; Virchem 931; Weather coat 

1000; ZP-DL; ZP-SB 

Zn3(PO4)2

O O 

O P O O P O 

Zn2+ O 

Zn 2+ O 

Zn 2+ 

7779-90-0 

TD0590000 

EPA hazardous waste No data 

 OHM/TADS No data 

 DOT/UN/NA/IMCO No data 

shipping 

HSDB No data 

NCI No data 

Sulfate de zinc (French); sulfuric acid zinc 

salt; sulfuric acid, zinc salt (1:1); white 

copperas; white vitriol; zinc sulfate; zinc 

vitriol; zinci sulfas; zincum sulfuricum 

Bonazenb

; Medizinc; Bufopto Zinc sulfate; 

Op-thal-zin; Optraex; Solvenzink; 

Verazinc; zincate; Zincomed; Zinkosite; 

AI3-03967; Orazinc; Zinc-200; Zinklet; 

Neozin; Optised; Prefrin-Z; Visine-AC; 

Zincfrin; Zink-Gro 

ZnSO4

c 

O O

Zn S
 

O
 O 

7733-02-0 

ZH5260000 

No data 

7216958 

NA 9161 

1063 

No data 
 

ZINC 124 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Zinc and Selected Compoundsa 

Charactersitic Zinc sulfide 

Synonyms Wurtzite (alpha)b; sphalerite (beta)b; zinc monosulfide; zinc blende; zinc 

sulphide 

Registered trade Albalith; Irtran Z; Irtran 2; CI Pigment White 7; Sachtolith; Sachtolith HD-S; 

name(s) Cleartran 

Chemical formula ZnS 

Chemical structure Zn=S 

Identification numbers: 

 CAS registry 1314-98-3 

 NIOSH RTECS ZH5400000 

EPA hazardous waste D003 

 OHM/TADS No data 

 DOT/UN/NA/IMCO UN 3077; Zinc sulfide, environmentally hazardous substance, solid, NO; 

shipping UN 3082; zinc sulfide, environmentally hazardous substance, liquid, NOS 

HSDB 5802 

NCI No data 

a

Unless otherwise specified, all data from Chemfinder 2003; ChemID 2003; HSDB 2003; NIOSH 1990; and RTECS 

2003 

b

HSDB 1990 

c

O’Neil et al. 2001 

CAS = Chemical Abstracts Service; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North 

America/International Maritime Dangerous Goods Code; EPA = Environmental Protection Agency; 

HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = National Institute for 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; 

RCRA = Resource Conservation and Recovery Act; RTECS = Registry of Toxic Effects of Chemical Substances 
ZINC 125 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Zinc and Selected Compoundsa 

Property Zinc Zinc acetate Zinc chloride 

Molecular 65.38 183.48 136.29 

weight 

Color Bluish-white, lustrous White granules White granulesb 

Physical state Solid metal Solid Solid 

Melting point 419.5 °C 237 °C (decomposes) 290 °C 

Boiling point 

Density (g/cm3

) 

Odor 

908 °C 

7.14 at 25 °C 

No data 

No applicable 

1.735 

Faint acetous odorc 

732 °C 

2.907 at 25 °C 

Odorless; fume has acrid odorc 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water Insolubled

 4.0x104 mg/L at 25 °C; 

6.7x104

 mg/L at 100 °Cc 

4.32x106 mg/L at 25 °C; 

6.14x106

 mg/L at 100 °C 

Other 

solvent(s) 

Soluble in acetic acid and 

alkali 

33 mg/L in alcohol 1 g/1.3 mL alcohol; 1 g/2 mL 

glyderol; 1 g/0.25 mL 2% hydrochloroacetic acid 

Partition coefficients: 

Kd (mL/g) 0.1–8,000e

; 40 (average)f; 

39 in sandy loam soil; 

12.2 in sandy soilg 

No data No data 

Kow No data No data No data 

Koc No data No data No data 

Vapor pressure 1 mm Hg at 487 °C Not data Not data 

Henry’s law 

constant 

Not applicable Not applicable Not applicable 

Autoignition 

temperature 

Flashpoint 

Flammability 

limits 

No data 

No data 

No data 

No data 

No data 

No data 

Not flammableh 

Not flammableh 

Not flammableh 

Conversion 

factor 

Not applicable mg Zn(C2H3O2)2 x 0.36 

= mg Zn 

mg ZnSO4 x 0.40 = mg Zn 

Explosive limits No data No data No data 
ZINC 126 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Zinc and Selected Compoundsa 

Property 

Molecular weight 

Color 

Physical state 

Melting point 

Zinc chromate 

181.37 

Lemon-yellow 

Solid 

No data 

Zinc cyanide 

117.42 

Whitec 

Powderc 

800 °C (decomposes)c 

Zinc hydroxide 

99.40 

Colorlessc 

Solidc 

Decomposes at 125 

°Cc 

Boiling point 

Density (g/cm3

) 

Odor 

No data 

3.40 

Odorless 

Not applicable 

1.852c 

No data 

Not applicable 

3.053c 

No data 

Odor threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

Water 

Other solvent(s) 

Insoluble in cold water; sparingly 

soluble 

Soluble in acids, liquid ammonia; 

insoluble in acetone 

Insolublec

; 

50 mg/L at 20 °Cc 

Almost insolublec 

Soluble in dilute mineral 

acids 

No data 

Partition coefficients: 

Kd (mL/g) 

Kow 

No data 

No data 

No data 

No data 

No data 

No data 

Koc No data No data No data 

Vapor pressure 

Henry’s law 

constant 

No data 

Not applicable 

No data 

Not applicable 

No data 

Not applicable 

Autoignition 

temperature 

Flashpoint 

Flammability limits 

Conversion factor 

Explosive limits 

No data 

No data 

No data 

mg ZnCrO4 x 0.36 = mg Zn 

No data 

No data 

No data 

No data 

mg Zn(CN)2 x 0.56 = 

mg Zn 

No data 

No data 

No data 

No data 

mg Zn(OH)2 x 0.66 = 

mg Zn 

No data 
 

 

 

ZINC 127 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Zinc and Selected Compoundsa 

Property Zinc oxide Zinc phosphate Zinc sulfate 

Molecular 81.38 386.11 161.44 

weight 

Color White/yellowish-white Whitec

 Colorlessi 

Physical state Solid Powderc

 Solid 

Melting point 1975 °C 900 °Cc 680 °C (decomposes) 

Boiling point Sublimes No data No applicable 

Density 5.607 at 20 °C 3.998 at 15 °Cc 3.54 at 25 °C 

(g/cm3

) 

Odor Odorless Odorless Not determined 

Odor 

threshold: 

Water No data No data No data 

Air No data No data No data 

Solubility: 

 Water 1.6 mg/L at 29 °Ci

 Insolublej Soluble in cold and hot 

wateri

; 4.19x105 mg/L at 

0 °C; 9.1x105

 mg/L at 70 

°C 

Other Soluble in dilute acetic or mineral Soluble in dilute mineral Slightly soluble in 

solvent(s) acids, ammonia, ammonium acids, ammonium alcohol; soluble in 

carbonate, fixed alkali hydroxide hydroxide and alkali methanol and glyceroli

; 

solution, and ammonium chloridei

; hydroxide solutions; 1 g/2.5 mL glycerol 

insoluble in alcoholi insoluble in alcohol 

Partition coefficients: 

Kd No data No data No data 

Kow No data No data No data 

Koc No data No data No data 

Vapor Not data No data No data 

pressure 

Henry’s law Not applicable No data Not applicable 

constant 

Autoignition Not flammableh No data Not flammableh 

temperature 

Flashpoint Not flammableh No data Not flammableh 

Flammability Not flammableh No data Not flammableh 

limits 

Conversion mg ZnO x 0.80 = mg Zn mg Zn3(PO4)2 x 0.51 = mg mg ZnSO4 x 0.40 = mg 

factor Zn Zn 

Explosive No data No data No data 

limits 
ZINC 128 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical and Chemical Properties of Zinc and Selected Compoundsa 

Property Zinc sulfide (α) Zinc sulfide (γ) 

Molecular weight 97.45 97.45 

Color Colorlessi

 Colorless 

Physical state Solid Solid 

Melting point 1,700±20 °C No data 

Boiling point 1,185 °C at 1 atm 1,185 °C at 1 atm 

Density (g/cm3

) 3.98 at 20 °Ci; 4.087 at 25 °C 4.102 at 25 °C 

Odor No data No data 

Odor threshold: 

Water No data No data 

Air No data No data 

Solubility: 

Water 6.9 mg/L at 18 °Ci 6.5 mg/L at 18 °Ci 

Organic solvents Very soluble in alcohol; soluble in dilute mineral Very soluble in alcohol; soluble in 

acids; insoluble in acetic acid; insoluble in dilute mineral acids; insoluble in 

alkalis alkalis 

Partition coefficients: 

Kd No data No data 

Kow No data No data 

Koc No data No data 

Vapor pressure No data No data 

Henry’s law Not applicable Not applicable 

constant 

Autoignition No data No data 

temperature 

Flashpoint No data No data 

Flammability No data No data 

limits 

Conversion factor mg ZnS x 0.67 = mg Zn mg ZnS x 0.67 = mg Zn 

Explosive limits No data No data 

a

Information obtained from O’Neil et al. (2001) except where noted. b

ACGIH 1991 

c

Lewis 1997 

d

HSDB 2003 

e

Baes and Sharp 1983 

f

Baes et al. 1984 

g

Gerritse et al. 1982 

h

Weiss 1986 

i

Weast 1988 

j

Goodwin 1998 

Zn = zinc; Zn(C2H3O2)2 = zinc acetate; ZnCl2 = zinc chloride; ZnCrO4 = zinc chromate; Zn(CN)2 = zinc cyanide; 

Zn(OH)2 = zinc hydroxide; ZnO = zinc oxide; Zn3(PO4)2 = zinc phosphate; ZnS = zinc sulfide; ZnSO4 = zinc sulfate 
ZINC 129 

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

5.1 PRODUCTION 

No information is available in the TRI database on facilities that manufacture or process zinc because this 

chemical is not required to be reported under Section 313 of the Emergency Planning and Community 

Right-to-Know Act (Title III of the Superfund Amendments and Reauthorization Act of 1986) (EPA 

1997). 

Zinc is widely distributed in nature, constituting 20–200 ppm (by weight) of the Earth's crust (Goodwin 

1998), but it is not found as elemental zinc in nature (Lloyd and Showak 1984). The procedure used to 

mine zinc varies with the composition of the ore. The mineral sphalerite (ZnS) provides ca. 90% of the 

zinc produced today (Goodwin 1998). Zinc ore is mined using both underground mining and open pit 

mining (Stokinger 1981). The mined zinc ores are too low in zinc content for direct reduction to refined 

metal; thus, they are first concentrated. Production of concentrates requires crushing and grinding 

followed by gravity or magnetic methods of separation or flotation. These processes may be combined, 

depending on the complexity of the ore. A caustic-leach process is used to decrease the extent of metal 

loss during the concentration process. In this process, the metal is leached by caustic soda, the resulting 

electrolyte is purified with zinc dust and lime, and the zinc is electrodeposited. The crude zinc may be 

dissolved in sulfuric acid and purified by electrodeposition. Two processes are used to produce metallic 

zinc from the ore concentrates that are not subjected to caustic soda leaching. In one process, the ore 

concentrate containing zinc sulfide is roasted in the presence of air to produce zinc oxide, which is 

combined with coke or coal and retorted to approximately 1,100 °C to produce metallic zinc. In the other 

process, the roasted zinc oxide is leached with sulfuric acid, and the solution is electrolyzed to produce 

zinc of >99.9% purity. The electrolytic processing of zinc is replacing smelting as the most commonly 

used process (Lloyd and Showak 1984; Stokinger 1981). 

Continued low zinc prices in 2001 have resulted in operation reductions and facility closures across the 

United States. By the end of 2001, 12 mines in 5 states were in operation in the United States. Alaska 

was the leading zinc-mining state, followed by (in descending order) Tennessee, Missouri, New York, 

and Montana. Alaska also had the largest production of recoverable zinc in the United States in 2001, 

followed by Missouri, Montana, and New York. In 2001, three companies operated three primary zinc 

refineries (Zinc Corporation of America, Monaco, Pennsylvania; Big River Zinc Corporation, Sauget, 
ZINC 130 

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

Illinois; and Pasminco Ltd., Clarksville, Tennessee) (USGS 2001). Tables 5-1 and 5-2 summarize the 

facilities that manufacture or process zinc and zinc compounds, respectively, in the United States. The 

information in this table was obtained from the Toxics Release Inventory (TRI), and it summarizes the 

reported release data for 2002 (TRI02 2004). However, this list does not include all facilities that 

manufacture or process zinc and zinc compounds. Tables 5-1 and 5-2 also list the maximum amounts of 

zinc and zinc compounds, respectively, that are present at these sites and the end uses of zinc. In 2001, 

approximately 799,000 metric tons of zinc was produced in the United States from domestic ores. The 

estimated world production from mines in 2001 was 8,850,000 metric tons. The world production of zinc 

has increased from 1997 to 2001 (USGS 2001). 

Zinc is available in many commercial forms, including ingots, lumps, sheets, wire, shot, strips, sticks, 

granules, granulated zinc (obtained when molten metal is poured into cold water), and powder (O’Neil et 

al. 2001). 

5.2 IMPORT/EXPORT 

In 2002, approximately 874,000 metric tons of zinc were imported to the United States as refined slab 

zinc, 122,000 metric tons were imported as ores and concentrates, and 7,240 metric tons were imported as 

rolled zinc. In 2002, the United States imported more refined slab and rolled zinc than in 2001, going 

against the trend observed in the previous 4 years. More ores and concentrate were imported in 2002 than 

in the previous 4 years (USGS 2003). 

In 2002, an estimated 822,000 metric tons of ores and concentrates, 1,160 metric tons of slab zinc, and 

7,200 metric tons of rolled zinc were exported from the United States. In contrast, exports of ores and 

concentrates reached approximately 23,000 metric tons in 1985 and 461,000 in 1997 (DOI 1988, 1991; 

USGS 2002). In 2001, the United States exported the largest amounts of zinc ores and concentrates to 

Japan (210,000 metric tons), Canada (171,000 metric tons) and Spain (122,000 metric tons) (USGS 

2002). 

5.3 USE 

Zinc metal is used most commonly as a protective coating of other metals, such as iron and steel. 

Methods, in general, include hot-dip galvanizing, continuous-line galvanizing, electro-galvanizing, zinc 
 

 

 

 

ZINC 131 

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

Table 5-1. Facilities that Produce, Process, or Use Zinc 

Maximum 

Number of Minimum amount amount on site in 

Statea facilities on site in poundsb poundsb Activities and usesc 

AK 1 0 99 1, 5 

AL 64 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

AR 57 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14 

AZ 23 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 13 

CA 112 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CO 25 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CT 25 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 

FL 27 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13 

GA 43 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 

IA 34 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

ID 10 0 49,999,999 1, 3, 5, 8, 12, 13 

IL 128 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

IN 64 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

KS 16 0 999,999 1, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13 

KY 59 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

LA 55 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MA 30 0 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MD 16 0 999,999 1, 2, 3, 4, 5, 7, 8, 9, 10, 11 

ME 7 100 49,999,999 8, 11 

MI 88 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MN 23 100 999,999 1, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13 

MO 52 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

MS 19 0 99,999,999 2, 3, 5, 7, 8, 9, 10, 11, 12 

NC 44 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

ND 1 100 999 12 

NE 18 100 49,999,999 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 13 

NH 7 0 99,999 1, 5, 7, 8, 12 

NJ 64 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

NM 4 1,000 9,999,999 1, 5, 8, 12 

NV 6 10,000 9,999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12 

NY 55 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

OH 115 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

OK 40 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

OR 19 100 999,999 1, 2, 3, 4, 5, 7, 8, 9, 11, 12 

PA 112 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

PR 11 100 999,999 1, 2, 3, 5, 7, 8, 10 

RI 11 100 999,999 1, 3, 4, 5, 8, 9, 10 

SC 44 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 
ZINC 132 

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

Table 5-1. Facilities that Produce, Process, or Use Zinc 

Maximum 

Number of Minimum amount amount on site in 

Statea facilities on site in poundsb poundsb Activities and usesc 

SD 6 1,000 99,999 1, 2, 3, 5, 7, 8, 12, 14 

TN 66 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

TX 97 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

UT 18 100 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13 

VA 42 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

VT 2 10,000 99,999 1, 5, 8 

WA 21 100 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13 

WI 57 0 99,999,999 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, 11, 12, 13 

WY 6 1,000 999,999 1, 4, 6, 9, 10, 12 

Source: TRI02 2004 (Data are from 2002) 

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 
ZINC 133 

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

Table 5-2. Facilities that Produce, Process, or Use Zinc Compounds 

Number of Minimum amount Maximum amount 

Statea facilities on site in poundsb on site in poundsb Activities and usesc 

AK 12 10,000 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13 

AL 166 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AR 146 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

AZ 66 100 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CA 237 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CO 47 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

CT 97 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

DE 36 100 999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

FL 97 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

GA 182 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

HI 13 100 999,999 1, 2, 3, 4, 5, 7, 9, 10, 12 

IA 127 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

ID 25 0 49,999,999 1, 2, 3, 5, 6, 7, 8, 10, 11, 12, 13 

IL 348 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

IN 241 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

KS 81 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

KY 134 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

LA 153 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MA 114 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MD 75 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

ME 31 0 999,999 1, 3, 5, 6, 7, 8, 10, 11, 12, 13 

MI 314 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MN 79 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MO 164 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MS 94 0 99,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

MT 16 100 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

NC 139 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

ND 9 1,000 99,999 1, 5, 7, 9, 12, 13 

NE 84 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

NH 18 0 999,999 1, 5, 6, 7, 8, 9, 10, 12 

NJ 173 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 

NM 22 0 10,000,000,000 1, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14 

NV 61 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

NY 180 0 10,000,000,000 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OH 405 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OK 105 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

OR 55 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

PA 279 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

PR 52 0 999,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 
 

 

ZINC 134 

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

Table 5-2. Facilities that Produce, Process, or Use Zinc Compounds 

Number of Minimum amount Maximum amount 

Statea facilities on site in poundsb on site in poundsb Activities and usesc 

RI 35 100 999,999 1, 2, 3, 4, 5, 6, 7, 8, 10, 11, 12 

SC 136 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

SD 15 100 9,999,999 1, 5, 7, 8, 9, 10, 11, 12, 13 

TN 209 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

TX 336 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

UT 68 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

VA 112 0 49,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

VT 6 1,000 99,999 6, 7 

WA 56 0 9,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

WI 156 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

WV 76 0 499,999,999 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 

WY 15 0 9,999,999 1, 3, 4, 5, 6, 7, 9, 12, 13 

Source: TRI02 2004 (Data are from 2002) 

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 
ZINC 135 

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

plating, zinc spraying, and painting with zinc-bearing paints. Some examples of galvanized materials 

include nails, water towers, and electrical transmission towers. Because zinc metal lacks strength, it is 

frequently alloyed with other metals (e.g., aluminum, copper, titanium, and magnesium) to impart a range 

of properties. When zinc metal is the primary component of the alloy, it is called a ‘zinc-base’ alloy, 

which is primarily used for casting and wrought applications. Other important applications of zinc alloys 

are in dye-casting, construction, and in other alloys (e.g., brass and bronze) which may be found in 

electrical components of many household goods. Also, alloys containing zinc and copper are used to 

make U.S. one-cent coins. Zinc metal dust is widely used in paint coatings, as a catalyst, and as a 

reducing and precipitating agent in organic and analytical chemistry (Goodwin 1998). As shown in 

Table 5-3, in 2002, the reported consumption of zinc by industry was 265,000 metric tons (53.4% of total 

consumption) for galvanizing; 103,000 metric tons (20.8% of total consumption) for zinc-based alloys; 

and 86,800 metric tons (17.5% of total consumption) for bass and bronze (USGS 2002). 

Zinc compounds have dental, medical, and household applications. In pharmaceuticals, zinc salts are 

used as solubilizing agents in many drugs, including insulin (Lloyd 1984; Lloyd and Showak 1984; 

Windholz 1983). Zinc compounds are utilized therapeutically in human medicine in the treatment of zinc 

deficiency (Keen and Hurley 1977). Zinc oxide accounts for the largest use of zinc compounds, and is 

used primarily by the rubber industry as a vulcanization activator and accelerator and to slow rubber 

aging by neutralizing sulfur and organic acids formed by oxidation. It also acts in rubber as a reinforcing 

agent, a heat conductor, a white pigment, and an absorber of UV light. In paints, zinc oxide serves as a 

mildewstat, acid buffer, and a pigment. It is used in animal feed as a zinc supplement and as a fertilizeradditive for zinc-deficient soils. Zinc oxide is used in cosmetics and drugs primarily for its fungicide 

properties, and in dentistry in dental cements. It is also used in ceramics, in glass manufacture, as a 

catalyst in organic synthesis, and in coated photocopy paper (Goodwin 1998). The largest uses of zinc 

chloride in the United States are in wood preservation, solder fluxes, and batteries. Solutions of zinc 

chloride are widely used in mercerizing cotton and as a mordant in dying. In medicine, zinc chloride is 

used as an antiseptic, disinfectant, deodorant, and in dental cements. Other uses are in organic synthesis, 

as a dehydrant, in rubber vulcanization, and in oil refining (Goodwin 1998). Zinc chloride is a primary 

ingredient in smoke bombs used for crowd dispersal, in fire-fighting exercises (by both military and 

civilian communities), and by the military for screening purposes (WHO 2001). Zinc sulfate is used in 

fertilizers, sprays, and animal feed as a trace element and disease-control agent. It is used in the 

manufacture of rayon (as crenulating agent), as a starting material for many zinc chemicals, in textile 

dying and printing, in flotation reagents, for electrogalvanizing, in paper bleaching, and in glue (Goodwin 

1998). Zinc sulfide is used as a phosphor (watches, TV screens), a white pigment, and in dental materials 
 

 

 

ZINC 136 

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

Table 5-3. Distribution of U.S. Zinc Consumption in 2002 

Use Total (metric tons) Percent of total 

Galvanizing 265,000 53.4 

Zinc-based alloys 103,000 20.8 

Brass and bronze 86,800 17.5 

Totala 496,000 100.0 

Source: USGS 2002 

a

The data were rounded off to three significant figures and therefore the sum of the total may not equal the total 

amount reported. A small unspecified amount of zinc was consumed for "other" uses. 
 

 

ZINC 137 

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

(especially in form of lithopone) (O’Neil et al. 2001). Uses for zinc acetate are as a wood preservative, a 

mordant for antiseptics, a catalyst, and a waterproofing agent. Zinc cyanide has two uses: electroplating 

and gold extraction. The primary uses of zinc phosphate are in preparation of metal coatings and as a 

dental cement (Goodwin 1998). Zinc chromate is used in pigments. Zinc hydroxide uses are as an 

intermediate, as an absorbent in surgical dressings, and in rubber compounding (Lewis 1997). 

5.4 DISPOSAL 

Zinc processing plants have attempted to limit releases to the environment by using techniques such as 

water reuse, control of particulate emissions, and filtration thickener overflow. In addition, liquid 

effluents are limed and allowed to settle so that zinc can precipitate out as the hydroxide (Lloyd and 

Showak 1984). Waste products containing zinc are also being used as a source of zinc for 

electrogalvanizing (Jolly 1988). Disposal procedures for spills include ferric hydroxide precipitation and 

cement-based fixation processes; the latter method is very effective in rendering zinc contaminants 

insoluble (Dawson and Mercer 1986). Unsalvageable zinc waste may be buried in an approved landfill 

while salvageable zinc is typically recycled. In 2003, an estimated 370,000 tons of zinc were recovered 

from waste and scrap in the United States; about 30% was recovered in the form of slab zinc and the 

remainder was recovered in alloys, oxide, and chemicals. Of the total amount of scrap recycled, in 2002, 

319,000 tons was derived from new scrap and 47,300 tons were derived from old scrap. About 

25,000 tons of scrap in the United States were exported mainly to China, India, and Taiwan. Most of this 

scrap (95%) came from Canada (USGS 2003). 

In 1989, EPA applied its revised interpretation of the Bevill Amendment (exclusion) to solid waste from 

the extraction, beneficiation, and processing of ores and minerals. The slag from the primary zinc 

processing is the only zinc-related waste remaining in the Bevill exclusion (DOI 1991). 

 

 

ZINC 139 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW
 

Zinc has been identified in at least 985 of the 1,662 hazardous waste sites that have been proposed for 

inclusion on the EPA National Priorities List (NPL) (HazDat 2005). However, the number of sites 

evaluated for zinc is not known. The frequency of these sites can be seen in Figure 6-1. Of these sites, 

969 are located within the United States, and 2, 12, and 2 sites are located in the Commonwealth of 

Guam, Puerto Rico, and the Virgin Islands, respectively. 

Zinc is an element commonly found in the Earth's crust. It is released to the environment from both 

natural and anthropogenic sources; however, releases from anthropogenic sources are greater than those 

from natural sources. The primary anthropogenic sources of zinc in the environment (air, water, soil) are 

related to mining and metallurgic operations involving zinc and use of commercial products containing 

zinc. Worldwide, releases to soil are probably the greatest source of zinc in the environment. The most 

important sources of anthropogenic zinc in soil come from discharges of smelter slags and wastes, mine 

tailings, coal and bottom fly ash, and the use of commercial products such as fertilizers and wood 

preservatives that contain zinc. Zinc does not volatilize from soil. Although zinc usually remains 

adsorbed to soil, leaching has been reported at waste disposal sites. Zinc does not volatilize from water 

but is deposited primarily in sediments through adsorption and precipitation. Severe zinc contamination 

tends to be confined to areas near emission sources. Large amounts of contaminated soil would need to 

be ingested in order to reach the registered dietary index value of 3.3–3.8 mg of zinc a day. It is therefore 

unlikely that the zinc found in the contaminated soil would pose a health risk if ingested. 

Zinc is capable of forming complexes with a variety of organic and inorganic groups (ligands). 

Biological activity can affect the mobility of zinc in the aquatic environment, although the biota contains 

relatively little zinc compared to the sediments. Zinc bioconcentrates moderately in aquatic organisms; 

bioconcentration is higher in crustaceans and bivalve species than in fish. Zinc does not concentrate in 

plants, and it does not biomagnify through terrestrial food chains. 

In some fish, it has been observed that the level of zinc found in their bodies did not directly relate to the 

exposure concentrations. A recent study shows that bioaccumulation of zinc in fish is inversely related to 
ZINC 140 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Zinc Contamination 

Frequency of 

NPL Sites 

1-14
 

15-29
 

30-44
 

45-59
 

Derived from HazDat 2005
 60-74
 

75-85
 
ZINC 141 

6. POTENTIAL FOR HUMAN EXPOSURE 

the aqueous exposure (McGeer et al. 2003). This evidence suggests that fish placed in environments with 

lower zinc concentrations can sequester zinc in their bodies. 

There are few data regarding the speciation of zinc released to the atmosphere. Zinc is removed from the 

air by dry and wet deposition, but zinc particles with small diameters and low densities suspended in the 

atmosphere travel long distances from emission sources. 

Zinc has been detected in air, surface water, groundwater, and soil; the frequency of detection and the 

concentrations are greatest near source areas (e.g., hazardous waste sites and industrial areas such as lead 

smelters). In a survey by the National Air Surveillance Network, the mean concentration of zinc in the air 

in the United States in 1977–1979 was 0.02–0.16 μg/m3

 for urban air compared to 0.01–0.05 μg/m3 for 

rural air. The concentrations of zinc in the air of remote areas range from <0.003 to 0.027 μg/m3

. The 

mean concentrations of zinc in ambient water and drinking water range from 0.02 to 0.05 mg/L and from 

0.01 to 0.1 mg/L, respectively. The concentration of zinc in drinking water can often be higher than the 

concentration in the raw water from which the drinking water was obtained because zinc may leach from 

transmission and distribution pipes. The concentration of zinc in standing water from galvanized 

household water pipes was ≤1.3 mg/L (Sharrett et al. 1982a). The concentration of zinc in cultivated soils 

in the United States ranged from <5 to 400 mg/kg, with a mean of 36 mg/kg, compared to a range of <10– 

2,000 mg/kg, with a mean of 51 mg/kg, in uncultivated soils; this probably results from the differences in 

soils used for farming rather than the use of zinc in agriculture. Concentrations of zinc can be high in 

soils from contaminated sites, such as waste dumps. 

The concentrations of zinc in various foods and human tissues have also been determined. Certain 

population groups may be exposed to higher concentrations of zinc than the general population. People 

who work in coal mines, people who work with the refining and smelting of nonferrous metals, and 

people who live near waste sites and metal smelting operations may be exposed to high levels of zinc. A 

study of the tissue of deceased copper smelter workers in Sweden showed that they had, on average, 

58.9 and 31.5 mg/kg wet weight of zinc in the liver and kidney, respectively, as compared to the controls, 

who had 47.2 and 23.3 mg/kg wet weight of zinc in the liver and kidney, respectively. The controls, 

however, had a higher concentration of zinc in the hair (233 mg/kg as opposed to the smelter workers 

who had 212 mg/kg) (Gerhardsson et al. 2002). People who consume large amounts of foods high in zinc 

content, such as oysters and mussels, may also be exposed to elevated levels of zinc. The zinc body 

burdens of the copper smelter workers were not significantly different than that of the controls. Higher 

exposure may or may not be manifested as increased body burden in the exposed individuals. 
 

 

ZINC 142 

6. POTENTIAL FOR HUMAN EXPOSURE 

According to NHANES 1999–2000 dietary data, a large portion of obese people over the age of 50 are 

not getting the recommended amount of zinc (Bermudez et al. 2003). The RDA for zinc is 11 mg/day for 

men and 8 mg/day for women (see Section 3.1). Much of the human zinc intake comes from eating meat 

and meat products. A typical Italian diet contains about10.6 mg of dietary zinc per day, where 4.3 mg of 

zinc comes from meat and meat products (Lombardi-Boccia et al. 2003). Nonvegetarians absorb a higher 

percentage of zinc (3.7 mg/day) than vegetarians (2.4 mg/day) (Hunt 2003; Hunt et al. 1998). Infants also 

need zinc, and the RDA for zinc in pregnant and nursing mothers is 12 mg/day. A recent study of breast 

milk in lactating mothers showed an average zinc concentration of about 5.65 mg/L. This average did not 

vary much depending on the age of the mother (Honda et al. 2003). 

6.2 RELEASES TO THE ENVIRONMENT 

The TRI data should be used with caution because only certain types of facilities are required to report 

(EPA 1997). This is not an exhaustive list. Manufacturing and processing facilities are required to report 

information to the Toxics Release Inventory only if they employ 10 or more full-time employees; if their 

facility is classified under Standard Industrial Classification (SIC) codes 20–39; and if their facility 

produces, 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 1997). 

Zinc is commonly found in the earth's crust, and natural releases to the environment can be significant. In 

addition, zinc is one of the most widely used metals in the world. The major industrial sources of zinc 

include electroplating, smelting and ore processing, and drainage from both active and inactive mining 

operations (Mirenda 1986). Furthermore, zinc is an important component of brass, bronze, die casting 

metal, other alloys, rubber, and paints. The environmental releases of zinc from sources of human origin 

far exceed the releases from natural sources (Fishbein 1981). 

6.2.1 Air 

Estimated releases of 0.91 million pounds (~413 metric tons) of zinc to the atmosphere from 

389 domestic manufacturing and processing facilities in 2002, accounted for about 1.9% of the estimated 

total environmental releases from facilities required to report to the TRI (TRI02 2004). These releases are 

summarized in Table 6-1. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ZINC 143 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that 

Produce, Process, or Use Zinca
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek 

On- and 

off-site 

AL 9 25,166 26,199 0 98,857 18,716 51,365 117,573 168,938 

AR 8 12,295 5 0 141,993 7,440 154,293 7,440 161,733 

AZ 2 500 0 0 0 0 500 0 500 

CA 21 4,853 19,219 0 1,155,909 339 1,161,251 19,069 1,180,320 

CO 5 1,385 383 0 13,847 5,808 12,978 8,445 21,423 

CT 3 500 0 0 0 0 500 0 500 

DE 1 No data No data No data No data No data No data No data No data 

FL 5 1,277 5 0 0 3,800 1,282 3,800 5,082 

GA 9 521 0 0 28,010 420 521 28,430 28,951 

IA 11 15,806 82 0 48,666 0 15,887 48,666 64,553 

ID 3 6,863 0 0 21,957,330 520 21,964,193 520 21,964,713 

IL 24 134,748 750 0 680,474 30,373 134,748 711,597 846,345 

IN 20 12,445 267 0 44,651 40,370 36,473 61,261 97,734 

KS 4 4,541 0 0 36,921 4 4,541 36,925 41,466 

KY 15 16,266 0 0 35,572 618 17,866 34,590 52,456 

LA 13 12,382 0 0 54,683 0 12,382 54,683 67,065 

MA 6 270 178 0 0 468 270 646 916 

MD 3 122 0 0 5,537 0 122 5,537 5,659 

ME 1 0 0 0 5,569 1,646 0 7,215 7,215 

MI 15 4,927 9 0 660,702 10,912 114,609 561,941 676,550 

MN 4 249 0 0 0 0 249 0 249 

MO 9 5,391 0 0 77,964 0 73,772 9,583 83,355 

MS 6 720 251 0 9,025 0 9,746 250 9,996 

NC 19 1,203 0 0 342,077 2,487,306 1,203 2,829,383 2,830,586 

NE 2 3,194 0 0 5 10 3,199 10 3,209 

NH 1 950 0 0 0 5 950 5 955 

NJ 7 10,681 0 0 5,700 14,623 10,681 20,323 31,004 

NM 1 0 0 0 252,500 0 252,500 0 252,500 

NV 2 972 0 0 70,226 0 71,198 0 71,198 

NY 10 8,103 0 0 11,278 525 18,203 1,703 19,906 

OH 32 85,004 6,334 0 9,415,075 6,165,482 9,389,168 6,282,727 15,671,896 

OK 8 17,406 50 0 0 42,403 17,456 42,403 59,859 
 

 

 

 

 

 

 

 

 

 

 

 

ZINC 144 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Releases to the Environment from Facilities that 

Produce, Process, or Use Zinca
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek 

On- and 

off-site 

OR 1 0 0 0 37,960 0 37,960 0 37,960 

PA 20 64,389 144 0 353,840 58,168 64,709 411,832 476,541 

PR 2 0 0 0 0 5 0 5 5 

RI 3 930 0 0 0 5 930 5 935 

SC 8 27,976 168 0 20,724 7,596 35,372 21,092 56,464 

SD 2 1,085 0 0 3,218 0 1,335 2,968 4,303 

TN 12 9,000 705 0 164,297 22,208 23,431 172,779 196,210 

TX 19 46,875 2,211 0 63,988 121,879 73,195 161,758 234,953 

UT 4 119 0 0 8,009 8 6,613 1,523 8,136 

VA 9 340,253 1,316 0 38,919 2,986 369,093 14,381 383,474 

WA 1 No data No data No data No data No data No data No data No data 

WI 17 4,738 250 0 1,228,914 4,607 4,988 1,233,521 1,238,509 

WV 9 26,652 0 0 52,674 6,111 79,326 6,111 85,437 

WY 3 208 0 0 42,767 0 39,672 3,303 42,975 

Total 389 910,964 58,525 0 37,167,881 9,055,361 34,268,728 12,924,002 47,192,731 

Source: TRI02 2004 (Data are from 2002) 

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, wastewater 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 
 

 

 

 

ZINC 145 

6. POTENTIAL FOR HUMAN EXPOSURE 

Natural emissions of zinc and its compounds to air are mainly due to windborne soil particles, volcanic 

emissions, and forest fires. The global flux of zinc due to erosion is estimated to be 915,000 tonnes/year; 

of this total, 681,000 tonnes comes from high-temperature thermal vents in mid-ocean ridges (WHO 

2001). Volcanic release of zinc has been estimated to be around 35,800 tonnes/year (Lantzy 1979). The 

eruption of Mt. Pinatubo alone released an estimated 800,000 tonnes of zinc into the atmosphere in 1991 

(Garrett 2000). Other natural sources of zinc in air are biogenic emissions and sea salt sprays with annual 

amounts estimated to be 8,100 and 440 metric tons, respectively (Nriagu 1989). 

Anthropogenic releases of zinc and its compounds to the atmosphere are from dust and fumes from 

mining, zinc production facilities, processing of zinc-bearing raw materials (e.g., lead smelters), brass 

works, coal and fuel combustion, refuse incineration, and iron and steel production (EPA 1980d; Ragaini 

et al. 1977). In urban East St. Louis, Illinois, industrial complexes, such as smelters, accounted for about 

86% of fine and course particulate matter emitted into air. In southeastern Chicago, Illinois, incinerator 

emissions accounted for 86% of fine particulate in the atmosphere while urban dust account for 93% of 

the course particulate emissions (Sweet et al. 1993). Estimated atmospheric zinc loss is 100 g/ton of zinc 

mined, and most of the loss comes from handling raw and concentrated ore and wind erosion of tailing 

piles (Lloyd and Showak 1984). Average zinc emissions to the atmosphere from stationary sources in the 

United States were 151,000 tons/year (137,000 metric tons/year) for 1969–1971 (Fishbein 1981). Based 

on emission studies in Western Europe, the United States, Canada, and the former Soviet Union, total 

worldwide zinc emissions to air were calculated to range from 70,250 to 193,500 metric tons in 1983. 

Emissions from the nonferrous metal industry account for the largest fraction of zinc emitted (50–70%) 

(Nriagu and Pacyna 1988). However, emissions have decreased considerably since the 1970s and 1980s 

as a result of improvements in contemporary zinc production facilities. Zinc emissions decreased 73% for 

air and 83% for water during the years 1985–1995 (WHO 2001). 

According to the TRI, estimated totals of 910,964 pounds (413 metric tons) of zinc (dust and fume) and 

6,415,067 pounds (2,909 metric tons) of zinc compounds, amounting to about 1.9 and 0.92%, 

respectively, of the total environmental on-site releases, were discharged into the atmosphere in the 

United States in 2001 from mining, manufacturing, processing, and electrical power generation industries 

listed in Tables 6-1 and 6-2 (TRI02 2004). Data for stack/point source emissions indicate releases of 

495,206 pounds (224 metric tons) of zinc (dust and fume) and 4,617,457 pounds (2,094 metric tons) of 

zinc compounds, while data for fugitive source emission indicate a release of 375,586 pounds (170 metric 

tons) of zinc (dust and fume) and 1,542,235 pounds (700 metric tons) of zinc compounds. The TRI data 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ZINC 146 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that 

Produce, Process, or Use Zinc Compoundsa
 

Reported amounts released in pounds per yearb 

Total release 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek 

On- and 

off-site 

AK 5 57,736 892 10,000,000 295,817,343 0 305,875,971 0 305,875,971 

AL 91 146,282 73,856 77,052 5,220,635 7,077,255 4,908,757 7,686,323 12,595,081 

AR 78 81,410 102,806 6,991 696,606 2,389,162 336,042 2,940,934 3,276,976 

AZ 21 32,825 20,160 144,780 25,217,086 2,004 25,376,638 40,217 25,416,855 

CA 119 63,649 19,734 9,665 595,116 20,349 398,970 309,543 708,513 

CO 19 57,253 344 25,996 198,087 10,270 176,373 115,577 291,950 

CT 32 5,722 28,075 0 133,452 134,880 7,120 295,010 302,129 

DE 13 10,020 17,921 0 107,926 17,708 58,714 94,861 153,575 

FL 66 72,363 93,297 48,570 2,000,003 88,270 1,937,933 364,570 2,302,503 

GA 114 244,067 98,139 0 1,233,070 210,195 1,099,676 685,796 1,785,472 

HI 1 20 0 0 37,942 0 20 37,942 37,962 

IA 95 77,263 117,986 31,317 1,768,665 95,611 488,463 1,602,378 2,090,841 

ID 12 41,585 2,108 0 3,669,321 95 3,700,829 12,280 3,713,109 

IL 221 395,491 149,295 163,316 27,247,648 1,294,295 22,947,032 6,303,014 29,250,046 

IN 157 723,924 286,946 15,177 37,744,073 24,151,185 8,875,522 54,045,784 62,921,306 

KS 42 97,372 1,625 1,685 450,609 101,544 304,823 348,012 652,835 

KY 92 83,843 125,476 4,375 2,453,652 183,585 2,167,004 683,927 2,850,931 

LA 77 147,835 81,079 167,914 4,761,318 340,895 3,238,709 2,260,332 5,499,041 

MA 50 9,766 2,381 0 363,863 136,582 35,580 477,012 512,592 

MD 34 17,599 23,384 10,389 205,405 149,224 178,885 227,116 406,001 

ME 8 16,887 16,090 0 449,015 5,450 174,943 312,499 487,442 

MI 159 213,987 286,754 16,000 43,809,978 423,988 909,641 43,841,066 44,750,707 

MN 55 19,108 49,405 0 1,393,144 329,519 507,238 1,283,938 1,791,176 

MO 97 565,546 27,386 20,266 31,884,266 142,655 32,046,061 594,058 32,640,118 

MS 54 256,284 98,069 375,083 311,418 174,217 709,670 505,401 1,215,070 

MT 6 6,244 21 0 10,787,188 1,745 10,775,448 19,750 10,795,198 

NC 99 45,630 24,744 39,813 1,600,363 305,408 827,882 1,188,075 2,015,958 

ND 4 760 23 0 180,026 0 77,783 103,026 180,809 

NE 42 237,066 6,864 0 635,674 3,396,549 566,918 3,709,235 4,276,152 

NH 10 333 825 0 5,165 5,467 2,148 9,642 11,791 

NJ 80 20,689 64,099 6,287 512,445 1,109,971 131,391 1,582,100 1,713,491 

NM 11 2,660 670 0 515,365 0 367,346 151,349 518,695 

NV 21 6,904 1,006 0 13,889,325 26,367 13,893,110 30,492 13,923,602 

NY 76 86,776 64,436 0 1,089,648 113,112 495,131 858,840 1,353,971 

OH 298 216,289 305,502 480,784 13,434,185 1,583,235 2,138,108 13,881,887 16,019,995 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ZINC 147 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Releases to the Environment from Facilities that 

Produce, Process, or Use Zinc Compoundsa
 

Reported amounts released in pounds per yearb 

Total release 

On- and 

Statec RFd Aire Waterf UIg Landh Otheri On-sitej Off-sitek off-site 

OK 50 24,320 14,242 88,407 1,035,166 665,664 489,512 1,338,287 1,827,799 

OR 31 17,533 19,513 0 262,676 267,398 54,083 513,037 567,120 

PA 187 1,452,852 198,276 73,781 11,446,276 22,981,774 2,213,480 33,939,479 36,152,959 

PR 15 3,800 463 0 31,944 272,783 35,858 273,133 308,991 

RI 6 217 45 0 65,720 3,314 217 69,079 69,296 

SC 76 213,093 47,512 14,331 1,823,765 13,098,684 1,644,194 13,553,191 15,197,385 

SD 12 5,521 59 5 1,067,005 0 1,053,460 19,130 1,072,590 

TN 118 229,905 90,647 12,856 24,051,495 479,494 22,909,614 1,954,784 24,864,397 

TX 211 201,120 344,154 2,103,302 2,913,177 344,478 2,118,673 3,787,557 5,906,230 

UT 24 12,446 3,747 0 6,728,264 270,481 6,738,249 276,689 7,014,938 

VA 62 95,445 70,786 3,429 4,932,625 679,941 848,684 4,933,543 5,782,227 

VT 3 0 0 0 46,117 0 0 46,117 46,117 

WA 25 15,956 12,218 0 299,308 27,754 120,295 234,941 355,236 

WI 108 62,409 17,693 4,857 3,218,796 168,323 110,208 3,361,870 3,472,078 

WV 34 14,267 95,866 0 1,323,140 192,671 1,132,148 493,795 1,625,944 

WY 7 4,993 2,410 0 140,640 9,543 119,725 37,861 157,586 

Total 3,328 6,415,067 3,109,033 13,946,427 589,805,136 83,483,093 485,324,282 211,434,474 696,758,756 

Source: TRI02 2004 (Data are from 2002) 

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, wastewater 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 
 

 

ZINC 148 

6. POTENTIAL FOR HUMAN EXPOSURE 

should be used with caution since only certain facilities are required to report. This is not an exhaustive 

list. 

Zinc has been identified in air at 37 sites collected from the 985 NPL hazardous waste sites where it was 

detected in some environmental media (HazDat 2005). 

6.2.2 Water 

Estimated releases of 0.059 million pounds of zinc to surface water from 389 domestic manufacturing and 

processing facilities in 2002, accounted for about 0.1% of the estimated total environmental releases 

(TRI02 2004). This value includes the amount that was released to publicly owned treatment works 

(POTWs) (TRI02 2004). These releases are summarized in Table 6-1. 

Zinc and its compounds are found in the earth's crust and are present in most rocks, certain minerals, and 

some carbonate sediments. As a result of weathering of these materials, soluble compounds of zinc are 

formed and may be released to water (NAS 1977). The largest input of zinc to water results from erosion 

of soil particles containing natural traces of zinc (45,400 metric tons/year) (EPA 1980d). Erosion 

resulting from human activities accounts for 70% of this soil loss; geologic or natural erosion constitutes 

the other 30% (EPA 1980d). However, this source of low levels of zinc is widely dispersed and is, 

therefore, unlikely to elevate aquatic concentrations significantly. Zinc flux to the oceans from high 

temperature hydrothermal fluids in mid-ocean ridges has been estimated to be approximately 

681,000 metric tons/year (WHO 2001). 

Urban runoff, mine drainage, and municipal and industrial effluents are smaller but more concentrated 

sources of zinc in water. Davis et al. (2001) estimated the zinc loadings in urban storm water runoff. In 

this study, buildings and automobiles were found to contribute 95% of loadings (0.646 kg/ha/year) to 

storm water runoff in urban environments. Data from this study are summarized in Table 6-3. The 

Nationwide Urban Runoff Program (NURP), initiated to evaluate the significance of priority pollutants in 

urban storm water runoff, reports a frequency of detection for zinc of 95%, with a concentration range of 

0.01–2.4 mg/L (Cole et al. 1984). Industries that discharge large quantities of zinc directly to water 

include iron and steel, zinc smelting, plastics, and electroplating (EPA 1980d). The arithmetic mean 

concentration of zinc in influents of 239 waste water treatment plants in the United States was 0.7 mg/L, 

with minimum and maximum concentrations of 0.0001 and 28.7 mg/L, respectively (Minear et al. 1981). 

Accidental zinc discharges to water are most often associated with smelting and refining operations. Zinc 
 

 

 

 

 

 

 

 

 

ZINC 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Zinc Loadings in Urban Storm Water Runoffa 

Buildings 

Siding 

Roof 

Total 

Rate 

180,000 m2/ha/year 

450,000 L/ha/year 

Unit value 

2,100 μg/m2 

100 μg/L 

Loading 

(kg/ha/year) 

0.423 

Percent of total 

58 

7 

65 

Autos 

Brakes 

Tires 

Oil leakage 

Total 

240,000 km/ha/year 

48,000 g tire/ha/year 

48 L-oil/ha/year 

88 μg/km 

3,400 μg/g 

1.25x105

 mg/L 

0.021 

0.163 

0.006 

0.190 

3 

25 

1 

29 

Total buildings and autos 

Wet deposition 

Dry deposition 

Total 

0.613 

0.013 

0.020 

0.646 

95 

2 

3 

100 

a

Source: Davis et al. 2001 
 

 

ZINC 150 

6. POTENTIAL FOR HUMAN EXPOSURE 

is present with cadmium and lead in these processes (NAS 1977). Urban runoff and drainage from 

inactive mines account for approximately 5,250 and 4,060 metric tons/year, respectively, of the total 

releases of zinc to water (EPA 1980d). Drainage from active mining areas is considerably less than from 

inactive areas because of the disposal methods currently employed. Hazardous waste sites, in which zinc 

has been improperly disposed of, are additional sources of the element. 

Metals, such as zinc, also enter estuaries from many natural and manufactured sources. Three important 

sources of zinc input into surface water are metal manufacturing (33,000–178,000 metric tons/year), 

domestic waste water (21,000–58,000 metric tons/year), and atmospheric fallout (2,600–31,000 metric 

tons/year). On an annual worldwide basis, an estimated 77,000–375,000 metric tons of zinc are 

discharged into water from anthropogenic sources (Nriagu and Pacyna 1988). Publicly owned treatment 

works are the largest total point source for zinc discharges. Publicly owned treatment works receive zinc 

contributions from the water supply and distribution system corrosion, combined sewer area runoff, 

industrial wastes, and human excrement (EPA 1980d). Crawford et al. (1995) reported the direct inputs 

of zinc contamination to the Newark Bay Estuary as follows (kg/day): municipal treatment systems, 

272.0; industry, 14.34; combined sewer overflows, 141.5; storm water runoff, 164.6; and tributary flow, 

307. Indirect inputs were 934.7 kg/day. The flux of zinc into the Hudson River Estuary from sewage has 

decreased from 924 kg/day in 1974 to 285 kg/day in 1997 as a result of improvements in controlling 

discharges from municipal and industrial waste water treatment plants since the Clean Water Act was 

enacted in 1972 (Sanudo-Wilhelmy and Gill 1999). 

According to the TRI, estimated totals of 58,525 pounds (26.5 metric tons) of zinc (dust and fume) and 

3,109,033 pounds (1,410 metric tons) of zinc compounds, amounting to about 0.1 and 0.44%, 

respectively, of the total environmental on-site releases, were discharged into surface water in the United 

States in 2002 from mining, manufacturing, processing, and electrical power generation industries listed 

in Tables 6-1 and 6-2. Estimated totals of 0 pounds (0 metric tons) of zinc (dust and fume) and 

13,946,427 pounds (6,325 metric tons) of zinc compounds, amounting to about 0.0 and 2% of the total 

environmental on-site releases, respectively, were injected underground in the United States in 2001 from 

mining, manufacturing, processing, and Resource Conservation and Recovery Act (RCRA)/Solvent 

Recovery industries listed in Tables 6-1 and 6-2 (TRI02 2004). The TRI data should be used with caution 

since only certain facilities are required to report. This is not an exhaustive list. 

The concentration of zinc in drinking water may increase as a result of the distribution system and 

household plumbing (EPA 1987c). Common piping materials used in distribution systems often contain 
 

 

ZINC 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

zinc, as well as other metals and alloys. Trace metals may enter the water through corrosion products or 

simply by the dissolution of small amounts of metals with which the water comes in contact. Reactions 

with materials of the distribution system, particularly in soft low-pH waters, very often have produced 

concentrations of zinc in tap water much greater than those in the raw or treated waters at the plant of 

origin (NAS 1977). The total quantity of annual releases of zinc from these sources has not been 

estimated. Environmental toxicity of zinc in water is dependent upon the concentration of other minerals 

and the pH of the solution, which affect the ligands that associate with zinc (Heijerick et al. 2002a; Paquin 

et al. 2002; Santore 2002). 

Zinc has been identified in surface water and groundwater at 393 and 685 sites, respectively, collected 

from the 985 NPL hazardous waste sites where it was detected in some environmental media (HazDat 

2005). 

6.2.3 Soil 

Estimated releases of 37 million pounds (16,856 metric tons) of zinc to soils from 389 domestic 

manufacturing and processing facilities in 2002, accounted for about 79% of the estimated total 

environmental releases from facilities required to report to the TRI (TRI02 2004). No material was 

released via underground injection (TRI02 2004). These releases are summarized in Table 6-1. 

Limited information is available on total releases of zinc to soil. Zinc is often present in soils and grasses 

as a result of atmospheric deposition. Furthermore, approximately 22,000 tons (20,000 metric tons) of 

zinc is used in fertilizers each year in the United States (NAS 1977). The extent to which zinc may run 

off into soil, rivers, and streams has not been evaluated. Hazardous waste sites are additional sources of 

zinc in soil. Municipal sludges applied to cropland soils can also be an important source of trace metals, 

including zinc (Chang et al. 1987). 

On a worldwide basis, an estimated 1,193,000–3,294,000 metric tons of zinc per year are released to soil 

from anthropogenic sources (Nriagu and Pacyna 1988). The four most important sources of zinc in soil 

were estimated to be smelter slugs and wastes, mine tailings, coal and bottom fly ash, and the discharge of 

commercial products such as fertilizers. 

Tire debris contains significant quantities of zinc, which may contaminate soils near roads. For example, 

snow collected on soil near an expressway in Montréal, Québec (Canada) contained higher levels zinc 
 

 

ZINC 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

near the expressway. At 15 m from expressway, a snow pack concentration of 0.143 mg/L was measured, 

while at 150 m from the expressway, the concentration of zinc in snow was 0.029 mg/L (Loranger et al. 

1996). Laboratory experiments indicated that a significant fraction of zinc may be released from tire 

rubber debris. Soil pH limits the mobilization of zinc in soil. Thus, zinc from tire debris will be less 

available and become immobile with soil interactions (Smolders and Degryse 2002). 

Metallic zinc may yield soluble zinc compounds under acidic conditions where the zinc hydroxidecarbonate layer is attacked from pollutants such as sulfur dioxide. Metallic zinc is washed off slowly and 

forms a diffuse source of zinc release to soils. Other releases of zinc include the use of sacrificial anodes 

in soil to protect steel structures from corrosion (WHO 2001). 

According to the TRI, estimated totals of 37,167,881 pounds (16,856 metric tons) of zinc (dust and fume) 

and 589,805,136 pounds (267,485 metric tons) of zinc compounds, amounting to about 79 and 85%, 

respectively, of the total environmental on-site releases, were released to land in the United States in 2001
 

from mining, manufacturing, processing, and electrical power generation industries (Tables 6-1 and 6-2) 

(TRI02 2004). Another 12,924,002 pounds (5,861 metric tons) of zinc (dust and fume) and 

211,434,474 pounds (95,889 metric tons) of zinc compounds were transferred to off-site treatment, 

storage, and disposal facilities. The TRI data should be used with caution since only certain types of 

facilities are required to report. This is not an exhaustive list. 

Zinc has been identified in soil and sediment at 522 and 370 sites, respectively, collected from the 

985 NPL hazardous waste sites where it was detected in some environmental media (HazDat 2005). 

6.3 ENVIRONMENTAL FATE 

Zinc occurs in the environment mainly in the +2 oxidation state (Lindsay 1979). Sorption is the dominant 

reaction, resulting in the enrichment of zinc in suspended and bed sediments (EPA 1979d). Zinc in 

aerobic waters is partitioned into sediments through sorption onto hydrous iron and manganese oxides, 

clay minerals, and organic material. The efficiency of these materials in removing zinc from solution 

varies according to their concentrations, pH, redox potential (Eh), salinity, nature and concentrations of 

complexing ligands, cation exchange capacity, and the concentration of zinc. Precipitation of soluble zinc 

compounds appears to be significant only under reducing conditions in highly polluted water. Generally, 

at lower pH values, zinc remains as the free ion. The free ion (Zn+2) tends to be adsorbed and transported 

by suspended solids in unpolluted waters. In polluted waters in which the concentration of zinc is high, 
ZINC 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

removal of zinc by precipitation of the hydroxide is possible, particularly when the pH is >8 (EPA 

1979d). In anaerobic environments and in the presence of sulfide ions, precipitation of zinc sulfide limits 

the mobility of zinc. The relative mobility of zinc in soil is determined by the same factors that affect its 

transport in aquatic systems (i.e., solubility of the compound, pH, and salinity) (Clement 1985). 

Zinc is an essential nutrient that is present in all organisms. Although biota appears to be a minor 

reservoir of zinc relative to soils and sediments, microbial decomposition of biota in water can produce 

ligands, such as humic acids, that can affect the mobility of zinc in the aquatic environment through zinc 

precipitation and adsorption (EPA 1979d). 

Zinc concentrations in the air are relatively low, except near industrial sources such as smelters. No 

estimate for the atmospheric lifetime of zinc is available at this time, but the fact that zinc is transported 

long distances in air indicates that its lifetime in air is at least on the order of days. 

6.3.1 Transport and Partitioning 

Air. In the atmosphere, zinc exists primarily in an oxidized form bound to aerosols, with the size of zinc 

particulates determined by the source of zinc emission (Nriagu and Davidson 1980; Sweet et al. 1993). A 

major proportion of zinc released from industrial processes is adsorbed on particulates that are small 

enough to be in the respirable range (Dorn et al. 1976). Wind-blown dust transports zinc bound to soil 

particulates into the atmosphere (EPA 1980d). The particulates may also contain other materials (Pacyna 

et al. 1989; Saltzman et al. 1985). 

Zinc-bearing particles in the atmosphere are transported to soil and water by wet deposition (rain and 

snow) and dry deposition (gravitational settling and deposition on water and soil surfaces). Zinc particles 

with low dry deposition velocities (i.e., particles with small diameters and low densities) can be 

transported from their emission source to distant regions (Pacyna et al. 1989). The atmospheric wet 

deposition of zinc (and other trace metals) was examined at two Maryland Chesapeake Bay sites from 

June 1990 to July 1991 as part of the Chesapeake Bay Atmospheric Deposition Study (Scudlark et al. 

1994). The average annual wet deposition at these two sites was 1,335 μg/m2

/year with 99% attributed to 

anthropogenic sources. As part of the Atmospheric Exchange over Lakes and Oceans Study (AEOLOS), 

dry deposition fluxes of zinc were measured over the southern basin of Lake Michigan near the urban 

area of Chicago and the nonurban area of South Haven, Michigan (Paode et al. 1998). In 1993, the 

average measured zinc fluxes were 200 μg/m2

/day in Chicago; 10 μg/m2/day over southern Lake 
 

 

 

ZINC 154 

6. POTENTIAL FOR HUMAN EXPOSURE 

Michigan; and 4 μg/m2/day in South Haven, Michigan. Between 1993 and 1995, Shahin et al. (2000) 

estimated the dry deposition flux of zinc in Chicago to be 4.4x104

 μg/m2/year. Atmospheric deposition 

rates of zinc for Lakes Superior, Erie, and Ontario were reported to be 3,310, 2,180, and 

5,650 μg/m2

/year, respectively (Nriagu et al. 1996). Detection of zinc in rain waters confirms the 

importance of wet precipitation in the removal of zinc particles from the atmosphere (Aten et al. 1983; 

Colin et al. 1990; Dasch and Wolff 1989; Golomb et al. 1997; Heaton et al. 1990). Golomb et al. (1997) 

measured the atmospheric deposition of zinc at Nahant, Massachusetts (near urban area of Boston) and at 

Truro, Massachusetts (on Cape Cod) for the years 1992–1993. Results indicated that wet deposition was 

a significant fraction of the total atmospheric deposition of zinc for Nahant (28%) and Truro (40%). 

Water. In water, zinc occurs in the environment primarily in the +2 oxidation state. It dissolves in acids 

to form hydrated Zn+2 cations and in strong bases to form zincate anions, which are hydroxo complexes, 

e.g., (Zn[OH]3)

-

, (Zn[OH]4)

2-, and (Zn[OH]4[H2O]2)2- (O’Neil et al. 2001). In most waters, zinc exists 

primarily as the hydrated form of the divalent cation. However, the metal often forms complexes with a 

variety of organic and inorganic ligands (EPA 1979d, 1984b, 1987c). 

Zinc can occur in both suspended and dissolved forms in surface water. Dissolved zinc may occur as the 

free (hydrated) zinc ion or as dissolved complexes and compounds with varying degrees of stability. 

Suspended (i.e., undissolved) zinc may be dissolved with changes in water conditions (e.g., pH, redox 

potential, solution speciation) or may sorb on to suspended matter. Gundersen and Steinnes (2003) 

reported that <10% of zinc was sorbed on particles or colloids in river water from two rivers with average 

pHs of 3.1 and 5.1 (rivers with mining activity near Roes, Norway), whereas 21% of zinc occurred in 

sorbed form in six pH neutral rivers. 

In the aquatic environment, zinc partitions to sediments or suspended solids in surface waters through 

sorption onto hydrous iron and manganese oxides, clay minerals, and organic material. Reservoirs 

located downstream from lead-zinc mining and milling areas were found to contain higher concentrations 

of zinc than reservoirs in other areas, and the zinc was more highly concentrated in reservoir bottom 

sediments than in the surrounding soils (Pita and Hyne 1975). In addition, the zinc content in sediment 

closely correlated with the depth, organic content, and clay content of the sediments. Phosphates and iron 

hydroxides affect the transfer of metals (including zinc) from river water to the sediments, according to a 

study by Houba et al. (1983). In this study, zinc was bound predominantly to carbonate and amorphous 

matter (iron, aluminum, and manganese hydroxides). In addition, mobile components of naturally 

occurring organic matter contributed to the increase in the metal hydroxide-bound fraction. 
ZINC 155 

6. POTENTIAL FOR HUMAN EXPOSURE 

The transport of zinc in the aquatic environment is controlled by anion species. In natural waters, 

complexing agents, such as humic acid, can bind zinc. The stability of zinc complexes depends on the pH 

of the water and the nature of the complex. The dissociation of the complex may determine the amount of 

free zinc ions in solution. Zinc-humic acid complexes may be 50% dissociated at pH 5.5 and the 

dissociation rate may be higher as the pH decreases (Guy and Chakrabarti 1976). Therefore, as the pH of 

the water decreases, the concentration of zinc ions in the water phase increases at the same rate as that of 

the release of zinc from the sediment. The magnesium found in the silicate minerals of igneous rocks is 

often replaced with the divalent zinc ion; consequently, weathering of this zinc-containing bedrock gives 

rise to Zn+2 in solution. The hydrated cation is the dominant form when the pH is ≤9 (EPA 1979d). 

The tendency of zinc to be sorbed is affected not only by the nature and concentration of the sorbent but 

also by pH and salinity (EPA 1979d). Zinc tends to sorb more readily at a high pH (pH >7) than at a low 

pH (EPA 1979d). Desorption of zinc from sediments occurs as salinity increases (Helz et al. 1975), 

apparently because of displacement of the adsorbed zinc ions by alkali and alkaline earth cations, which 

are abundant in brackish and saline waters (EPA 1979d). In column leaching tests with sediment 

collected from the banks of the Rhone River, the presence of dissolved organic matter and pH was found 

to be the factors controlling the adsorption and mobility of zinc (Bourg and Darmendrail 1992). 

A small fraction of zinc will exist in the aquatic phase as soluble inorganic zinc compounds (e.g., zinc 

chloride, zinc sulfate). Soluble inorganic zinc compounds hydrolyze in solution, forming zinc hydroxide 

precipitates. Hydrolysis may lower pH, but the buffering action present in most natural water prevents a 

significant alteration in pH. The precipitation of zinc hydroxide and zinc carbonate was studied by 

Patterson et al. (1977), who found that zinc hydroxide precipitates faster than zinc carbonate. Zinc 

carbonate is soluble in pure water at 25 °C at concentrations of ≤107 mg zinc/L. The hydroxide is soluble 

only at concentrations of ≤0.2 mg zinc/L. As a result, some of the inorganic forms of zinc that are 

expected to be present in water are basic carbonate (Zn2[OH]2CO3), hydroxide (Zn[OH]2), and silicate 

(Zn2SiO4) (Florence 1980; NAS 1977). When the pH is ≥8, most of these compounds will precipitate; 

however, as the pH decreases, more and more of these compounds will dissolve and remain in the water 

phase (EPA 1979d). 

The effect of pH on the mobilization of zinc in a few highly acidic clean lakes has been studied (Sprenger 

et al. 1987; White and Driscoll 1987). In these lakes, in which the pH was ≤3.6, concentrations of zinc 

were elevated in the water column, and the concentration of zinc in the upper layer of sediment was 
 

 

ZINC 156 

6. POTENTIAL FOR HUMAN EXPOSURE 

substantially lower than values reported for other lakes at higher pH values. The relatively higher 

concentration of zinc in the water column compared to the sediment may be the result of lower adsorption 

of zinc on oxide surfaces due to low pH, solubilization of inorganic zinc from the sediment layer, and the 

dissociation of bound organic complexes of zinc present in the sediment and their subsequent release into 

the water phase. 

The precipitation of zinc sulfide affects the mobility of zinc in reducing environments, especially when 

hydrogen sulfide is formed. The precipitation of the hydroxide, carbonate, or basic sulfate may become 

more significant at high concentrations of zinc. Hesterberg et al. (1997) reports that zinc (hydr)oxides 

and not sulfides are the dominant species in aquifers solids under reducing conditions. The hydroxides 

and hydrous oxides of iron and manganese are often components of the clay fraction of sediments and 

often exist as coatings on the surfaces of other minerals (NAS 1977). Zinc may coprecipitate with 

hydrous oxides when reduced iron or manganese oxides are oxidized. As the new solids are formed, they 

can trap various ions in their crystal lattices (EPA 1979d). 

Soil. The redox status of the soil may shift zinc partitioning. Reductive dissolution of iron and 

manganese (hydr)oxides under suboxic conditions release zinc into the aqueous phase; the persistence of 

suboxic conditions may then lead to a repartitioning of zinc into sulfide and carbonate solids. Bostick et 

al. (2001) describe zinc speciation in contaminated wetland soil that undergoes seasonal flooding. In dry 

oxidized soils, the authors found that zinc was associated with (hydr)oxide phases, while in flooded 

systems, zinc was associated with sulfides and carbonates. Reversible change occurred with flooding 

from dry soil. However, a small fraction of zinc became recalcitrant with (hydr)oxides fraction. 

Zinc sorbs strongly onto soil particulates. Little water-soluble and exchangeable heavy metals were 

found in soil irrigated with raw waste water (Schalscha et al. 1982). Although considerable amounts of 

metals were added to the soil in soluble and exchangeable forms during waste-water irrigation, they were 

converted into the less chemically active forms (i.e., organically bonded and inorganic precipitates). 

Further examination showed that zinc accumulation in soil resulting from waste disposal occurred 

primarily as inorganic precipitates. 

The mobility of zinc in soil depends on the solubility of the speciated forms of the element and on soil 

properties such as cation exchange capacity, pH, redox potential, and chemical species present in soil; 

under anaerobic conditions, zinc sulfide is the controlling species (EPA 1980d; Kalbasi et al. 1978). 

Since zinc sulfide is insoluble, the mobility of zinc in anaerobic soil is low. In a study of the effect of pH 
 

 

 

ZINC 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

on zinc solubility, Saeed and Fox (1977) showed that, when the pH is <7, an inverse relationship exists 

between the pH and the amount of zinc in solution. As negative charges on soil surfaces increase with 

increasing pH, additional sites for zinc adsorption are activated and the amount of zinc in solution 

decreases. The active zinc species in the adsorbed state is the singly charged zinc hydroxide species (i.e., 

Zn[OH]+

) (Sanders and Kherbawy 1987). Other investigators have also shown that the mobility of zinc in 

soil increases at lower soil pH under oxidizing conditions and at a lower cation exchange capacity of soil 

(Bergkvist et al. 1989; Hermann and Neumann-Mahlkau 1985; Tyler and McBride 1982). On the other 

hand, the amount of zinc in solution generally increases when the pH is >7 in soils high in organic matter. 

This is a result of the release of organically complexed zinc, reduced zinc adsorption at higher pH, or an 

increase in the concentration of chelating agents in soil (Saeed and Fox 1977). For calcareous soils, the 

relationship between zinc solubility and pH is nonlinear. At a high pH, zinc in solution is precipitated as 

Zn(OH)2, zinc carbonate (ZnCO3), or calcium zincate (Saeed and Fox 1977). Clay and metal oxides are 

capable of sorbing zinc and tend to retard its mobility in soil. Warwick et al. (1998) studied the mobility 

of zinc ions in sand. Zinc was more mobile at pH 4 than at pH 6.5 as a consequence of sorption. Goethite 

(i.e., iron oxyhydroxide) caused a greater decrease in mobility, and increased retardation was also 

observed with humic acid. 

Distribution constants (Kd=concentration of sorbed zinc/concentration of zinc in solution) for zinc in soil 

range widely from 0.1 to 8,000 L/kg (or mL/g) (Baes and Sharp 1983; Bunzl and Schimmack 1989; Gao 

et al. 1997; Gerritse et al. 1982; Janssen et al. 1997). Kd values of 100±770 mL/g for sandy loam soil and 

0.2±4 mL/g for sandy soils were reported by Gerritse et al. (1982). Kd values ranging from 0.1 to 

8,000 mL/g were reported by Baes and Sharp (1983). Kd values for zinc of 140 and 41 L/kg were 

determined for the O-horizon (organic layer) and E-horizon (silty sand), respectively, of a podzol forest 

soil (Bunzl and Schimmack 1989). Field-based Kp ranged from 6 to 6,762 L/kg for 20 Dutch agricultural 

soils (Janssen et al. 1997). Kd values for nine soils treated with sewage sludge supernatant ranged from 

0.034 to 1.359 L/g at pH 4.5 while at pH 6.5, Kd values ranged from 0.425 to 2.896 L/g (Gao et al. 1997). 

Zinc in a soluble form (e.g., zinc sulfate) is moderately mobile in most soils. However, relatively little 

land-disposed zinc at waste sites is in the soluble form. Thus, mobility is limited by a slow rate of 

dissolution. Consequently, movement towards groundwater is expected to be slow unless zinc is applied 

to soil in soluble form (such as in agricultural applications) or accompanied by corrosive substances (such 

as in mine tailings) (EPA 1980d). Yet, soil conditions not suitable for zinc sorption may lead to leaching. 

Low pH (pH <7) and high ionic strength of the leaching solution favor desorption (EPA 1987c; Saeed and 

Fox 1977). 
ZINC 158 

6. POTENTIAL FOR HUMAN EXPOSURE 

Consequently, zinc primarily remains in recalcitrant, immobile forms in contaminated soils (Chlopecka et 

al. 1996; Kabala and Singh 2001; Kaminiski and Landsberger 2000b; Ma and Rao 1997a). Ma and Rao 

(1997) studied the chemical fractionation of zinc in nine soils from various U.S. locations contaminated 

by agriculture and industrial activities. Zinc was found to be concentrated in the residual (or recalcitrant) 

fraction (range, 55.8–97.6%), which reflected greater tendency of zinc to become unavailable once in 

soils. However, some zinc was found in exchangeable and carbonate fractions at levels ranging from 

0.73 to 25%, which suggests that some zinc may be available to plants. In soil from East St. Louis, 

Illinois, an area heavily contaminated with metals, sequential extraction analysis of soil revealed that the 

largest fraction of zinc was partitioned in the iron-manganese oxide fraction (47.2%) followed by 

carbonate (37.9%) and organic (14.1%) and exchangeable (0.8%) fractions (Kaminiski and Landsberger 

2000b). Kabala and Singh (2001) reported that water-soluble zinc was present in only very small 

amounts (<1%) in most contaminated soils. However, concentrations of exchangeable zinc were 

significantly higher in surface horizons (4–19% of total zinc) than in subsurface layers. In subsurface 

horizons of the studied soils, zinc was concentrated in the residual (or recalcitrant) fraction. The 

percentage of residual zinc ranged from 45% in silty soils to 94% in clay-loam soil. The nonresidual 

fractions prevailed only in the surface horizons in both contaminated and uncontaminated soil (65–91% of 

total zinc) (Kabala and Singh 2001). Soils from Southwestern Poland subjected to severe metal 

contamination contained zinc at concentrations ranging from 20 to 10,000 mg/kg (Chlopecka et al. 1996). 

Acidic soils (pH<5.6) contained a greater fraction of exchangeable zinc, while for other soils (pH>5.6), 

zinc was found primarily in the oxide and residual (or recalcitrant) fractions with moderate amounts in the 

organic, carbonate, and exchangeable forms. 

Zinc is an essential nutrient and occurs in the tissues of organisms, even at normal ambient water and soil 

concentrations. Zinc can accumulate in freshwater animals at 51–1,130 times the concentration present in 

the water (EPA 1987c). Microcosm studies indicate, in general, that zinc does not biomagnify through 

food chains (Biddinger and Gloss 1984; EPA 1979d; Hegstrom and West 1989). Furthermore, although 

zinc actively bioaccumulates in aquatic systems, biota appears to represent a relatively minor sink 

compared to sediments. Steady-state zinc bioconcentration factors (BCFs) for 12 aquatic species range 

from 4 to 24,000 (EPA 1987c). Crustaceans and fish can accumulate zinc from both water and food. A 

BCF of 1,000 was reported for both aquatic plants and fish, and a value of 10,000 was reported for 

aquatic invertebrates (Fishbein 1981). The order of enrichment of zinc in different aquatic organisms was 

as follows (zinc concentrations in μg/g dry weight appear in parentheses): fish (25), shrimp (50), mussel 

(60), periphyton (260), zooplankton (330), and oyster (3,300) (Ramelow et al. 1989). The high 
ZINC 159 

6. POTENTIAL FOR HUMAN EXPOSURE 

enrichment in oysters may be due to their ingestion of particulate matter containing higher concentrations 

of zinc than ambient water. Other investigators have also indicated that organisms associated with 

sediments have higher zinc concentrations than organisms living in the aqueous layer (Biddinger and 

Gloss 1984). With respect to bioconcentration from soil by terrestrial plants, invertebrates, and mammals, 

BCFs of 0.4, 8, and 0.6, respectively, have been reported. The concentration of zinc in plants depends on 

the plant species, soil pH, and the composition of the soil (Dudka and Chlopecka 1990; Rudd et al. 1988). 

Plant species do not concentrate zinc above the levels present in soil (Levine et al. 1989). 

6.3.2 Transformation and Degradation 

As an element, zinc does not degrade in the environment. Degradation of an element is a nuclear process 

by definition, and stable elements, such as zinc, typically undergo such processes only at insignificant 

rates in the environment. Zinc can change from one form to another, sometimes reversibly, in numerous 

chemical reactions that can proceed under a wide range of common environmental conditions. 

6.3.2.1 Air 

The chemical interaction of zinc compounds in the atmosphere may change the anionic speciation of the 

compound. Atmospheric interactions are greatest for particles with small aerodynamic diameters 

(Fishbein 1981). Zinc is found in the atmosphere at the highest concentrations in the smallest particles 

(Fishbein 1981). Atmospheric emissions of zinc, consisting primarily of zinc sorbed to submicron 

particulate matter in the form of zinc oxide (ZnO), are expected to dissipate quickly as a result of 

deposition to soil and surface waters (EPA 1980d). 

In the atmosphere, zinc-bearing particles may undergo chemical transformation before deposition. The 

association of zinc particles in aerosols in Arizona was studied, and five zinc-bearing particles were 

identified with an automated scanning electron microscope (Anderson et al. 1988). These particles, in 

decreasing order of concentration in the aerosol, were zinc sulfide (ZnS), ferrous zinc (FexZny), zinc 

phosphides (Zn3P2), zinc chloride (ZnCl2), and metallic zinc (Zn). The presence of zinc sulfide in an area 

adjacent to mining and smelting activities was not unanticipated, but no conclusion regarding the 

speciation of zinc in the atmosphere could be drawn from this investigation. However, the relative 

concentration of zinc ions in rainwater from a rural area was approximately 10 times higher than in 
 

 

ZINC 160 

6. POTENTIAL FOR HUMAN EXPOSURE 

airborne particulates (Aten et al. 1983). This finding suggests that zinc sulfide in the atmosphere is 

oxidized to a more water-soluble form, zinc sulfate. 

6.3.2.2 Water 

Zinc is in the +2 form in aqueous solution and exhibits amphoteric properties; zinc metal and compounds 

dissolve in acids to form hydrated Zn+2 cations and in strong bases to form zincate anions, which are 

hydroxo complexes, such as [Zn(OH)3]

-

, [Zn(OH)4]

2-, and [Zn(OH)4(H2O)2]2- (EPA 1979d; O’Neil et al. 

2001). However, at the pH of most natural waters, the formation of anionic zinc species is not likely. 

A small part of the available zinc may partition into the aquatic phase through the formation of soluble 

zinc chloride and sulfate compounds. These compounds hydrolyze in solution to form the hydroxide or 

hydrated zinc oxide precipitate with a resultant decrease in pH. The decrease in pH can increase the 

solubility of zinc hydroxide and increase the zinc concentration in water. However, the buffering action 

of most natural waters prevents any significant change of pH due to the hydrolysis reactions. As a result, 

in the water phase, the solubility of its carbonate and hydroxide is likely to control the availability of zinc. 

It was reported by Patterson et al. (1977) that Zn(OH)2 precipitates faster than ZnCO3. Zinc is not 

directly affected by changes in Eh; however, the valences and reactivity of ligands reacting with zinc are 

affected by Eh. Zinc is an active reducing agent for many metal ions such as iron (Fe+3) and 

permanganate (MnO4

-2) ions (Stokinger 1981). As a result of the reducing reactions, the manganese 

oxides and ferric salts may precipitate and, in the process, may entrap soluble zinc in the precipitate, 

thereby reducing the zinc concentration in the water phase. 

Because alkyl zinc compounds are unstable in water and oxygen, biomethylation of zinc compounds in 

aquatic ecosystems probably does not occur (EPA 1979d). Insoluble zinc compounds (e.g., zinc oxide) 

are solubilized indirectly under anaerobic conditions with reduction of iron sulfides, which reduces the 

solution pH (Couillard et al. 1994; Francis and Dodge 1988). No evidence was found that photolysis in 

the aquatic environment significantly affects the fate of zinc compounds. 

6.3.2.3 Sediment and Soil 

Zinc undergoes reactions in sediment and soil involving precipitation/dissolution, complexation/dissociation, and adsorption/desorption. These reactions are controlled by the pH, redox potential (Eh), the 
 

 

 

ZINC 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

concentration of zinc ions and other ions in the soil pore water, the number and type of adsorption sites 

associated with the solid phase, and the organic ligands present that are capable of forming complexes 

with zinc. In acidic sediments and soils, more zinc is available in ionic forms, and cation exchange 

processes influence its fate. Depending on the nature and concentrations of other mobile metals in 

sediments and soils, competition for the binding sites probably occurs. In the absence of suitable binding 

sites, zinc may be mobilized (ICF 1986). In alkaline soils, the chemistry of zinc is dominated by 

interactions with organic ligands. The ecological toxicity of sediment is complex and appears to be 

correlated to the ratio of zinc to acid volatile sulfide (Berry et al. 1996; Di Toro et al. 1992; Sibley et al. 

1996). 

Biological degradation of zinc complexes in soil is necessary for the normal operation of ecosystems to 

facilitate the recycling of zinc from litter, feces, and dead organisms. In some environments, bacteria and 

fungi are able to oxidize zinc sulfide producing zinc sulfate, which will solubilize in the soil solution 

(WHO 2001). 

6.3.2.4 Other Media 

During composting of organic wastes, zinc remains in mobile and bioavailable forms. Zinc carbonates 

are formed, although not at the expense of zinc sulfide levels, which remain unaltered during the 

composing process (Ciba et al. 1997). No further data were located in the literature for the transformation 

and degradation of zinc in other media. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

Reliable evaluation of the potential for human exposure to zinc depends in part on the reliability of 

supporting analytical data from environmental samples and biological specimens. Concentrations of zinc 

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 zinc 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 zinc in a variety of 

environmental media are detailed in Chapter 7. 
 

 

ZINC 162 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.1 Air 

Zinc concentrations in air are relatively low and fairly constant except near sources such as smelters. 

Average atmospheric concentrations of zinc resulting from releases from automobiles, fuel combustion, 

incineration, soil erosion, and industrial, commercial, and construction activity throughout the United 

States generally are <1 μg/m3

 (EPA 1980d; Lloyd and Showak 1984). In 1990, the median concentration 

of zinc in air samples collected across Minnesota was 0.012 μg/m3

 (maximum, 0.187 μg/m3) (Pratt et al. 

2000). At six measurement sites in Columbus, Ohio, the mean atmospheric particulate concentration of 

zinc for samples collected in 1989 was 0.01±0.01 μg/m3

 (Spicer et al. 1996). Data on zinc concentrations 

in New York City during 1972–1975 show that the average atmospheric zinc concentration ranged from 

0.293 to 0.380 μg/m3

 annually (Lioy et al. 1978). An average ambient zinc concentration of 0.127 μg/m3 

(concentration range, 0.027–0.500 μg/m3

) was determined from analyses of particulate samples collected 

at nine air monitoring sites in the San Francisco Bay area (John et al. 1973). The concentrations of zinc in 

atmospheric samples collected from seven cities in the United States during 1968–1971 ranged from 

0.17 to 0.67 μg/m3

, whereas the concentrations at two rural sites ranged from 0.02 to 0.16 μg/m3 

(Saltzman et al. 1985). The concentrations of zinc during 1977–1979 from the National Air Surveillance 

Networks were reported by Evans et al. (1984). The arithmetic mean zinc concentrations in urban areas 

in the United States ranged from 0.02 to 0.16 μg/m3

, whereas the concentrations in nonurban areas ranged 

from 0.01 to 0.05 μg/m3

. The geometric mean concentrations of zinc from three urban areas in New 

Jersey monitored in 1981–1982 ranged from 0.07 to 0.59 μg/m3

, whereas the concentrations at a rural site 

ranged from 0.02 to 0.06 μg/m3

 (Daisey 1987). Davidson et al. (1988) measured the atmospheric zinc 

concentrations at Great Smoky Mountains and Olympic National Parks where crustal weathering, sea 

spray, and long-range transport of zinc were likely to influence concentrations. The average atmospheric 

concentrations of zinc were 0.0033 and 0.0089 μg/m3

 for Great Smoky Mountains in 1979 and Olympic 

National Parks in 1980, respectively. The reported concentration range of zinc in air at remote sites 

(arctic) was <0.003–0.027 μg/m3

 (Barrie and Hoff 1985; Duce et al. 1975; Zoller et al. 1974). In aerosol 

samples of the lower troposphere collected over the Southern Bight of the North Sea between September 

1988 and October 1989, the average zinc concentration was 0.067 μg/m3

 (standard deviation, 

0.054 μg/m3

; range, 0.003–0.22 μg/m3; n=108 samples) (Injuk et al. 1992). The concentration of 

atmospheric zinc is usually lower in winter than in summer (Barrie and Hoff 1985; Daisey 1987). 

Indoor air from other regions of the world has been reported to contain zinc in particulate matter at low 

levels. In 1991, household dust sampled from Bahrain in Persian Gulf region contained zinc at a 

concentration of 64.4 μg/g (Akhter and Madany 1993). As part of the Southeastern Brazil Indoor Air 
ZINC 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

Quality Study (SEBIAQS) in the summer of 1993, indoor and outdoor air samples were collected at 

12 sites in the cities of São Paulo and Rio de Janeiro, Brazil. Indoor air particulate samples had higher 

levels of zinc than outdoor samples. The concentration of zinc in indoor air particulates from São Paulo 

and Rio de Janeiro, Brazil were 0.046–0.30 and 0.036–0.38 μg/m3

, respectively, while outdoor samples 

ranged from not detected to 0.23 and from 0.05 to 0.29 μg/m3

, respectively (Miguel et al. 1995). 

Although data are sparse, higher-than-background concentrations have been reported near iron- and steelproducing factories and zinc, lead, and copper smelters. During zinc smelting operations, concentrated 

zinc ore goes through a roasting procedure to convert zinc sulfide to zinc oxide. This process accounts 

for a large portion of the total atmospheric zinc emission during primary production (EPA 1980d). About 

1.5 miles from a smelter in Kellogg, Idaho, Ragaini et al. (1977) detected high annual mean 

concentrations of zinc in ambient air of 5 μg/m3

. The 24-hour values for zinc ranged from 0.27 to 

15.7 μg/m3

; the average lead and cadmium concentrations at this smelter site were 11 and 0.8 μg/m3, 

respectively, indicating severe environmental pollution. Higher concentrations of zinc in the vicinity of a 

copper smelter than in reference areas were also reported by Patterson et al. (1977). 

6.4.2 Water 

In general, zinc is more concentrated in the sediments of streams and rivers than in the water column. It 

is reported by NAS (1977) that zinc is probably detectable in 75% of all water samples from various 

locations. The zinc background concentrations in surface waters are usually <50 μg/L (EPA 1980d), but 

concentrations in surface waters and groundwater can range from 0.002 to 50 mg/L (NAS 1977). 

Table 6-4 summarizes the typical concentrations of dissolved zinc in rivers of the United States (Shiller 

and Boyle 1985). The concentration of dissolved zinc in water from three Adirondack lakes was highest 

for low pH waters (Heit et al. 1989). Lake water from Darts Lake (pH 5.1–5.4) contained 7.9 ng zinc/mL 

while Moss Lake, a lake with variable acidity (pH 5.8–6.7), contained zinc at 2.9 ng/mL and Rondoxe 

Lake, a neutral lake (pH 6.5–6.8), contained 2.5 ng zinc/mL. 

In many locations (e.g., New England, the southeast, the Missouri River basin, the Rio Grande River 

basin, and the Upper Colorado River basin), higher-than-background concentrations of zinc are common 

and appear to be correlated with mining activities in these areas and/or geological areas rich in zinc (EPA 

1980d). However, in all river basins, there are some locations with zinc concentrations of 0.1–1.0 mg/L 

(EPA 1980d). In the Upper Rio Grande River, the dissolved zinc concentration upriver of Willow Creek, 

which drains a metal mining district, was approximately 2–3 μg/L. Immediately downstream of the 
 

 

 

 

 

ZINC 164 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Dissolved Zinc in Rivers of the United Statesa 

Riverb Datec pH Zinc (μg/L at 20 °C)d 

Ohio Valley 

Allegheny (Pittsburgh, PA) May 1984 6.86 1.89, 2.02 

Monongahela (Pittsburgh, PA) May 1984 7.22 2.54, 2.87 

Ohio (Wheeling, WV) May 1984 7.34 3.19, 3.19 

Muskingum (Zanesville, OH) May 1984 7.55 1.04, 1.24 

Muskingum (Marietta, OH) May 1984 7.66 0.63, 0.63 

Kanawha (Winfield, WV) May 1984 7.4 0.33, 0.35 

Big Sandy (Louisa, KY) May 1984 7.15 0.33,0.33 

Ohio (Greenup Dam) May 1984 7.42 0.78, 0.91 

Sciotto (Portsmouth, OH) May 1984 7.87 1.30, 1.43 

Little Miami (Milford, OH) May 1984 8.1 0.85, 1.04 

Licking (Alexandria, KY) May 1984 7.63 0.07 

Great Miami (Cleves, OH) May 1984 8.0 4.24, 4.30 

Whitewater (Elizabethtown, OH) May 1984 7.95 0.16 

Ohio (Warsaw, KY) May 1984 7.45 0.39, 0.42 

Kentucky (Lockport, KY) May 1984 7.28 0.12, 0.15 

Ohio (Cannelton Dam) May 1984 7.27 0.61 

Green (Beach Grove, KY) May 1984 7.32 0.16, 0.16 

Wabash (New Harmony, IN) May 1984 8.1 0.49 

Cumberland (Barkley Dam) May 1984 7.44 0.10, 0.10 

Tennessee (Kentucky Dam) May 1984 7.10 0.12, 0.12 

Ohio (Mound City, IL) May 1984 7.49 0.29, 0.29 

Mississippi River 

Mississippi (Cape Girardeau, MO) May 1984 7.70 0.19, 0.23 

Mississippi (Baton Rouge, LA) Sept 1983 8.1 0.10, 0.12 

Mississippi (Baton Rouge, LA) Apr 1984 7.72 0.18, 0.19 

Atchafalaya (Krotz Springs, LA) Apr 1984 7.6 0.18 

Other U.S. rivers 

Connecticut (Old Saybrook, CT) Apr 1983 7.1 0.91, 1.04 

Mullica Aug 1983 5.81 2.54, 2.61 

Merrimack (West Newbury, MA) Feb 1983 6.73 13.04. 13.04 

Vermilion, (Lafayette, LA) Apr 1984 7.1 0.25, 0.27 

Delaware (West Trenton, NJ) Apr 1984 7.38 3.91, 3.98 

Delaware (Philadelphia, PA) Apr 1984 7.05 13.04, 15.65 

Schuykill (Philadelphia, PA) Apr 1984 7.58 4.56, 4.89 
ZINC 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Dissolved Zinc in Rivers of the United Statesa 

Riverb Datec pH Zinc (μg/L at 20 °C)d 

Susquehanna (Holtwood, PA) Apr 1984 7.54 0.78, 0.85 

Potomac (Great Falls, MD) Apr 1984 7.75 0.54, 0.55 

a

Source: Shiller and Boyle 1985 

b

Post office state abbreviations are used. 

c

Apr = April; Aug = August; Feb = February; Sept = September 

d

Calculated from nmol/kg using density of water at 20 °C (0.99707 g/mL) and zinc molecular weight of 65.39 g/mole.
 
 

 

ZINC 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

Willow Creek confluence, zinc concentrations were >20 μg/L and elevated concentrations occurred for 

the next 100 km (Taylor et al. 2001). The concentrations of zinc in water samples from Whitewood 

Creek, South Dakota, were measured by Hale (1977). The samples were collected upstream from the 

discharge of a local mining company. In 42 analyses, zinc concentrations ranged from <0.004 to 

0.048 mg/L with a mean concentration of 0.018 mg/L. May et al. (2001) reported that water samples 

analyzed in 1996 from this contaminated watershed contained zinc at concentrations of 2.4–21 and 3.8– 

30 μg/L for filtered and unfiltered samples, respectively. 

The average levels of dissolved zinc in water from Lakes Superior, Erie, and Ontario were 277, 87, and 

160 ng/L, respectively, for samples collected between 1991 (Lake Superior) and 1993 (Lakes Ontario and 

Erie) (Nriagu et al. 1996). Coale and Flegal (1989) reported that concentration of dissolved zinc in water 

from Lakes Erie and Ontario ranged from 3x10-6 to 1.1x10-4 mg/L. In summer, there is a marked 

depletion of zinc in the epilimnion (i.e., area of warmest water) of Great Lakes off-shore waters, which 

may be attributed to biological processes (Nriagu et al. 1996). Groundwater from a shallow alluvial 

aquifer beneath a major urban center (Denver, Colorado) contained dissolved zinc at a median 

concentration of 3 μg/L (range, 2–28 μg/L) (Bruce and McMahon 1996). 

Scudlark et al. (1994) reported that the average concentration of zinc in water from the Chesapeake Bay 

was 1.21±0.95 μg/L (n=5) for samples collected from 1990 to 1991. The median concentration of zinc in 

the Hudson River estuary decreased from 200 nM (1.6 ng/L) in 1974 to approximately 25 nM (13 ng/L) 

in 1997 (Sañudo-Wilhelmy and Gill 1999). The declining levels of zinc and other metals is a result of the 

decreased metal flux to the estuary from sewage effluents. Zinc concentrations in remote regions of the 

Atlantic Ocean ranged from 0.023 to 0.097 μg/L in the Northeast region and averaged 0.004 μg/L in the 

Northwest region (Helmers and Schrens 1995). Yeats (1988) reported that the concentrations of 

dissolved zinc in ocean water from the Sargasso Sea and Northeast Pacific were 0.3–3.0 nM (20– 

200 ng/L) in 1984 and 3.6–9.2 nM (240–600 ng/L) in 1981, respectively. Seawater from lagoons of the 

Gulf of Mexico contained average dissolved zinc concentrations of 2.37, 5.12, and 9.76 μg/L for locations 

at Alvarado, San Andres, and Sedue (in Mexico), respectively (Vazquez et al. 1995). The concentration 

of zinc in surficial seawater from the Indian River lagoon (Florida) ranged from 0.01 to 6.6 μg/L 

(average, 0.8±1.4 μg/L) in 1992 (Trocine and Trefry 1996). 

Zinc concentration in precipitation from remote regions of the Atlantic Ocean ranged from 0.359 to 

3.93 μg/L (Helmers and Schrens 1995). Heaton et al. (1990) reported that precipitation collected from 

three locations Rhode Island between 1985 and 1988 contained zinc at median concentration of 4.5 ppb 
 

 

ZINC 167 

6. POTENTIAL FOR HUMAN EXPOSURE 

(n=269). Levels of zinc were higher in samples collected in warm periods (5.8 ppb) versus cold periods 

(3.7 ppb). Nearly all zinc was dissolved in these samples. Trace amounts of zinc were measured in cloud 

water (n=3; range, <10–43 μg/L) collected from Whiteface Mountain (Adirondacks Region, New York) 

in the summer of 1987 (Khwaja et al. 1995). Municipal waste incineration was the primary source of zinc 

in these wet deposition samples. Snow near an expressway in Montréal, Québec, Canada, contained zinc 

at average concentrations of 0.143, 0.33, 0.034, and 0.029 mg/L at 15, 20, 125, and 150 meters from the 

roadway, respectively (Loranger et al. 1996). Higher zinc concentrations near expressway were the result 

of road dust from tire abrasion. 

Available data suggest that zinc concentrations in drinking water are far less than levels required to meet 

a daily intake level of 11 mg/day (assuming an adult water consumption of 2 L/day) (IOM 2002). 

Concentrations of zinc in drinking water can be higher than levels in surface waters. Concentrations of 

0.002–1.2 mg/L were detected in 77% of 1,577 surface water samples while levels of 0.003–2.0 mg/L 

were found in 380 drinking water samples (NAS 1977). Higher concentrations in drinking waters are a 

result of water treatment and of contamination from plumbing of the water distribution system. 

Zinc was found in drinking water at levels as great as several mg/L as a result of galvanized pipes and 

tanks in alkaline-water distribution systems. Drinking water samples from galvanized pipe plumbing 

systems in Seattle, Washington, contained zinc concentrations of 0.128–1.279 mg/L; these levels were 

>10 times higher than those in homes with copper pipe plumbing systems (Sharrett et al. 1982a). Fortythree tap-water samples collected from homes in Dallas, Texas and analyzed for trace metals reported 

maximum, minimum, median, and average zinc concentrations of 0.049, 0.005, 0.011, and 0.0124 mg 

zinc/L, respectively (NAS 1977). High zinc concentrations in these water samples were believed to be 

due to the household plumbing. In a study investigating associations between inorganic constituents of 

drinking water and cardiovascular diseases, Greathouse and Osborne (1980) collected and analyzed tap 

water samples in 35 geographic areas in the United States; 100–110 tap-water samples were collected 

from each area. The maximum, minimum, and mean concentrations were 1.447, 0.025, and 0.144 mg 

zinc/L, respectively. Seventy-five percent of the zinc values were below 0.236 mg/L. Other investigators 

have attributed the higher concentrations of zinc in household tap waters, compared to finished drinking 

water, to distribution and transmission lines (Maessen et al. 1985; Ohanian 1986; Schock and Neff 1988). 

The median concentration of zinc in leachate from municipal landfills in the United States ranged from 

0.68 to 1.7 mg/L with a high concentration of 250 mg/L (Roy 1994). 
 

 

ZINC 168 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.3 Sediment and Soil 

Zinc is found in soils and surficial materials of the conterminous United States at concentrations between 

<5 and 2,900 mg/kg, with a mean of 60 mg/kg (Schacklette and Boerngen 1984). Zinc concentrations 

measured across the United Stated ranged from <5 to 400 mg/kg and from <10 to 2,000 mg/kg, with 

corresponding means of 36 and 51 mg/kg in cultivated and uncultivated subsurface soils, respectively 

(Connor and Shacklette 1975); however, these differences in zinc concentration may be attributed to 

differences in the soils prior to use (and not to cultivation). The sampling survey was designed to 

determine zinc concentrations of surficial materials unaltered from their natural condition. Chen et al. 

(1999) determined the baseline concentration of zinc in 448 representative Florida surface soils as part of 

the Florida Cooperative Soil Survey Program. Baseline soil samples represent natural elemental 

concentrations without human influence. The mean concentration of zinc was 8.35±13.8 mg/kg (range, 

0.9–169 mg/kg) in archived soil samples from this study. 

Soils near highways and smelters contained high zinc concentrations as a result of deposition of zinc 

released in tire abrasion and stack emissions (EPA 1980d; Norrström and Jacks 1999). Urban alluvial 

soils from New Orleans, Louisiana had higher levels of zinc as a result of highway traffic (130 μg/g) than 

freshly deposited lower Mississippi River delta spillway alluvium (11.1 μg/g) (Mielke et al. 1999, 2000). 

A study was designed by Hutchinson and Wai (1979) to investigate the distribution of cadmium, lead, and 

zinc in the soil and vegetation at two reclaimed waste dumps from phosphate ore mines in southeastern 

Idaho. Zinc concentrations in the soil of the waste dumps averaged from 443±210 to 1,112±124 mg/kg. 

These values were high compared to those found in the control plot (54±16 mg/kg). Zinc concentrations 

in vegetation from the reclaimed waste dumps were also high compared to the control plot. Moderate-tohigh levels of zinc contamination were found in leafy vegetables (lettuce) and their supporting soil in a 

zone with a 0–5-km radius around a copper smelter (Beavington 1975). The mean concentrations of zinc 

in 17 soil samples and 12 lettuce samples collected in this zone were 229±17 and 316±64 mg/kg dry 

weight, respectively. Significant relationships were found between the distance from the smelter and the 

levels of easily extractable zinc in the soil, and between the distance from the smelter and the content of 

zinc in herbage. The concentration of zinc in soil at the Palmerton zinc smelter site in eastern 

Pennsylvania was determined 6 years after zinc smelting was terminated in 1980 (Storm et al. 1994). 

Levels in soils were highest (4,160 mg/kg) at sites close to the former smelter and decreased with 

distance. Zinc concentrations in urban top soils from the western half of East St. Louis, Illinois (a city 

with historical industrial activities such as smelting of nonferrous metals) ranged from 79 to 10,360 μg/g 
 

 

ZINC 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

with an average concentration of 1,034 μg/g (Kaminski and Landsberger 2000). Concentrations of zinc in 

soil irrigated with waste water or river water were measured by Schalscha et al. (1982). The total 

concentration of zinc in waste water-treated soils was 228 mg/kg. The total concentration of zinc in soils 

irrigated with river water ranged from 103 to 136 mg/kg. 

Soils around galvanized water and electrical transmission towers have been reported to have elevated 

levels of zinc (Jones and Burgess 1984). Near Peterborough, Ontario, Canada, soil nearest to a 

galvanized water tower contained zinc at a concentration of 11,480±2,966 μg/g dry weight, while the 

concentration of zinc in soil 50 meters from the tower was 54±16 μg/g dry weight. 

Municipal sludge and municipal incineration ash contain considerably higher levels of zinc than 

uncontaminated soils (Mumma et al. 1984, 1990, 1991). Therefore, application of sludge and municipal 

ash to soil will elevate the levels of zinc in these soils. The mean concentrations (mg/kg) of zinc 

according to four land use types were as follows: agricultural, 25; suburban residential, 75; mixed 

industrial/residential, 157; and industrial inner urban area, 360 (Haines 1984). 

Zinc in water is transported to the sediment in the adsorbed or precipitated phase; the concentration of 

zinc in sediments of most waters is higher than the zinc concentration in aqueous phase. From 1992 to 

1996, streambed sediments samples were collected from 541 locations at more than 50 river basins across 

the conterminous United States (illustrated in Table 6-5) as part of the National Water-Quality 

Assessment Program (Rice 1999; USGS 2002). The median zinc concentration in these sediments was 

110 μg/g dry weight (range, <4.0–9,000 μg/g dry weight). Samples collected from urban settings were 

enriched in zinc relative to agricultural or forest settings. The highest median concentration was observed 

in the Upper Colorado River Basin while the lowest was observed in Central Nebraska Basins (USGS 

2002). Bed sediments from the South Platte River basin sampled from 1992 to 1993 contained zinc at 

concentrations ranging from 82 to 3,700 μg/g dry weight (average, 454 μg/g dry weight) (Heiny and Tat 

1997). The highest concentrations were observed near the urban region around Denver, Colorado and in 

the Rocky Mountains. In 1979–1980, as part of the Apalachicola River Quality Assessment, fine grained 

sediment (<20 μm particle size) of the Apalachicola River was reported to contain zinc at a median 

concentration of 70 μg/g dry weight (n=15; range, 20–150 μg/g dry weight) (Elder and Mattraw 1984). 

Surficial lake sediments from four locations in Rock Mountain National Park contained zinc at mean 

concentrations ranging from 72±4 to 125±3 μg/g dry weight (Heit et al. 1984). The geometric mean and 

range of zinc levels in lake sediment from 189 sites in 52 Quebec and Ontario, Canada lakes were 

125.2 and 3.0–559.9 μg/g dry weight, respectively (Rowan and Kalff 1993). The concentrations of zinc 
ZINC 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Median Zinc Levels in Bed Sediment from River Basins of the 

United Statesa
 

Median concentration of zinc 

NAWQA study unitb (μg/g dry weight) 

Acadian-Ponchartrain (ACAD) 120 

Albemarle-Pamlico Drainage (ALBE) 99 

Allegheny and Monongahela River Basins (ALMN) 195 

Apalachicola-Chattahoochee-Flint River Basin (ACFB) 130 

Central Arizona Basins (CAZB) 160 

Central Columbia Plateau (CCPT) 82 

Central Nebraska Basins (CNBR) 69 

Connecticut, Housatonic, and Thames River Basins (CONN) 200 

Cook Inlet Basin (COOK) 110 

Delaware River Basin (DELR) 290 

Eastern Iowa Basins (EIWA) 72.5 

Georgia-Florida Coastal Plain (GAFL) 100 

Great and Little Miami River Basins (MIAM) 130 

Hudson River Basin (HDSN) 180 

Kanawha-New River Basin (KANA) 200 

Lake Erie-Lake St. Clair Drainage (LERI) 120 

Long Island and New Jersey Coastal Drainages (LINJ) 245 

Lower Illinois River Basin (LIRB) 88 

Lower Susquehanna River Basin (LSUS) 300 

Lower Tennessee River Basin (LTEN) 84 

Mississippi Embayment (MISE) 91.5 

Mobile River and Tributaries (MOBL) 110 

Nevada Basin and Range (NVBR) 100 

New England Coastal Basins (NECB) 295 

Northern Rockies Intermontane Basins (NROK) 108 

Oahu (OAHU) 375 

Ozark Plateaus (OZRK) 90 

Potomac River Basin (POTO) 130 

Puget Sound Basin (PUGT) 130 

Red River of the North (REDN) 95 

Rio Grande Valley (RIOG) 82.5 

Sacramento River Basin (SACR) 120 

San Joaquin-Tulare Basin (SANJ) 110 

Santa Ana Basin (SANA) 160 

Santee Basin and Costal Drainages (SANT) 94 

South Central Texas (SCTX) 77 

South Platte River Basin (SPLT) 180 

Trinity River Basin (TRIN) 77.5 
ZINC 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Median Zinc Levels in Bed Sediment from River Basins of the 

United Statesa
 

Median concentration of zinc 

NAWQA study unitb (μg/g dry weight) 

Upper Colorado River Basin (UCOL) 940 

Upper Illinois River Basin (UIRB) 110 

Upper Mississippi Basin (UMIS) 110 

Upper Snake River Basin (USNK) 81 

Upper Tennessee River Basin (UTEN) 140 

Western Lake Michigan Drainage (WMIC) 98 

White River Basin (WHIT) 100 

Willamette River Basin (WILL) 120 

National median 110 

a

Source: USGS 2000 

b

( ) = acronym for study unit 
ZINC 172 

6. POTENTIAL FOR HUMAN EXPOSURE 

in sediments of the upper Columbia River, British Columbia, ranged from 45 to 51 mg/kg, while zinc 

concentrations in sediments from Lake Roosevelt, Washington were 60–26,840 mg/kg (Johnson et al. 

1990). The higher zinc concentrations in lake sediments were due to discharges from a lead-zinc smelter 

and a refinery. Contaminated sediments in the West Branch of the Grand Calumet River (Indiana/ 

Illinois), a river system heavily impacted by various industrial activities for many years, were found to 

contain zinc at concentrations ranging from 325 to 9,281 ppm (mean, 1,270±1,097 ppm) (Cahill and 

Unger 1993). Sediment samples collected from streams in the Black Hills, South Dakota, an area 

impacted by gold mining operations, contained zinc at levels ranging from 3.8 to 250 μg/g dry weight 

(May et al. 2001). 

Marine sediments also contain elevated concentrations of zinc with respect to concentrations of zinc in 

seawater. The concentration of zinc in Hamilton Harbor sediments ranged from 1,050 to 2,900 mg/kg, 

compared to zinc concentrations of 6–48 μg/L in the aqueous phase (Mayer and Manning 1990). 

Surficial sediments from the Newark Bay Estuary, Hackensack River, Newark Bay, Arthur Kill, and Kill 

van Kull contained zinc at mean concentrations of 739.5±243.9, 426±600.5, 489.8±238.1, 769.1±715.2, 

and 331.3±213.7 ppm, respectively (Crawford et al. 1995). Sediment samples collected from the Hudson 

River Estuary in 1991 contained zinc at levels of 27–215 and 400–2,500 mg/kg in bottom and suspended 

sediment, respectively (Gibbs 1994). Marine sediment samples from the border region of Baja California 

(Mexico) and California (United States) contained zinc at concentration levels ranging from 39 to 

188 μg/g dry weight (mean, 68.3 μg/g dry weight) in the fine fraction (<63 μm) of sediment. A relative 

enrichment of >350% was observed with respect to nonpolluted sediments of the region (VillascusaCelaya et al. 2000). Marine sediment in coastal areas of Mexico (Pacific Ocean and Gulf of Mexico) was 

found to contain zinc at mean concentrations ranging from 4.0 to 227.0 μg/g dry weight (Villanueva and 

Botello 1998). Soto-Jimenez and Páez-Osuna (2001) reported mean concentrations of zinc ranging from 

84.3±38.7 to 359±76.5 mg/kg dry weight for marine sediments collected in November 1994 from 

Mazatlán Harbor, Mexico (southeastern Gulf of California). This harbor receives land runoff and 

untreated or partially treated industrial, shipping, and domestic effluents from local point sources. During 

the period of 1984–1985, marine sediment samples were collected from the San Andres lagoon of the 

Gulf of Mexico, which is located near two industrial ports and industrial effluent is discharged into the 

lagoon year round. Sediments from this region were found to contain zinc at a concentration of 

10.1 mg/kg dry weight (Vasquez et al. 1994). 
 

 

 

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6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.4 Other Environmental Media 

As part of the National Water Quality Assessment (NAWQA) Program, the concentration of zinc in 

various species of fish was measured (USGS 2000a, 2000b, 2001). The concentration of zinc in fish fillet 

sampled from the Lower Tennessee River Basin ranged from 3.0 to 46.0 μg/g dry weight for 79 of 

102 positive detections from 1980 to 1998 (USGS 2001). Fish fillets collected from the Clark Fork-Pend 

Oreille and Spokane River Basins (Washington, Idaho, and Montana) contained zinc at concentrations 

ranging from 11 to 36 μg/g dry weight (n=15; median 16 μg/g dry weight) in 1998 (USGS 2000b). In the 

National Contaminant Biomonitoring Program, the geometric mean concentration of zinc in various 

whole fish was 21.7 mg/kg wet weight (Schmitt and Brumbaugh 1990). Of all fish tested (e.g., bloater, 

sucker, white perch, bass, catfish, etc.), common carp showed the highest level of zinc. No significant 

trend in the level of zinc in whole fish was observed during 1978–1984. Blevens and Pancorbo (1986) 

determined the zinc concentrations in muscle tissue of fish from aquatic systems in east Tennessee, from 

1980 to 1984. Mean levels of zinc in fish from Nolichucky and Little Chucky Creeks ranged from 12 to 

19 ppm wet weight. Fish from Watauga and Boone Lakes had a range of mean zinc concentrations of 

8.3–12 ppm wet weight; in the Holston River Basin, the range of mean concentrations of zinc was 4.6– 

28 ppm wet weight. The mean concentration of zinc in muscle tissue of tuna (Thunnus thynnus) collected 

from the northwest Atlantic Ocean was 17 μg/g dry weight (range, 12–25 μg/g dry weight) in 1990 

(Hellou et al. 1992). 

Zinc will not concentrate in fish tissues with exposure to elevated concentrations. The concentration of 

zinc in yellow perch (Perca flavescens) from six acidic lakes in northwestern New Jersey ranged from 

26.1 to 66.2 mg/kg dry weight (Sprenger et al. 1988). Although the concentrations of mercury and lead in 

fish from acidic lakes were higher compared to fish collected from nonacidic lakes, the concentrations of 

zinc showed no significant difference. Similarly, high concentrations of zinc were not found in white 

suckers (Catostomus commersoni) and brown bullheads (Ictalurus nebulosus) collected from two acidic 

Adirondack lakes in New York (Heit and Klusek 1985). Fish from the Milltown Reservoir Superfund 

Site in Montana (characterized by elevated concentrations of metals in wetland soils, surface water, and 

groundwater) contained zinc in whole body tissues at a concentration of 26.3 mg/kg wet weight (Pascoe 

et al. 1996). Redear sunfish (Lepomis microlophus), largemouth bass (Micropterus salmoides), and 

bluegill sunfish (Lepomis macrochirus) were collected from storm water ponds and natural lakes and 

ponds in Orlando, Florida between 1991 and 1992 (Campbell 1994). The mean concentrations of zinc in 

whole fish collected from storm water ponds were 42.2, 29.99, and 36.1 mg/kg wet weight for redear 

sunfish, largemouth bass, and bluegill sunfish, respectively. At natural lakes and ponds (controls sites), 
 

 

ZINC 174 

6. POTENTIAL FOR HUMAN EXPOSURE 

the mean concentrations of zinc were 24.83, 21.18, and 30.72 mg/kg wet weight for redear sunfish, 

largemouth bass, and bluegill sunfish, respectively. 

Bivalves and other sessile estuarine organisms are often used as a measure of contamination of estuarine 

water because they usually contain higher levels of metals than fish. The arithmetic mean concentration 

of zinc in oysters (Crassostrea virginica) from the Mississippi Sound collected in 1988 was 640 mg/kg 

wet weight (Lytle and Lytle 1990). Oysters collected from the San Andres lagoon (Gulf of Mexico) from 

1984 to 1985 contained zinc at a concentration of 3,180 mg/kg dry weight (Vazquez et al. 1994). The 

mean concentration of zinc in oysters (C. virginica) collected from the U.S. coastline of the Gulf of 

Mexico during 1986–1988 was 2,150 mg/kg dry weight (Presley et al. 1990). In a nationwide mussel 

watch program, the mean concentrations of zinc in molluscs (Mytilus edulis) around the coast of the 

United States during 1976–1988 ranged from 67 to 3,700 mg/kg dry weight (Lauenstein et al. 1990). 

Although the concentration on a nationwide basis varied depending on sampling sites, the level of zinc 

showed little evidence of statistically significant change during 1976–1988. Clams endevors (Corbicula 

manilmsis) collected as part of the Apalachicola River Quality Assessment between 1979 and 1980 

contained zinc at a median concentration of 20 μg/g dry weight (range, 2.1–26 μg/g dry weight) (Elder 

and Mattraw 1984). Blue crabs (Callinectes sapidus) from the Quinnipac and Connecticut Rivers 

(Connecticut), which are mostly harvested for personal consumption, contained zinc in muscle and 

heltopancreas tissues at concentrations of 31–33 and 27–28 mg/kg wet weight, respectively (Jop et al. 

1997). 

Vegetation may accumulate higher levels zinc if grown on contaminated soils. Jones et al. (1988) found 

that corn plants and young corn plants (Zea mays) grown beneath and close to a galvanized electrical 

transmission tower had elevated concentrations of zinc due to corrosion of the zinc protective layer on the 

steel. Corn seedlings grown in a highly contaminated soil (1,425 μg zinc/g soil) a meter from the tower 

had zinc concentration in shoots and roots of 484±103 and 1,330±250 μg/g dry weight, respectively. In 

contrast, seedlings grown in soil 50 meters from tower (67.3 μg zinc/g soil) had zinc concentrations in 

shoots and roots of 25.3±4.2 and 21.0±2.6 μg/g dry weight, respectively. Bache et al. (1991) found 

concentrations of zinc were highest in grass samples (Phleum pratense L.; Agropyron repens L.; Bromus 

inermis L; Phalaris arundinacea L.) collected immediately adjacent to the a municipal waste incinerator 

(135.7 μg/g dry weight) compared to grass samples collected upwind or a distance from the incinerator 

(17.82–73.78 μg/g dry weight). Grasses collected from the Milltown Reservoir Superfund Site in 

Montana contained zinc at concentrations of 153.7 and 882.1 mg/kg for above- and below-ground 

samples, respectively (Pascoe et al. 1996). In contrast, control samples from a reference area contained 
 

 

ZINC 175 

6. POTENTIAL FOR HUMAN EXPOSURE 

zinc at concentrations of 71.8 and 36.2 mg/kg for above- and below-ground samples, respectively. Other 

studies have not shown significant correlations between zinc concentrations in soils and vegetation 

(Fytianos et al. 2001; Schuhmacher et al. 1998). 

Sewage sludge and compost, which may be used in agriculture as a soil amendment, have high levels of 

zinc. The average concentrations of zinc in municipal solid waste compost and sewage from the United 

States were found to be 609 and 1,202 mg/kg dry weight, respectively (He et al. 1995). The median 

concentration of zinc found in residential compost from Toronto, Canada was 190 mg/kg dry weight 

(range, 100–410 mg/kg dry weight) (Evans and Tan 1998). Biowaste, composed of organic waste 

products from indoors and outdoors, contained zinc at concentrations of 120±25, 129±13, and 

338±58 mg/kg dry matter in the >5 mm, 1–5 mm, and <0.05 mm fractions, respectively (Veeken and 

Hamelers 2002). 

Other environmental concentrations of significance include coal and paint. Coal from the United States 

was found to contain zinc at a mean concentration of 53±440 ppm (n=7,908; maximum=19,000 ppm) 

(Finkelman 1999). Zinc was present at a median concentration of 31,101 μg/g (n=31; range, 52– 

98,056 μg/g) in paint from historic old homes of New Orleans, Louisiana (Mielke et al. 2001). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

General Population. Zinc is essential element needed by the body in small amounts and ranks as one of 

the most abundant trace metals in humans. Sources of exposure to zinc include ingestion of food, 

drinking water, food, polluted air, tobacco products, and occupational exposure, with ingestion of food 

being the primary route of exposure. NAS established the RDA for zinc at 11 mg/day for men and 

8 mg/day for women (IOM 2002). 

The average daily intake (AVDI) of zinc in humans is on the order of 5.2–16.2 mg zinc/day (Pennington 

et al. 1986). The dietary intake of an average teenage male has been estimated to be 0.27 mg 

zinc/(kg/day). Dietary supplements may provide up to an additional 1 mg zinc/(kg/day) (EPA 1980d). In 

an extensive survey of foods in the total diets of individuals in the United States, conducted by FDA 

during 1982–1984, the following values for daily zinc intakes (mg/day) were estimated in eight age and 

sex groups: 6–11-month-old infants, 5.24; 2-year-old children, 7.37; 14–16-year-old girls, 9.90; 14– 

16-year-old boys, 15.61; 25–30-year-old women, 9.56; 25–30-year-old men, 16.15; 60–65-year-old 

women, 8.51; and 60–85-year-old men, 12.64 (Pennington et al. 1986). FDA included drinking water in 
ZINC 176 

6. POTENTIAL FOR HUMAN EXPOSURE 

the total diet. In 1986, the average daily intakes of 40 African-Americans (age 21–65 years old living in 

Washington D.C. area) were 7.7±0.4 mg for men and 9.1±0.7 mg for women (Ellis et al. 1997). These 

results are comparable with data from the USDA’s Continuing Survey of Food Intakes by Individuals 

(CSFII) and the National Health and Nutrition Examination Survey (NHANES) III, which reported 

average daily intakes as follows: NHANES III, 40–49 year old value, male (12.3 mg/day), female 

(8.5 mg/day); CSFII, >20-year-old value, male (12.9 mg/day), female, (8.3 mg/day). The estimated 

average daily intakes of zinc were reported to be 14, 11, 14, and 13.2 mg/day in France, Spain, Sweden, 

and Belgium, respectively (Biego et al. 1998). Using a market basket method, the average daily intakes 

of zinc for residents of Japan were estimated as 8,700 and 8,500 μg/day for the years 1991 and 1992, 

respectively (Tsuda et al. 1995). 

After a review of the literature, the National Research Council concluded that zinc concentrations in 

drinking water are generally well below 5 mg/L (NAS 1977). Assuming a daily intake of 2 L of water 

and an average body weight of 70 kg, a daily intake of <0.14 mg zinc/kg/day from drinking water can be 

estimated. Based on a body weight of 70 kg, the mean daily intakes of zinc in drinking water for 

residents of homes with galvanized and copper pipe plumbing systems in Seattle, Washington, were 

estimated to be 0.017–0.028 and 0.002–0.006 mg/kg/day, respectively (Sharrett et al. 1982b). 

Food is the major source of zinc for the general population (EPA 1987c). Zinc is widespread in 

commonly consumed foods but tends to be higher in those of animal origin, particularly some seafoods 

(e.g., one serving of oysters will more than meet the daily dietary requirements of zinc) (NAS/NRC 

1979). Meat products contain relatively high concentrations of zinc, whereas fruits and vegetables have 

relatively low concentrations. Meats, fish, and poultry contained an average of 24.5 mg zinc/kg, whereas 

grains (or cereal products) and potatoes contained 8 and 6 mg/kg, respectively (Mahaffey et al. 1975). 

Zinc was present in all of the examined food classes. A diet of dairy products, meat, fish, poultry, grains, 

and cereals provides approximately 77% of the daily zinc intake. Data reported by the Food Safety and 

Inspection Service of the U.S. Department of Agriculture indicate that zinc was detected in 99.4–100% of 

the samples of healthy livestock and poultry randomly selected from among the specimens presented for 

slaughter in 1985–1986. Zinc concentrations in muscle tissue ranged from 0.20 ppm in young turkeys 

(n=61) to 1.92 ppm in heifers/steers (n=287) (Coleman et al. 1992). In a review of zinc levels in 

vegetables and other foods and beverages of plant origin, Weigert (1991) reported the following average 

concentrations (mg/kg): wheat, 41; rye, 13; rice, 8–20; potatoes, 3.51; vegetables, 4.31; fruit, 1.66; 

mushrooms, 9.7; cocoa, 35; tea, 35; and coffee, 6.7. Zinc is found in onions, peas, and potatoes from 

Denmark at mean concentrations of 3.4, 3.3–5.5, and 7.9 mg/kg fresh weight, respectively (Bibak et al. 
 

 

 

ZINC 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

1998a, 1998b; 1999). Zinc has also been detected in wines from Seville, Spain, at concentrations of 0.3– 

5.40 μg/mL, while concentrations of zinc in sherry wines ranged from 0.12 to 5.08 mg/L (López-Artiguez 

et al. 1990, 1996). As part of the U.S. FDA’s Total Diet Study (TDS), market basket food items from 

locations in United States were sampled from 1991 through 1999 (FDA 2000). Results from this survey 

showed the highest amounts of zinc in cereals ranging from a mean of 147 mg/kg for fruit-sweetened 

cereals to 8.2 mg/kg for corn flakes. Beef and other meat products also included a large amount of zinc, 

with the highest meat product mean being 81 mg/kg for baked beef chuck roast. In France, the estimated 

dietary intake of zinc from different foods were determined as follows (μg/day): vegetables, 807; fruits, 

143; beverages, 143; cereals, 2,572; fish-crustaceans, 795; meat-poultry-eggs, 8,318; milk-dairy products, 

1,127; condiments-sugar-oils, 140; canned foods, 383; and total, 14,429 (Biego et al. 1998). The largest 

percentage of zinc is from meat-poultry-eggs (58%) followed by cereals (18%) and milk-dairy products 

(8%). 

Federal regulations permit the use of zinc acetate, zinc oxide, and zinc sulfide as components of 

adhesives, coatings, or rubber packaging materials intended for food contact (FDA 1987b, 1987c, 1987d). 

Federal regulations also permit the use of zinc chloride, zinc oxide, zinc stearate, and zinc sulfate as 

GRAS (Generally Recognized As Safe) food additives when they are used "in accordance with good 

manufacturing practices" (FDA 1987e, 1987f, 1987g, 1987h, 1987i, 1987j). In addition, the use of zinc 

oxide as a color additive in drugs and cosmetics is also permitted with certain restrictions (FDA 1987a). 

Negligible quantities of zinc are inhaled in ambient air. Exposure to airborne zinc is largely occupational 

through the inhalation of industrial dusts or fumes. Individuals occupationally exposed to metallic zinc 

and zinc compounds are those involved in galvanizing, smelting, welding, or brass foundry operations. In 

such operations, zinc as ore or metal and its alloys are often exposed in an oxidizing atmosphere to 

temperatures near the metal's boiling point of 907 °C. This heating results in the formation of fresh zinc 

oxide particles (0.2–1.0 μm), which may subsequently be inhaled. Inhalation of zinc oxide particles and 

fumes by workers can result in metal fume fever (Martin et al. 1999). Inhalation was reported to be the 

most probable route of exposure to zinc for 26 lead smelter workers found to have significantly (p<0.01) 

elevated blood plasma levels of zinc. Mean plasma zinc concentrations were 12.9 mmol/L (range, 9.8– 

16.7) for the workers versus 10.9 mmol/L (range, 8.1–14.6) for a nonlead-exposed control group 

(Vasikaran et al. 1992). Twenty workers in a zinc foundry in Baiyin, China were investigated for 

exposure to zinc oxide fumes (Martin et al. 1999). Eighteen of the workers had worked at the foundry 

since its opening 6 years earlier. Thirteen of the subjects reported at least one of the symptoms associated 

with metal fume fever during their tenure at the foundry. Workers were examined before the start of the 
 

 

ZINC 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

shift, in the middle of the shift, and after the shift. Despite zinc exposures as high as 36.3 mg/m3 over 

<4 hours and a mean air sample concentration of 3.16 mg/m3

, no cases of metal fume fever were observed 

for these workers. Concentrations of zinc in serum and urine for these workers averaged 11.515 μmol/L 

(752.85 μg/L) and 3.6705 μmol/L (239.98 μg/L), respectively, during the period of an 8-hour shift. 

Zinc is found in human tissues and body fluids. As part of the 1982 National Human Adipose Tissue 

Survey (NHATS) conducted in the United States, the concentration of zinc in adipose tissue ranged from 

1.1 to 6.0 μg/g (EPA 1986). The mean concentration of zinc was 6.95±1.08 μg/mL in whole blood 

samples from residents of Baajoz, Spain (a region with low environmental pollution) with zinc levels 

increasing with age (Moreno et al. 1999). Individuals <30, 30–45, and >45 years old had whole blood 

zinc concentrations of 4.85, 6.85, and 7.32 μg/mL, respectively. Blood and serum collected from 

372 adolescents (15 years old) from the Swedish cities of Uppsala and Trollhättan contained zinc at 

median concentrations of 6.1 and 0.99 mg/L, respectively (Bárány et al. 2002). The mean concentration 

of zinc in the fingernails and toenails of populations from the United States, Canada, and Japan were 105, 

109, and 94 mg/kg, respectively (Takagi et al. 1988). Hayashi et al. (1993) reported that human fingernail 

samples from Japanese individuals had higher mean levels of zinc in the spring (145–149 μg/g) compared 

to winter (122–136 μg/g). The geometric mean concentrations of zinc in toenails (129 mg/kg) and scalp 

hair (108 mg/kg) of pre-school children in Germany were about the same (Wilhelm et al. 1991). The total 

concentrations of zinc in 29 body tissues of 55 human cadavers were measured (Saltzman et al. 1990). 

The lowest concentration (mean of 1.5±2.2 mg/kg wet weight) of zinc in both males and females was 

found in adipose tissues, while the highest concentrations were detected in the skull of males (mean of 

54.3 mg/kg wet weight) and in the skeletal muscle of females (mean of 59.0 mg/kg wet weight). The 

mean concentrations of zinc in the feces of low-income urban Hispanics and rural Blacks in the United 

States were 75 and 94 mg/kg wet weight, respectively (Prevost et al. 1985). Body tissue and fluid 

samples were collected from two nonoccupationally exposed individuals living in the Los Angeles, 

California area (Krishnan and Que Hee 1992). Ear wax, blood plasma, sweat, and skin from these 

individuals contained zinc at levels of 88–103, 0.79–1.7, 0.50–1.58, and 15.6–1,000 μg/g dry weight, 

respectively. 

Concentrations of zinc in human milk are affected by the stages lactation. Arnaud and Favier (1995) 

found that the level of zinc in human milk will rise to a peak 2-days postpartum (183±70 μmol/L or 

12.0±4 mg/L) and then decline during the duration of lactation (e.g., at 6-days postpartum, 77±22 μmol/L 

or 5.0±1.4 mg/L). At 6-months, the concentration of zinc in human milk is only 12% of its initial levels 

(Dórea 2002). Wasowicz et al. (2001) observed an inverse relationship between zinc levels in blood 
 

 

 

ZINC 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

plasma and human milk for lactating women from Poland. Mean levels of zinc in blood plasma increased 

from 0.51±0.13 mg/L (0–4 days postpartum) to 0.76±0.20 mg/L (10–30 days postpartum), while mean 

levels of zinc in human milk decreased from 8.2±2.8 mg/L (0–4 days postpartum) to 1.4±0.7 mg/L 

(10–30 days postpartum). 

Zinc levels in maternal blood are normally higher than levels in cord blood. Maternal and cord blood of 

56 mothers living in Singapore were analyzed for zinc (Ong et al. 1993). For these mothers, the mean 

concentrations of zinc were 4.97±1.15 and 1.58±0.45 mg/L in maternal and cord blood, respectively. 

During the period of 1993–1997, Raghunath et al. (2000) determined the concentration of zinc in 

maternal and cord blood for 148 mothers (20–25 years old) living Mumbai City, India. The mean 

concentrations of zinc were 6.335 and 2.527 mg/L in maternal and cord blood, respectively. 

Occupational. As part of the National Occupational Exposure Survey (NOES) conducted from 1980 to 

1983, NIOSH statistically estimated that 269 workers (including 22 women) in 22 plants were potentially 

exposed to elemental zinc in the workplace; also, 133,608 workers (including 17,586 women) in 

6,157 plants were potentially exposed to other forms of zinc (of undefined composition) in the workplace 

(NIOSH 1984b). All of the workers exposed to elemental zinc were employed in the fabricated metal 

products industry as millwrights or assemblers. The largest numbers of workers exposed to other forms 

of zinc worked in the primary metal industries, with fabricated metal products, with transportation 

equipment, with stone, clay, and glass products, and in special trade contractors industries. Occupational 

groups with the largest numbers of exposed workers were miscellaneous machine operators (not 

elsewhere classified or not specified), molding and casting machine operators, janitors and cleaners, and 

machinists. Exposure estimates were derived from observations of the actual use of the compound and 

the use of trade name products known to contain the compound. 

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 
ZINC 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

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, 

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 for adults, sources of exposure for children to zinc include ingestion of food, drinking water, and 

polluted air, with ingestion of food being the primary route of exposure. In an extensive survey of foods 

in the total diets of children in the United States, conducted by FDA during 1982–1984, the following 

values for daily zinc intakes (mg/day) were estimated: 6–11-month-old infants, 5.24; 2-year-old children, 

7.37; 14–16-year-old girls, 9.90; and 14–16-year-old boys, 15.61 (Pennington et al. 1986). The FDA also 

included drinking water in the total diet. Hair samples collected from children (10–12 years old) living 

rural and industrial areas of southern Poland and analyzed for zinc (Zachwieja et al. 1995). Hair samples 

of children from Kraków-Shakina (urban areas), Tarnów-Czechowice-Dziedzice (industrial areas), and 

rural areas contained zinc at concentrations of 171.5, 185.0, and 244.6 ppm, respectively (Zachwieja et al. 

1995). Whole blood samples from children (3–6 years old) living in Mumbai and Hyderabad, 

industrialized urban areas of India, contained zinc at mean concentrations of 398.9 and 483.4 μg/dL, 

respectively (Tripathi et al. 2001). 

At waste sites, zinc that is found in excess of natural background levels is most likely to be in soil, and 

presents a special hazard for young children. Hand-to-mouth activity and eating contaminated dirt will 

result in oral exposure to zinc. The hazard in this case depends on the form of zinc that is present at the 

waste site. Zinc in soil at waste sites is in both soluble and insoluble forms; zinc in insoluble forms would 

be expected to be less available than more soluble forms. 

Zinc exposure to children from parents’ work clothes, skin, hair, tools, or other objects from the 

workplace is possible if the parent uses zinc or its compounds at work. Household products or products 

used in crafts, hobbies, or cottage industries which contain galvanized materials (e.g., nails) or zinccontaining paint will have significant amounts of zinc. Hand-to-mouth activity, chewing, and eating these 

materials may result in higher exposure to zinc. However, no cases of home exposure to zinc were 

located in the literature. 
 

 

ZINC 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Certain populations receive greater-than-average exposures to zinc from environmental sources. For 

example, higher levels of zinc have been reported in soil and water near waste sites, metal smelters, and 

areas exposed to untreated waste water (Hutchinson and Wai 1979; Ragaini et al. 1977; Schalscha et al. 

1982). Other populations at risk of high exposure are those that have galvanized plumbing in their 

residences, and those that intentionally consume large doses of zinc as a dietary supplement. Patients 

who receive chronic treatment with drugs containing zinc salts (such as injectable insulin) are exposed to 

higher zinc levels than the general population. Allergic reactions to the zinc in insulin have been reported 

(Bruni et al. 1986). People in certain occupations (e.g., nonferrous metal smelting) are likely to be 

exposed to higher concentrations of zinc than the general population (see Section 6.5). However, the 

higher exposure may not be indicative of a long-term increase in body burden. For example, the median 

zinc concentration in the lung tissues of 21 Swedish workers previously employed in the refining and 

smelting of nonferrous metals was about the same as in a control group (11.0 versus 10.7 mg/kg wet 

weight) (Hewitt 1988). On the other hand, the median concentration of zinc in lung tissues of eight 

deceased coal miners from England was 72 mg/kg wet weight compared to a median value of 54 mg/kg 

wet weight for a control group (Hewitt 1988); however, the study author did not provide any evidence 

that the difference in zinc concentrations in the lungs of unexposed controls is statistically significant. 

Individuals who smoke or who use zinc supplementation will have greater exposure to zinc. Zinc was 

measured in samples of cigarette tobacco from the United States at concentrations ranging from 30 to 

69 μg/g (Jenkins 1986). Levels of zinc in smoke from these cigarettes ranged from 0.34 to 

1.21 μg/cigarette. Individuals, who use high-dose zinc supplementation as a potential treatment for agerelated macular degeneration, will have higher exposures to zinc. Hiller et al. (1995) reported that zinc 

supplements will have an effect on the concentration of serum zinc in the body. 

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 zinc 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 zinc. 
 

 

ZINC 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

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. Data are available that adequately characterize the physical 

and chemical properties of the various forms of zinc to permit estimation of their environmental fate 

(ACGIH 1991; Baes and Sharp 1983; Baes et al. 1984; Gerritse et al. 1982; HSDB 1986, 1990; NIOSH 

1990; Weast 1988; Weiss 1986; Windholz 1983). 

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 2002, became available in May of 2004. This database is updated yearly and should 

provide a list of industrial production facilities and emissions. 

Information about current and future production of zinc and zinc compounds is available. Zinc is also one 

of the most widely used metals in the world (Mirenda 1986). In 2001, approximately 799,000 metric tons 

of zinc were produced in the United States from domestic ores. The estimated world production from 

mines in 2001 was 8,850,000 metric tons (USGS 2001). Information on the use of zinc and its 

compounds in the home, environment, and workplace is available. Zinc is most commonly used as a 

protective coating for other metals. It is also used in alloys such as bronze and brass, for electrical 

apparatus, and in organic chemical extractions. Zinc salts have numerous applications, including wood 

preservation. Zinc chloride is a primary ingredient in smoke bombs. In pharmaceuticals, zinc salts are 

used as solubilizing agents in drugs, including insulin (Lloyd 1984; Lloyd and Showak 1984; Windholz 

1983). Zinc oxide is found in ointments used to treat burns and infectious and skin diseases (EPA 

1987d). Zinc is also utilized therapeutically in human medicine in the treatment of zinc deficiency 

(Elinder 1986). Information on typical releases of zinc and its compounds in the home, environment, and 

workplace, and which environmental media are likely to be contaminated with significant quantities of 

zinc are available. Zinc is ubiquitous in the environment. Both natural releases and releases of human 
 

 

ZINC 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

origin to the environment can be significant (EPA 1980d; Fishbein 1981; Mirenda 1986; NAS 1977; 

Nriagu 1989; Ragaini et al. 1977; TRI02 2004). Soils and sediments are likely to contain significant 

quantities of zinc and its compounds (Connor and Shacklette 1975; Rice 1999; Shacklette and Boerngen 

1984; USGS 2002). Current disposal methods are efficient (Dawson and Mercer 1986; Lloyd and 

Showak 1984). No data were located regarding the amount of zinc being disposed. Rules and regulations 

regarding the disposal of zinc are available (Dawson and Mercer 1986; DOI 1991). According to the 

Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries 

are required to submit chemical release and off-site transfer information to EPA. The Toxics Release 

Inventory (TRI) contains this information for 2001. Environmental releases of zinc and zinc compounds 

from manufacturing and processing facilities required to report their releases are listed in Tables 6-1 and 

6-2. This database is updated yearly and should provide a list of industrial production facilities and 

emissions. 

Environmental Fate. Zinc partitions to the air, water, and soil (EPA 1979d; Guy and Chakrabarti 

1976; Houba et al. 1983; Pita and Hyne 1975). Zinc occurs in the environment mainly in the +2 oxidation 

state (Lindsey 1979). Adsorption is the dominant fate of zinc, resulting in enrichment of zinc in 

suspended and bed sediments (EPA 1979d). The mobility of zinc in soil has been characterized (Baes and 

Sharp 1983; Bergkvist et al. 1989; EPA 1980d; Hermann and Neumann-Mahlkau 1985; Kalbasi et al. 

1978; Saeed and Fox 1977; Tyler and McBride 1982). No estimate for the atmospheric lifetime of zinc is 

available. Development of pertinent data on the atmospheric processes important for zinc speciation in 

the atmosphere would be helpful. Development of this information would permit construction of a 

comprehensive model for the transport and interaction of zinc not only in air but in other media as well. 

Transformation in air and water can occur as a result of changes in chemical speciation (Anderson et al. 

1988; EPA 1979d, 1980d; Stokinger 1981). Data that describe the transformation processes for zinc in 

soil or the fate of zinc in soil are needed. A model of zinc flux from all environmental compartments 

would be useful for providing information on the overall environmental fate of zinc. 

The primary anthropogenic sources of zinc in the environment (i.e., air, water, soil) are related to mining 

and metallurgic operations involving zinc and use of commercial products containing zinc (EPA 1980d; 

NAS 1977; Nriagu and Pacyna 1988; Ragaini et al. 1977; TRI02 2004). Zinc has been detected in air, 

surface water, groundwater, and soil, with the frequency of detection and the concentrations greatest near 

source areas (e.g., hazardous waste sites and industrial areas such as lead smelters) (EPA 1980d; HazDat 

2005; Lioy et al. 1978; Lloyd and Showak 1984; Mumma et al. 1984, 1990, 1991; NAS 1977). 
ZINC 184 

6. POTENTIAL FOR HUMAN EXPOSURE 

Bioavailability from Environmental Media. Zinc can be absorbed following inhalation (Drinker 

and Drinker 1928; Hamdi 1969), ingestion (Aamodt et al. 1983; Davies 1980; Johnson et al. 1988; 

Methfessel and Spencer 1973; NAS/NRC 1979; Spencer et al. 1985), or dermal contact (Agren 1990; 

Gordon et al. 1981; Hallmans 1977; Keen and Hurley 1977). No estimates of the bioavailability of zinc 

after inhalation of zinc particles in air, ingestion from water and soil, or skin contact with bath water or 

soil were located. The bioavailability of zinc is higher in media with a low pH, as a result of increased 

zinc solubility and ionization. If zinc is partly present in an irreversibly adsorbed state in soil, this part is 

not available for skin absorption. It would be useful to develop quantitative data on the bioavailability of 

zinc from various environmental media. 

Food Chain Bioaccumulation. Zinc bioconcentrates moderately in aquatic organisms, and this 

bioconcentration is higher in crustaceans and bivalve species than in fish (EPA 1987c; Ramelow et al. 

1989). Zinc may concentrate in plants grown on contaminated soils. However, it does not biomagnify 

through the terrestrial food chain (Biddinger and Gloss 1984; EPA 1979d; Hegstrom and West 1989; 

Levine et al. 1989). 

Exposure Levels in Environmental Media. Reliable monitoring data for the levels of zinc in 

contaminated media at hazardous waste sites are needed so that the information obtained on levels of zinc 

in the environment can be used in combination with the known body burden of zinc to assess the potential 

risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 

Zinc has been detected in air (Barrie and Hoff 1985; Duce et al. 1975; EPA 1980d; Evans et al. 1984; 

John et al. 1973; Lioy et al. 1978; Lloyd and Showak 1984; Patterson et al. 1977; Pratt et al. 2000; 

Ragaini et al. 1977; Saltzman et al. 1985; Spicer et al. 1996; Zoller et al. 1974), water (Bruce and 

McMahon 1996; Coale and Flegal 1989; Cole et al. 1984; EPA 1980d; Hale 1977; HazDat 2005; Heit et 

al. 1989; Maessen et al. 1985; Minear et al. 1981; NAS 1977; Nriagu et al. 1996; Ohanian 1986; SañudoWilhelmy and Gill 1999; Schock and Neff 1988; Scudlark et al. 1994; Shiller and Boyle 1985; Taylor et 

al. 2001; Windom et al. 1991), soil (Beavington 1975; Chen et al. 1999; Connor and Shacklette 1975; 

EPA 1980d; Haines 1984; HazDat 2005; Johnson et al. 1990; Mayer and Manning 1990; Mielke et al. 

1999, 2000; Mumma et al. 1984, 1990, 1991; Norrström and Jacks 1999; Schalscha et al. 1982; Storm et 

al. 1994), and food (Coleman et al. 1992; FDA 2001; Gartrell et al. 1986a; Mahaffey et al. 1975; Weigert 

1991). However, since most of the data are not current, i.e., within the last 3 years, additional data would 

be useful to provide a more complete characterization of human exposure and the trend in zinc 

concentrations in various environmental media. Estimates have been made for human intake of zinc from 
ZINC 185 

6. POTENTIAL FOR HUMAN EXPOSURE 

food and drinking water (EPA 1980d; Gartrell et al. 1986a; IOM 2002; Pennington et al. 1986; Sharrett et 

al. 1982a, 1982b). Further data are needed on estimated daily intakes from inhalation resulting from 

occupational exposures. 

Reliable monitoring data for the levels of zinc in contaminated media at hazardous waste sites are needed 

so that the information obtained on levels of zinc in the environment can be used in combination with the 

known body burden of zinc to assess the potential risk of adverse health effects in populations living in 

the vicinity of hazardous waste sites. 

Exposure Levels in Humans. Zinc has been detected in fingernails, toenails, hair, all tissues, 

organs, skull and skeletal muscle, blood, feces, urine, sweat, and saliva (Greger and Sickles 1979; 

Hambidge et al. 1972; Henkin et al. 1975a; Llobet et al. 1988a; NAS/NRC 1979; Prasad et al. 1963a; 

Prevost et al. 1985; Saltzman et al. 1990; Schroeder et al. 1967; Takagi et al. 1988; Wastney et al. 1986; 

Wilhelm et al. 1991). Most of the data on occupational exposure levels of zinc are outdated (NIOSH 

1976, 1984b). Additional information on potentially exposed workers and exposure levels would provide 

a more accurate characterization of occupational exposures in the United States. Current biological 

monitoring data on zinc are needed for populations surrounding hazardous waste sites. This information 

is necessary for assessing the need to conduct health studies on these populations. 

This information is necessary for assessing the need to conduct health studies on these populations. 

Exposures of Children. Limited data are available regarding the exposure and body burdens of 

children to zinc. Children, like adults, are primarily exposed to zinc through the diet. Zinc was identified 

in the postpartum human milk of women at concentrations of 5 to 12 mg/L (Arnaud and Favier 1995). In 

an extensive survey of foods in the total diets of individuals in the United States, conducted by FDA 

during 1982–1984, the following values for daily zinc intakes (mg/day) were estimated for children: 6– 

11-month-old infants, 5.24; 2-year-old children, 7.37; 14–16-year-old girls, 9.90; and 14–16-year-old 

boys, 15.61 (Pennington et al. 1986). Since zinc is found in soil and children ingest soil either 

intentionally through pica or unintentionally through hand-to-mouth activity, pica is a unique exposure 

pathway for children. While zinc is found in home products such as paint, ointments, galvanized metals, 

coins, and dietary supplements, this exposure route should be low and will not disproportionally affect 

children. Continued monitoring data are necessary to understand potentially dangerous routes of 

childhood exposure. 
ZINC 186 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 zinc 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 sub-registries 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. 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2004) 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 6-6. 
 

 

ZINC 187 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Ongoing Studies on the Environmental Effects of Zinca 

Investigator Affiliation Study Sponsor 

Ahner BA 

Basta N, Raun WR 

Basta NT 

Bleam WF, Helmke 

PA 

Chaney RL 

Chaney RL 

Chaney RL 

Chaney RL, Angle 

JS 

Cox FR 

Fish RH 

Guo MG, Tyzbir R 

Harsh JB, Zamora 

BA, Kuo S, Pan W, 

Stevens RG, Flury M 

Heil D 

Helmke PA, Bleam 

WF 

Hesterberg DL 

Kinraide TB 

Kochian LV, Paolillo 

DJ 

Cornell University, 

Biological and 

Environmental Engineering 

Oklahoma State University, 

Agronomy 

Oklahoma State University, 

Agronomy 

University of Wisconsin 

Soil Science 

Beltsville Agricultural 

Research Center 

Beltsville Agricultural 

Research Center 

Beltsville Agricultural 

Research Center 

University of Maryland, 

Agronomy 

North Carolina State 

University, Soil Science 

Lawrence Berkeley 

Laboratory, University of 

California 

University Of Vermont, 

Nutritional Sciences 

Washington State 

University, Crop and Soil 

Sciences 

Colorado State University, 

Soil and Crop Science 

University of Wisconsin Soil 

Science 

North Carolina State 

University, Soil Science 

Agricultural Research 

Service 

Cornell University, Plant 

Biology 

Monitoring the bioavailability of toxic 

metals in soil 

Chemistry and bioavailability of waste 

constituents in soils 

Heavy metal and trace element 

chemistry in soils: Chemical speciation 

and bioavailability 

Verifying and quantifying the specific 

complexation of metals to humic 

substances 

Characterization and remediation of 

potential trace element and phosphate 

risks from contaminated soils 

Development of methods to control 

heavy metal contents in soils at benign 

or beneficial levels 

Long-term phytoavailability and 

bioavailability of soil metals 

Phytoavailability and bioavailability of 

heavy metals from heavy metal 

contaminated soil 

Effects of P, Cu, and Zn from animal 

waste and fertilizer on crop responses 

and soil test interpretations 

Removal and recovery of toxic metal ions 

from aqueous streams by utilization of 

polymer pendant ligands 

Solubility and distribution of trace 

elements in milk based infant formula 

Physical chemical state and plant 

availability of uranium, lead, cadmium, 

zinc, and arsenic in selected Washington 

soils 

Biogeochemistry and management of 

salts and potentially toxic trace elements 

in arid-zone soils, sediments, and water 

Reactions controlling free ion activities 

and solubility of soil trace elements 

Molecular-scale characterization and fate 

of soil contaminants 

The role of binding and electrostatic 

attraction to roots in the uptake of heavy 

metals by plants 

Mechanisms of aluminum tolerance and 

heavy metal accumulation in plants 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

DOE 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 
 

 

 

 

ZINC 188 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Ongoing Studies on the Environmental Effects of Zinca 

Investigator Affiliation Study Sponsor 

Kochian LV 

Kochian LV 

KpomblekouAdemawou K, 

Ankumah RO 

Kuo S 

Little RE 

McBride MB 

McBride MB 

Norvell WA, Duxbury 

JM 

Norvell WA, Welch 

RM, Degloria SD 

Odom JW 

Parker DR 

Pierzynski GM 

Ross DS 

Salt DE 

Slaton NA 

Agricultural Research 

Service 

Agricultural Research 

Service 

Tuskegee University, 

Agriculture and Home 

Economics 

Washington State 

University, Puyallup 

Research and Extension 

Center 

NIEHS, National Institutes 

of Health 

Cornell University, Soil, 

Crop and Atmospheric 

Science 

Cornell University, Soil, 

Crop and Atmospheric 

Science 

Cornell University 

Cornell University 

Auburn University, 

Agronomy and Soils 

University of California, 

Environmental Sciences 

Kansas State University, 

Agronomy 

University of Vermont, 

Plant and Soil Science 

Purdue University, 

Horticulture 

University of Arkansas, 

Crop, Soil and 

Environmental Sciences 

Investigation of heavy metal 

bioaccumulation in plants grown on 

metal-polluted soils 

Mechanisms of heavy metal and 

radionuclide hyper-accumulation and 

bioavailability in higher plants 

Trace elements in broiler littered soils: 

fate and effects on nitrogen 

transformation 

Chemistry and bioavailability of waste 

constituents in soils 

Environmental pollution in eastern and 

central Europe 

Heavy metal solubility in contaminated 

soils 

Reaction and availability of toxic metals 

in soils 

Plant availability and geographical 

distribution of essential and toxic 

elements 

Bioavailability and geographic 

distribution of nutritionally important 

elements in crops and soils 

Occurrence, measurement and mapping 

of plant micronutrient and trace elements 

in Alabama soils 

Predicting trace-metal bioavailability from 

soil solution speciation: can it be done 

Chemistry and bioavailability of waste 

constituents in soils 

Soil manganese oxides: Oxidation and 

retention of contaminant metals and 

organics 

A dissection of the molecular 

mechanisms underlying metal 

hyperaccumulation in plants 

Evaluation of fertilization practices, soil 

fertility, and plant nutrition for crops 

produced in Arkansas 

USDA 

USDA 

USDA 

USDA 

NIH 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

USDA 

Sparks DL, Ford RG University of Delaware, Influence of aging and competitive USDA 

Plant and Soil Sciences sorption on stabilization of metals via 

surface precipitation in soils 

Thompson ML Iowa State University, Co-migration of metals and dissolved USDA 

Agronomy humic substances in aquifer material 
 

 

ZINC	 189 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Ongoing Studies on the Environmental Effects of Zinca 

Investigator Affiliation Study	 Sponsor 

Thompson ML Iowa State University, 

Agronomy 

Welch RM, Norvell Agricultural Research 

WA, Kochian LV Service 

Zelazny LW Virginia Polytechnic 

Institute, Crop and Soil 

Environmental Sciences 

Sustainable and environmentally safe USDA 

management of soil resources 

Agricultural approaches to human health USDA 

through understanding soil-planthuman/animal food systems 

Soil mineralogical controls on nutrient USDA 

availability and mobility 

a

Source: FEDRIP 2004 

DOE = Department of Energy; FEDRIP = Federal Research in Progress Database; NIEHS = National Institute of 

Environmental Health Services; NIH = National Institute of Health; USDA = United Stated Department of Agriculture 

ZINC 191 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring zinc, its metabolites, and other biomarkers of exposure and effect to zinc. 

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. 

Zinc is ubiquitous in both the environment and the laboratory. Since many biological and environmental 

samples contain low levels of zinc, it is easy to contaminate samples. Thus, it is imperative that special 

precautions be taken to avoid sample contamination in order to obtain accurate results and ensure the 

integrity of samples. Precautions must be taken to avoid contamination during sample collection and 

analysis from sources such as sampling and filtration equipment, inadequate reagent purity, and 

atmospheric deposition. For ultratrace analysis, the use of a clean-room laboratory with a laminar flow 

work station is highly recommended to avoid contamination of samples and standards with airborne 

particulates. In blood analysis, collection tubes are potential sources of zinc contamination (Delves 

1981). An example of failure to institute proper measures to control sample contamination, which led to 

inaccuracies in reported data, was described by Windom et al. (1991). Methods that can be used to avoid 

reporting erroneous results include interlaboratory data comparison (Galloway et al. 1983) or use of 

standard reference materials, such as certified SRM 1549 (nonfat powdered milk) available from the 

National Institute of Standards and Technology (Perry 1990). 

Zinc concentrations are typically quantified using instrumental methods such as atomic absorption, 

emission, or mass spectroscopies; x-ray fluorescence; electro-analytical techniques (e.g., stripping 

voltammetry); and neutron activation analysis. 
 

 

 

 

ZINC 192 

7. ANALYTICAL METHODS 

7.1 BIOLOGICAL MATERIALS 

Table 7-1 lists the applicable analytical methods used for determining zinc in biological fluids and tissues. 

Inductively coupled plasma-atomic emission spectroscopy (ICP-AES) is used for zinc determinations in 

blood and tissue samples (NIOSH Method 8005) and in urine (NIOSH Method 8310). Detection limits in 

blood and tissue are 1 μg/100 g and 0.2 μg/g, respectively, with recoveries of 100% (NIOSH 1994). 

Sample preparation involves acid digestion with concentrated acids. Detection of zinc in urine samples 

requires extraction of the metals with a polydithiocarbamate resin prior to digestion and analysis (NIOSH 

1984). Detection limits in urine are 0.1 μg/sample. Inductively coupled plasma-mass spectroscopy (ICPMS) has been used to determine the concentration of zinc in milk samples and brain tissue (Panayi et al. 

2002; Patterson et al. 1992). Detection limits are 0.06 μg/sample for milk and 10.7 ng/g (for a 150 mg 

sample) for brain tissue samples. Recoveries ranged from 99–111% for brain tissue samples (Panayi et al. 

2002). 

Atomic absorption spectrometry (AAS) is a common and simple laboratory technique capable of routine 

zinc analysis of biological samples including bone, liver, hair, blood, and urine. Graphite furnace AAS 

(GF-AAS) is more sensitive than flame AAS and has been used to determine very low levels of zinc 

(detection limit, 0.052 μmol/L) in human milk (Arnaud et al. 1991). GF-AAS has been used to determine 

zinc in human semen. Recovery (96–104%) was good, and preparation by microwave wet acid 

dissolution was more accurate than the standard water dilution method (Alvarado et al. 1991). Zinc 

concentrations in liver have been accurately quantified by flame AAS. Homogenization of tissue samples 

coupled with flame AAS resulted in 100% recoveries, accuracies of 0–3%, and a detection limit of 

0.04 mg/L (Luterotti et al. 1992). AAS has also been used to determine zinc in bloodstains on filter 

paper. This method is accurate, reproducible, and acceptable for routine clinical testing using both dry 

ashing and direct extraction sample preparation (Fan et al. 1991). 

The use of stable isotopes or tracers to study zinc absorption in humans with subsequent analysis by mass 

spectrometry has been reported in the literature. Analysis of fecal samples obtained 3 and 6 days after the 

administration of zinc-65 isotope in food showed that between 45 and 75% of zinc isotope was absorbed 

(Johnson 1982). The results indicated satisfactory detection of the zinc-67 isotope in human feces, while 

the zinc-70 isotope was not as detectable. Better precision and recovery were obtained for the 

zinc-67 isotope (2.4% CV [coefficient of variation]; >95% recovery) than for the zinc-70 isotope (38% 
 

 

 

 

ZINC	 193 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Zinc in Biological Materials 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Blood or tissue Acid digestion with 

HNO3/HClO4, H2SO4, measure 

at 213.9 nm 

Urine Acid digestion of oxygen 

plasma ashing; extract with 

polydithiocarbamate resin; 

measure at 213.9 nm 

Semen Microwave wet acid digestion 

Fingernails Digest nail samples with 

concentrated nitric acid; heat at 

65 °C for 1 hour; cool and dilute 

with deionized water 

Liver Acid digestion with mixtures of 

different acids; distill volatile 

elements 

Liver Homogenize sample with water; 

add HCl; shake; centrifuge; 

dilute 

Muscle tissue Mineralize sample in muffle 

furnace; dissolve in HNO3 

Blood Separate serum from blood by 

centrifugation; transfer a portion 

of serum into an ampule of 

highly pure silica and dry; 

irradiate capsules at a thermal 

neutron density of 

5x103

n/cm-2/second-1 

Blood Feed radiotracer 65zinc; 

measure zinc activity in blood at 

14 days 

Blood serum Feed 68zinc and 70zinc and 

and red blood measure blood levels in a 

cells 24-hour sample and a sample 

taken immediately after zinc 

administration; wet ash sample; 

add APDC precipitant; dissolve 

precipitate in HNO3 irradiate 

Blood Feed 65ZnCl2 orally; measure 

zinc blood levels and whole 

blood count 

ICP-AES 

ICP-AES 

GF-AAS 

GF-AAS 

Radiochemical NAA 

Flame AAS 

FIA 

Instrumental 

NAA 

Tracer 

technique 

Isotope tracer 

technique 

Radiotracer 

technique– 

whole blood 

count and 

blood level 

measurement 

1 μg/100 g 

(blood); 

0.2 μg/g 

(tissue) 

0.1 μg/sample 

400 μg/L 

No data 

No data 

40 μg/L 

3 μg/L 

No data 

No data 

No data 

No data 

103	 NIOSH 1994 

(method 

8005) 

100 NIOSH 1994 

(method 

8310) 

96–104 Alvarado et 

al. 1991 

No data Sohler et al. 

1976 

98 Lievens et al. 

1977 

100 Luterotti et al. 

1992 

No data Fernandez et 

al. 1992b 

>100	 Jurgensen 

and Behne 

1977 

88 Watson et al. 

1987 

No data Janghorbani 

et al. 1981 

88 Watson et al. 

1987 
 

 

 

 

 

ZINC 194 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Zinc in Biological Materials 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Bloodstain Place drop of blood on filter Flame AAS No data No data Fan et al. 

paper; cut away excess paper; 1991 

optional dry ash; add HCl; 

shake 

Thoracic Homogenize sample; complete Flame AAS No data No data Marks et al. 

aorta, lung, wet ashing with HNO3 1972 

myocardium, 

spleen 

Brain tissue Digest with HNO3 using ICP-MS 32 mg/L 99–111 Panayi et al. 

microwave digestion; dilute (10.7 ng/g for 2002 

150 mg 

sample) 

Feces Give 67Zn through diet; treat 

fecal samples with H2O2; 

prepare chelates 

Isotope tracer 

technique 

No data >95 

(

67Zn); 

71 (70Zn) 

Johnson 

1982 

Feces Feed 70Zn, 68Zn, and 64Zn orally; Isotope tracer No data No data Ni et al. 1991 

homogenize sample; evaporate; technique; 

ash; HNO3 digestion; boil; NAA 

evaporate; add HCl; transfer to 

anion exchange column; 

prepare eluate; irradiate 

Bone Acid digestion of dried bone ash Flame AAS No data No data Szpunar et 

with concentrated HNO3; al. 1978 

evaporate to dryness and add 

more concentrated HNO3; 

remove silica residue by 

filtration; transfer samples to 

polyethylene bottles 

Hair Digest clean sample in acid Flame AAS 20 μg/g No data Wilhelm et al. 

mixture 1991 

Hair Rinse sample with hexane; wet EDXRF 0.001 μg/L No data Folin et al. 

or dry ash with HNO3 1991 

Hair Rinse sample with hexane; wet Flame AAS 0.001 μg/L No data Folin et al. 

or dry ash with HNO3 1991 

Hair Digest clean sample in acid ICP-AES No data 81–102 Takagi et al. 

mixture 1988 

Serum Add Brij 35 to sample; mix Flame AAS ~0.6 μg/mL No data AOAC 1990 

(animal) (method 

991.11) 

Serum and Separate serum and plasma by Flame AAS No data No data Shaw et al. 

plasma centrifugation; keep stored in 1982 

glass tubes at -20 °C until 

analysis; thaw to room 

temperature prior to analysis 
 

 

ZINC 195 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Zinc in Biological Materials 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Milk Ash; lyophilize; wet-ash with 

HNO3; add H2O2; dry; dissolve 

in HCl and NH4Cl; extract with 

DDDC 

ICP-MS 0.06 μg/sample No data Patterson et 

al. 1992 

Milk Dilute sample with Triton X-100 GF-AAS 0.052 μmol/L 86–106 Arnaud et al. 

1991 

Saliva Lashley cup place over one of 

the Stenson’s ducts; secretion 

stimulated with lemon candies; 

discard first 5–10 mL; collect 

≈120 mL 

GF-AAS No data No data Langmyhr et 

al. 1979 

AAS = atomic absorption spectroscopy; AES = atomic emission spectroscopy; APDC = ammonium pyrolidine 

dithiocarbamate; Brij 35 = polyoxyethylene (35) lauryl ether; DDDC = diethylammonium diethyldithiocarbamate; 

EDXRF = energy dispersive x-ray fluorescence; FIA = flow injection analysis; GF = graphite furnace; 

HCl = hydrochloric acid; HClO4 = perchloric acid; HNO3 = nitric acid; H2O2 = hydrogen peroxide; H2SO4 = sulfuric 

acid; ICP = inductively coupled plasma spectroscopy; MS = mass spectrometry; NAA = neutron activation analysis; 

NH4Cl = ammonium chloride; Zn = zinc; ZnCl2 = zinc chloride 
ZINC 196 

7. ANALYTICAL METHODS 

CV; 71% recovery). Sample detection limits were not reported. Total reported sample preparation time 

was <2 hours, and it took only 5–10 minutes to analyze each sample on the mass spectrometer. 

Multi-elemental analysis has been used to detect zinc and other trace metals in biological fluids and 

tissues. For determination of metallic constituents in biological samples, such as liver, samples were 

digested with mixtures of different acids, volatile elements were distilled by selective distillation, and a 

cleanup step was performed using ion exchange chromatography prior to assay by neutron activation 

analysis (NAA) (Lievens et al. 1977). Recovery (98%) and precision (<10% CV) were excellent. 

Although the limit of detection for zinc was not reported, based on the reported results, this method can 

detect levels ranging from the low- to the sub-ppm range (Lievens et al. 1977). The NAA technique has 

also been used to detect zinc in urine and blood samples. Jurgensen and Behne (1977) used the technique 

to measure human serum levels of trace elements including zinc. Recovery and precision for this method 

are very good. Sensitivity was not reported. 

A practical method, based on NAA, was developed for accurate measurement of the stable isotopes 

zinc-68 and zinc-70 in human plasma and red blood cells (Janghorbani et al. 1981). This method can 

provide an alternative to the use of radiolabeled zinc. It is more complex and time consuming than those 

used to measure radiolabeled zinc levels. As with any isotopic method, isotope exchange may invalidate 

calculation of net absorption, but this potential problem was not investigated. Precision was very good 

(<10%). Sensitivity and accuracy were not reported. 

Radionuclide studies offer an additional method to investigate the factors that affect trace element 

absorption. Radioactivity emitted by the radionuclide was measured in blood 14 days after the oral 

ingestion of zinc-65 and compared with the amount of radioactivity emission determined by whole-body 

counting (Watson et al. 1987). The results indicated that, where whole-body counting facilities were not 

available, measurement of radioactivity emitted in blood was a reasonable alternative for the prediction of 

zinc absorption. Recovery for this method was adequate (88%); precision was acceptable (<17% CV). 

The limit of detection for zinc was not reported. 

Other analytical methods include flow injection analysis (FIA). FIA has been used to determine very low 

levels of zinc in muscle tissue. This method provides very high sensitivity, low detection limits 

(3 ng/mL), good precision, and high selectivity at trace levels (Fernandez et al. 1992b). 
 

 

 

ZINC 197 

7. ANALYTICAL METHODS 

Animal and human tissues samples are usually analyzed without drying and concentrations are reported as 

wet weight. For some samples, freeze-drying has been used. Care should be taken during the acid 

dissolution of blood and urine samples as frothing of natural surfactants during digestion can lead to 

losses. This problem can be prevented by allowing the sample to stand overnight after the addition of 

acid (WHO 2001). 

7.2 ENVIRONMENTAL SAMPLES 

Table 7-2 lists the methods used for analyzing zinc in environmental samples. 

ICP-AES is used to determine concentrations of zinc in air (NIOSH method 7300), water (EPA methods 

3120 B, 6010 C, 200.7; APHA methods 3120B, 3125B, 3130B), solid wastes (AOAC method 990.08), 

and soil (EPA methods 6010, 3050) (AOAC 1998; APHA 1998; EPA 1986a, 1994; NIOSH 1994). 

Detection limits in air, water, and solid wastes are 0.6, 2, and, 2 μg/L, respectively (AOAC 1998; EPA 

1994; NIOSH 1994). Preparation for water samples typically involves acid digestion with concentrated 

acids. The concentration of zinc in soil was determined by ICP-AES coupled with an ammonium 

bicarbonate-diethylenetriaminepentaacetic acid (NH4HCO3-DTPA) extraction procedure. This method 

can be used to screen soils for zinc (Boon and Soltanpour 1991). ICP-MS has been used to determine the 

concentration of zinc in water (EPA methods 200.8, 1638; APHA method 3125 B), (APHA 1998; EPA 

1994, 1996). Detection limits have been reported to be as low as 0.017 μg/L using 66Zn isotope. 

Recoveries range from 99 to 117% (APHA 1998). 

Flame AAS has been used to determine zinc concentrations in natural waters (Fishman 1966). AAS is a 

rapid method of measuring zinc, with a detection limit of 0.005 ppm. Brooks et al. (1967) demonstrated a 

simple extraction system consisting of two reagents, ammonium pyrollidine dithiocarbamate (APDC) and 

methyl isobutylketone (MIBK), with subsequent analysis by flame AAS to measure particulate and 

"soluble" zinc in seawater. Sensitivity was in the sub-ppm range, and precision was good (3% CV). 

Flame AAS, coupled with microwave digestion and GF-AAS, has been used to determine the 

concentration of zinc in food and shellfish samples. Limits of detection ranged from 0.12 to 0.24 ppm, 

with recoveries ranging from 80 to 113%. Precision and recovery using microwave digestion were 

comparable to traditional wet ashing and superior to dry ashing in shellfish samples (AOAC 1984; 

McCarthy and Ellis 1991; Morales-Rubio et al. 1992). GF-AAS was also used to determine low levels of 

zinc in beer. Recovery (94–106%) and precision (4.2% CV) were excellent. Sensitivity was not reported 

(Wagner et al. 1991). Flame AAS has been used to measure heavy metals, including zinc, in various oil 
 

 

 

 

 

ZINC 198 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Zinc in Environmental Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample 

detection limit 

Percent 

recovery Reference 

Air Collect air particulates on 

Teflon filters; digest with 

HNO3 

NAA (nondestructive) No data No data Zoller et al. 1974 

Air Collect sample on cellulose 

filter; wet ash filter with 

HNO3/HClO4; dilute 

ICP-AES 0.6 ng/mL 94–101 NIOSH 1994 

(method 7300) 

Air Collect sample on cellulose 

filter; wet ash with HNO3; 

dilute 

Flame AAS 3 μg/sample No data NIOSH 1994 

(method 7030) 

Air (as zinc 

oxide) 

Collect sample on PVCacrylonitrile filter XRD 5 μg/sample No data NIOSH 1994 

(method 7502) 

Atmospheric Collect sample on cellulose Anodic 13.7 μg/L No data Casassas et al. 

aerosols filter; digest with HNO3; filter; stripping 1991 

dry; add HNO3; adjust pH; voltammetry 

add KNO3 

Water Acidify; dilute ICP-MS 0.14 μg/L No data EPA 1996 

(method 1638) 

Water Reflux with HNO3/HCl; dilute GF-AAS 0.14 μg/L No data EPA 1996 

(method 1639) 

Water Acidify (digest if necessary); ICP-AES 2 μg/L No data EPA 1994 

dilute (method 200.7) 

Water Acidify (digest if necessary); ICP-MS 1.8 μg/L No data EPA 1994 

dilute (method 200.8) 

Water Acid digestion; dilute ICP-AES 1.2 μg/L No data EPA 2000 

(method 6010 C) 

Water Dissolve in HCl; dilute Flame AAS 5 μg/L No data APHA 1998 

(method 3111 B) 

Water Chelation with ammonium Flame AAS No data No data APHA 1998 

pyrrolidine dithiocarbamate (method 3111C) 

and extraction into MIBK 

Water Acidify; dilute ICP-AES 2 μg/L No data APHA 1998 

(method 3120 B) 

Water Acidify; dilute ICP-MS 0.017 μg/L 

(

66Zn) 

99–117 

(

66Zn) 

APHA 1998 

(method 3125 B) 

0.020 μg/L 

(

68Zn) 

98–116 

(

66Zn) 

Water Dilute with HNO3 Anodic <1 μg/L No data APHA 1998 

stripping (method 3130 B) 

voltammetry 

Water Add sodium ascorbate; KCN; Colormetry No data No data APHA 1998 

zircon (2-carboxy­ (method 

2’-hydroxy-5’-sulfoformazyl 3500-Zn B) 

benzene) 

Water and Acid digestion Flame AAS 5 μg/L No data EPA 1979 

waste water (method 289.1) 
 

 

 

ZINC	 199 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Zinc in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Water and Acidify; dilute GF-AAS 0.05 μg/L No data EPA 1979 

waste water (method 289.2) 

Water Mineralize sample in muffle FIA 3 μg/L No data Fernandez et al. 

furnace; dissolve in HNO3 1992b 

Seawater APDC-MIBK extraction Flame AAS 0.05 ppb No data Brooks et al. 

1967 

Seawater	 Take a sample digest in the Cathodic 7x10-11 M No data van den Berg 

electrochemical cell; adjust stripping 1986 

pH; add chelating agent and voltammetry 

aerate 

Crude oil Digest sample with HNO3; Flame AAS 0.8 μg/g No data Elson et al. 1981 

extract with MIBK or dilute 

with MIBK 

Soil, solid Acid digestion ICP-AES or 2 μg/L (in 102.5 at EPA 1986a 

waste, flame AAS solution) 80 μg/L (methods 6010 

sludges and 3050) 

Soil, solid None Flame AAS 0.005 μg/L No data EPA 1986a 

waste and (method 7950) 

sludges 

Solid wastes No data ICP-AES 2 μg/L No data AOAC 1998 

(method 990.08) 

Soil Extract with DTPA and ICP-AES No data No data Boon and 

NH4HCO3-DTPA Soltanpour 1991 

Plants Digest samples with acids Flame AAS No data No data AOAC 1984 

(method 3.013) 

Plants Digest samples with acid; Mixed and No data No data AOAC 1984 

extract with dithiozone single color (methods 3.054 

reagent and CCl4; add HCl methods – and 3.061) 

and CCl4; read at 525 nm for spectrophotomixed-color method and at metric analysis 

535 nm for single-color 

method 

Food Digest sample with acid Colorimetry No data No data AOAC 1984 

mixtures; remove sulfide, (method 25.168) 

nickel, and cobalt; add 

dithioxone and CCl4; 

measure transmission at 

540 nm 

Food Wet ash using Kjeldahl Flame AAS No data No data AOAC 1990 

digestion HNO3/H2SO4 with (method 969.32) 

heat; dilute; alternatively, dry 

ash; dissolve in HCl with 

heat 

Food Digest samples with acid Flame AAS No data No data AOAC 1990 

mixtures; dilute (method 986.15) 

Food Dry ash sample in muffle Flame AAS; 0.24 μg/g 97–100 Morales-Rubio et 

oven; dilute with HNO3 Flame AES al. 1992 
 

 

ZINC 200 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Zinc in Environmental Samples 

Sample Analytical Sample Percent 

matrix Preparation method method detection limit recovery Reference 

Food Clarify; de-gas; dilute with GF-AAS No data 90–113 Wagner et al. 

deionized water; add HNO3 1991 

to solid samples 

Food Blend; lyophilize; grind; EDXRF 0.8 ppm No data Nielson et al. 

oven-dry; press into pellets 1991 

Shellfish HNO3 digestion in Flame AAS 0.12 ppm 80 McCarthy and 

microwave; dilute Ellis 1991 

AAS = atomic absorption spectroscopy; AES = atomic emission spectrometry; APDC = ammonium pyrolidine 

dithiocarbamate; CCl4 = carbon tetrachloride; DTPA = diethylenetriaminepentaacetic acid; EDXRF = energy 

dispersive x-ray fluorescence; FIA = flow-injection analysis; GF = graphite furnace; HCl = hydrochloric acid; 

HClO4 = perchloric acid; HNO3 = nitric acid; H2SO4 = sulfuric acid; ICP = inductively coupled plasma spectroscopy; 

KCN = potassium cyanide; KNO3 = potassium nitrite; MIBK = methyl isobutyl ketone; NAA = neutron activation 

analysis; NH4HCO3-DTPA = ammonium bicarbonate-diethlyenetriaminepentaacetic acid; PVC = polyvinyl chloride; 

XRD = x-ray diffraction; Zn = zinc 
 

 

ZINC 201 

7. ANALYTICAL METHODS 

samples collected at different stages of oil refining (Elson et al. 1981). These samples were prepared 

using three techniques (digestion, extraction, and dilution) prior to AAS analysis; recovery from crude oil 

was higher with wet digestion. Sensitivity for zinc was in the low-ppm range. 

Cathodic stripping voltammetry, also known as adsorption voltammetry, has been used to detect various 

metal ions in a 10-10–10-11 M range in seawater (van den Berg 1986). APDC was used as a chelating 

agent for zinc. Because of the great sensitivity and specificity of APDC for zinc, it can be detected 

directly in the unaltered sample. Similarly, differential pulse cathodic stripping voltammetry (DPCSV) 

and differential pulse anodic stripping voltammetry (DPASV) after complexation with APDC have been 

used for determining zinc speciation at nanomolar concentrations in ocean waters (Donat and Bruland 

1990). Anodic stripping voltammetry (ASV) has been used to detect zinc and other metal ions 

simultaneously at trace levels in atmospheric aerosols. This method is primarily used for small samples 

with very low concentrations of zinc. The limit of detection was 13.7 ng/L (Casassas et al. 1991). 

An ion chromatographic method has been proposed for simultaneous determination of several elements 

including zinc in soil (Basta and Tabatabai 1990). In this method, after preliminary sample treatment, the 

metals are separated by ion chromatography, and the separated elements are quantified by ultravioletvisible detection of zinc-PAR (4-[2-pyridylazo] resorcinol) colored complexes. The limit of detection for 

zinc by this method was 5 ppb in soil extract. Precision was ≤2.5% CV. 

Other analytical methods include energy dispersive x-ray fluorescence (EDXRF). This technique has 

been used to detect zinc in dried food samples with better precision (e.g., detection limit, 0.8 ppm) than 

AAS methods (Nielson et al. 1991). 

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 zinc 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 zinc. 
ZINC 202 

7. ANALYTICAL METHODS 

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. 

Exposure. ICP-AES, ICP-MS, and AAS are the most commonly used analytical methods to determine 

zinc levels in plasma, bone, fingernails, hair, and other biological tissues and body fluids (Alvarado et al. 

1991; AOAC 1990; Arnaud et al. 1991; Fan et al. 1991; Folin et al. 1991; Langmyhr et al. 1979; Luterotti 

et al. 1992; Marks et al. 1972; NIOSH 1984a, 1994; Panayi et al. 2002; Patterson et al. 1992; Shaw et al. 

1982; Sohler et al. 1976; Szpunar et al. 1978; Takagi et al. 1988; Wilhelm et al. 1991). These methods 

generally are sensitive enough to measure background levels in the population and levels at which 

biological effects occur. However, improved sensitivity and recovery data are needed in order to better 

evaluate the relationship between body and environmental exposure levels of zinc. Other methods that 

are specific for measuring zinc in biological fluids and tissues include NAA, FIA, and isotope tracers 

techniques (Fernandez et al. 1992b; Janghorbani et al. 1981; Johnson 1982; Lievens et al. 1977; NIOSH 

1984a; Watson et al. 1987). Sensitivity and/or recovery data for these methods are needed to more fully 

evaluate the reliability of these methods as predictors of environmental exposure. 

Effect. Although several biomarkers for the effects of zinc have been identified (increased levels of 

serum amylases and lipase, noniron responsive anemia, and decreased HDL cholesterol levels), these 

biomarkers of effect are not specific for zinc (Cotran et al. 1989; Suber 1989). Standard laboratory tests 

are available that can measure these biomarkers (Henry 1984). These methods are sensitive, accurate, and 

reliable enough to measure background levels in the population and levels at which biological effects 

occur. The development of methods for determining biomarkers of effect specific for zinc would be 

beneficial in assessing whether an individual has been exposed to elevated levels of zinc. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods of adequate sensitivity and specificity are available for determining levels of zinc in 
ZINC 203 

7. ANALYTICAL METHODS 

environmental media (AOAC 1984; APHA 1998; Basta and Tabatabai 1990; Brooks et al. 1967; Casassas 

et al. 1991; Donat and Bruland 1990; Elson et al. 1981; EPA 1979c, 1986a, 1994, 1996, 2000; Fishman 

1966; McCarthy and Ellis 1991; Morales-Rubio et al. 1992; Nielson et al. 1991; NIOSH 1994; van den 

Berg 1986; Wagner et al. 1991; Zoller et al. 1974). Most of these methods are precise and sensitive 

enough to measure background levels in the environment and levels at which health effects occur. Some 

methods can distinguish between soluble zinc, insoluble zinc, and chelated zinc in water (Donat and 

Bruland 1990). 

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 2004) 
 

 

ZINC 204 

7. ANALYTICAL METHODS 

Table 7-3. Ongoing Studies on Analytical Methods for Zinca 

Investigator Affiliation Study Sponsor 

Michel RG, Freake 

HC, Zinn SA et al. 

University of Connecticut Capillary electrophoresis to enable 

zinc speciation for studies of zinc 

homeostasis 

USDA 

Panemangalore M Kentucky State University, 

Human Nutrition Research 

Program 

Evaluation of biomarkers of zinc and 

copper status in animals and humans 

USDA 

a

Source: FEDRIP 2004 

FEDRIP = Federal Research in Progress Database; USDA = United States Department of Agriculture 

ZINC 205 

8. REGULATIONS AND ADVISORIES 

Zinc (fume and dust) and its compounds are on the list of chemicals appearing in "Toxic Chemicals 

Subject to Section 313 of the Emergency Planning and Community Right-to-Know Act of 1986" (EPA 

2003j). 

The national and state regulations and guidelines pertaining to zinc and compounds in air, water, food, 

and other media are summarized in Table 8-1. No international regulations or guidelines applicable to 

zinc or its compounds were found. 

ATSDR has derived an intermediate-duration oral MRL of 0.3 mg Zn/kg/day for zinc based on decreased 

erythrocyte superoxide dismutase, a sensitive indicator of body copper status, and changes in serum 

ferritin in women given supplements containing zinc gluconate for 10 weeks (Yadrick et al. 1989). It 

should be noted that the MRL is calculated based on the assumption of healthy dietary levels of zinc (and 

copper), and represents the level of exposure above and beyond the normal diet that is believed to be 

without an appreciable risk of toxic response. The MRL is based on soluble zinc salts; it is less likely that 

nonsoluble zinc compounds would have these effects at similar exposure levels. The intermediate oral 

MRL has been adopted as the chronic oral MRL. 

EPA has derived an oral reference dose (RfD) of 0.3 mg/kg/day for zinc (IRIS 2005). EPA has not 

derived an inhalation reference concentration (RfC) for zinc. 
 

 

 

ZINC	 206 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Zinc and Zinc Compounds 

Agency Description	 Information Reference 

INTERNATIONAL 

Guidelines: 

IARC Carcinogenicity classification 

WHO Drinking water and air quality 

guidelines 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) 

EPA Hazardous air pollutant pursuant 

to Section 112 of the Clean Air 

Act 

NIOSH REL (10-hour TWA) 

Zinc chloride (fume) 

Zinc oxide (dust and fume) 

STEL (15-minute TWA) 

Zinc chloride (fume) 

 Zinc oxide (fume) 

Ceiling 

 Zinc oxide (dust) 

IDLH 

Zinc chloride (fume) 

 Zinc oxide 

OSHA PEL (8-hour TWA) for general 

industry 

Zinc chloride (fume) 

Zinc oxide (fume and 

respirable 

fraction of dust) 

Zinc oxide (total dust) 

PEL (8-hour TWA) for construction 

industry 

Zinc chloride (fume) 

Zinc oxide (fume and 

respirable 

fraction of dust) 

Zinc oxide (total dust) 

PEL (8-hour TWA) for shipyard 

industry 

Zinc chloride (fume) 

Zinc oxide (fume and 

respirable 

fraction of dust) 

Zinc oxide (total dust) 

No data 

No data 

No data 

Zinc and zinc oxide 

1 mg/m3 

5 mg/m3 

2 mg/m3 

10 mg/m3 

15 mg/m3 

50 mg/m3 

500 mg/m3 

1 mg/m3 

5 mg/m3 

15 mg/m3 

1 mg/m3 

5 mg/m3 

15 mg/m3 

1 mg/m3 

5 mg/m3 

15 mg/m3 

EPA 2003e 

40 CFR 61.01 

NIOSH 2003a, 2003b 

OSHA 2003a 

29 CFR 1910.1000, 

Table Z-1 

OSHA 2003c 

29 CFR 1926.55, 

Appendix A 

OSHA 2003b 

29 CFR 1915.1000 
 

 

 

 

ZINC 207 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Zinc and Zinc Compounds 

Agency Description Information Reference 

NATIONAL (cont.)

b. Water 

EPA Drinking water health advisories 

 1-day (10-kg child) 

10-day (10-kg child)

 DWELa

 Lifetimeb 

EPA Hazardous substance in 

accordance with Section 311 

(b)(2)(A) of the Clean Water Act 

Hazardous substance in 

accordance with Section 311 of 

the Clean Water Act; reportable 

quantities 

 Zinc chloride

 Zinc sulfate 

National secondary drinking water 

regulations; secondary MCL for 

zinc 

Pollutants of initial focus in the 

Great Lakes Water Quality 

Initiative 

Reportable quantities of hazardous substances designated 

pursuant to Section 311 of the 

Clean Water Act 

 Zinc chloride

 Zinc sulfate 

Toxic pollutant designation 

pursuant to Section 307(a)(1) of 

the Clean Water Act 

c. Food 

EPA Tolerances for residues (ppm) of a 

fungicide (mancozeb), which 

contains 20% manganese, 

2.5% zinc, and 77.5% ethylenebisdithiocarbamate 

EPA 2002 

6 mg/L 

6 mg/L 

10 mg/L 

2 mg/L 

Zinc chloride EPA 2003k 

Zinc sulfate 40 CFR 116.4 

EPA 2003g 

40 CFR 117.3 

1,000 pounds 

1,000 pounds 

5 mg/L EPA 2003f 

40 CFR 143.3 

Zinc EPA 2003l 

40 CFR 132, 

Table 6 

1,000 pounds 

1,000 pounds 

Zinc and compounds EPA 2003c 

40 CFR 401.15 

EPA 2003i 

40 CFR 180.176 
 

 

 

ZINC 208 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Zinc and Zinc Compounds 

Agency Description Information Reference 

NATIONAL (cont.)

 EPA 

Apple 7 

 Asparagus 0.1 

Banana 4 

Banana, pulp (no peel) 0.5 

 Barley, grain 5 

Barley, milled feed fractions 20 

 Barley, straw 25 

 Beet, sugar 2 

Beet, sugar tops 65 

 Carrots 2 

 Celery 5 

Corn, fodder and forage 5 

 Corn, grain 0.1 

 Cottonseed 0.5 

 Crabapple 10 

 Cranberry 7 

 Cucumber 4 

Fennel 10 

Tolerances for residues (cont.) 0.5 

 Fresh Corn 7 

 Grape 0.5 

Kidney 0.5 

Liver 4 

Melon 20 

Oat, bran and milled feed 

fractions 5 

 Oat, grain 25 

 Oat, straw 0.5 

Onion, dry bulb 10 

Papaya 0.5 

Peanut 65 

Peanut vine hay 10 

Pear 0.5 

 Popcorn grain 10 

 Quince 5 

 Rye, grain 20 

Rye, milled feed fractions 25 

 Rye, straw 4 

 Squash, summer 4 

Tomato 5 

 Wheat, grain 20 

Wheat, milled feed fractions 25 

 Wheat, straw
 

EPA 2003i 

40 CFR 180.176 

EPA 2003i 

40 CFR 180.176 
 

 

 

 

ZINC 209 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Zinc and Zinc Compounds 

Agency Description Information Reference 

NATIONAL (cont.)

FDA Bottled drinking water (allowable 

concentration of zinc); mineral 

water is exempt based on 

aesthetically allowable levels 

and do not relate to health 

concern 

Drug products containing certain 

active ingredients offered overthe-counter (OTC) for certain 

uses; ingredients used in skin 

protectant drug products 

Nutrition labeling of food; 

statement of the amount per 

serving of zinc calculated as a 

percent of the RDI and 

expressed as percent of Daily 

Value 

Substances generally recognized 

as safe; trace minerals added to 

animal feeds as nutritional 

dietary supplements when 

added at levels consistent with 

good feeding practices 

Substances generally recognized 

as safe when used in accordance with good manufacturing 

practices 

d. Other 

EPA Carcinogenicity classification 

RfC 

RfD 

Community right-to-know; release 

reporting; effective date of 

reporting for zinc (fume and 

dust) 

Designated as a hazardous 

substance pursuant to 

Section 311(b)(2) of the Clean 

Water Act; reportable quantity 

Zinc and compounds 

Designated as a hazardous 

substance pursuant to 

Section 307(a) of the Clean 

Water Act; reportable quantities 

 Zinc chloride

 Zinc sulfate 

5.0 mg/L 

Zinc chloride 

Zinc oxide 

Zinc sulfate 

15 mg 

Zinc chloride 

Zinc oxide 

Zinc sulfate 

Zinc oxide and zinc 

sulfate 

Dc 

No data 

3x10-1 mg/kg/day 

01/01/87 

Not assigned 

1,000 pounds 

1,000 pounds 

FDA 2003a 

21 CFR 165.110 

FDA 2003c 

21 CFR 310.545 

FDA 2003b 

21 CFR 101.9 

FDA 2003d 

21 CFR 582.80 

FDA 2003e 

21 CFR 182.8991; 

21 CFR 182.8997 

IRIS 2003 

IRIS 2003 

IRIS 2003 

EPA 2003j 

40 CFR 372.65 

EPA 2003b 

40 CFR 302.4 

EPA 2003b 

40 CFR 302.4 
 

 

 

 

ZINC 210 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Zinc and Zinc Compounds 

Agency 

NATIONAL (cont.)

d. Other 

EPA 

STATE 

a. Air 

b. Water 

Arizona 

Illinois 

Minnesota 

c. Food 

d. Other 

Description Information 

Hazardous constituent for 

municipal solid waste landfills 

Land disposal restrictions; 

universal treatment standards 

for zinc

 Waste water standard 

 Non-waste water standard 

Standards for owners and 

operators of hazardous waste 

TSD facilities; groundwater 

monitoring for zinc 

No data 

Drinking water guideline (zinc and 

zinc compounds) 

Drinking water standard (zinc and 

zinc compounds) 

Drinking water guideline (zinc and 

zinc compounds) 

No data 

No data 

Reference 

Zinc EPA 2003a 

40 CFR 258, 

Appendix II 

EPA 2003d 

40 CFR 268.48 

2.61 mg/L 

4.3 mg/L TCLP 

Suggested EPA 2003h 

method PQL 40 CFR 264, 

6010 20 μg/L Appendix IX 

7950 50 μg/L 

7951 0.5 μg/L 

5 mg/L HSDB 2003 

5 mg/L HSDB 2003 

2 mg/L HSDB 2003 

a

DWEL: a lifetime exposure concentration protective of adverse, non-cancer health effects, that assumes all of the 

exposure to a contaminant is from drinking water. 

b

Lifetime: the concentration of a chemical in drinking water that is not expected to cause any adverse 

noncarcinogenic effects for a lifetime of exposure. The lifetime HA is based on exposure of a 70-kg adult consuming 

2 L water/day. 

c

D: not classifiable as to human carcinogenicity
 

ACGIH = American Conference of Governmental Industrial Hygienists; CFR = Code of Federal Regulations; 

DWEL = drinking water equivalent level; EPA = Environmental Protection Agency; FDA = Food and Drug
 

Administration; HA = health advisory; HSDB = Hazardous Substances Data Bank; IARC = International Agency for 

Research on Cancer; IDLH = immediately dangerous to life or health; IRIS = Integrated Risk Information System; 

MCL = maximum contaminant level; NIOSH = National Institute for Occupational Safety and Health; 

OSHA = Occupational Safety and Health Administration; OTC = over-the-counter; PEL = permissible exposure limit; 

PQL = practical quantitation level; RDI = recommended daily intake; REL = recommended exposure limit; 

RfC = inhalation reference concentration; RfD = oral reference dose; STEL = short-term exposure limit; 

TCLP = toxicity characteristic leachate procedure; TLV = threshold limit values; TSD = treatment, storage, and 

disposal; TWA = time-weighted average; WHO = World Health Organization
 
 

 

_______________________ 

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*Zaporowska H, Wasilewski W. 1992. Combined effect of vanadium and zinc on certain selected 

hematological indices in rats. Comp Biochem Physiol 103C(1):143-147. 

Zarcinas BA, Rogers SL. 2002. Copper, lead and zinc mobility and bioavailability in a river sediment 

contaminated with paint stripping residue. Environ Geochem Health 24:191-203. 

Zavaleta N, Abrams S, Lonnerdal B. 2002. Iron (Fe) and zinc (Zn) absorption in 1-yr-old Peruvian 

children consuming a diet based on wheat flour fortified with Fe with/without Zn and/or vitamin A. 

FASEB J 16:A749. 

*Zerahn B, Kofoed-Enevoldsen A, Jensen BV, et al. 1999. Pulmonary damage after modest exposure to 

zinc chloride smoke. Resp Med 93:885-890. 

Zhang H. 2004. In-situ speciation of Ni and Zn in freshwaters: Comparison between DGT 

measurements and speciation models. Environ Sci Technol 38(5):1421-1427. 

Zheng M, Fang M. 2000. Correlations between organic and inorganic species in atmospheric aerosols. 

Environ Sci Technol 34:2721-2726. 

Zhou JR, Fordyce CJ, Raboy V, et al. 1992. Reduction of phytic acid in soybean products improves zinc 

bioavailability in rats. J Nutr 122(12):2466-2473. 

*Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12:29-34. 

Zirschky J, Crawford D, Norton L, et al. 1989. Metals removal in overland flow. J Water Pollut Control 

Fed 61:470-475. 

Zodl B, Zeiner M, Sargazi M, et al. 2003. Toxic and biochemical effects of zinc in Caco-2 cells. J Inorg 

Biochem 97(4):324-330. 
ZINC 299 

9. REFERENCES 

*Zoller WH, Gladney ES, Duce RA. 1974. Atmospheric concentrations and sources of trace metals at 

the South Pole. Science 183:198-200. 

Zyleski RA, Siddiqui MS, Mayhew JF, et al. 2004. Zinc pennies in the esophagus. Pediatrics 

113(1):176-177. 

ZINC 301 

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. 

Anthropogenic—Caused by human activities. 

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. 
ZINC 302 

10. GLOSSARY 

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. 

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. 
ZINC 303 

10. GLOSSARY 

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. 

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. 
ZINC 304 

10. GLOSSARY 

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. 

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. 
ZINC 305 

10. GLOSSARY 

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 

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. 
 

 

ZINC 306 

10. GLOSSARY 

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. 

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. 
ZINC 307 

10. GLOSSARY 

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. 

ZINC 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. 
ZINC A-2 

APPENDIX A 

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 

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, 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, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road NE, Mailstop F-32, Atlanta, Georgia 30333. 
 

 

 

 

 

 

 

 

 

ZINC A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical name: Zinc and compounds 

CAS number: 

Date: May 6, 2005 

Profile status: Final Draft Post-Public 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [X] Intermediate [ ] Chronic 

Key to figure: 25 

Species: Human 

MRL: 0.3 [X] mg/kg/day [ ] ppm [ ] mg/m3 

Reference: Yadrick MK, Kenney MA, Winterfelt EA. 1989. Iron, copper, and zinc status: Response to 

supplementation with zinc or zinc and iron in adult females. Am J Clin Nutr 49:145-150. 

Experimental design: Eighteen healthy women, ages 25–40 years, were given zinc gluconate 

supplements twice daily (50 mg supplemental zinc/day, or 0.83 mg supplemental zinc/kg/day assuming a 

60-kg mean body weight for healthy women) for a 10-week period (Yadrick et al. 1989). Blood was 

drawn from each subject prior to treatment for use as a referent. Erythrocyte superoxide dismutase 

(ESOD) activity declined over the 10-week supplementation period and, at 10 weeks, was significantly 

(p<0.05) lower (47% decrease) than pretreatment values; a decrease at 6 weeks of exposure (15%) was 

not statistically significant. ESOD levels are considered to be a sensitive indicator of systemic copper 

status. Ceruloplasmin levels were not altered. Serum zinc was significantly increased at both 6 and 

10 weeks. There was also a significant decline in serum ferritin (23%) and hematocrit (4%) values at 

10 weeks. In women similarly-exposed but also receiving 0.42 mg supplemental iron/day, serum ferritin 

was increased at both 6 and 10 weeks of exposure, while serum ESOD levels were significantly decreased 

at 6 weeks (24%) and 10 weeks (47%). 

Effects noted in study and corresponding doses: Statistically significant decreases in erythrocyte SOD 

and serum ferritin levels at 0.83 mg supplemental zinc/kg/day. Since these effects were subclinical, they 

were designated as non-adverse, as described below. 

Dose end point used for MRL derivation: Yadrick et al. (1989) reported a significant decrease in ESOD, 

which is considered to be a sensitive indicator of body copper status, in women exposed to 50 mg 

supplemental zinc/day. Because the observed effect is considered to be a precursor event to the more 

severe symptoms seen with zinc-induced copper deficiency, rather than a toxic effect of itself, the 50 mg 

supplemental zinc/day value is considered to be NOAEL. At the same exposure level, serum ferritin 

levels decreased from 36.6 to 28.2 μg/L (23% decrease), which was statistically significant. According to 

the most recent NHANES data (cited in IOM 2000), the median range for serum ferritin levels in 

menstruating women is 36–40 μg/L, while a value of <12 μg/L represents depleted iron stores. Thus, the 

subjects dropped below the median range for women of their age group, but were still considerably above 

the level that would represent a depletion of iron stores; in the absence of other effects indicating changes 

in iron status, this subclinical effect was also designated as a NOAEL. Assuming a reference female body 

weight of 60 kg, this represents 0.83 mg zinc/kg/day. 

[X] NOAEL [ ] LOAEL 
 

 

 

ZINC A-4 

APPENDIX A 

Uncertainty factors used in MRL derivation: 

[ ] 1 [ ] 3 [ ] 10 (for use of a LOAEL)
 

[ ] 1 [ ] 3 [ ] 10 (for extrapolation from animals to humans) 

[ ] 1 [X] 3 [ ] 10 (for human variability) 

The intermediate oral MRL for zinc is derived as follows: 

MRL = NOAEL÷ UF 

MRL = 0.83 mg zinc/kg/day ÷ 3 

MRL = 0.3 mg zinc/kg/day 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? No. 

Was a conversion used from intermittent to continuous exposure? If so, explain: No. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Not 

applicable. 

Other additional studies or pertinent information that lend support to this MRL: 

It should be noted that the MRL is calculated based on the assumption of healthy dietary levels of zinc 

(and copper), and represents the level of exposure above and beyond the normal diet that is believed to be 

without an appreciable risk of toxic response. 

Fischer et al. (1984) gave groups of 13 healthy adult male volunteers (ages not specified) 0 (cornstarch) or 

25 mg supplemental zinc (as zinc gluconate) twice daily for 6 weeks (0 or 0.71 mg supplemental 

zinc/kg/day). Nonfasting blood samples were taken at the beginning and at biweekly intervals and tested 

for measures of copper status. ESOD activity decreased after 4 weeks in the supplement group and was 

significantly lower than controls by 6 weeks. An inverse correlation between plasma zinc levels and 

erythrocyte superoxide dismutase activity was also observed at 6 weeks. Plasma copper levels and levels 

of ferroxidase activity did not change during the course of the study. 

Groups (n=10–13) of postmenopausal women (mean age 64.9±6.7 years) with an average body weight of 

65.1±9.5 kg were evaluated for the effects of excess zinc exposure (Davis et al. 2000; Milne et al., 2001). 

After an initial equilibration period during which they received 2 mg Cu and 9 mg zinc/day (the RDA for 

women of that age is 8 mg zinc/day) for 10 days, subjects received either low (1 mg) or high (3 mg) 

copper diets, and either low (3 mg) or high (56 mg) zinc for 90 days; it is noteworthy that the “low 

copper” subjects were still receiving copper levels greater than the current RDA for copper. After a 

10-day equilibration period, the study was repeated with the same copper level in the diet, such that each 

subject received both low and high zinc throughout the course of the study. Blood was drawn during each 

equilibration period, and twice monthly during the exposure periods. Levels during the equilibration 

periods were used as the referent for the exposure periods. Zinc supplementation resulted in significant 

increases in plasma and platelet zinc levels. In high-zinc subjects, increases were seen in bone-specific 

alkaline phosphatase levels (~25%) and extracellular superoxide dismutase (~15%), while significant 

decreases were seen in mononuclear white cell 5'-nucleotidase (~30%) and plasma 5'-nucleotidase 

activity (~36%). Slight (<10%) changes were also seen in erythrocyte copper/zinc SOD and plasma free 

thyroxine. Other evaluated end points were not significantly modified by zinc supplementation. Copper 

status indicators were decreased by supplementation with zinc, including copper balance 

(total intake-total eliminated in urine and feces), serum-immunoreactive ceruloplasmin, platelet 
ZINC A-5 

APPENDIX A 

cytochrome-c oxidase activity, total cholesterol, glutathione, and glutathione peroxidase activity. No 

effect was seen on concentration of zinc in red blood cells or on indicators of iron status. 

Groups of 9, 13, or 9 healthy white men were administered 0, 50, or 75 mg/day supplemental zinc as zinc 

gluconate (total zinc intakes were 0.16, 0.85, and 1.10 mg supplemental zinc/kg/day, respectively, based 

on mean group body weights) for 12 weeks (Black et al. 1988). The subjects were given instructions to 

avoid foods high in calcium, fiber, and phytic acid, dietary constituents that are known to decrease zinc 

absorption. Subjects were also told to restrict their intake of zinc-rich foods in order to minimize the 

variation in daily dietary zinc. There was a general decline in the mean serum HDL-cholesterol for the 

75-mg supplement group between weeks 6 and 12. HDL values for this group were significantly lower 

than those for the placebo group at weeks 6 and 12 (p<0.05). There was also a decline in the HDL values 

for the 50-mg group between weeks 8 through 12; however, this decline was not significantly different 

from that for the controls until the 12th week of treatment. Serum zinc, copper, total cholesterol, LDLcholesterol, and triglycerides did not appear to be affected by treatment. 

Freeland-Graves et al. (1982) exposed groups of eight healthy women to 0, 15, 50, or 100 mg 

supplemental zinc as zinc acetate (approximately 0, 0.25, 0.83, or 1.7 mg supplemental zinc/kg/day, 

assuming a reference female body weight of 60 kg) daily for 60 days. In the highest exposure group only, 

plasma HDL-cholesterol was significantly reduced at 4 weeks of exposure, but not at any other timepoint 

examined. A correlation between dietary zinc and whole-blood copper was observed in treated subjects. 

In the 50 and 100 mg groups, some bloating, nausea, and abdominal cramps were reported unless the 

supplement was taken with a large glass of water at mealtime. 

Prasad et al. (1978) fed a patient with sickle cell anemia supplements of 150–200 mg supplemental 

zinc/day for 2 years. The supplement resulted in copper deficiency; serum copper and plasma 

ceruloplasmin levels were decreased. When copper was administered, the plasma ceruloplasmin levels 

became normal. In a follow-up study, of 13 patients on zinc therapy (similar treatment levels assumed), 

7 patients had ceruloplasmin levels at the lower limit of normal after 24 weeks of dosing. 

Agency Contact (Chemical Managers): Nickolette Roney, M.S.; Cassandra V. Smith, M.S.; Malcolm 

Williams, D.V.M., Ph.D. 

 

 

ZINC	 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 
 

 

 

ZINC B-2 

APPENDIX B 

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. 

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. 
ZINC 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, 
ZINC B-4 

APPENDIX B 

which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see 

footnote "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. 
ZINC 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. 
1 SAMPLE → 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 → INTERMEDIATE EXPOSURE 5 6 3 → Systemic ↓ ↓ 18 Rat 13 wk 4 → 5 d/wk 6 hr/d CHRONIC EXPOSURE 

Cancer 38 Rat 18 mo 

5 d/wk 7 hr/d 

39 Rat 89–104 wk 

5 d/wk 6 hr/d 

40 Mouse 79–103 wk 

5 d/wk 6 hr/d 

7 8 9 

↓ ↓ ↓

3b Resp 10 (hyperplasia) 

11 ↓20 (CEL, multiple 

organs) 

10 (CEL, lung tumors, 

nasal tumors) 

10 (CEL, lung tumors, 

hemangiosarcomas) 

10 

↓

NitWNTNT

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). 


ZINC 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 
 

 

ZINC C-2 

APPENDIX C 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

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 
 

 

ZINC C-3 

APPENDIX C 

MCLG maximum contaminant level goal 

MF modifying factor 

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 
ZINC C-4 

APPENDIX C 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

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 
ZINC 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 

ZINC D-1 

APPENDIX D. INDEX 

absorbed dose..............................................................................................................................................94 

active transport............................................................................................................................................82 

adenocarcinomas.........................................................................................................................................68 

adipose tissue ............................................................................................................................................178 

adrenal gland...............................................................................................................................................90 

adsorbed .................................................................................................... 139, 152, 153, 155, 157, 169, 184 

adsorption.................................................................................................. 139, 153, 155, 156, 157, 160, 201 

aerobic.......................................................................................................................................................152 

ambient air .................................................................................................................................. 32, 163, 177 

anaerobic................................................................................................................................... 153, 156, 160 

anemia......................................... 5, 13, 15, 17, 19, 34, 58, 59, 69, 88, 95, 98, 102, 107, 110, 111, 113, 202 

bioaccumulation................................................................................................................................ 139, 188 

bioavailability ............................................................................................................... 79, 99, 184, 187, 188 

bioconcentration factor .............................................................................................................................158 

bioconcentration factors............................................................................................................................158 

biomarker .......................................................................................................................... 93, 94, 95, 96, 111 

biomarkers .............................................................................................. 93, 94, 96, 111, 117, 191, 202, 204 

body weight effects ............................................................................................................................... 24, 63 

breast milk......................................................................................................................................... 142, 179 

cancer ............................................................................................................................ 4, 13, 37, 67, 92, 210 

carcinogenic ............................................................................................................ 12, 13, 16, 22, 38, 67, 68 

carcinogenicity.......................................................................................................... 5, 13, 68, 106, 109, 210 

carcinoma....................................................................................................................................................38 

cardiovascular ................................................................................................................... 33, 39, 57, 69, 167 

cardiovascular effects................................................................................................................ 32, 33, 39, 57 

chromosomal aberrations .................................................................................................................... 73, 109 

clearance ................................................................................................................................... 13, 33, 75, 77 

crustaceans ................................................................................................................................ 139, 177, 184 

death................................................................................................................ 22, 23, 24, 38, 39, 69, 92, 104 

deoxyribonucleic acid (see DNA)......................................................................................................... 21, 74 

dermal effects............................................................................................................................ 62, 69, 72, 93 

DNA (see deoxyribonucleic acid)....................................................................... 21, 31, 74, 94, 98, 100, 109 

dopamine.....................................................................................................................................................15 

endocrine......................................................................................................................................... 24, 62, 89 

endocrine effects .........................................................................................................................................62 

ferritin ....................................................................................................................... 18, 19, 58, 97, 108, 205 

fetus................................................................................................................................................. 81, 91, 92 

gastrointestinal effects ........................................................................................................ 13, 33, 34, 57, 58
 

general population................................................................................................. 11, 93, 100, 141, 176, 181 

genotoxic............................................................................................................................................. 22, 109 

genotoxicity................................................................................................................................. 98, 106, 109 

groundwater .......................................................................................... 3, 141, 151, 157, 163, 173, 183, 210 

growth retardation........................................................................................................................... 11, 21, 92 

half-life.................................................................................................................................................. 77, 93 

hematological effects ........................................................................................................ 34, 58, 59, 69, 108 

hepatic effects ................................................................................................................................. 34, 60, 61 

hydrolysis..................................................................................................................................................160 

immune system ............................................................................................................................. 63, 95, 110 
ZINC D-2 

APPENDIX D 

immunological ........................................................................................................................ 17, 22, 63, 106 

immunological effects...............................................................................................................................106 

Kow .................................................................................................................................... 125, 126, 127, 128 

LD50............................................................................................................................................... 38, 39, 107 

lymphoreticular...........................................................................................................................................63 

mass spectroscopy.....................................................................................................................................192 

metabolic effects .........................................................................................................................................39 

metal fume fever ............................... 4, 12, 14, 16, 29, 30, 34, 35, 36, 88, 95, 103, 106, 107, 110, 113, 177 

milk ............................................................................................... 79, 81, 101, 177, 178, 185, 187, 191, 192
 

mucociliary ........................................................................................................................................... 13, 33 

musculoskeletal effects ...............................................................................................................................60 

neurobehavioral...........................................................................................................................................89 

nuclear............................................................................................................................................... 116, 159 

ocular effects................................................................................................................................. 35, 62, 104 

pharmacodynamic.......................................................................................................................................84 

pharmacokinetic........................................................................................................................ 84, 85, 86, 91 

photolysis ..................................................................................................................................................160 

placenta ................................................................................................................................................. 67, 81 

pulmonary fibrosis .............................................................................................................................. 32, 103 

renal effects........................................................................................................................................... 35, 61 

retention .......................................................................................................................... 77, 84, 88, 111, 188 

solubility ....................................................................................... 38, 75, 116, 153, 156, 160, 184, 187, 188
 

superoxide dismutase...................................................................... 11, 15, 17, 18, 21, 58, 98, 108, 117, 205 

T3................................................................................................................................................................62 

T4.......................................................................................................................................................... 62, 63 

thyroid.......................................................................................................................................................116 

thyroid stimulating hormone (see TSH)......................................................................................................62 

toxicokinetic.......................................................................................................................... 21, 75, 108, 112 

toxicokinetics ............................................................................................................................................112 

TSH (see thyroid stimulating hormone)................................................................................................ 62, 63 

tumors ........................................................................................................................................... 68, 98, 100 

weanling......................................................................................................................................................60