THE AMERICAN COUNCILON SCIENCE AND HEALTHTHE AMERICAN COUNCILON SCIENCE AND HEALTH

AMERICAN COUNCIL ON SCIENCE AND HEALTH1995 Broadway, 2nd Floor, New York, NY 10023-5860

Tel. (212) 362-7044 • Fax (212) 362-4919URL: http://www.acsh.org • E-mail: acsh@acsh.org

Traces of EnvironmentalChemicals in the Human

Body:

Prepared for The American Council on Science and Health

by Daland R. Juberg, Ph.D.

Project Coordinators:

Ruth Kava, Ph.D., R.D.Director of Nutrition

Alicia Lukachko, M.P.H.Assistant Director of Public Health

Art DirectorYelena Ponirovskaya

April 1999

Walter S. Barrows, Sr.,Ph.D. Carpinteria, CA

Hinrich L. Bohn, Ph.D. University of Arizona

Joseph F. Borzelleca,Ph.D. Virginia CommonwealthUniversity

C. Jelleff Carr, Ph.D. Columbia, MD

Donald G. Cochran,Ph.D. Hampstead, NC

Robert M. Devlin,Ph.D. University ofMassachusetts

John Doull, M.D.,Ph.D. University of Kansas

Michael A. Dubick,Ph.D. U.S. Army Institute ofSurgical Research

Kenneth D. Fisher,Ph.D. Office of DiseasePrevention and HealthPromotionWashington, DC

Ronald E. Gots, M.D.,Ph.D. Rockville, MD

William W. Greaves,M.D. Medical College ofWisconsin

Richard M. Hoar,Ph.D. Williamstown, MA

Joseph H. Hotchkiss,Ph.D. Cornell University

Michael Kamrin, Ph.D. Michigan State University

John C. Kirschman,Ph.D. Emmaus, PA

Manfred Kroger, Ph.D. The Pennsylvania StateUniversity

Frank C. Lu, M.D. Miami, FL

Roger P. Maickel,Ph.D. Purdue University

Thomas H. Milby,M.D. Walnut Creek, CA

Joseph M. Miller, M.D. University ofNew Hampshire

William J. Miller,Ph.D. University of Georgia

Dade W. Moeller,Ph.D. New Bern, NC

Ian C. Munro, Ph.D. Mississauga, ON

James E. Oldfield,Ph.D. Oregon State University

Stanley T. Omaye,Ph.D. University of Nevada,Reno

Jane M. Orient, M.D. Tucson, AZ

M. Alice Ottoboni,Ph.D. Sparks, NV

Gilbert L. Ross, M.D.American Council onScience and Health

Sidney Shindell, M.D. Milwaukee, WI

Fredric M. Steinberg,M.D. England

Elizabeth M. Whelan,D.Sc., M.P.H.American Council onScience and Health

ACSH GRATEFULLY ACKNOWLEDGES THE COMMENTSAND CONTRIBUTIONS OF THE FOLLOWING REVIEWERS

ACSH accepts unrestricted grants on the condition that it is solely responsible for theconduct of its research and the dissemination of its work to the public. The organizationdoes not perform proprietary research, nor does it accept support from individual corpo-rations for specific research projects. All contributions to ACSH—a publicly fundedorganization under Section 501(c)(3) of the Internal Revenue Code—are tax deductible.

Individual copies of this report are available at a cost of $5.00. Reduced prices for 10 ormore copies are available upon request.

April 1999-4000. Entire contents © American Council on Science and Health, Inc.

Executive Summary 5

Introduction 6

How Does the Human Body Handle Foreign Substances? 7

Biomarkers and Their Significance

for Human Health Assessment 8

How Can We Use Biomarkers of Exposure? 8

What Types of Chemicals are Frequently Found

in the Body, and How Do They Get There? 11

How are Such Exposures Monitored? 11

Monitoring intake of environmental chemicals 11

Monitoring body levels of environmental chemicals 12

Biomonitoring and Exposure Assessment

in Occupational Settings 13

Toxicology: What Is It, and How Do Toxicologists Interpret

Trace Levels of Chemicals in the Body? 14

Dose–Response Relationships:

A Cornerstone of Toxicology 14

Hormesis 16

Trends in Trace-Level Environmental Chemical Exposure 17

Summary and Conclusions 18

Glossary 19

References 20

Figure 1. Trends in Intake by Children and Adults

of Three Environmental Chemicals 10

Figure 2. Examples of Different Types of

Dose–Response Relationships 15

All living organisms are continually exposed to foreign chemicals,also known as “xenobiotics.” These chemicals include substancesthat are natural (e.g., toxins produced by molds, plants, and ani-

mals) and man-made (e.g., drugs, industrial chemicals, pesticides, and pol-lutants).

As a result of this exposure, human tissues and body fluids may con-tain many different xenobiotics, most of them present at trace levels andsome of them essential to life.

Trace chemicals in the body can be detected through the study of “bio-markers”—alterations in cells or biochemical processes—in the blood, inother body fluids, or in tissues.

A biomarker is useful primarily as a signal of exposure to a given sub-stance rather than as a direct indicator of any harmful effect the substancemay have caused. Biomarkers are most useful in the assessment of short-term effects or recent exposures. They are used less frequently as indicatorsof past exposures.

When they are studied in conjunction with other toxicological or clini-cal signs, biomarkers can help clinicians diagnose or predict the develop-ment of diseases that might be related to patients’exposures to foreign sub-stances. But improvements in analytical methods now make possible thedetection in the body of increasingly smaller traces of xenobiotic sub-stances. The relationships between biomarkers, exposure, and risk ofadverse health effects thus have become less certain.

The presence in the body of a trace chemical generally signifies occu-pational or lifestyle-related exposure to that substance. Such a presencealone should not be overinterpreted as necessarily injurious to health, how-ever. For the vast majority of exogenous chemicals (chemicals originatingoutside the body), there is no evidence to suggest that trace con-centrations in the body present a risk to human health.

Traces of Environmental Chemicals in the Human Body:

The presence of trace levels of environmental chemicals in hair, bodyfluids, and tissues is a reflection of our daily exposure to many suchchemicals. These substances include natural chemicals, pharmaceuti-

cal agents, and environmental pollutants. Knowledge of this is not new.1

Many of these substances are eliminated naturally from the body inthe course of normal metabolism* and excretion. Some others, however,may accumulate in the body’s tissues.

Evidence of exposure to various trace chemicals may be found inhuman body fluids or tissues. These markers of exposure are called “bio-markers”* and can serve as useful tools for the medical and occupational-health communities.

Biomarkers—short for “biological markers”—may be defined as anymeasurable alterations in cells or biochemical processes. Some biomarkerscan be found through routine clinical tests using blood and urine samples.Biomarkers thus found can be considered as useful pieces of evidenceamong the many often utilized in making clinical evaluations. Finding, forexample, children’s blood lead levels that are elevated above generallyaccepted limits may indicate household exposures to lead that merit atten-tion. Similarly, a forensic* toxicologist will rely on biomarkers in blood,urine, and tissue samples to identify causes of death or to confirm possibleexposures to noxious substances.

Occupational physicians, clinicians, and other scientists use “environ-mental biomarkers” as tools to assist their evaluations of human health. Theuse of biomarkers alone to determine health risks is not generally accepted,however, because of biomarkers’limited ability to aid in the diagnosis ofadverse health effects or disease. The detection of a biomarker does notalways indicate the presence of a disease or a toxic process. More common-ly, it simply indicates an exposure to a substance.

Finally, while the term “biomarker” may be used to refer to endoge-nous* (originating inside the body; e.g., elevated cholesterol levels) as wellas exogenous* (originating outside the body) substances, in the context ofthis report we will use the term primarily to refer to the exogenous type.

In this report we will briefly describe how the body deals with traceamounts of environmental chemicals and will illustrate how biomarkers are

used to help evaluate the possible consequences to human healthof exposure to such substances.

* See Glossary, page 19, for definitions of starred terms.

Chemicals that are foreign to the body are known as “xenobiotics.”*

Such substances can be either natural (chemicals produced by molds,plants, and animals) or man-made (drugs, industrial chemicals, pesti-

cides, and pollutants). Common routes of exposure to these environmentalchemicals include inhalation, ingestion, and absorption through the skin.

The body may handle such trace chemicals by altering their chemicalforms. The substances thus formed may then be detectable in blood, inurine, or in body tissues and are considered biomarkers. Virtually all sub-stances to which a person is exposed are absorbed into the blood, wherethey are either transported freely or bound to proteins in the blood. Theythen are distributed to various tissues (including storage sites) in the bodyand/or eliminated from the body.

The human body handles trace chemicals in numerous ways. For somesubstances, various tissues or organs may act as storage depots. As thestored chemical is processed and its breakdown products excreted from thebody, more and more of the chemical is released from the storage site(s) tobe metabolized and eliminated.

Many substances absorbed by the body must first be converted towater-soluble* (dissolvable in water) forms before they can be excreted inthe urine. This conversion is often performed by the liver. The kidneys alsoplay a major role in filtering and eliminating many such substances from thebody. Other organs that help eliminate various substances from the bodyinclude the lungs—which may excrete volatile chemicals such as acetone,carbon dioxide, and sulfur dioxide—and, as indicated above, the liver,which is responsible for the metabolism and excretion of a widerange of substances.

Traces of Environmental Chemicals in the Human Body:

It is important both to distinguish the various types of biomarkers and toshow how they might be used to evaluate human health and exposure totrace chemicals.

The different types of biomarkers may be described generally as follows:

• The term “biomarker of exposure” refers to any exogenous substance orits by-product that can be measured in the body. One example is a bloodalcohol level greater than zero—an indication that a person had recentlyconsumed an alcoholic beverage.

• The term “biomarker of effect” refers to measurable alteration in somebiological response. Some examples are a decrease in the number ofblood cells or changes in the level or activity of a particular enzyme.*

• A “biomarker of adverse effect” is an indicator identifying harmful bio-logical changes that have occurred as a result of exposure to a toxicant.*

One example is anemia (a decreased number of red blood cells) in a per-son exposed to high levels of benzene.

The distinctions between these definitions are significant, particularlywith regard to “biomarkers of exposure” and “biomarkers of adverseeffect.” The mere fact that we can measure a trace chemical or its byprod-ucts in the body does not mean that that level of that chemical will cause anadverse effect—or even that it will produce any biological response at all.

The relationship between evidence of exposure and adverse effect iscomplex. There are many steps between the initial indication of exposureand the subsequent manifestation of an actual adverse health effect. Thebodies of many species, humans included, have natural defense systems andbuilt-in detoxification and repair mechanisms. These systems and mecha-nisms often prevent an adverse health effect from occurring after an expo-sure. When we detect trace concentrations of xenobiotics in the body, there-fore, we must uncover additional scientific evidence before we can con-clude that there are adverse effects resulting from such an exposure.

For certain substances, biomarkers can provide a historicalrecord of past exposures. Trace levels of some chemicals in cer-tain tissues or fluids—lead in the blood, for example—general-

ly indicate a recent exposure. In contrast, trace levels of lead in hair or bonesuggest exposure in the more distant past.

Some substances—alcohol and caffeine, for example, and drugs thatare processed rapidly by the body—are excreted within a relatively shorttime, often within a few hours. The presence of such substances in theblood thus indicates recent exposure. For a substance that is lipid soluble,*

that has a long half-life,* or that is stored within the body, its presence in theblood may reflect either of two things. It may indicate a recent exposure, orit may indicate a state of equilibrium* between the amount of the substancein a storage site and the amount in the blood. The interpretation of the sim-ple presence of a substance in blood or tissues is thus not always straight-forward.

The significance and interpretation of biomarkers of exposure alsodepend on several other key factors. Some of the questions that must beasked are as follows:

• Are blood or tissue concentrations of the substance in question aboveknown acceptable tolerance levels and/or known normal concentrationswithin the population as a whole?

• Is the presence of a trace substance associated with a state that predictsdamage to health (benzene-related bone marrow abnormalities, forexample)?

• Are there confounding variables? Such factors as diet, body size, fatcontent, and the use of tobacco, for example, can significantly influencethe diagnostic utility and accuracy of biomarkers.

• Are there exposures to the same substance from multiple sources? Aperson might have an occupational exposure to cadmium, for example,and then be further exposed to the metal through eating certain shellfishin which cadmium is present in trace amounts.

• Is the biomarker being measured in special subpopulations of individu-als? Some groups of people may be particularly sensitive to chemicalsthat produce biomarkers; for these groups the hazard potential of thechemicals may be increased.

Thus, the presence in someone’s body of a certain biomarker may sig-nal a need for further clinical testing and investigation to determine why thebiomarker is present, what exogenous substance was involved, how the per-son was exposed to that substance, and whether or not the pres-ence of the biomarker indicates an adverse effect on the per-son’s health.

Traces of Environmental Chemicals in the Human Body:

Figure 1. Trends in Intake by Children and Adults of Three Environmental Chemicals *

* Adapted from data presented in Gunderson EL. FDAtotal diet study, July 1986–April 1991,dietary intakes of pesticides, selected elements, and other chemicals. J AOAC Int.1995;78:1353–1362.

Dietary intake is a primary source of human exposure to a variety oftrace chemicals—such as metals and pesticides—that are found in our envi-ronment.

How are Such Exposures Monitored?MONITORING INTAKE OF ENVIRONMENTAL CHEMICALS. Each year, in an effort todetermine human intakes of selected pesticides, synthetic chemicals, andmineral elements, the U.S. Food and Drug Administration (FDA) conductswhat is known as “the Market Basket Survey” or “Total Diet Studies.” Firstconducted in 1961, the Market Basket Survey involves the retail purchaseof foods considered to be representative of the “total diet” of the U.S. popu-lation. The survey includes analyses of 234 items that make up the diets ofeight population groups of different ages and both sexes.

The Market Basket Survey report for the period 1986–1991 includesdata on the dietary intakes of nearly 120 compounds for the eight popula-tion groups. The individuals surveyed range from infants to the elderly.2

The report indicates that during the period of the survey, the daily intake ofselected pesticides and metals either remained stable or decreased.Importantly, the survey did not reveal an increasing dietary exposure tothese substances. This is particularly true of lead intake (see Figure 1).

Lead exposures from dietary sources have decreased dramatically,largely as a result of the diminishing use of lead in paint, in soldered cans,and in household plumbing. Other factors contributing to the dramaticdecrease in dietary lead exposures have been the removal of lead from gaso-line and the increased testing of drinking water.

The 1986–1991 Market Basket Survey data show that daily intakesof arsenic, cadmium, lead, and mercury were well below provisional toler-able daily intake levels in the period studied. The survey also reported on113 synthetic chemicals; intakes of all pesticides analyzed were far belowthe acceptable daily intake (ADI) levels set by the World Health Org a n i z a -tion and the United Nations Food and Agriculture Org a n i z a t i o n .3 T h ehighest pesticide intake—that of dieldrin—averaged only about 3 percentof the ADI levels for the teenage male and young adult male populationg r o u p s .2

The levels of pesticide residues found in individual foods in the1986–1991 Market Basket Survey did not even approach the residue toler-ances applicable to raw agricultural products as established by the U.S.Environmental Protection Agency (EPA).4 It is also apparent from the sur-vey data that intakes of some persistent pesticides such as DDThave declined steadily since the end of their use in agriculture.

The 1986–1991 survey data confirm that the population is

Traces of Environmental Chemicals in the Human Body:

exposed to trace levels of chemicals through food and that while thesechemicals can be detected in blood, the concentrations generally fall wellbelow acceptable tolerance levels. These concentrations thus are not expect-ed to pose a risk to human health.

MONITORING BODY LEVELS OF ENVIRONMENTAL CHEMICALS. For the last twodecades internationally supported programs for specimen banking* havebecome an important component of long-term environmental monitoring.Such monitoring of trace levels of various essential and nonessential ele-ments is of interest to nutritionists as well as to toxicologists, because whilecertain heavy metals in the environment may pose a health risk to humansat certain exposure levels, these same metals at lower concentrations areessential for biological functioning.5

One study examined the concentration and distribution of certain ele-ments in the tissues of healthy persons in the United Kingdom.6 The resultsshowed about 40 different elements concentrated in a number of organs andtissues. But trace metals such as copper, zinc, manganese, and chromiumare essential for life. They are found in low concentrations in blood and tis-sues as a result of the consumption of grains, shellfish, and other foods thatcontain these elements; and their presence in the body and blood should notnecessarily be viewed as reason for concern. Elevated concentrations ofthese elements—concentrations beyond those typically found in people—might indicate occupational or environmental exposures, however. Suchexposures could come, for example, from living near a factory where theseelements were used, and might be regarded as cause for further clinicalevaluation.

Some individuals may be predisposed to higher than normal concen-trations of trace elements or contaminants as a result of occupational expo-sures to industrial chemicals and products. People in occupations associatedwith agriculture, for example, often have higher exposures to pesticides as aresult of their intensive use of these materials.

A recent study recorded blood levels in agricultural workers of severalpesticides associated with dietary exposure and a history of local use.7 Theauthors of the study reported that for the majority of the pesticides studied,the blood levels for farmers were similar to typical levels found in the gen-eral U.S. population. Furthermore, the blood levels of these pesticides in thefarm workers showed no significant daily or seasonal variation for a majori-ty of the populations studied. Higher levels of several specific pesticideswere observed in a few individuals in the study, but whether or not healtheffects were associated with these higher levels was not reported. Suchstudies suggest that certain biomarkers of exposure warrant further analysisand evaluation, particularly with regard to populations potentially at risk

from exposure.Another study evaluated the distribution of 23 elements in

the kidneys, livers, and lungs of workers from a smelter and metal refineryin northern Sweden and compared the results with results from a controlgroup.8 Typical concentrations of antimony, arsenic, cadmium, chromium,cobalt, lanthanum, lead, and selenium were found to be from 2 to 16 timeshigher in the metal workers than in the control group. This study of knownoccupational exposures among smelter and refinery workers supports theusefulness of analyzing biomarkers along with other clinical measurementsto identify individuals who are at particular risk due to elevated blood or tis-sue levels of substances recognized as hazardous.

Biomonitoring and Exposure Assessment in Occupational SettingsThe field of biological monitoring, or “biomonitoring”—the analysis

of blood, tissue, urine, and fecal samples to find specific substances or tracechemicals—began with the measurement of normal physiological* valuesfor clinical and diagnostic purposes. Many blood enzymes (alkaline phos-phatase, glutathione peroxidase, and cholinesterase, for example) and otherblood constituents (hemoglobin, white blood cells, proteins, and cholesterol)have characteristic ranges. A medical diagnosis can be simplified whenthese biological yardsticks are used to determine if an individual’s bloodlevel falls outside the normal or typical range. Examples of such biomoni-toring are the use of cholesterol as a biomarker or indicator of the risk ofheart disease and the use of blood glucose levels in the assessment of dia-betes.

Exposure assessment provides occupational-health personnel with atool to assess workers’exposures to specific chemicals. Health personnelcan measure concentrations of a chemical in the work environment and usethose measurements to estimate, for example, workers’potential inhalationexposure. The estimates can then be compared to acceptable exposure lim-its. This type of sampling does not produce data about actual amounts ofchemicals absorbed by the body, however.

To get an accurate assessment of workers’actual overall exposure to achemical, occupational-health personnel can turn to biological monitoringof specimens collected from individuals. The concentrations of the chemicalin the specimens can then be compared with biological exposure indices(BEIs) for that chemical.9 BEIs are measurements that serve as referencevalues and that are intended as guidelines for the evaluation of potentialhealth hazards in the workplace.

The BEIs for specific chemicals are developed based on informationabout the absorption, biotransformation,* and elimination of those chemicalsand the correlation between chemical exposures and biological effects inworkers. The biomarker of exposure can be the chemical itself, its byprod-uct(s), or evidence of a biochemical change induced by thatchemical. Measurements can be taken from exhaled air, fromurine, from blood, or from other biological specimens collected

Traces of Environmental Chemicals in the Human Body:

from the exposed workers. Depending on the chemical, the type of speci-men being used, and the time of the sampling, the values for a biomarkerconcentration may indicate the intensity of a recent exposure, an averagedaily exposure, or a chronic cumulative exposure.

Biomonitoring is particularly useful when dealing with substances thathave relatively short half-lives (between 8 and 48 hours); where analyticalmethods are available; where the pharmacokinetics (the manner in whichthe substance is handled by the body) of the chemical being tested for areunderstood; and where the appropriate reference values with which to com-pare the newly derived biomarker concentrations are known.

Toxicology* involves the study of dose–response relationships relatingto exposures to chemicals, drugs, and other substances and the potentialeffects of those exposures on human health. Toxicology thus is an appropri-ate scientific discipline to turn to when evaluating the potential healthimpact of trace chemicals.

The potential impact a trace chemical has on human health depends onseveral aspects of the way the body handles that chemical. Some of thevariables involved include whether the chemical is converted to a moretoxic or a less toxic substance; the speed with which the chemical isprocessed by, distributed through, and excreted from the body; the easewith which the chemical dissolves in lipid (fat-like) materials such as cellmembranes; the concentration of the chemical at the target tissue or organ;

and the chemical’s residence time (represented by its half-life)in the body. Toxicologists can use such information to predictboth the potential health effects of a trace chemical and the pos-

Figure 2. Examples of Different Types of Dose–Response Relationships

In curve A, a small increase in dose causes a large response. In curve B, the size of theresponse to an increase in dose depends on the actual size of the dose. In curve C, anincrease in dose causes only a small response.

sible mechanisms for such effects. A cornerstone of toxicological science is the toxicologist’s ability to

demonstrate a relationship between the amount (dose) of a given substanceand a subsequent response by the body exposed to it. Such a dose–responserelationship confirms that the response elicited by a given chemical is relatedto the level of the chemical exposure.

As the concentration or dose of a substances increases, there is a greaterlikelihood that a response will be elicited. In some cases this may be a rela-tively greater—or more adverse—response (see Figure 2).

Some chemicals have “steep” dose–response curves. This means thatthe response or effect of such chemicals on the body changes rapidly withsmall changes in the dose. Other chemicals have “flatter”dose–response curves: It takes much more of one of these chemi-cals—a considerably higher dose, in other words—to elicit aresponse by or effect on the body.

Traces of Environmental Chemicals in the Human Body:

The body’s response to a chemical can be a response of simple expo-sure—the induction of an enzyme* that causes metabolism of that chemicalto occur. Or, if the dose of the chemical is high enough, the response can beone that results in injury to the organs or tissues of the body.

It is widely believed that for noncancer effects—and possibly formany cancers—there is a threshold dose below which no effects are dis-cernible. The concentrations in the body of most trace chemicals are typi-cally well below this threshold, which is why no effects are observed.

“Hormesis”* may be defined as a dose–response relationship that isstimulatory at low doses but inhibitory at higher doses. In a hormeticresponse the effect of an exogenous chemical is believed not only to bestimulatory at low doses, but actually to be positive relative to the healthstatus or well-being of the individual being exposed. Hormesis can be seenin the human body’s response to some essential nutrients, such as vitaminsA and D. Low doses of these nutrients are essential and beneficial, buthigher levels are toxic.

The concept of hormesis has drawn considerable interest in a numberof scientific fields. Much of the focus on and support for the existence ofthis phenomenon has been derived from studies of growth and reproductionin aquatic species. There are, however, other endpoints—toxicity and can-cer among them—that could be affected by this phenomenon should it beproved to occur for various chemicals.

It should be noted that currently there is much debate and discussion,both as to the existence of a true hormetic response with respect to environ-mental chemicals, and as to what chemicals or compounds this type ofdose–response relationship might exist for.

For most chemicals tested, the traditional dose–response relationshiphas not shown a positive effect at very low doses. But no attempt to findsuch effects for most environmental chemicals has yet been made. In partthis is because the positive effects of low-dose chemicals have not been thefocus of regulatory activities: Regulatory agencies typically focus theirattentions on protecting the public from health risks rather than on enhanc-ing positive health effects.

Thus, at present we do not know whether trace levels of exogenouschemicals exert a hormetic response or not; and it is premature, at thispoint, for us to speculate on the possibility. It is to be hoped that futureresearch and debate will clarify whether—or to what extent—hormesisapplies to trace levels of exogenous chemicals in humans.

As our analytical techniques become more and more sophisticated,they allow us to measure smaller and smaller quantities of substances in avariety of media—air, water, soil, and human body fluids.

The tendency of some evaluators has been to assume that anydetectable level of an exogenous substance implies an “adverse effect.” Thisapproach is both unscientific and misguided, however, because it fails toconsider dose–response relationships, detoxification mechanisms, and otherimportant factors that must be taken into consideration when we try to eval-uate whether specific chemical exposures might be related to health effects.

The reduction of chemical contaminants in the environment and thedecreasing levels of such trace chemicals in humans in recent years areencouraging. Studies continue to report decreasing levels of contaminants inair, water, and soil. In large part, these decreases result from pollution con-trols that have been placed on individual sources (also called pointsources)—thereby resulting in reduced release of chemicals into the envi-ronment.10,11,12

The trend in blood lead levels in the U.S. population best illustratesthis tendency.A study done in 1994 as part of a broad national surveyreported a significant decline since the mid 1970s in blood lead levels in thepopulation as a whole and among children in particular.13 This decline hascome about as a result of the virtual elimination of lead from certain keymanufacturing processes and consumer products, most notably leaded gaso-line and lead-based paints.

Traces of Environmental Chemicals in the Human Body:

The health implications of finding trace amounts of certain substancesin human tissues are certainly valid causes for concern. An importantprinciple of toxicology, however, is that “the dose makes the poi-

son.” This means that the toxicity or other adverse effects of a given exoge-nous substance in the body depend on the amount of that substance towhich the body has been exposed. It is important, too, to keep in mind thatthe simple presence of a chemical in the body should not necessarily beequated with toxicity. For the vast majority of the trace chemicals we mightfind in the body, we can reasonably conclude that the concentrations arebelow any discernible effect level.

Every day of our lives, every one of us is exposed to a multitude ofpotentially toxic and carcinogenic substances, both natural and synthetic.But we humans are equipped with a set of biological defense mechanismsthat can handle—and successfully manage—our exposures to many foreignsubstances. We need not feel undue anxiety when faced with positiveresults after a blood-screening analysis.

Such an analysis provides a snapshot in time, both of a person’slifestyle and of that person’s relationship to his or her environment. Thepresence of certain biomarkers may, indeed, indicate a high-exposure situa-tion and may point to a need for further clinical evaluation. Whatever thesituation, however, the following key questions can provide a context inwhich to interpret the presence of trace chemicals in the body.

1. What is the concentration in the body of the substance of concern ascompared with typical or expected ranges for that substance?

2. Has the chemical ever been associated with a particular health hazard?

3. Are there predisposing exposure factors (occupational or environmentalfactors, for example) that might contribute a heightened body burden orblood concentration of the substance in a particular individual?

4. Are there factors of increased susceptibility—such as compromisedhealth status, age, or genetic predisposition—in a particular indi-vidual (in a young child with high blood lead levels, for exam-ple)?

5. Are there other clinical or toxicological correlates (clinical chemistryvalues, actual pathology, clinical observations) that suggest adversehealth effects resulting from exposure?

The last few decades have seen notable decreases in the release ofchemicals into the air, the water, and the land. As a result, our environmenthas improved with respect to the quantities of such chemicals present in it.With this trend continuing, the levels of trace chemicals in our bodiesshould continue to decline as well. The trace chemicals in our blood andbodies often serve as biomarkers of background environmental exposure,but no data or evidence exists for most chemicals that would suggest anincreased health risk from these background exposures.

Biomarker: Shortened form of “biological marker”; any alteration in cells orbiochemical processes that can be measured in a biological system orsample.

Biotransformation. Changes in the structure of a substance due to its inter-action with biological processes in the body (e.g., changes caused by theaction of a body enzyme).

Endogenous: Refers to a substance or process that originates inside thebody.

Enzyme: A protein molecule that speeds up chemical reactions in the bodywithout itself being altered or destroyed during such reactions.

Enzyme induction: The process of increasing the amount or activity of anenzyme in the body.

Equilibrium:A state of balance.

Exogenous: Refers to a substance or process that originates outside thebody.

Forensic: Refers to legal proceedings. In this case, the term

Traces of Environmental Chemicals in the Human Body:

“forensic toxicology” often refers to tests conducted on blood or otherbiological samples to determine disease state or cause of death.

Half-life: The time required for the decay or elimination of half of a sub-stance from the body.

Hormesis: The stimulatory effect of low concentrations of any toxic sub-stance on an organism.

Lipid soluble: Refers to substances that dissolve in lipid or fat-like materialsbut do not dissolve in water.

Metabolism: The clinical processes and reactions that occur during and areinvolved in the absorption, detoxification, and excretion of a substance.The product of a chemical reaction in the body—the result of metabo-lism—is called a metabolite.

Physiological: Relating to the organic processes and phenomena of anorganism or any of its parts or of a particular bodily process.

Specimen banking. A systematic gathering and storing of biological samplesfor future clinical, biochemical, or other types of analyses.

Toxicant or toxin : A chemical agent or poison that has the potential to causeinjury or harm to an organism.

Toxicology: The scientific study of chemicals, poisons, drugs, and other sub-stances and the ways in which they may exert adverse effects in humans.

Water soluble: Refers to a substance that dissolves in water but not in lipidor fat.

Xenobiotic: A chemical or other substance that is foreign to the body.

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Nutrition and Biochemistry of Milk/Maintenance. New York:Academic Press, Inc.; 1974:135–158.

2. Gunderson EL. FDA total diet study, July 1986–April

1991, dietary intakes of pesticides, selected elements, and otherchemicals. J AOAC Int. 1995;78:1353–1362.

3. World Health Organization. Evaluation of Certain Food Additivesand Contaminants—41st Report of the Joint FAO/WHO ExpertCommittee on Food Additives. Geneva, Switzerland: World HealthOrganization, 1993.

4. Code of Federal Regulations. Title 40, US Government PrintingOffice. Washington, DC: US Government Printing Office, 1993.Parts 180 and 185.

5. Lu FC. Recent advances in studies on selenium: an overview of asymposium held in China. Reg Toxicol Pharmacol. 1998;27:204–206.

6. Hamilton EI, Minski MJ, Cleary JJ. The concentration and distribu-tion of some stable elements in healthy human tissues from theUnited Kingdom. An environmental study. Sci Tot Environ.1972;1:341–374.

7. Brock JW, Melnyk LJ, Caudill SP, Needham LL, Bond AE. Serumlevels of several organochlorine pesticides in farmers correspondwith dietary exposure and local use history. Toxicol Indust Health.1998;14:275–289.

8. Brune D, Nordberg G, Wester PO. Distribution of 23 elements in thekidney, liver and lungs of workers from a smeltery and refinery innorth Sweden exposed to a number of elements and of a controlgroup. Sci Tot Environ. 1980;16:13–35.

9. American Conference of Governmental and Industrial Hygienists.1997 TLVs and BEIs. Threshold Limits Values for ChemicalSubstances and Physical Agents. Biological Exposure Indices.Cincinnati, Ohio: American Conference of Governmental andIndustrial Hygienists, 1997.

10. SOLEC: State of the Great Lakes. Environment Canada/U.S.Environmental Protection Agency, 1995.

11. Health Canada. State of Knowledge Report on EnvironmentalContaminants and Human Health in the Great Lakes Basin, 1997.

12. International Joint Commission Great Lakes Science AdvisoryBoard’s Workgroup on Ecosystem Health. Workshop onEnvironmental Results: Monitoring and Trends of Effects Caused byPersistent Toxic Substances, 1996.

13. Brody DJ, Prikle JL, Kramer RA, Flegal KM, Matte TD, Gunter EW,Paschal, DC. Blood lead levels in the U.S. population. Phase 1 of theThird National Health and Nutrition Examination Survey (NHANESIII, 1988 to 1991). JAMA. 1994;272:277–283.

A C S H E X E C U T I V E S T A F F

Elizabeth M. Whelan, Sc.D., M.P.H.President

A C S H B O A R D O F D I R E C T O R S

A. Alan Moghissi, Ph . DC h a i r m a nof the Board, ACSH Institute for Re g u l a t o ry Science

No rman E. Borlaug, Ph.D. Texas A&M Un i ve r s i t y

Taiwo K. Danmola, C.P. A .Arthur Andersen LLP

F. J. Francis, Ph.D. Un i versity of Ma s s a c h u s e t t s

Raymond Gambino, M.D. Quest Diagnostics In c o r p o ra t e d

Jerald L. Hill, Esq. Appellate Ad va n t a g e

Roger P. Maickel, Ph.D. Pu rdue Un i ve r s i t y

He n ry I. Mi l l e r, M.D.Ho over Institution

A l b e rt G. Nickel Lyons Lavey Nickel Swift, In c .

Ka ry D. Presten U.S. Trust Co.

R . T. Ravenholt, M.D., M.P.H. Population Health Im p e ra t i ve s

Fre d rick J. St a re, M.D., Ph.D. Ha rva rd School of Public He a l t h

Fre d ric M. Steinberg, M.D.Del Ray Beach, FL

Stephen S. St e rnberg, M.D. Memorial Sl o a n - Kettering Cancer Ce n t e r

Lorraine Thelian Ketchum Public Re l a t i o n s

Elizabeth M. Whelan, Sc.D., M.P.H. President, AC S H

Ro b e rt J. White, M.D., Ph.D. Case We s t e rn Re s e rve Un i ve r s i ty

A C S H B O A R D O F S C I E N T I F I C A N D P O L I C Y A D V I S O R S

Julie A. Albrecht, Ph . D .U. of Ne b raska, Li n c o l n

Roslyn B. Alfin-Sl a t e r, Ph . D .U C LA

Thomas S. Allems, M.D., M.P. H .San Fra n c i s c o, CA

R i c h a rd G. Allison, Ph . D .American Institute of Nutrition (FA S E B )

John B. Allred, Ph . D .Ohio State Un i ve r s i t y

Philip R. Alper, M.D.U. of Ca l i f o rnia, San Fra n c i s c o

Dennis T. Ave ryHudson In s t i t u t e

Ro b e rt S. Baratz, D.D.S., Ph.D., M.D.Boston Un i versity School of Me d i c i n e

Stephen Ba r rett, M.D.Al l e n t own, PA

Walter S. Ba r rows Sr., Ph . D .Carpinteria, CA

Thomas G. Ba u m g a rt n e r, M.Ed . ,Ph a rm . D .Un i versity of Florida, Ga i n e s v i l l e

Blaine L. Blad, Ph . D .Un i versity of Ne b ra s k a

Hi n rich L. Bohn, Ph . D .Un i versity of Ar i zo n a

Ben Wilsman Bolch, Ph . D .Nashville, T N

J. F. Borzelleca, Ph . D .Medical College of Vi r g i n i a

Michael K. Botts, Esq.Ne vada, IA

Michael B. Bracken, Ph.D., M.P. H .Yale Un i ve r s i t y

George A. Br a y, M.D.Pennington Biomedical Re s e a rch Ce n t e r

Allan Brett, M.D.Un i versity of South Ca ro l i n a

C h ristine M. Bruhn, Ph . D .Center for Consumer Re s e a rc h

Gale A. Buchanan, Ph . D .Un i versity of Ge o r g i a

Ed w a rd E. Bu rns, Ph . D .Texas A&M Un i ve r s i t y

Francis F. Busta, Ph . D .Un i versity of Mi n n e s o t a

Earl L. Butz, Ph . D .Pu rdue Un i ve r s i t y

William G. Cahan, M.D.Memorial Sl o a n - Kettering Cancer Ce n t e r

Elwood F. Ca l d well, Ph.D., M.B.A.Un i versity of Mi n n e s o t a

Barbara N. Campaigne, Ph . D .American College of Sp o rts Me d i c i n e

Zerle L. Ca r p e n t e r, Ph . D .Texas A&M Un i versity Sy s t e m

C. Jelleff Ca r r, Ph . D .Columbia, MD

Ro b e rt G. Cassens, Ph . D .Un i versity of Wi s c o n s i n

James J. Cerda, M.D.Un i versity of Fl o r i d a

Bruce M. Chassy, Ph . D .Un i versity of Il l i n o i s

Dale J. Chodos, M.D.K a l a m a zo o, MI

Emil William Chynn, M.D.Manhattan Eye and Ear In f i rm a ry

Walter L. Clark, Ph . D .Chapman Un i ve r s i t y

Dean O. Clive r, Ph . D .Un i versity of Ca l i f o rnia, Da v i s

F. M. Clydesdale, Ph . D .Un i versity of Ma s s a c h u s e t t s

Donald G. Cochran, Ph . D .Hampstead, NC

W. Ronnie Coffman, Ph . D .C o rnell Un i ve r s i t y

Be rn a rd L. Cohen, D.Sc.Un i versity of Pi t t s b u r g h

Neville Colman, M.D., Ph . D .St. Lu k e’s Ro o s e velt Hospital Ce n t e r

Gerald F. Combs, Jr., Ph . D .C o rnell Un i ve r s i t y

Michael D. Corbett, Ph . D .Omaha, NE

Eliot Cord a y, M.D.Ce d a r s - Sinai Medical Ce n t e r

Roger A. Coulombe, Ph . D .Utah State Un i ve r s i t y

H. Russell Cross, Ph . D .Texas A&M Un i ve r s i t y

Charles R. Cu rtis, Ph . D .Ohio State Un i ve r s i t y

Ilene R. Danse, M.D.En v i romed Health Se rv i c e s

Ernst M. Davis, Ph . D .U. of Texas at Ho u s t o n

Ha r ry G. Da y, Sc.D.Indiana Un i ve r s i t y

Je rome J. DeCosse, M.D.N . Y. Ho s p i t a l – C o rnell Medical Ce n t e r

Thomas R. De Gre g o ri, Ph . D .Un i versity of Ho u s t o n

Ro b e rt M. Devlin, Ph . D .Un i versity of Ma s s a c h u s e t t s

Seymour Diamond, M.D.Diamond Headache Clinic

Donald C. Dickson, M.S.Gi l b e rt, AZ

John Di e b o l dThe Diebold Institute for Public Po l i c ySt u d i e s

Ralph E. Dittman, M.D., M.P. H .Houston, TX

John. E. Dodes, D.D.S.National Council Against Health Fra u d

John Doull, Ph.D., M.D.Un i versity of Kansas

T h e ron W. Downes, Ph . D .Michigan State Un i ve r s i t y

Adam Dre w n owski, Ph . D .Un i versity of Wa s h i n g t o n

Michael A. Dubick, Ph . D .U.S. Army Institute of Surgical Re s e a rc h

Ed w a rd R. Duffie Jr., M.D.Sa vannah, GA

James R. Dunn, Ph . D .Averill Pa rk, NY

Ro b e rt L. Du Pont, M.D.D u Pont Associates, P. A .

He n ry A. Dymsza, Ph . D .Un i versity of Rhode Is l a n d

Michael W. Easley, D.D.S., M.P. H .State Un i versity of New Yo rk

Michael P. Elston, M.D., M.S.Rapid City Regional Ho s p i t a l

James E. En s t rom, Ph.D., M.P. H .U C LA

My ron E. Essex, D.V.M., Ph . D .Ha rva rd School of Public He a l t h

Te r ry D. Et h e rton, Ph . D .Pe n n s y l vania State Un i ve r s i t y

Daniel F. Fa rkas, Ph . D .Oregon State Un i ve r s i t y

R i c h a rd S. Fa wcett, Ph . D .Hu x l e y, IA

John B. Fe n g e r, M.D.Phoenix, AZ

O wen R. Fennema, Ph . D .Un i versity of Wi s c o n s i n

Madelon Lubin Finkel, Ph . D .C o rnell Un i ve r s i t y

Jack C. Fi s h e r, M.D.U. of Ca l i f o rnia, San Diego

Kenneth D. Fi s h e r, Ph . D .Commission on Dietary Supplement Labels

L e o n a rd T. Flynn, Ph.D., M.B.A.Morganville, NJ

William H. Foege, M.D., M.P. H .Em o ry Un i ve r s i t y

Ralph W. Fogleman, D.V. M .Upper Black Ed d y, PA

E.M. Fo s t e r, Ph . D .Un i versity of Wi s c o n s i n

Glenn Froning, Ph . D .U. of Ne b raska, Li n c o l n

A rthur Furst, Ph.D., Sc.D.Un i versity of San Fra n c i s c o

Charles O. Gallina, Ph . D .Illinois Dept. of Nuclear Sa f e t y

L a Nelle E. Geddes, Ph.D., R.N.Pu rdue Un i ve r s i t y

K. H. Gi n zel, M.D.Un i versity of Ar i zo n a

William Paul Gl e zen, M.D.Baylor College of Me d i c i n e

Jay Alexander Gold, M.D., J.D., M.P. H .Medical College of Wi s c o n s i n

Roger E. Gold, Ph . D .Texas A&M Un i ve r s i t y

Timothy N. Gorski, M.D.Arlington, TX

Ronald E. Gots, M.D., Ph . D .In t e rnational Center forTox i c o l o gy and Me d i c i n e

Michael Gough, Ph . D .Cato In s t i t u t e

He n ry G. Gr a b owski, Ph . D .Duke Un i ve r s i t y

John D. Graham, Ph . D .Ha rva rd Center for Risk An a l y s i s

James Ian Gr a y, Ph . D .Michigan State Un i ve r s i t y

William W. Gre a ves, M.D., M.S.P. H .Medical College of Wi s c o n s i n

Saul Green, Ph . D .Zol Consultants, In c .

R i c h a rd A. Greenberg, Ph . D .Hinsdale, IL

Go rdon W. Gribble, Ph . D .Da rtmouth College

William Grierson, Ph . D .Un i versity of Fl o r i d a

Lester Grinspoon, M.D.Ha rva rd Medical School

Helen A. Gu t h rie, Ph . D .Pe n n s y l vania State Un i ve r s i t y

Philip S. Gu zelian, M.D.Un i versity of Colora d o

A l f red E. Ha r p e r, Ph . D .Un i versity of Wi s c o n s i n

Ro b e rt D. Ha ve n e rS o l vang, CA

Virgil W. Hays, Ph . D .Un i versity of Ke n t u c k y

Dwight B. Heath, Ph . D .Brown Un i ve r s i t y

No rman D. Heidelbaugh, V. M . D . ,M . P.H., S.M., Ph . D .Texas A&M Un i ve r s i t y

Zane R. Helsel, Ph . D .Rutgers Un i ve r s i t y

L. M. Henderson, Ph . D .Un i versity of Mi n n e s o t a

Victor He r b e rt, M.D., J.D.Bronx Ve t e rans Affairs Medical Ce m t e r

A C S H B O A R D O F S C I E N T I F I C A N D P O L I C Y A D V I S O R S

The opinions expressed in ACSH publications do not necessarily represent the views of all ACSH Directors and Advisors.ACSH Directors and Advisors serve without compensation.

John Higginson, M.D., F. R . C . P.Sa vannah, GA

R i c h a rd M. Ho a r, Ph . D .Wi l l i a m s t own, MA

John H. Ho l b rook, M.D.Un i versity of Ut a h

Ro b e rt M. Ho l l i n g w o rth, Ph . D .Michigan State Un i ve r s i t y

Ed w a rd S. Ho rton, M.D.Joslin Diabetes Ce n t e r

Joseph H. Hotchkiss, Ph . D .C o rnell Un i ve r s i t y

Susanne L. Hu t t n e r, Ph . D .U. of Ca l i f o rnia, Be rk e l e y

Lucien R. Jacobs, M.D.U C LA School of Me d i c i n e

Rudolph J. Ja e g e r, Ph . D .Environmental Medicine, In c .

G. Richard Jansen, Ph . D .C o l o rado State Un i ve r s i t y

William T. Ja rvis, Ph . D .Loma Linda Un i ve r s i t y

Ed w a rd S. Josephson, Ph . D .Un i versity of Rhode Is l a n d

Michael Ka m rin, Ph . D .Michigan State Un i ve r s i t y

John B. Kaneene, D.V.M., M.P. H . ,Ph.D. Michigan State Un i ve r s i t y

Philip G. Ke e n e y, Ph . D .Pe n n s y l vania State Un i ve r s i t y

John G. Ke l l e r, Ph.D. Ol n e y, MD

George R. Ke r r, M.D.Un i versity of Texas

George A. Ke y w o rth II, Ph . D .Pro g ress and Freedom Fo u n d a t i o n

Michael Kirsch, M.D.Highland Heights, OH

John C. Kirschman, Ph . D .Emmaus, PA

Ronald E. Kleinman, M.D.Massachussetts Ge n e ral Ho s p i t a l

Ka t h ryn M. Kolasa, Ph.D., R.D.East Ca rolina Un i ve r s i t y

David Kri t c h e v s k y, Ph . D .The Wistar Institute, Ph i l a d e l p h i a

Ma n f red Kro g e r, Ph . D .Pe n n s y l vania State Un i ve r s i t y

J. Laurence Kulp, Ph . D .Fe d e ral Wa y, WA

Ca rolyn J. Lackey, Ph.D., R.D.No rth Ca rolina State Un i ve r s i t y

J. Clayburn LaFo rce, Ph . D .U C LA

L a w rence E. LambSan An t o n i o, TX

Lillian Langseth, Dr. P. H .Lyda Associates, Palisades, NY

L a r ry Laudan, Ph . D .National Au t o n o m o u sUn i versity of Me x i c o

Brian C. Lentle, M.D.Va n c o u ver Ge n e ral Ho s p i t a l

Fl oy Lilley, J.D.Un i versity of Texas, Au s t i n

Be rn a rd J. Liska, Ph . D .Pu rdue Un i ve r s i t y

William M. London, Ed.D., M.P. H . .Fo rt Lee, NJ

James A. Lowell, Ph . D .Pima Community College

Frank C. Lu, M.D.Miami, FL

William M. Lunch, Ph . D .Oregon State Un i ve r s i t y

Da ryl Lund, Ph . D .C o rnell Un i ve r s i t y

Ha rold Lyons, Ph . D .Rhodes College

How a rd D. Maccabee, Ph.D., M.D.Radiation On c o l o gy Ce n t e r

He n ry G. Manne, J.S.D.George Mason Un i ve r s i t y

Karl Ma r a m o rosch, Ph . D .Rutgers Un i ve r s i t y

Judith A. Marlett, Ph.D., R.D.Un i versity of Wisconsin, Ma d i s o n

James R. Marshall, Ph . D .Ar i zona Cancer Ce n t e r

James D. McKean, D.V.M., J.D.Iowa State Un i ve r s i t y

John J. McKetta, Ph . D .Un i versity of Texas, Au s t i n

Donald J. McNamara, Ph . D .Egg Nutrition Ce n t e r

Pa t rick J. Michaels, Ph . D .Un i versity of Vi r g i n i a

Thomas H. Mi l by, M.D., M.P. H .Walnut Creek, CA

Joseph M. Mi l l e r, M.D., M.P. H .Un i versity of New Ha m p s h i re

William J. Mi l l e r, Ph . D .Un i versity of Ge o r g i a

John A. Mi l n e r, Ph . D .Pe n n s y l vania State Un i ve r s i t y

Dade W. Mo e l l e r, Ph . D .Ha rva rd School of Public He a l t h

Grace P. Monaco, J.D.Medical Ca re Mgmt. Corp.

Brian E. Mondell, M.D.Ba l t i m o re Headache In s t i t u t e

Eric W. Mood, LL.D., M.P. H .Yale Un i versity

John P. Morgan, M.D.City Un i versity of New Yo rk

John W. Morgan, Dr. P. H .Loma Linda Un i ve r s i t y

W. K. C. Morgan, M.D.Un i versity Hospital, On t a r i o

Stephen J. Moss, D.D.S., M.S.David B. Kriser Dental Ce n t e r

Ian C. Mu n ro, Ph . D .Ca n Tox, In c .

Kevin B. Mu r p h yMerrill Lynch, Pi e rce, Fenner & Sm i t h

Philip E. Nelson, Ph . D .Pu rdue Un i ve r s i t y

Malden C. Nesheim, Ph . D .C o rnell Un i ve r s i t y

John S. Ne u b e r g e r, Dr. P. H .Un i versity of Kansas

Go rdon W. Ne well, Ph . D .Palo Al t o, CA

James L. Oblinger, Ph.D.No rth Ca rolina State Un i ve r s i t y

R i c h a rd Oksas, M.P.H., Ph a rm . D .Medication In f o rmation Se rv i c e

J. E. Oldfield, Ph . D .Oregon State Un i ve r s i t y

Stanley T. Om a ye, Ph . D .Un i versity of Ne va d a

Jane M. Orient, M.D.Tucson, AZ

M. Alice Ottoboni, Ph . D .Sp a rks, NV

L o ren Pankratz, Ph . D .Oregon Health Sciences Un i ve r s i t y

Michael W. Pa riza, Ph . D .Un i versity of Wi s c o n s i n

Timothy Dukes Phillips, Ph . D .Texas A&M Un i ve r s i t y

Ma ry Frances Picciano, Ph . D .Pe n n s y l vania State Un i ve r s i t y

Thomas T. Poleman, Ph . D .C o rnell Un i ve r s i t y

Charles Polk, Ph . D .Un i versity of Rhode Is l a n d

Ga ry P. Po s n e r, M.D.Tampa, FL

John J. Powers, Ph . D .Un i versity of Ge o r g i a

William D. Pow rie, Ph . D .Un i versity of British Columbia

Kenneth M. Pr a g e r, M.D.Columbia Pre s byterian Medical Ce n t e r

Daniel J. Raiten, Ph . D .FA S E B

Russel J. Re i t e r, Ph.D., D.Me d .Un i versity of Texas

John H. Re n n e r, M.D.Independence, MO

Rita Ricard o - Campbell, Ph . D .Ho over In s t i t u t i o n

William O. Ro b e rtson, M.D.Un i versity of Wa s h i n g t o n

J. D. Robinson, M.D.Ge o r g e t own Un i ve r s i t y

David B. Roll, Ph . D .Un i versity of Ut a h

Dale R. Romsos, Ph . D .Michigan State Un i ve r s i t y

St e ven T. Rosen, M.D.No rt h we s t e rn Un i versity Me d i c a lS c h o o l

Kenneth J. Rothman, Dr. P. H .Ed i t o r, Ep i d e m i o l o gy

Stanley Rothman, Ph . D .Smith College

Ed w a rd C. A. Runge, Ph . D .Texas A&M Un i ve r s i t y

Stephen H. Safe, D.Ph i l .Texas A&M Un i ve r s i t y

Paul D. Saltman, Ph . D .U. of California, San Diego

Wallace I. Sampson, M.D.St a n f o rd U. School of Me d i c i n e

Ha rold H. Sandstead, M.D.Un i versity of Texas Medical Bra n c h

He r b e rt P. Sa rett, Ph . D .Sa rasota, FL

L owell D. Satterlee, Ph . D .Oklahoma State Un i ve r s i t y

Ma rvin J. Schissel, D.D.S.Wo o d h a ven, NY

Barbara Schneeman, Ph . D .Un i versity of Ca l i f o rnia, Da v i s

Edgar J. Schoen, M.D.Kaiser Pe rmanente Medical Ce n t e r

Pa t rick J. Shea, Ph . D .Un i versity of Ne b raska, Li n c o l n

Sidney Shindell, M.D., LL.B.Medical College of Wi s c o n s i n

Sarah Sh o rt, Ph.D., Ed.D., R.D.Sy racuse Un i ve r s i t y

A. J. Si e d l e r, Ph . D .Un i versity of Il l i n o i s

S. Fred Si n g e r, Ph . D .Science & En v i ronmental Policy Pro j e c t

Ro b e rt B. Sk l a roff, M.D.Elkins Pa rk, PA

Ga ry C. Smith, Ph . D .C o l o rado State Un i ve r s i t y

My ron Solberg, Ph . D .Cook College, Rutgers Un i ve r s i t y

Roy F. Spalding, Ph . D .Un i versity of Ne b ra s k a

L e o n a rd T. Sp e r ry, M.D., Ph . D .Medical College of Wi s c o n s i n

Ro b e rt A. Sq u i re, D.V.M., Ph . D .Johns Hopkins Un i ve r s i t y

Ronald T. Stanko, M.D.Un i versity of Pi t t s b u r g h

James H. Steele, D.V.M., M.P. H .Un i versity of Te x a s

Ro b e rt D. Steele, Ph . D .Pe n n s y l vania State Un i ve r s i t y

Judith S. St e rn, Sc.D.Un i versity of Ca l i f o rnia, Da v i s

C. Joseph St e t l e r, Esq.Bethesda, MD

Ma rtha Ba rnes Stone, Ph . D .C o l o rado State Un i ve r s i t y

Glenn Swogger Jr., M.D.Topeka, KS

Sita R. Tatini, Ph.D. Un i versity of Mi n n e s o t a

Ma rk C. Ta y l o r, M.D.Physicians for a Sm o k e - Free Ca n a d a

St e ve L. Ta y l o r, Ph . D .Un i versity of Ne b ra s k a

Murray M. Tu c k e rman, Ph . D .Winchendon Springs, MA

Joe B. Tye, M.S., M.B.A.Pa ra d ox 21

Va r ro E. Ty l e r, Ph.D., Sc.D.Pu rdue Un i ve r s i t y

Ro b e rt P. Up c h u rch, Ph.D. Un i versity of Ar i zo n a

Ma rk J. Utell, M.D.U. of Rochester Medical Ce n t e r

Shashi B. Ve rma, Ph . D .U. of Ne b raska, Li n c o l n

Wi l l a rd J. Visek, Ph.D., M.D.Un i versity of Il l i n o i s

W. F. Wa rd owski, Ph.D. Un i versity of Fl o r i d a

Miles We i n b e r g e r, M.D. Un i versity of Iowa Hospitals and Clinics

St e ven D. We x n e r, M.D.C l e veland Clinic, FL

Joel E. White, M.D.Me t rohealth Medical Ce n t e r

Ca rol Whitlock, Ph.D., R.D.Rochester Inst. of Te c h n o l o gy

C h ristopher F. Wilkinson, Ph.D. Jellinek, Schwartz & Connolly, In c .

Carl K. Wi n t e r, Ph . D .Un i versity of Ca l i f o rnia, Da v i s

James J. Wo rman, Ph . D .Rochester Institute of Te c h n o l o gy

James Ha rvey Young, Ph . D .Em o ry Un i ve r s i t y

Panayiotis Michael Za vos, Ph.D. Un i versity of Kentucky

Ek h a rd E. Zi e g l e r, M.D.Un i versity of Iow a