reducing cancer risk pcp_report_08!09!508

8/9/2019 Reducing Cancer Risk Pcp_report_08!09!508

http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 1/2402008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

2008–2009 Annual Report i President’s Cancer Panel

REDUCINGENVIRONMENTAL

CANCER RISKWhat We Can Do Now

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of HealthNational Cancer Institute



T e President’s Cancer Panel

LaSalle D. Leffall, Jr., M.D., F.A.C.S., Chair Charles R. Drew Professor of SurgerHoward Universit College of MedicineWashington, DC 20059

Margaret L. Kripke, P .D.Vivian L. Smith Chair and Professor EmeritaThe Universit of TexasM.D. Anderson Cancer CenterHouston, TX 77030

This report is submitted to the President of the United States

in ful llment of the obligations of the President’s Cancer Panelto appraise the National Cancer Program as established inaccordance with the National Cancer Act of 1971 (P.L. 92-218), theHealth Research Extension Act of 1987 (P.L. 99-158), the National

Institutes of Health Revitali ation Act of 1993 (P.L. 103-43), andTitle V, Part A, Public Health Service Act (42 U.S.C. 281 et seq. ).

April 2010For further information on the President’s Cancer Panel

or additional copies of this report, please contact:

Abb B. Sandler, Ph.D.Executive Secretar

President’s Cancer Panel

6116 Executive BoulevardSuite 220, MSC 8349

Bethesda, MD 20814-8349301-451-9399

pcp-r @mail.nih.gov http://pcp.cancer.gov

mailto:[email protected]



http://pcp.cancer.gov/

http://pcp.cancer.gov/



http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 3/240

2008–2009 Annual Report i President’s Cancer Panel

REDUCINGENVIRONMENTAL

CANCER RISKWhat We Can Do Now

Suzanne H. Reubenfor

The President’s Cancer Panel

April 2010

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

National Cancer Institute



The PresidentThe White HouseWashington, DC 20500

Dear Mr. President:

Though overall cancer incidence and mortality have continued to decline in recent years, the

disease continues to devastate the lives of far too many Americans. In 2009 alone, approximately1.5 million American men, women, and children were diagnosed with cancer, and 562,000 diedfrom the disease. With the growing body of evidence linking environmental exposures to cancer,the public is becoming increasingly aware of the unacceptable burden of cancer resulting fromenvironmental and occupational exposures that could have been prevented through appropriatenational action. The Administration’s commitment to the cancer community and recent focuson critically needed reform of the Toxic Substances Control Act is praiseworthy. However, ourNation still has much work ahead to identify the many existing but unrecognized environmentalcarcinogens and eliminate those that are known from our workplaces, schools, and homes.

To jumpstart this national effort, the President’s Cancer Panel (the Panel) dedicated its2008–2009 activities to examining the impact of environmental factors on cancer risk. ThePanel considered industrial, occupational, and agricultural exposures as well as exposuresrelated to medical practice, military activities, modern lifestyles, and natural sources. Inaddition, key regulatory, political, industrial, and cultural barriers to understanding and reducingenvironmental and occupational carcinogenic exposures were identi ed. The attached reportpresents the Panel’s recommendations to mitigate or eliminate these barriers.

The Panel was particularly concerned to nd that the true burden of environmentally inducedcancer has been grossly underestimated. With nearly 80,000 chemicals on the market in theUnited States, many of which are used by millions of Americans in their daily lives and areun- or understudied and largely unregulated, exposure to potential environmental carcinogens iswidespread. One such ubiquitous chemical, bisphenol A (BPA), is still found in many consumerproducts and remains unregulated in the United States, despite the growing link between BPAand several diseases, including various cancers.

While BPA has received considerable media coverage, the public remains unaware of manycommon environmental carcinogens such as naturally occurring radon and manufacturingand combustion by-products such as formaldehyde and benzene. Most also are unaware thatchildren are far more vulnerable to environmental toxins and radiation than adults. Efforts toinform the public of such harmful exposures and how to prevent them must be increased. Alllevels of government, from federal to local, must work to protect every American from needlessdisease through rigorous regulation of environmental pollutants.

Environmental exposures that increase the national cancer burden do not represent a new frontin the ongoing war on cancer. However, the grievous harm from this group of carcinogens hasnot been addressed adequately by the National Cancer Program. The American people—evenbefore they are born—are bombarded continually with myriad combinations of these dangerousexposures. The Panel urges you most strongly to use the power of your of ce to remove thecarcinogens and other toxins from our food, water, and air that needlessly increase health carecosts, cripple our Nation’s productivity, and devastate American lives.

Sincerely,

LaSalle D. Leffall, Jr., M.D., F.A.C.S.Chair

Margaret L. Kripke, Ph.D.



Executive Summary i

Preface

PART 1Overview 1

PART 2Sources and Types of Environmental Contaminants 25

Chapter 1 Exposure to Contaminants from Industrial and Manufacturing Sources 29

Chapter 2 Exposure to Contaminants from Agricultural Sources 43

Chapter 3 Environmental Exposures Related to Modern Lifest les 51

Chapter 4 Exposure to Ha ards from Medical Sources 63

Chapter 5 Exposure to Contaminants and Other Ha ards from Militar Sources 77

Chapter 6 Exposure to Environmental Ha ards from Natural Sources 89

PART 3

Taking Action to Reduce Environmental Cancer Risk:What We Can Do 95

Conclusions 97

Polic , Research, and Program Recommendations 103

What Individuals Can Do: Recommendations 111

References 115

AppendicesAppendix A President’s Cancer Panel Meetings:

Environmental Factors in Cancer—Participants A-1

Appendix B Recommendations of NIOSH Expert Panel for ImprovingOccupational Cancer Research Methods A-5

Appendix C Selected International, U.S., and European Carcinogen Classi cation S stems A-9

Appendix D Selected Federal Laws Related to Environmental Ha ards A-17

Appendix E Federal Agencies Involved in Environmental Regulation or Research A-31

Appendix F Summar of Environmental and Occupational Links with Cancer A-37

Appendix G Electromagnetic Energ —Overview A-47

Appendix H Electromagnetic Energ Units of Measure A-51

Appendix I Research Recommended b PCP Meeting Participants A-53

T A B L

E O F C O N

T E N T S



Environmental Cancer ResearchResearch on environmental causes ofcancer has been limited by low priorityand inadequate funding. As a result, thecadre of environmental oncologists isrelatively small, and both the consequencesof cumulative lifetime exposure to knowncarcinogens and the interaction of speci cenvironmental contaminants remain largelyunstudied. There is a lack of emphasis onenvironmental research as a route to primarycancer prevention, particularly comparedwith research emphases on genetic andmolecular mechanisms in cancer.

Environmental ExposureMeasurement, Methodologic,Assessment, and Classi cationIssuesEfforts to identify, quantify, and controlenvironmental exposures that raise cancerrisk, including both single agents andcombinations of exposures, have beencomplicated by the use of different measures,exposure limits, assessment processes, andclassi cation structures across agencies

in the U.S. and among nations. In addition,efforts have been compromised by a lackof effective measurement methods andtools; delay in adopting available newertechnologies; inadequate computationalmodels; and weak, awed, or uncorroboratedstudies.

Some scientists maintain that current toxicitytesting and exposure limit-setting methodsfail to accurately represent the nature ofhuman exposure to potentially harmful

chemicals. Current toxicity testing reliesheavily on animal studies that utilize dosessubstantially higher than those likely to be

encountered by humans. These data—andthe exposure limits extrapolated from them—fail to take into account harmful effects thatmay occur only at very low doses. Further,chemicals typically are administered whenlaboratory animals are in their adolescence,a methodology that fails to assess the impactof in utero , childhood, and lifelong exposures.In addition, agents are tested singly ratherthan in combination.

Regulation of EnvironmentalContaminantsThe prevailing regulatory approach in theUnited States is reactionary rather thanprecautionary. That is, instead of taking

preventive action when uncertainty existsabout the potential harm a chemical orother environmental contaminant maycause, a hazard must be incontrovertiblydemonstrated before action to ameliorate itis initiated. Moreover, instead of requiringindustry or other proponents of speci cchemicals, devices, or activities to provetheir safety, the public bears the burden ofproving that a given environmental exposureis harmful. Only a few hundred of themore than 80,000 chemicals in use in theUnited States have been tested for safety.

U.S. regulation of environmentalcontaminants is rendered ineffective by vemajor problems: (1) inadequate fundingand insuf cient staf ng, (2) fragmented andoverlapping authorities coupled with unevenand decentralized enforcement, (3) excessiveregulatory complexity, (4) weak laws andregulations, and (5) undue industry in uence.Too often, these factors, either singly or in

combination, result in agency dysfunctionand a lack of will to identify and removehazards.



Sources and Types ofEnvironmental ContaminantsThe line between occupational andenvironmental contaminants is ne and

often dif cult to demarcate. Many knownor suspected carcinogens rst identi edthrough studies of industrial and agriculturaloccupational exposures have sincefound their way into soil, air, water, andnumerous consumer products. People fromdisadvantaged populations are more likelyto be employed in occupations with higherlevels of exposure (e.g., mining, construction,manufacturing, agriculture, certain servicesector occupations) and to live in more highlycontaminated communities. The reality ofthis unequal burden is not just a health issue,but an issue of environmental justice.

While all Americans now carry manyforeign chemicals in their bodies, womenoften have higher levels of many toxic andhormone-disrupting substances than domen. Some of these chemicals have beenfound in maternal blood, placental tissue,and breast milk samples from pregnantwomen and mothers who recently gavebirth. Thus, chemical contaminants arebeing passed on to the next generation, bothprenatally and during breastfeeding. Somechemicals indirectly increase cancer riskby contributing to immune and endocrinedysfunction that can in uence the effect ofcarcinogens.

Children of all ages are considerably morevulnerable than adults to increased cancerrisk and other adverse effects from virtuallyall harmful environmental exposures. In

addition, some toxics have adverse effectsnot only on those exposed directly (includingin utero ), but on the offspring of exposedindividuals.

Exposure to Contaminants fromIndustrial and ManufacturingSourcesManufacturing and other industrial productsand processes are responsible for a greatmany of the hazardous occupational andenvironmental exposures experienced byAmericans. Many of these contaminants—even substances banned more than 30 yearsago—remain ubiquitous in the environmentbecause they break down very slowly, if atall. Other industrial chemicals or processeshave hazardous by-products or metabolites.Numerous chemicals used in manufacturingremain in or on the product as residues,while others are integral components of

the products themselves. Further, in theongoing quest for more effective and ef cientways of making industrial and consumerproducts, new chemicals and othersubstances are being created continuallyand existing substances are being put tonew uses. Limited research to date onunintended health effects of nanomaterials,for example, suggests that unanticipatedenvironmental hazards may emerge from thepush for progress.

Exposure to Contaminants fromAgricultural SourcesThe entire U.S. population is exposed ona daily basis to numerous agriculturalchemicals, some of which also are used inresidential and commercial landscaping.Many of these chemicals have known orsuspected carcinogenic or endocrine-disrupting properties. Pesticides(insecticides, herbicides, and fungicides)approved for use by the U.S. EnvironmentalProtection Agency (EPA) contain nearly900 active ingredients, many of which aretoxic. Many of the solvents, llers, and other


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 12/240v 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

chemicals listed as inert ingredients onpesticide labels also are toxic, but are notrequired to be tested for their potential tocause chronic diseases such as cancer. Inaddition to pesticides, agricultural fertilizersand veterinary pharmaceuticals are majorcontributors to water pollution, both directlyand as a result of chemical processesthat form toxic by-products when thesesubstances enter the water supply. Farmersand their families, including migrantworkers, are at highest risk from agriculturalexposures. Because agricultural chemicalsoften are applied as mixtures, it has beendif cult to clearly distinguish cancer risksassociated with individual agents.

Environmental Exposures Relatedto Modern Lifest lesConveniences of modern life—automobileand airplane travel, dry cleaning, potabletap water, electricity, and cellularcommunications, to name a few—have madedaily life easier for virtually all Americans.Some of these conveniences, however,have come at a considerable price to theenvironment and human health, and the truehealth impact of others is uncon rmed. Forexample, mobile source air emissions (e.g.,from cars, trucks, other passenger vehicles,ships), especially diesel particulate pollution,are responsible for approximately 30 percentof cancer resulting from air pollution.Disinfection of public water supplies hasdramatically reduced the incidence ofwaterborne illnesses and related mortalityin the United States, but research indicatesthat long-term exposure to disinfectionby-products such as trihalomethanes may

increase cancer risk. Chemicals usedfor household pest control can become acomponent of carpet dust, posing a risk tochildren when they play on the oor.

Sharp controversy exists in the scienti ccommunity as to possible adverse healtheffects from exposure to low frequencyelectromagnetic energy. The use of cellphones and other wireless technologyis of great concern, particularly sincethese devices are being used regularly byever larger and younger segments of thepopulation. At this time, there is no evidenceto support a link between cell phone use andcancer. However, the research on cancerand other disease risk among long-termand heavy users of contemporary wirelessdevices is extremely limited. Similarly,current and potential harms from extremelylow frequency radiation are unclear andrequire further study. In addition, ultraviolet

radiation from excess sun exposureand tanning devices has been proven tosubstantially increase skin cancer risk.

Exposure to Ha ards fromMedical SourcesIn the past two decades, improvedimaging technologies, nuclear medicineexaminations, and new pharmaceuticalinterventions have made possible signi cantstrides in our ability to diagnose and treathuman disease, including cancer. It isbecoming increasingly clear, however, thatsome of these same technologies and drugsthat have contributed so greatly to healthstatus and longevity also carry risks.

While ionizing radiation exposures fromradon, occupational, and other sources haveremained essentially stable over the past30 years, Americans now are estimated toreceive nearly half of their total radiation

exposure from medical imaging and othermedical sources, compared with only15 percent in the early 1980s. The increasein medical radiation has nearly doubled thetotal average effective radiation dose per



individual in the United States. Computedtomography (CT) and nuclear medicinetests alone now contribute 36 percent of thetotal radiation exposure and 75 percent ofthe medical radiation exposure of the U.S.population. Medical imaging of children isof special concern; compared with adults,children have many more years of life duringwhich a malignancy initiated by medicalradiation can develop. Many referringphysicians, radiology professionals, and thepublic are unaware of the radiation doseassociated with various tests or the totalradiation dose and related increased cancerrisk individuals may accumulate over alifetime. People who receive multiple scansor other tests that require radiation may

accumulate doses equal to or exceeding thatof Hiroshima atomic bomb survivors. It isbelieved that a single large dose of ionizingradiation and numerous low doses equal tothe single large dose have much the sameeffect on the body over time.

Moreover, radiation dose for the sametest can vary dramatically depending onthe equipment used, technologist skill,application of dose-reduction strategies, andpatient size, age, and gender. Licensure of

imaging and radiation therapy technologistsvaries depending on the type of testperformed by the technologist. Some stateshave only partial regulation; six states andthe District of Columbia have no licensure orregulatory provisions of any kind.

In addition, pharmaceuticals have becomea considerable source of environmentalcontamination. Drugs of all types enterthe water supply when they are excreted orimproperly disposed of; the health impact oflong-term exposure to varying mixtures ofthese compounds is unknown.

Exposure to Contaminantsand Other Ha ards fromMilitar SourcesThe military is a major source of toxicoccupational and environmental exposuresthat can increase cancer risk. Information isavailable about some military activities thathave directly or indirectly exposed militaryand civilian personnel to carcinogens andcontaminated soil and water in numerouslocations in the United States and abroad.However, we may never know the full extentof environmental contamination frommilitary sources. Nearly 900 Superfund sitesare abandoned military facilities or facilitiesthat produced materials and products for or

otherwise supported military needs. Someof these sites and the areas surroundingthem became heavily contaminated due toimproper storage and disposal of known orsuspected carcinogens including solvents,machining oils, metalworking uids, andmetals. In some cases, these contaminantshave spread far beyond their points of originbecause they have been transported by windcurrents or have leached into drinking watersupplies.

Hundreds of thousands of military personneland civilians in the United States receivedsigni cant radiation doses as a result of theirparticipation in nuclear weapons testingand supporting occupations and industries,including nuclear fuel and weaponsproduction, and uranium mining, milling,and ore transport. Hundreds of thousandsmore were irradiated at levels suf cient tocause cancer and other diseases. Thesepopulations include the families of military

and civilian workers, and people—knownas “downwinders”—living or working incommunities surrounding or downstreamfrom testing and related activities, and in


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 14/240i 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

relatively distant areas to which nuclearfallout or other radioactive material spread.Federal responses to the plight of affectedindividuals have been unsatisfactory. Thoseaffected lack knowledge about the extent oftheir exposure or potential health problemsthey may face. Similarly, most health careproviders are not aware of cancer and otherlatent radiation effects and therefore areunlikely to adequately monitor patients forthese health conditions. Exposure to ionizingradiation related to nuclear weapons testingis an underappreciated issue worldwide.

Exposure to EnvironmentalHa ards from Natural Sources

Most environmental hazards with thepotential to raise cancer risk are the productof human activity, but some environmentalcarcinogens come from natural sources. Forexample, radon gas, which forms naturallyfrom the breakdown of uranium mineraldeposits, is the second leading cause oflung cancer in the United States and theleading cause of lung cancer among peoplewho have never smoked. Radon-inducedlung cancer is responsible for an estimatedaverage of 21,000 deaths annually. Peoplewho smoke and also are exposed to radonhave a higher risk of lung cancer than fromeither exposure alone.

Although human activities such as mining,ore processing, use of arsenic-containingpesticides, and burning of fossil fuels aremajor contributors to waterborne arsenic inthe U.S., most inorganic arsenic in drinkingwater is from natural sources. Inorganicarsenic in drinking water has been linked

to skin, lung, bladder, and kidney cancerin both sexes and with prostate cancer inmen, as well as numerous non-cancerousconditions including endocrine, reproductive,and developmental effects.

Reducing EnvironmentalCancer Risk: A Call to ActionThe burgeoning number and complexityof known or suspected environmental

carcinogens compel us to act to protectpublic health, even though we may lackirrefutable proof of harm. Action is possibleat several levels: conducting scienti cresearch to enhance our understandingand by extension, our ability to prevent andrespond to environmental carcinogens;enforcing existing policies and regulationsthat protect workers and the public;implementing policy and regulatory changesthat support public health and reduce theburden of cancer; and taking personal action.

The Panel concludes that:

We Need to Determine theFull Extent of EnvironmentalIn uences on Cancer.At this time, we do not know how muchenvironmental exposures in uence cancerrisk and related immune and endocrinedysfunction. Environmental contaminationvaries greatly by type and magnitudeacross the nation, and the lifetime effectsof exposure to combinations of chemicalsand other agents are largely unstudied.Similarly, the cancer impact of exposuresduring key “windows of vulnerability” suchas the prenatal period, early life, and pubertyare not well understood. Nonetheless, whilethese diverse effects often are dif cult toquantify with existing technologies andresearch methods, in a great many instances,we know enough to act.



The Nation Needs aComprehensive, Cohesive PolicAgenda Regarding EnvironmentalContaminants and Protection ofHuman Health.Environmental health, including cancerrisk, has been largely excluded from overallnational policy on protecting and improvingthe health of Americans. It is more effectiveto prevent disease than to treat it, but cancerprevention efforts have focused narrowlyon smoking, other lifestyle behaviors, andchemopreventive interventions. Scienti cevidence on individual and multipleenvironmental exposure effects on diseaseinitiation and outcomes, and consequenthealth system and societal costs, are notbeing adequately integrated into nationalpolicy decisions and strategies for diseaseprevention, health care access, and healthsystem reform.

Children Are at Special Risk forCancer Due to EnvironmentalContaminants and Should BeProtected.Opportunities for eliminating or minimizingcancer-causing and cancer-promotingenvironmental exposures must be actedupon to protect all Americans, but especiallychildren. They are at special risk due totheir smaller body mass and rapid physicaldevelopment, both of which magnifytheir vulnerability to known or suspectedcarcinogens, including radiation. Numerousenvironmental contaminants can cross theplacental barrier; to a disturbing extent,

babies are born “pre-polluted.” Childrenalso can be harmed by genetic or otherdamage resulting from environmentalexposures sustained by the mother (and insome cases, the father). There is a criticallack of knowledge and appreciation ofenvironmental threats to children’s health

and a severe shortage of researchers andclinicians trained in children’s environmentalhealth.

Continued Epidemiologic

and Other EnvironmentalCancer Research Is Needed.Available evidence on the level of potentialharm and increased cancer risk from manyenvironmental exposures is insuf cientor equivocal. The Panel is particularlyconcerned that the impact, mechanisms ofaction, and potential interactions of someknown and suspected carcinogens are poorlyde ned.

Meaningful measurement and assessmentof the cancer risk associated with manyenvironmental exposures are hamperedby a lack of accurate measurement toolsand methodologies. This is particularlytrue regarding cumulative exposure tospeci c established or possible carcinogens,gene-environment interactions, emergingtechnologies, and the effects of multipleagent exposures. Single-agent toxicitytesting and reliance on animal testingare inadequate to address the backlog ofuntested chemicals already in use and theplethora of new chemicals introduced everyyear. Some high-throughput screening (HTS)technologies are available to enable testingof many chemicals and other contaminantssimultaneously, but many remain to bedeveloped to meet chemical testing needs.Support also is needed to develop methodsfor interpreting the wealth of data thatHTS technologies generate. At this time,incentives to encourage development of this

research are nearly non-existent.

Support for large, longitudinal studiesto clarify the nature and magnitude ofcancer risk attributable to environmentalcontaminants must continue. The capacityto collect biologic samples at the inception


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 16/240iii 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

of studies is essential; even if currenttechnologies do not allow these samplesto be fully utilized at this time, it must beassumed that such technologies will evolveand enable use of collected biosamplesto provide essential study baseline data.Personal health data privacy issues thatcurrently limit research access to data andbiosamples will need to be addressed.

Cancer risk assessment also is hamperedby lack of access to existing exposuredata, especially for occupational/industrialexposures, and regarding levels of radon,asbestos, and other contaminants in schoolsand day care centers.

An Environmental HealthParadigm for Long-LatencDisease Is Needed.Recognizing that results of laboratoryand animal studies do not always predicthuman responses, an environmental healthparadigm for long-latency diseases isneeded to enable regulatory action basedon compelling animal and in vitro evidencebefore cause and effect in humans has beenproven.

Existing Regulations forEnvironmental ContaminantsNeed to Be Enforced and Updated;Stronger Regulation Is Needed.Weak laws and regulations, inef cientenforcement, regulatory complexity, andfragmented authority allow avoidableexposures to known or suspected cancer-

causing and cancer-promoting agents tocontinue and proliferate in the workplaceand the community. Existing regulations,and the exposure assessments on whichthey are based, are outdated in most cases,

and many known or suspected carcinogensare completely unregulated. Enforcement ofmost existing regulations is poor. In virtuallyall cases, regulations fail to take multipleexposures and exposure interactionsinto account. In addition, regulations forworkplace environments are focused moreon safety than on health.

Industry has exploited regulatoryweaknesses, such as government’sreactionary (rather than precautionary)approach to regulation. Likewise, industryhas exploited government’s use of anoutdated methodology for assessing

“attributable fractions” of the cancer burdendue to speci c environmental exposures.This methodology has been used effectivelyby industry to justify introducing untestedchemicals into the environment.

Radiation Exposure from MedicalSources Is Underappreciated.The use of radiation-emitting medical testsis growing rapidly. Efforts are needed toeliminate unnecessary testing and improveboth equipment capability and operatorskill to ensure that radiation doses areas low as reasonably achievable withoutsacri cing image or test data quality. Atleast one initiative is underway to improveand disseminate radiation reductionstrategies and educate physicians, devicemanufacturers, their training staff, andothers about radiation doses associatedwith speci c tests. No mechanism currentlyexists to enable individuals to estimate theirpersonal cumulative radiation exposure,which would help patients and physicians

weigh the bene ts and potential harm ofcontemplated imaging and nuclear medicinetests.



Medical Professionals Needto Consider Occupational andEnvironmental Factors WhenDiagnosing Patient Illness.

Physicians and other medical professionalsask infrequently about patient workplace andhome environments when taking a medicalhistory. Such information can be invaluablein discovering underlying causes of disease.Moreover, gathering this information wouldcontribute substantially to the body ofknowledge on environmental cancer risk.

Workers, Other Populationswith Known Exposures, and the

General Public Require FullDisclosure of Knowledge aboutEnvironmental Cancer Risks.Individuals and communities are notbeing provided all available informationabout environmental exposures they haveexperienced, the cumulative effects of suchexposures, and how to minimize harmfulexposures. The disproportionate burden ofexposure to known or suspected carcinogensexperienced by speci c populations (e.g.,agricultural and chemical workers andtheir families, radiation-exposed groupssuch as uranium mine workers, nuclearindustry workers, nuclear test site workersand “downwinders,” residents of cancer “hotspots” or other contaminated areas) has notbeen fully acknowledged.

The Militar Needs to AggressivelAddress the Toxic Environmental

Exposures It Has Caused.Toxic materials produced for and used by themilitary have caused widespread air, soil,and water pollution across the United Statesand beyond our borders, including chemical

and radiation contamination in and aroundcurrent and former military installations,materiel production facilities, and mines.These contaminants, many of which mayhave serious long-term and latent effectsincluding cancer, are a danger both tomilitary personnel and civilians. Overall,the military has not responded adequatelyto health problems associated with itsoperations absent substantial pressurefrom those affected, advocacy groups, orthe media. Of special concern, the U.S. hasnot met its obligation to provide for ongoinghealth needs of the people of the Republic ofthe Marshall Islands resulting from radiationexposures they received during U.S. nuclearweapons testing in the Paci c from 1946–

1958.

Safer Alternatives to ManCurrentl Used ChemicalsAre Urgentl Needed.The requisite knowledge and technologiesexist to develop alternatives to manycurrently used chemical agents known orbelieved to cause or promote cancer. Manychemists require additional training to

understand environmental hazards andreformulate products. Importantly, “greenchemistry” alternative products themselvesrequire longitudinal study to ensure that theydo not pose unexpected health hazards.

The Panel believes that just as thereare many opportunities for harmfulenvironmental exposures, ampleopportunities also exist to intervene in,ameliorate, and prevent environmentalhealth hazards. Governments, industry,

the academic and medical communities,and individuals all have untapped powerto protect the health of current and futuregenerations of Americans and reduce thenational burden of cancer.


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 20/240ii 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

RECOMMENDATIONRESPONSIbLE AGENCIES,

STAKEhOLDERS, ANDOThER ENTITIES*

2. A thorough new assessment of workplace chemicaland other exposures is needed to quantify currenthealth risks. Previous estimates of occupationalcancer risk are outdated and should no longer be usedby government or industry.

Congress

National Academy of Science/Institute of MedicineNational Science Foundation (NSF)

General Accountability Of ceOther multidisciplinary groupappointed for this taskHHS/National Institute forOccupational Safety and Health(NIOSH)DOL:

OSHA•Mine Safety and Health•

Administration (MSHA)

3. In large measure, adequate environmental healthregulatory agencies and infrastructures alreadyexist, but agencies responsible for promulgatingand enforcing regulations related to environmentalexposures are failing to carry out their responsibilities.The following are needed:

A more integrated, coordinated, and transparent•system for promulgating and enforcingenvironmental contaminant policy and regulations,driven by science and free of political or industryin uence, must be developed to protect public

health.

EPAHHS/FDA

USDADOL:

OSHA•MSHA•

Better concordance of exposure measures and•standards is needed to facilitate interagency andinternational regulatory policy and enforcement andto identify research needs.

HHS/National Institute ofEnvironmental Health Services(NIEHS)EPADOL/OSHA

The United States should carefully consider the•potential impact on consumers and commerce ofthe Globally Harmonized System for classifyingcarcinogens.

President/AdministrationCongress





Information sharing among the public, researchers,•regulatory agencies, industry, and otherstakeholders must be a bedrock component of theenvironmental health regulatory system mission.

EPA

DOL:OSHA•MSHA•

HHS:FDA•Center for Disease Control and•Prevention (CDC)

USDADepartment of Defense (DoD)

Department of Energy (DOE)Environmental and cancer researchcommunities

IndustryMedia

Environmental and public health advocates should•be included in developing the environmental cancerresearch and policy agendas and in informationdissemination.

Advocates

EPAHHS:

FDA•CDC•

DOE

4. Epidemiologic and hazard assessment researchmust be continued and strengthened in areas in

which the evidence is unclear, especially researchon workplace exposures, the impact of in utero andchildhood exposures, and exposures that appear tohave multigenerational effects. Current funding forfederally supported occupational and environmentalepidemiologic cancer research is inadequate.

CongressEPA

HHS:National Cancer Institute (NCI)•NIEHS•National Institute for Child Health•and Human DevelopmentNIOSH•

EPANSF

Nongovernmental research funders


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 22/240iv 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL



5. Measurement tool development and exposureassessment research, including the developmentof new research models and endpoints, shouldbe accelerated to enable better quanti cation ofexposures at individual, occupational, and populationlevels.

High-throughput screening technologies and•related data interpretation models should bedeveloped and used to evaluate multiple exposuressimultaneously. It may be possible to screenapparently similar suspect chemicals together andregulate these as a group as indicated by ndings.

HHSNIEHS•NIOSH•

NSFDoD/Applied Research ProjectsAgencyIndustry

Methods for long-term monitoring and• quanti cation of electromagnetic energy exposuresrelated to cell phones and wireless technologies areurgently needed given the escalating use of thesedevices by larger and younger segments of thepopulation and the higher radiofrequencies newerdevices produce.

DOEHHS/NIOSH

EPANational Council on RadiationProtection and Measurements(NCRP)

6. The cancer risk attributable to residential radonexposure has been clearly demonstrated and must bebetter addressed. The following are needed:

The Environmental Protection Agency (EPA) should•consider lowering its current action level (4 pCi/L)

for radon exposure, taking into account data onradon-related cancer risk developed since theexisting action level was established.

EPA

Public and health care provider education should•be developed and broadly disseminated to raiseawareness of radon-related cancer risk.

HHS

Health care provider professionalorganizationsMedia

Improved testing methods for residential radon•exposure and better methods for assessingcumulative exposure should be developed. Taxdeductions or other incentives should beimplemented to encourage radon mitigation

retro tting of existing housing. Building codechanges should be made to require radon reductionventing in new construction.

Industry

CongressInternal Revenue Service

State and local governments

All schools, day care centers, and workplaces•should be tested at regular intervals for radon.Radon level data must be made available to thepublic. Buildings found to have levels in excess ofthe EPA action level should be mitigated.






7. Actions must be taken to minimize radiation exposurefrom medical sources. Speci cally:

Health care providers, radiology technicians, and•the public must be informed about the extentof radiation exposure from commonly usedimaging and nuclear medicine examinations andthe potential health risks of these procedures.Referring physicians are responsible for discussingwith the patient the balance of bene t and riskassociated with each imaging or nuclear medicineprocedure being recommended. An educational/decision-making tool that considers each patient’scumulative lifetime radiation exposure shouldbe developed to facilitate these provider-patientcommunications.

Physicians and other health careprovidersHealth professional organizationsAdvocates

MediaHHS:

Agency for Healthcare Research•and QualityNCI•

The estimated effective radiation dose of all imaging•and nuclear medicine tests performed should be arequired element in patient records and should bea core data element in all electronic health recordssystems. In addition, patients should be assistedto reconstruct an estimate of the total medicalradiation dose they have received.

Joint Commission for Accreditation ofHealthcare Organizations (JCAHO)

HHS:FDA•Centers for Medicare and•Medicaid Services (CMS)CDC•Health Resources and Services•Administration (HRSA)Indian Health Service (IHS)•Of ce of the National Coordinator•for Health Information Technology(ONCHIT)

Department of Veterans Affairs (VA)DoD

Physicians and other health careproviders

Radiation dose-lowering techniques must be•implemented consistently and to the maximumextent feasible.


Inspection of radiation-emitting medical equipment•and pharmaceuticals must become more stringent,and uniform credentialing of technicians whoadminister scans is needed.

JCAHO

Radiation technologist professionalorganizations

HHS/FDA


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 24/240vi 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL



8. The unequal burden of exposure to known andsuspected carcinogens must be addressed.

Individuals exposed to nuclear fallout and other•nuclear contamination by biologically importantradionuclides must be provided all availableinformation on these exposures. A system mustbe developed to enable affected individuals toreconstruct and add radiation doses received sothat they can adequately assess their cumulativeexposure and potential health risks, includingcancer.

DoDDOE

Nuclear Regulatory CommissionHHS/NCIVA

NCRP

The Advisory Committee on Energy-related•Epidemiologic Research (ACERER) should berechartered, or a similar body convened, to enableindividuals exposed to nuclear testing fallout andother nuclear exposures to participate in policymaking and other decisions that will affect theiraccess to health care and compensation related tothose exposures.

DOE

Geographic areas and vulnerable populations•(including but not limited to children, migrant andother farm workers, and residents of high-povertyareas and cancer "hot spots") should be studiedto determine environmental in uences on cancerrisk; identi ed risks must be remediated to themaximum extent possible.

EPA

HHS/NIEHSDoD

USDA

The U.S. Government should honor and make•payments according to the judgment of theMarshall Islands Tribunal.

President/Administration

Congress





9. Physicians and other medical personnel shouldroutinely query patients about their previous andcurrent workplace and home environments as partof the standard medical history. This information willincrease the likelihood that environmental factors incancer and other illnesses are considered and willstrengthen the body of information on environmentalexposures and disease. Data on workplace and homeenvironmental history should be incorporated intoexisting and developing automated medical recordssystems.


HHS:ONCHIT•NCI: Surveillance, Epidemiology,•and End Results ProgramCDC: National Program of Cancer•RegistriesCMS•HRSA•IHS•

DoD: TRICARE

VA: Veterans Health InformationSystem and Technology Architecture

Private insurer patient databases

10. “Green chemistry” initiatives and research, includingprocess redesign, should be pursued and supportedmore aggressively, but new products must be well-studied prior to and following their introduction intothe environment and stringently regulated to ensuretheir short- and long-term safety.

HHS/NIEHSEPA

NSF

11. Public health messages should be developed anddisseminated to raise awareness of environmentalcancer risks and encourage people to reduce oreliminate exposures whenever possible.

HHS:FDA•CDC•HRSA•

CMS•USDADOE

Federal CommunicationsCommissionAdvocates

Media

* The Panel recognizes that entities other than those listed may have a vital role or interest in implementation of the recommendations.


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 26/240viii 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL



What Individuals Can Do:RecommendationsMuch remains to be learned about the effects of environmental exposures on cancer risk.Based on what is known, however, there is much that government and industry can do now toaddress environmental cancer risk. The Panel’s recommendations in this regard are detailedabove. At the same time, individuals can take important steps in their own lives to reducetheir exposure to environmental elements that increase risk for cancer and other diseases.And collectively, individual small actions can drastically reduce the number and levels ofenvironmental contaminants.

ChILDREN

1. It is vitally important to recognize that children are far more susceptible to damage fromenvironmental carcinogens and endocrine-disrupting compounds than adults. To the extentpossible, parents and child care providers should choose foods, house and garden products,play spaces, toys, medicines, and medical tests that will minimize children’s exposure to toxics.Ideally, both mothers and fathers should avoid exposure to endocrine-disrupting chemicals andknown or suspected carcinogens prior to a child’s conception and throughout pregnancy andearly life, when risk of damage is greatest.

ChEMICAL ExPOSURES

2. Individuals and families have many opportunities to reduce or eliminate chemical exposures. Forexample:

Family exposure to numerous occupational chemicals can be reduced by removing shoes•

before entering the home and washing work clothes separately from the other family laundry.Filtering home tap or well water can decrease exposure to numerous known or suspected•carcinogens and endocrine-disrupting chemicals. Unless the home water source is knownto be contaminated, it is preferable to use ltered tap water instead of commercially bottledwater.

Storing and carrying water in stainless steel, glass, or BPA- and phthalate-free containers•will reduce exposure to endocrine-disrupting and other chemicals that may leach into waterfrom plastics. This action also will decrease the need for plastic bottles, the manufactureof which produces toxic by-products, and reduce the need to dispose of and recycle plasticbottles. Similarly, microwaving food and beverages in ceramic or glass instead of plasticcontainers will reduce exposure to endocrine-disrupting chemicals that may leach into foodwhen containers are heated.


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 28/240x 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

Exposure to pesticides can be decreased by choosing, to the extent possible, food grown•without pesticides or chemical fertilizers and washing conventionally grown produce toremove residues. Similarly, exposure to antibiotics, growth hormones, and toxic run-offfrom livestock feed lots can be minimized by eating free-range meat raised without thesemedications if it is available. Avoiding or minimizing consumption of processed, charred, andwell-done meats will reduce exposure to carcinogenic heterocyclic amines and polyaromatic

hydrocarbons.Individuals can consult information sources such as the Household Products Database to help•them make informed decisions about the products they buy and use.

Properly disposing of pharmaceuticals, household chemicals, paints, and other materials will•minimize drinking water and soil contamination. Individuals also can choose products madewith non-toxic substances or environmentally safe chemicals. Similarly, reducing or ceasinglandscaping pesticide and fertilizer use will help keep these chemicals from contaminatingdrinking water supplies.

Turning off lights and electrical devices when not in use reduces exposure to petroleum•combustion by-products because doing so reduces the need for electricity, much of which isgenerated using fossil fuels. Driving a fuel-ef cient car, biking or walking when possible, orusing public transportation also cuts the amount of toxic auto exhaust in the air.

Individuals can reduce or eliminate exposure to secondhand tobacco smoke in the home, auto,•and public places. Most counseling and medications to help smokers quit are covered byhealth insurance or available at little or no cost.

RADIATION

3. Adults and children can reduce their exposure to electromagnetic energy by wearing a headsetwhen using a cell phone, texting instead of calling, and keeping calls brief.

4. It is advisable to periodically check home radon levels. Home buyers should conduct a radon testin any home they are considering purchasing.

5. To reduce exposure to radiation from medical sources, patients should discuss with their healthcare providers the need for medical tests or procedures that involve radiation exposure. Keyconsiderations include personal history of radiation exposure, the expected bene t of the test,and alternative ways of obtaining the same information. In addition, to help limit cumulativemedical radiation exposure, individuals can create a record of all imaging or nuclear medicinetests received and, if known, the estimated radiation dose for each test.

6. Adults and children can avoid overexposure to ultraviolet light by wearing protective clothing andsunscreens when outdoors and avoiding exposure when the sunlight is most intense.

SELF-ADVOCACY

7. Each person can become an active voice in his or her community. To a greater extent than manyrealize, individuals have the power to affect public policy by letting policymakers know thatthey strongly support environmental cancer research and measures that will reduce or removefrom the environment toxics that are known or suspected carcinogens or endocrine-disruptingchemicals. Individuals also can in uence industry by selecting non-toxic products and, wherethese do not exist, communicating with manufacturers and trade organizations about their desirefor safer products.


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 30/240xii 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 32/240xiv 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

The Panel received testimony from 45 experts from academia, government, industry, and theenvironmental and cancer advocacy communities, as well as from the public.

This report begins with an overview of the estimated cancer burden due to environmentalexposures, biologic mechanisms that may be responsible for the effects of exposure to

environmental contaminants, environmental cancer research and hazard assessment issues,and the current regulatory environment. Though not intended to be a complete evaluation ofall sources and types of environmental contaminants, subsequent chapters describe the majorsources of these contaminants and the known or suspected in uence of selected substanceson cancer risk. The Panel’s conclusions, based on the testimony received and additionalinformation gathered prior to and after the meetings, are followed by recommendations forassessing and mitigating cancer risk due to environmental factors. Appendices include aroster of meeting participants and other supplemental information.


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 33/2402008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 34/240xvi 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL



P A R T1

OverviewDespite modest overall decreases in cancer incidence and mortality, cancer continues

to devastate—and in far too many cases end—the lives of Americans. In 2009, nearly1.5 million new cases of cancer are expected to be diagnosed in the United States, andan estimated 562,000 Americans will die from this disease. 1 Approximately 41 percentof people in the U.S. will be diagnosed with cancer at some point in their lives, and about21 percent of Americans will die from cancer. 2

Apart from the incalculable suffering and personal loss cancer causes patients and theirfamilies, cancer also exacts a heavy economic toll on the nation. The National Institutesof Health (NIH) estimates that in 2009, cancer cost the nation $243.4 billion—$99 billionfor direct medical costs, $19.6 billion for indirect morbidity costs (cost of lost productivitydue to illness), and $124.8 billion for indirect mortality costs (cost of lost productivity dueto premature death). 3

The paragraphs below brie y describe our current understanding of environmentallyinduced cancer, biologic mechanisms by which environmental contaminants mayincrease cancer risk, environmental cancer research investments and needs, and keyissues regarding the regulation of environmental pollutants.

Estimated In uence of EnvironmentalFactors on Cancer in t e United StatesThough many important insights have yet to be achieved, we now understand betterthan ever before how human cancers develop, grow, and spread. Single-gene inheritedcancer syndromes are believed to account for less than 5 percent of malignancies in theUnited States. 4 An unknown percentage of cancers develop due to normal endogenous(internal) processes. For example, cellular detoxi cation processes can produce oxygenradicals that damage DNA. Aging cells tend to make more errors in DNA replicationthan younger cells, and some DNA copying errors are inevitable due to the sheer volumeof replication that occurs every day.

Other cancers develop as a result of exogenous (outside of the body) factors, some ofwhich are controllable. It is not known exactly what percentage of all cancers either areinitiated or promoted by an environmental trigger. Some exposures to an environmental



hazard occur as a single acute episode, butmost often, individual or multiple harmfulexposures take place over a period of weeks,months, years, or a lifetime. However,susceptibility to cancers resulting fromenvironmental exposures may be inheritedif a parent is exposed to a carcinogen thatcauses germ cell genetic changes, whichsubsequently are passed on to a child. 5

The widely quoted estimates of avoidablecancer deaths due to environmental factorsdeveloped by Doll and Peto in 1981 6 (andestimated in similar later studies using thesame methodology 7,8) are woefully out ofdate, given our current understanding ofcancer initiation as a complex multifactorial,multistage process. 9 Subsequent to the1981 publication, Sir Richard Doll recognized

methodologic problems underlying theestimated fractions of the total cancerburden attributable to discrete, yet oftencomplex factors (e.g., diet). Estimates of

“attributable fractions” of the cancer burdendue to occupation (approximately 4 percent),pollution (2 percent), industrial products(<1 percent), and medicines and medicalprocedures (1 percent) are now believedto underestimate signi cantly the true tollof cancer related to these exposures. Dolland Peto relied primarily on epidemiologicstudies of workers in large industries andfailed to include minorities, deaths amongpersons aged 65 and older, exposures insmaller workplaces, and the effects ofindirect contact with carcinogens.

The greatest shortcoming of the Doll andPeto estimates, however, is that calculationof attributable fractions does not fullyaccount for the fact that environmental

contaminants interact with each other andthat all avoidable causes of cancer are notknown. Since the Doll and Peto estimateswere published, environmental exposureshave become more diverse and numerous.Perhaps most importantly, the impact ofvarious exposures, whether individual,simultaneous, sequential, or cumulativeover a lifetime, may not be simply additive.Instead, combinations of exposures may havesynergistic effects that intensify or otherwisealter their impact compared with the effectof each contaminant alone. 10,11 In addition,we now recognize that critical periods oftime exist across the life span (e.g., prenataland early life, puberty) when individuals areparticularly susceptible to damage from

environmental contaminants. Moreover, aperson’s genetic make-up can signi cantlyaffect his or her susceptibility to the harmfuleffects of an environmental agent, and it alsois becoming clear that some exposures canhave effects across multiple generations.

…genes and environment interact in ways t at are socomple t at it’s really not wort arguing in my mind

a out ow muc plays w at role ecause... we cannotc ange our ancestors. So a rational place to egin a

program of cancer prevention [is]... wit t e environment,and lifestyle is wound up in t e environment.

SANDRA STEINGRABERITHACA COLLEGE

Known or SuspectedMec anisms y W icEnvironmental Factors

May Increase Cancer RiskExposure to environmental contaminants canresult in harm to health because they mayalter or interfere with a variety of biologicprocesses:

Hormone Production and FunctionMany substances affect the production andfunction of hormones, which are crucialto normal growth and development, andto the maintenance of numerous biologicprocesses. For example, some syntheticchemicals and natural compounds act asweak estrogens in the human body. Amongother effects, these substances appear to becontributing to earlier puberty and, therefore,to a longer period of estrogen exposure inwomen. Longer lifetime estrogen exposureis linked to higher risk of hormone-dependent cancers. 12 Male hormone



function also can be affected by thesecompounds. Known as endocrine-disruptingchemicals (EDCs), these substances typicallyare not listed as carcinogens by regulatoryagencies, but the body of evidence linkingEDCs to breast and other cancers isgrowing.13–15

In ammationThe importance of in ammation as acontributor to or cause of numerousdiseases (e.g., cardiovascular, certaindigestive system diseases) is becomingincreasingly understood. For example, ithas long been known that the in ammationof lung tissue, caused by inhaling asbestos

bers, tobacco smoke, or ne particles in theair from diesel engine exhaust and industrialsources, is a major factor in lung and otherrespiratory tract cancers. 16

DNA DamageSome environmental exposures, particularlyradiation, can damage DNA. Errorscommonly occur when DNA is copiedduring cell division, but the cell has built-inmechanisms for identifying such errors andrepairing them. If the damage is irreparable,the cell typically self-destructs. However,exposure to environmental carcinogens canresult in more frequent DNA replicationerrors and can damage the cell’s abilityto identify and repair faulty DNA. Thisdamaged DNA can result in gene mutationsthat permit or promote cancer developmentand can, in some cases, be passed on tosubsequent generations.

Gene Suppression orOverexpressionGenes direct the initiation, moderation, orcessation of biologic processes, includingcell growth and normal cell death.Numerous external in uences, includingenvironmental contaminants, can interferewith these processes by altering DNAstructure without changing the underlying

DNA sequences. Alterations such as these,referred to as epigenetic changes, canhave signi cant effects on gene behavior. 17 Epigenetic changes may suppress geneexpression (function) or cause geneoverexpression. For instance, gene productsthat suppress tumor growth may not beproduced, allowing individual tumor cells inthe body to grow out of control, leading tocancer.

In addition, epigenetic inheritance 18 canoccur, in which the behavior of genes inoffspring is affected by the life experience(including exposure to environmentalcontaminants) of the parents. For example,from 1938 to 1971, thousands of pregnantwomen were prescribed diethylstilbestrol(DES), a drug intended to preventmiscarriage. 19 Some daughters born tothese women (referred to as DES Daughters)

have reproductive system malformationsand have been predisposed to a rare type ofvaginal and cervical cancer. 20 In some cases,epigenetic changes also may be passed on tofuture generations; 18 limited data 21,22 suggestthat DES Granddaughters may have anincreased risk for ovarian cancer.

Environmental contaminants can damageimmune system and other types of cellsso that they cannot function normallyto maintain and protect the body. Cellsinteract continually with those around them,receiving and sending biochemical andbioelectric signals that maintain normalbiologic functions and equilibrium. 23 Ifthese signaling processes are alteredor interrupted, the intracellular and/orintercellular (micro) environments maychange such that tumor cells are able toproliferate. These problems may result fromepigenetic changes.

...low levels of e posure at a speci c point in t edevelopment of an organism… could ave really,really signi cant c anges in ways t at t e classicalidea a out genetics would not predict.

WILLIAM CHAMEIDESDUKE UNIVERSITy



Figure 1 SEER Delay-Adjusted Incidence and U.S. MortalityAll C ild ood Cancers, Under 20 Years of Age

bot Se es, All Races, 1975–2006

0

5

10

15

20

Source: SEER 9 areas and U.S. Mortality Files, National Center for Health Statistics, Centers for Disease Control and Prevention. Rates are age-adjusted tothe 2000 U.S. Std Population (19 age groups—Census P25-1103).

Regression lines are calculated using the Joinpoint Regression Program Version 3.3.1, April 2008, National Cancer Institute.

Delay-adjusted incidence is an algorithm used to estimate incidence if it were unaffected by reporting delays.

…epidemiology in t e conte t of environmentalepidemiology and occupational epidemiology,

ut particularly environmental epidemiology, is avery lunt tool. It’s an area w ere we need a ne

scalpel ut we ave just t is jack ammer.

LyNN KATz CHERRyINDIANA TOXIC ACTION

T e Special Vulnera ilitiesof C ildrenInfants, children, and adolescents comprise40 percent of the world’s population. 24 Incrucial respects (e.g., ability to control theirenvironment, ability to care for and defendthemselves), they are the most vulnerablegroup. Mortality from childhood cancers has

dropped dramatically since 1975 due to vastlyimproved treatments that have resulted from

high levels of participation by children incancer treatment clinical trials. Yet over thesame period (1975–2006), cancer incidencein U.S. children under 20 years of age hasincreased (Figure 1).

The causes of this increase are not known,but as a meeting presenter emphasized,the changes have been too rapid to be ofgenetic origin. Nor can these increases beexplained by the advent of better diagnostictechniques such as computed tomography(CT) and magnetic resonance imaging (MRI).Increased incidence due to better diagnosismight be expected to cause a one-timespike in rates, but not the steady increasesthat have occurred in these cancers overa 30-year span. The extent to whichenvironmental exposures are responsible forthis trend remains to be determined.



Children are exposed to toxic andcarcinogenic chemicals and radiationthrough the air they breathe, the food andwater they consume, medications they aregiven, and the environment in which theylive, including their homes, schools, daycare centers, and even the motor vehiclesin which they ride. 25 Pound for pound,children take in more food, water, air, andother environmental substances than adults.Children also can be exposed to toxinsin utero via placental transfer and/or afterbirth via breast milk. Tests of umbilical cordblood26 found traces of nearly 300 pollutantsin newborns’ bodies, such as chemicals usedin fast-food packaging, ame retardantspresent in household dust, and pesticides.

An analysis by the National Academy ofSciences 27 found that children are particularlyvulnerable to environmental contaminantsfor several reasons. Due to their smallersize, children’s exposures to toxics aredisproportionately large compared withadults. Because their metabolic pathwaysare immature (particularly during fetaldevelopment and in the rst months afterbirth), they are slower to metabolize, detoxify,and excrete many environmental chemicals.

As a result, toxins remain active in theirbodies for a longer period of time than wouldbe the case in adults. In addition, childrenhave lower levels of some chemical-bindingproteins, allowing more of a toxic agent toreach various organs, and their blood-brainbarrier is more porous than that of adults,allowing greater chemical exposures tothe developing brain. Children’s bodiesalso are less able to repair damage due totoxic exposures, and the complex processesthat take place during the rapid growthand development of children’s nervous,respiratory, immune, reproductive, and otherorgan systems are easily disrupted.

Children have many more years of life aheadof them than do adults—more time in whichto be exposed to environmental toxics andtime to develop diseases (including cancer)with long latency periods initiated by earlyexposures. At this time, little is known about

interactions among multiple exposures overtime, but many exposures to environmentalcontaminants are cumulative and some mayhave intergenerational effects.

EnvironmentalCancer ResearcResearch on environmental causes ofcancer has been limited by low priorityand inadequate funding. As a result, thecadre of environmental oncologists isrelatively small, and the consequencesof cumulative lifetime exposure to knowncarcinogens and the interaction of speci cenvironmental contaminants remain largely

unstudied. There is a lack of emphasis onenvironmental research as a route to primarycancer prevention, particularly comparedwith research emphases on genetic andmolecular mechanisms in cancer. At theNational Cancer Institute (NCI), the FiscalYear (FY) 2008 budget for occupationaland environmental carcinogenesis andenvironmental epidemiology (intramural andextramural combined) comprised no morethan 14 percent of NCI’s nearly $4.83 billionbudget. 28

Unfortunately, w ile udgets ave wa ed andwaned on t e federal level, a consistent nding,I would say, is t at occupational and environmentale posures ave een under addressed.

ELIzABETH FONTHAMLOUISIANA STATE UNIVERSITy

At the National Institute for EnvironmentalHealth Sciences (NIEHS), funding forcancer-related environmental research hasremained at since FY 1999 at approximately28 percent of total appropriations,excluding funding related to Superfundsites. Superfund is the Federal governmentprogram to identify and clean up the nation’sworst uncontrolled hazardous wastesites. 29 NIEHS receives funding speci callyto conduct research on health effects ofhazardous substances that aids in Superfundassessment and clean-up decisions. 30



Studying t ese comple [gene-environmentinteractions] takes large multicenter studies t atare costly and t ey need to e a national priority.

We need to etter study t ese relations ips so t atwe can come up wit etter prevention efforts.

JOHN VENAUNIVERSITy OF GEORGIA

NIEHS and NCI recently published a Requestfor Applications for the Breast Cancer andthe Environment Research Program tosupport parallel ongoing investigations andnew laboratory and epidemiologic studies ofenvironmental in uences during windows ofsusceptibility on breast cancer risk. 31

Table 1

T e 12 Principles ofGreen C emistry

Prevent waste that requires•treatment or clean-up.Design chemicals and products to•be fully effective but have little orno toxicity.Develop less hazardous ways to•synthesize chemicals.

Use renewable raw materials.•Use catalysts to make chemicals•instead of reagents that createmore waste.

Avoid chemical derivatives.•Reduce wasted atoms.•

Avoid using solvents whenever•possible or use innocuous solvents.

Increase energy ef ciency by running•chemical reactions at ambienttemperatures.

Design chemicals to break down• after use.Monitor for by-products in real time.•Minimize the potential for chemical•accidents.

Sources: U.S. Environmental Protection Agency. Twelveprinciples of green chemistry [Internet]. [cited 2010 Mar 12]Available from: http://www.epa.gov/greenchemistry/pubs/principles.html. Adapted from: Anastas P, Warner J. Greenchemistry: theory and p ractice. New York: Oxford UniversityPress; 1998.

Some additional funding for environmentalcarcinogenesis research is available outsideof the Federal government. For example,in FY 2007–2008, American Cancer Societyfunding for environmental carcinogenesistotaled nearly $3.8 million. 32

To address the many gaps in knowledgeabout the relationship between variousenvironmental contaminants and humancancer, it has been suggested that academiccenters for environmental oncology researchand policy be established. 33 These cross-disciplinary centers would focus moreattention and resources on primary cancerprevention, bringing basic (includinggenomic, proteomic, metabolomic, and otherbiomarker research) and epidemiologicsciences to bear to identify underlyingcauses of cancer incidence and progressionas they relate to environmental stimuli.These centers also could develop bettermeasurement tools and interventions toimprove cancer prevention and developpolicy recommendations based on research

ndings. Moreover, greater priority andimproved funding for environmental cancerresearch could be expected to attract youngresearchers to this eld.

Green ChemistrSpeakers emphasized the need for “greenchemistry” research to identify alternativeways of obtaining desired social goodwithout contaminating the environment,including accelerating initiatives to developenvironmentally safe substitutes for harmfulchemicals and manufacturing processes.The principles of green chemistry werede ned more than a decade ago (see Table 1).

Due to growing public concern about thebioaccumulation of environmental chemicals(also re ected in retailers’ new interestin environmentally safer products), somecompanies are devoting more resources todeveloping non-toxic alternatives to existingproducts. 34,35 However, many chemists lacktraining in understanding environmental



hazards and how to develop saferalternatives; they also face industry barriersto change. 35

Research support for green chemistryis limited. At the Federal level, theEnvironmental Protection Agency (EPA)sponsors some green chemistry researchthrough grants and fellowships, the SmallBusiness Innovation Research program,and sustainable technologies research at itsNational Center for Environmental Research.EPA also has a program of awards torecognize companies and individuals forinnovative green chemistry technologies.The National Science Foundation (NSF)supports a Science and Technology Centerfor Environmentally Responsible Solventsand Processes, based at the University ofNorth Carolina-Chapel Hill. 36 Its missionis to support multidisciplinary fundamentalresearch to identify and enable sustainableprocesses and products using carbondioxide-related technology. In addition toresearch, the Center supports educationaland information exchange initiatives.Some NSF green research is conducted jointly with EPA.37

Green chemistry initiatives are gainingmomentum at the state level. For example,Michigan enacted the Michigan GreenChemistry Directive 38 in 2006 to supportresearch and development for non-toxicchemicals and encourage the use ofchemical products and technologies thatreduce or eliminate hazardous substancesduring their design, manufacture, and use.Among other activities, the initiative alsosupports expanded education and training ingreen chemistry for chemists and chemicalengineers in the state, including throughindustry partnerships.

A 2008 report39 by the CaliforniaEnvironmental Protection Agency (Cal/EPA) outlines a plan to give consumers,manufacturers, and retailers new ways toassess the dangers of common chemicalsthat people use every day. Manufacturers

and suppliers would be required to discloseall of the chemicals in products sold in thestate; the data would be published in anonline database. A companion databasewould contain all known information onchemical hazards, enabling consumers todetermine whether to expose themselvesor their families to speci c products.This proposed initiative is similar to theHousehold Products Database maintainedby the National Library of Medicine at

NIH.40 Other recommendations in the Cal/EPA report call for developing educationalprograms to encourage green chemistryinnovation and requiring manufacturersto nd ways to make things more safelyand with little or no waste that requiresenvironmental clean-up.

…a simple way of t inking a out moving to a ealt yand sustaina le world is t at it re uires greenenergy and green c emistry and green products.

MICHAEL LERNERCOMMONWEAL

Environmental E posureMeasurement, Met odologic,Assessment, andClassi cation IssuesAffecting Researcand RegulationEfforts to identify and control environmentalexposures that raise cancer risk, includingboth single agents and combinations ofexposures, have been complicated andcompromised by the use of differentmeasures, standards, assessmentprocesses, and classi cation schemesacross agencies in the U.S. and amongnations; a lack of effective measurementmethods and tools; delay in adopting newertechnologies; inadequate computationalmodels; and weak, awed, or uncorroboratedstudies.



Reference DoseStandards (exposure limits) are establishedbased on the estimated effect of a toxic agenton a person with speci ed characteristics.This benchmark dosage is known as thereference dose. The traditional approachto determining the reference dose is basedon the assumption that “the dose makesthe poison.” 41 To nd the reference dose,several different dosages of a substanceare tested on laboratory animals. Startingat the highest dose, the toxicologistcontinues to lower doses until effects areno longer detectable (i.e., the dose at whichexperimental animals no longer differ fromcontrols). This dose, called the “no observedadverse effect level” (NOAEL), is consideredthe highest dose that poses an acceptablerisk. The NOAEL is then adjusted for aseries of safety factors to determine the

nal reference dose. Once the NOAEL isestablished for a substance, testing at lowerdoses is seldom conducted, and very low-dose effects are unlikely to be detected.

A key underpinning of realistic referencedose establishment is appropriate

characterization of the population to whichthe reference dose applies. For example,reference doses for radiation exposures havelong been based on their assessed impacton a “Reference Man” 42—a hypotheticalmale, 5’7” tall, weighing 157 pounds, whois “Western European or North American inhabitat and custom.” This standard humanwas created by the International Commissionon Radiological Protection (ICRP) in 1975.Such an individual is representative of onlya very small percentage of the current andfuture populations of the United States.Reference Man certainly is of questionablerelevance to women (who are now knownto face a risk approximately 50 percenthigher than Reference Man from the same

radiation dose43,44

), to people who are not“Western European or North Americanin habitat and custom,” and those whoare substantially smaller or larger thanReference Man. In particular, this standarddoes not address growing concern aboutradiation exposures experienced in utero and by infants and children. Because oftheir smaller body mass, thinner bones,and rapid physical development, the effectof radiation exposures that may not harm



adults may be ampli ed several-fold to alevel that increases cancer risk in children.EPA maintains that it moved away from usingReference Man as a basis for estimatingradiation doses around 1990, but neitherEPA nor the Nuclear Regulatory Commissionhas yet established new parameters morere ective of the population. 45

Diversit in U.S. ToxicantStandardsThe U.S. does not use most of theinternational measures, standards, orclassi cation structures for environmentaltoxins that have broad acceptance in mostother countries. Instead, U.S. agencies have

developed their own metrics and systemsfor quantifying environmental exposures,with standards that often are less stringentthan international equivalents. With aglobal scienti c community, multinationalemployers, and a worldwide marketplace,these differences increase the dif culty ofcomparing research ndings and conductinginternational commerce.

In addition, more than one U.S. agency maybe responsible for measuring and settingexposure limits for the same environmentaltoxics and may do so using differingmetrics. For example, both EPA and theU.S. Geological Survey (USGS) measurecontaminants in drinking water; EPAdetermines Maximum Contaminant Levels,or MCLs, while USGS assigns Health-BasedScreening Levels (HBSLs). 46

Professional groups also may developmetrics and standards. In some instances,these privately developed standards arebased on data more current than thatused by government agencies. Public andprivate organizations may elect to adoptthe privately generated standards ratherthan those developed by government.Occupational Exposure Limits (OELs)that apply to U.S. workers exemplify thissituation. Several organizations are involvedin protecting worker health, each setting a

different type of OEL with a distinct methodand purpose. The primary organizationsinvolved in OEL-setting are the AmericanConference of Governmental IndustrialHygienists (ACGIH), the Occupational Safetyand Health Administration (OSHA), and theNational Institute for Occupational Safetyand Health (NIOSH). ACGIH is a non-governmental organization of industrialhygiene professionals 47 that sets ThresholdLimit Values (TLVs), which are levels that willproduce no adverse health effect in nearlyall workers with repeated daily exposure.ACGIH also establishes Biological ExposureIndices (BEIs) that set maximum levelsof chemical concentrations in biologicaltissues and uids. TLVs and BEIs are health

guidelines based on ACGIH committee reviewof recent scienti c literature. TLVs andBEIs do not consider economic or technicalfeasibility issues associated with meeting thestandards and do not have the force of law. 48

…OShA standards are feasi ility standards.T ey are not pu lic ealt standards.

JEANNE MAGER STELLMANSUNy-DOWNSTATE MEDICAL CENTER

Both NIOSH and OSHA were establishedin 1970 by the Occupational Safety andHealth (OSH) Act (P.L. 91-596). They havea shared mission to “assure safe andhealthful working conditions for workingmen and women.” 49,50 NIOSH, part of theU.S. Department of Health and HumanServices (DHHS), is a research agencycharged to generate new knowledge inoccupational health and safety. NIOSHdevelops Recommended Exposure Limits(RELs) that do not have the force of law, butare considered by OSHA as it establishesPermissible Exposure Limits (PELs) fortoxic substances. 49 OSHA, part of the U.S.Department of Labor, is a regulatory agencywith the power to set standards and conductworkplace inspections. 50 OSHA PELs areinformed by health sciences, but compliancemust be economically and technologicallyfeasible. 51 When OSHA was established, it


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 44/2400 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

adopted the ACGIH TLVs from 1968 as PELs.Less than two dozen of these PELs havebeen updated since that time. 52 NIOSH RELswere last updated in 2005.

We need researc met ods development.We need it in epidemiology as well as in t e

la oratory, and t at needs to e funded...


In addition to granting OSHA authority toestablish PELs, the OSH Act provided amechanism for unions to petition OSHA topromulgate rulemaking on harmful workerexposures. 50 In 1973, the Oil, Chemical,

and Atomic Workers Union, in conjunctionwith the Public Citizen Health ResearchGroup, petitioned OSHA for an emergencytemporary standard on certain wellestablished carcinogens. 53 In response,OSHA developed the 13 CarcinogensStandard that did not lower exposure limits,but added requirements for increasedworker safety controls in workplaces wherethe 13 chemicals are used. 54

Despite the stricter nature of TLVs and their

lack of legal authority, they have becomethe accepted standard of the industrialhygiene industry. Many large corporations,all branches of the U.S. military, and manyother nations use the most recent ACGIHTLVs as OEL benchmarks. 55

Research Methodolog and DataCollection IssuesIn addition to measurement andstandard-setting issues, environmentaland occupational cancer researchand assessment have suffered frommethodologic and data collectionweaknesses. For example, an importantweakness of occupational cancer researchto date has been the failure to adequatelyinclude women’s exposures in traditionaland unpaid labor settings or their growingparticipation in the paid workforce. 56 In

addition, information on occupationalhistory and work and home environmentsis not collected routinely as part of themedical history by primary care and mostother medical professionals. 57 These datahave the potential to improve diagnosisand treatment, and would capture crucialinformation researchers need to studythe impact of environmental exposuresover time. Dif culties in obtaining healthdepartment records or other data also havebeen barriers to population-based state orregional studies of exposures. 58

In an effort to expand the robustness andaccessibility of environmental health data,EPA launched the National EnvironmentalPublic Health Tracking Network 59 in 2009.The network is intended to build on CDC’sexisting state-based tracking systemto create a system of integrated health,exposure, and hazard data and otherinformation from a variety of national, state,and city sources. Data are being collectedon a variety of health conditions includingcancer, and the database will includeinformation on home environments, outdoorair, and water. It will be possible to generatemaps, charts, and tables on data subsets of

interest to governments, researchers, andthe public.

In 1996, NIOSH convened a group ofexperts from academia, business,labor, and government to identify thegaps in occupational cancer researchmethods. 60 The group’s recommendationsfor strengthening research methods,which became part of NIOSH’s NationalOccupational Research Agenda, focusedon four broad areas: identi cation ofoccupational carcinogens, design ofepidemiologic studies, risk assessment,and primary and secondary prevention (seeAppendix B).

The prospective National Children’s Study(NCS)61 is intended to address many ofthe weaknesses of environmental cancerresearch to date. Though it was authorizedunder the Children’s Health Act of 2000, 62



recruitment for the study did not beginuntil January 2009. Administered by theEunice Kennedy Shriver National Instituteof Child Health and Human Development(NICHD), the NCS will follow more than100,000 children, representative of all babiesborn in the U.S., from conception to age21 years. During that time, environmentalexposures will be assessed through multipleevaluations of the external environmentand through measurements of biomarkersat predetermined intervals throughoutpregnancy and childhood. A geneticevaluation of each child will provideinformation on individual susceptibilities.To increase the power of the study to detectenvironmental causes of childhood cancer,

NICHD will collaborate with the InternationalChildhood Cancer Cohort Consortium. 63 The Consortium is comprised of researchersconducting 11 infant/child cohort studieson four continents. The studies togetherrepresent approximately 700,000 children.

Toxicit Testing MethodsCurrent toxicity testing relies heavily onanimal studies. One speaker at the Panel’smeetings stated that a shortcoming of mostanimal toxicity testing is that chemicals areadministered to experimental animals intheir adolescence; they later are sacri ced

at a point in life corresponding to a humanage of 60–65 years. This approach failsto capture the impacts of early exposuresand misses the late effects of suchexposures. 64 Lifetime toxicity studies providean alternative approach to better answerquestions about early exposures and latenteffects. Chemicals are administered toanimals in utero or shortly after birth,

and the animals are followed over theirentire natural life span. Some lifetimetoxicity studies 65 are being done and aredemonstrating that early exposures aresigni cantly more likely to cause cancerthan similar exposures in adult life. Thesestudies have strong potential for improvingunderstanding and prevention of childhoodcancer and may provide insight into adultcancers related to early exposures.

We need ways to carry out surveillance to watc forsurprises and pro a ly as we look to t e future and t inka out new co orts we need to t ink a out ow to do t emef ciently; for e ample, using administrative data ases.

JONATHAN SAMETUNIVERSITy OF SOUTHERN CALIFORNIA

Our science looks at a su stance- y-su stancee posure and doesn’t take into account t e multitudeof e posures we e perience in daily life. If we did,it mig t c ange our risk paradigm. T e potentialrisks associated wit e tremely low-level e posuremay e underestimated or missed entirely.

HEATHER LOGANCANADIAN CANCER SOCIETy

However, a majority of scientists in theelds of risk assessment and toxicology

acknowledge that long-term, high-doseexposure regimens typically used foranimal models yield results that may notbe applicable to typical human exposures. 66 The need to nd better and faster waysof characterizing the possible toxicity ofchemicals and other potentially harmfulsubstances is widely recognized. In addition,the cost and ethical considerations of animaltesting increasingly are being questioned.



health. However, these agencies cannotdevelop or enforce regulations. Studiesof environmental exposures and relatedguidelines also come from academic andother independent research funded byfoundations, advocacy organizations, andother non-governmental entities.

Similarly, several international agenciesstudy and provide guidance for policydevelopment on environmental cancerissues. The World Health Organization(WHO) reviews existing evidence andtakes positions or develops guidelines ona wide range of health issues, includingenvironmentally induced cancer. TheInternational Atomic Energy Agency (IAEA)73 assesses radiation safety issues andprovides expertise on radiation medicine andtechnologies, including patient protectionfrom excess radiation. Among otheractivities, ICRP74 develops reference dosedata and recommendations for protectionagainst excess exposure to ionizing radiation.WHO, IAEA, and ICRP are not regulatorybodies, but their assessments and guidanceare used by regulators and the scienti ccommunity worldwide.

Like IAEA and ICRP, the InternationalAgency for Research on Cancer (IARC),75 anagency of WHO, is not a regulatory body. Theagency coordinates and conducts researchon the causes of human cancer and themechanisms of carcinogenesis, and developsstrategies for cancer prevention and control.IARC’s monographs on carcinogenesis,considered the “gold standard” in evaluatingevidence on cancer causation, are usedby countries around the world. To guideits assessment and classi cation ofpotential carcinogens, IARC de ned criteria(summarized in Table 2) for con rming orrefuting whether exposure to a speci cchemical, radiation source, or other agentcauses cancer. 76

Classi cation of Potential Carcinogens

Several U.S., European, and internationalsystems exist for classifying the carcinogenic

potential of speci c environmental and

workplace exposures. Table 3 arrays theclassi cation schemes adopted by selectedagencies. Though other classi cationschema exist, the table illustrates thediversity in how potential carcinogens areevaluated and classi ed. The terminologyused by these various agencies in somecases is nearly identical, but the evidencerequired to assign a chemical or otheragent to a particular category may differsubstantially (see Appendix C for detailedde nitions and evidence requirements).Thus, a toxic may be judged clearlycarcinogenic to humans under oneclassi cation system, while another mayclassify the same substance a probable orlikely carcinogen. Or, a chemical may beassigned to similarly named categoriesunder two different systems (e.g., probablycarcinogenic/likely carcinogenic), butthe levels of evidence required for thatclassi cation may differ under each system.

Table 2

IARC Criteria for AssessingCancer Causation Due to

Environmental E posures

The link or association between the•exposure and cancer is strong.The risk of cancer increases with•more exposure to the agent.Multiple studies by different•investigators with different groups ofpeople yield the same nding.The exposure to the agent came•before the cancer.There is a plausible biological•explanation for how the agent wouldcause the cancer.The link is speci c, and the agent•causes a speci c type of cancer.

The link is consistent with what is•known from other studies.

Sources: International Agency for Research on Cancer.IARC monographs on the evaluation of carcinogenic risks tohumans—preamble. Lyon, France: IARC; 2006, and EmanuelEJ. Will your cell phone kill you? The New Republic. 2008April 9.



Table 3 Selected Carcinogen Classi cation Systems*

EUROPE INTERNATIONAL UNITED STATES

EU GhS** IARC ACGIh EPA NTP

Category 1 :Substancesknown to becarcinogenicto man

Category 1,

Subcategory1A: KnownHumanCarcinogen

Group 1 :Carcinogenicto Humans

A1: Con rmedHumanCarcinogen

Carcinogenicto Humans

Known toBe HumanCarcinogen

Category 2 :Substanceswhich shouldbe regardedas if they arecarcinogenicto man

Category 1,Subcategory1B: PresumedHumanCarcinogen

Group 2A:ProbablyCarcinogenicto Humans

A2: SuspectedHumanCarcinogen

Likely to BeCarcinogenicto Humans

ReasonablyAnticipatedto BeCarcinogenic

Category 3 :Substanceswhich causeconcern forman owingto possiblecarcinogeniceffects butin respectof which theavailableinformation isnot adequatefor making asatisfactoryassessment

Category 2 :SuspectedCarcinogen

Group 2B :PossiblyCarcinogenicto Humans

A3: AnimalCarcinogen

SuggestiveEvidence ofCarcinogenicPotential

Group 3 :NotClassi ableas toCarcinogenicityto Humans

A4: NotClassi edas a HumanCarcinogen

InadequateInformationto AssessCarcinogenicPotential

Group 4 :Probably NotCarcinogenicto Humans

A5: NotSuspectedas a HumanCarcinogen

Not Likelyto BeCarcinogenicto Humans

* Carcinogen categories are not equivalent across systems. See Appendix C for de nitions and evidence requirements.

** Under development.

EU–European Union; GHS–Globally Harmonized System; I ARC–International Agency for Research on Cancer; ACGIH–American College of GovernmentalIndustrial Hygienists; EPA–Environmental Protection Agency; NTP–National Toxicology Program

Sources:U.S. Department of Health and Human Services. Listing criteria. [Internet] National Toxicology Program [cited 2009 July 1] Available from:http://ntp.niehs.nih.gov/?objectid=47B37760-F1F6-975E-7C15022B9C93B5A6.

International Agency for Research on Cancer. Complete list of agents evaluated and their classi cation. [Internet; cited 2009 August 30] Available from:http://monographs.iarc.fr/ENG/Classi cation/index.php.

Duffus JH, Nordberg M, Templeton DM. IUPAC glossary of terms used in toxicology, second edition, annex II I: classi cation of carcinogenicity. Pure andApplied Chemistry. 2007;79(7):1153-1344.



These differences may lead to differentregulatory policies that may affect workerand public safety as well as internationalcommerce.

Considerable differences also exist in thenumber of agents that have been classi edusing each system, though in all cases thenumber is small compared to the tens ofthousands of chemicals and other potentiallyharmful substances in use. For example,the U.S. National Toxicology Program’s (NTP)most recent Report on Carcinogens 77 lists58 agents as known human carcinogens andclassi es another 188 agents as “reasonablyanticipated to be human carcinogens.” Asof April 2009, IARC had evaluated nearly950 agents; of these, 108 were classi ed ascarcinogenic to humans, 63 were identi edas probably carcinogenic to humans, and248 were deemed possibly carcinogenic tohumans. However, 515 agents could not beclassi ed as to their carcinogenicity due tolack of evidence or insuf cient high-qualityevidence. 78

An initiative is underway to address thesafety, health, and commercial problemscreated by multiple chemical classi cation

systems. Though substantially lessrobust than some existing classi cations(particularly IARC and ACGIH), a GloballyHarmonized System (GHS)79 is beingdeveloped under the leadership of theUnited Nations to standardize chemicalclassi cation, assessment processes, andlabeling worldwide. The goal is to provideuniform information and protection to thosewho would be exposed to a given chemicaland to facilitate trade. Companies wouldonly have to submit product informationfor classi cation once for all authoritiesthat implement GHS. Under GHS, theburden of proving chemical safety will beshifted to industry. Nations around theworld are in various stages of consideringor implementing GHS. In the U.S., EPA,the Consumer Product Safety Commission(CPSC), OSHA, and the Department ofTransportation have formed an interagencyworking group to coordinate U.S. government

participation in GHS activities. The StateDepartment and other agencies also will beinvolved as appropriate. It is likely to takeat least a few years before a substantialnumber of countries adopt GHS.

Comprehensive Assessment ofOccupational and EnvironmentalExposuresThe preceding sections have discussedassessment in the context of evaluatingevidence for the carcinogenicity of speci cagents or exposure settings. But exposureassessment also is needed more broadlyto evaluate cancer risk associated withworkplace or environmental exposures inthe aggregate. In the U.S., most availableexposure assessments are badly outdated.A comprehensive assessment of the extentof all workplace exposures, for example,has not been conducted since the awedDoll and Peto estimates published in 1981. 6 Although OSHA’s mission is to ensure thatworkplace environments are safe, it does notconduct a comprehensive national review ofcarcinogens in the workplace.

The newest EPA National Air ToxicsAssessment (NATA) is based on 2002 data. 80 The next NATA is scheduled to be released inlate 2009 or early 2010, but it will be basedon 2005 data. Moreover, EPA emphasizesthat NATA’s purpose is not to characterizerisks at a level suf cient to supportregulation. It is designed to help EPAand others identify pollutants and sourcecategories of greatest potential concern,and to set priorities for collecting additionalinformation to improve future assessments.

Environmental exposures can changemarkedly over a 5- to 10-year period dueto changes in agricultural practices, localindustrial growth (or shrinkage), shiftingpopulation densities, and other factors.Up-to-date exposure assessments arecrucial to set exposure limits and implementcorresponding regulatory amendments toprotect the health of workers and the public.



Regulation of EnvironmentalContaminantsThe number and prevalence of knownor suspected carcinogens is growing.

Many environmental contaminants aremanufactured synthetic chemicals; wasteand by-products of industrial processes;chemical fertilizers, pesticides, andother chemicals used in farming and forlandscaping; chemicals used in othercommercial activities; combustion by-products of petroleum-powered engines;water disinfection/chlorination by-products;and both man-made and natural sources ofradiation.

Rig t now, t e num ers for ow many workers aree posed to most of t e known carcinogens are 20 to 30

years old so we don’t really know w at t e contemporaryworkforce is e periencing in terms of e posure.

PAUL SCHULTENATIONAL INSTITUTE FOR OCCUPATIONAL SAFETy AND HEALTH

In the United States, about 42 billion poundsof chemicals are produced or importeddaily. Many of these chemicals are used inmassive quantities exceeding one milliontons per year. 81 Exposure limits have beenset for some of these substances, but thevast majority are unregulated. Of equalconcern, according to numerous speakersat the Panel’s meetings, many of the currentU.S. standards and related regulations forchemical and other exposures were set inthe 1950s, and few are stringently enforced.

Reactionar versus PrecautionarApproaches to RegulationEven where reference doses and exposurelimits have been established, a numberof environmental health scientists andadvocates believe that some exposurelevels deemed safe by regulators are in facttoo high. They maintain that exposuresfar below the reference dose are causingharm and in some cases, inducing cancer

development. Moreover, they believe thatsome agents cause harm at very low dosesthat is not manifested at higher doses andthat regulatory prudence is indicated untilpotential effects such as these are betterunderstood.

However, the prevailing regulatory approachin the United States is reactionary in that it:

Requires incontrovertible evidence of•harm before preventive action is taken.

Places the burden on the public to show•that a given chemical is harmful.

Does not consider potential health and•environmental impacts when designingnew technologies.

Discourages public participation in•decision making about the control ofhazards and the introduction of newtechnologies, chemicals, or otherexposures. 82

This reactionary approach typicallyengenders secondary prevention measures(e.g., screening, other methods for earlydetection of disease) once a health hazardhas become evident, rather than action toremove the hazard from the environment(primary prevention).



An alternative approach to regulationthat supports primary cancer and otherdisease prevention is precautionary. 83 In 1998, a conference of internationalenvironmental scientists, scholars,activists, treaty negotiators, and othersconvened to discuss implementation ofthe Precautionary Principle 84 asserted in aconsensus statement that “when an activityraises threats of harm to human health orthe environment, precautionary measuresshould be taken even if some cause andeffect relationships are not fully establishedscienti cally.”85 The core tenets of thePrecautionary Principle are:

Taking preventive action in the face of•uncertainty.

Shifting the burden of proof to proponents•of an activity.

Exploring a wide range of alternatives to•possibly harmful actions.

Including public participation in decision•making.

According to one speaker, precaution shouldbe a key component of a sound approachto managing and communicating risk and

uncertainty about risk, but should be appliedselectively. 86 Speci cally, when there is noevidence of risk, precaution is not warrantedand no action is needed. If con dence existsthat there is a hazard, prevention is calledfor, not precaution. However, when credibleevidence exists that there may be a hazard,a precautionary approach should be adoptedand alternatives should be sought to removethe potential hazard and still achieve thesame social bene t. Such an approachacknowledges the uncertainty of identifying

cancer risks in complex, poorly understoodenvironmental systems. The determinationof when suf cient evidence exists forpreventive action often depends on contextand the consequences of inaction or actingin error.

One author cautions that operationalizingthe precautionary principle using decisionmodels rather than intuitions or inclinations

can be challenging and has the potential tohave unintended consequences. 87 If decisioncriteria are not carefully selected, it mightbe decided to stop the use of a chemicalor technology that actually would not haveadverse effects, or conversely, allow the useof agents that will have negative effects onpeople or the environment. In either case,the monetary, health, and social costs andbene ts to consumers and producers may beincorrectly distributed.

…w en an activity raises t reats of arm to umanealt or t e environment, precautionary measures

s ould e taken even if some cause-and-effectrelations ips are not yet fully esta lis ed scienti cally…we don’t need to wait until every single scienti c

uestion as een answered efore we take action.HEATHER LOGANCANADIAN CANCER SOCIETy

Those who support a precautionary approachto the regulation of environmental agentsemphasize that while at a speci c point intime average individual risk from exposureto one or more carcinogens may be low,health problems due to these exposuresmay develop over time. When populations

exposed to the same carcinogen(s) developrelated health problems, the result maybe both higher health care costs at theindividual level and potentially signi cantpublic health issues and societal costs.

…OShA as not moved fast enoug to control e posure toknown uman carcinogens. Instead of t e precautionaryparadigm of decision-making in t e face of uncertainty,we ave a refusal to act in t e face of certainty.

FRANK MIRER

HUNTER COLLEGE

Participants at the Panel’s meetingssuggested that precautionary approachesmay encourage innovation because oncea chemical or other agent is identi ed aspotentially hazardous, efforts to identifysafer alternatives are likely to follow. Thisdynamic has recently been demonstrated.Consumers have become increasingly



anxious about the estrogenic effects ofan organic compound, bisphenol A (BPA)that is used to harden plastics (e.g., babyand water bottles) and line the inside offood and beverage cans, including infantformula cans. BPA, which is detectable atbiologically active levels88 in the urine of anestimated 93 percent of Americans, 89,90 canleach into food when the plastic containersare heated in a microwave oven or washedin a dishwasher. Over the past decade, more

than 130 studies have linked BPA to breastcancer, obesity, and other disorders. 91 In2007, a group of 38 independent NIH-fundedinvestigators concluded there was strongcause for concern that exposure could resultin cancer and early puberty. 88 A 2008 studyfound that adults with higher urinary BPAlevels had elevated rates of heart disease,diabetes, and liver abnormalities. 92 Studiesalso suggest that BPA may interfere withcancer treatments. 93,94

Although the Food and Drug Administration(FDA) ruled in 2008 that BPA is safeeven for infants (Letter from Stephen R.Mason, Acting Assistant Commissioner forLegislation, Food, and Drug Administration,to Rep. John D. Dingell, Chairman, HouseCommittee on Energy and Commerce,2008 Feb 25), Canada banned its use inbaby bottles and infant formula cans thesame year. More than 20 states (e.g., MN,CT, CA) and a number of municipalitiesin the U.S. (e.g., Chicago; Suffolk County,NY) are following suit with proposed orenacted BPA bans. In the face of consumerprotests, many large retailers have pulledBPA-containing products from their shelvesand manufacturers have moved rapidly to

replace BPA with other chemicals that canharden plastics. While this case showsthat industry can and will respond to strongconsumer concerns, it should be noted thatthe safety of the substitute chemical(s) is yetunknown. Due to public concern about BPAand scienti c criticism of its 2008 ruling, FDAconducted another review of the scienti cevidence regarding BPA health effects. InJanuary 2010, the agency acknowledgedthat there is cause for concern about BPA’seffects, but concluded that there wasinsuf cient scienti c evidence to support aproduct ban or even a requirement to labelBPA-containing products. 95

In June 2007, the EC shifted to a markedlymore precautionary approach to chemicalregulation. The EC establishes healthand safety policies that apply to the 27EU member states. In addition to knowncarcinogens, the EC lists chemicals “ofconcern”—having a chemical on thislist sends a signal to industry that asafer alternative should be sought. TheRegistration, Evaluation, Authorisation,and Restriction of Chemical Substances(REACH)96 initiative is a major reformof the EC chemicals policy affecting all

global supply chains that produce anduse chemicals. REACH aims to improveprotection of human health and theenvironment through better and earlieridenti cation of intrinsic properties ofchemical substances, while simultaneouslyencouraging the innovative capability andcompetitiveness of the EU chemicalsindustry. The initiative requires industry totake a greater role in managing risks fromchemicals and to provide safety informationon its products; these data will be registeredin a central database available to consumersand professionals. REACH provisions arebeing phased in over an 11-year period. 97 U.S. chemical companies that wish to dobusiness in EC member states must complywith REACH. The U.S. chemical industryhas vigorously opposed suggestions thatU.S. chemical management policy shoulduse REACH as a model.

…we ave companies t at are formulating productsin t e United States t at are different from t ose in

Europe ecause t ere is no regulation [in t e UnitedStates] re uiring t e more stringent standards.

JEANNE RIzzOBREAST CANCER FUND



Ke Issues in U.S. Regulation ofEnvironmental ContaminantsIn general, adequate infrastructure existsat the Federal level to perform necessaryregulatory functions related to themanufacture, use, disposal, and exposurelimits of known or suspected environmentalcarcinogens. However, key agenciesare not ful lling their responsibilities toprotect public health. U.S. regulation ofenvironmental contaminants is renderedineffective by ve major problems: (1)inadequate funding and insuf cient staf ng,(2) fragmented and overlapping authoritiescoupled with uneven and decentralizedenforcement, (3) excessive regulatorycomplexity, (4) weak laws and regulations,and (5) undue industry in uence. Too often,these factors, either singly or in combination,result in agency dysfunction and a lack ofwill to identify and remove hazards.

I t ink we need national programs on a lot oft ings, and pesticide regulation is one of t em,

ut EPA as c osen to give [regulation of] t eadministration of pesticides to t e various states.

MARION MOSESPESTICIDE EDUCATION CENTER

Inadequate Funding and Insuf cientStaf ng; Decentralized and UnevenEnforcement

Inadequate regulatory program funding andunderstaf ng are partly to blame for many

of the shortcomings in U.S. regulation ofenvironmental and occupational hazards.For example, according to a former directorof EPA’s Of ce of Prevention, Pesticides, andToxic Substances, staf ng there has droppedfrom a one-time high of 600 employees to320 in 2009.98

Staf ng shortfalls such as these occur atthe Federal level, but also lead to problemsat the state level. In many instances,enforcement of Federal regulations is the

responsibility of state agencies that lack thefunding and staff to carry out this functioneffectively. This issue is described in a 2007Government Accountability Of ce (GAO) studyon EPA-state enforcement partnerships,which noted that overall funding to regionsand participating states increased from1997–2006, but that the increases did notkeep pace either with in ation or the growthin enforcement responsibilities. 99

In December 2006, the FDA Science Boardformed a subcommittee composed ofthree of its members and other expertsrepresenting industry, academia, and othergovernment agencies to assess whetherscience and technology at FDA can supportcurrent and future regulatory needs. The

subcommittee concluded that science atthe FDA is de cient and the agency is notprepared to meet regulatory responsibilitiesbecause of soaring demands coupled with

at funding. Between 1998 and 2007, FDAreceived responsibility for 123 new statutes,



while gaining fewer than 700 employees andlosing $300 million in funding to in ation.As a result, FDA suffers from an erodedscienti c base with a weak organizationalstructure, insuf cient workforce capacityand capability, and inadequate informationtechnology infrastructure. 100

Fragmented and Overlapping Authorities

Responsibility for regulating themanufacture, use, disposal, and exposurelevels of known and suspected environmentalcontaminants is sometimes divided amongnumerous Federal agencies. Appendices D and E do not provide exhaustive inventoriesof Federal laws related to environmentalhazards or the regulatory responsibilities ofthe agencies charged to implement them,respectively. However, they illustrate thefragmentation of authority that often resultsin regulatory gaps and lapses in enforcingexisting regulations. In some cases, theregulatory responsibilities of agencies

overlap and coordination among agencies isinconsistent. For example, some agencies,such as OSHA and CPSC, are focused moreheavily on safety (e.g., preventing injury dueto product or other mechanical failure orhazardous manufacturing processes) thanon health issues (e.g., exposures that leadto disease) that are the principal focus ofagencies like EPA and FDA. These differing

missions and overlapping authorities may notbe harmonized for the greatest bene t to thepublic’s health and well-being.

Regulatory Complexity

In some instances, the regulatory processis slowed by complex requirements dictatedby the regulations themselves, affectingboth industry documentation submissionsand review processes at the regulatoryagency. For example, Figure 2 illustratesthe EPA registration (approval) process fora new pesticide or a previously registeredpesticide having a new ingredient or proposednew use. Note that this process involvesmultiple EPA operational units with distinct

roles in evaluating data submitted by themanufacturer, exposure assessment andlimit-setting, and approval. Other processesare in place for active ingredients suspectedof endocrine disruption, an entire differentdivision for registration of biopesticidesand antimicrobial products, and a separatedivision still to do pesticide reregistration forchemicals that were brought to market before1984. Evaluation and standard setting forindustrial chemicals are handled by yet otherEPA divisions and of ces.

EPA and OShA ave a terri le psyc ological relations ipand often end up moving pollution from t e workplace to

t e environment and ack again. If we ad t ese folksworking toget er rat er t an apart, it would e goodfor t e workers, good for t e environment, and good

for industry, w o could use a little more predicta ilitya out w at t ey’re going to e asked to do.

ADAM FINKELUNIVERSITy OF MEDICINE AND DENTISTRy OF NEW JERSEy

...industry as a lot of data on t ese c emicals.T ey just don’t ave to give it to any ody.

RICHARD WILESENVIRONMENTAL WORKING GROUP

Weak Laws and Regulations

The Toxic Substances Control Act of 1976(TSCA)101 may be the most egregious exampleof ineffective regulation of environmentalcontaminants. This legislation was intendedto give EPA authority to control healthrisks from chemicals in commerce. TSCAgrandfathered in approximately 62,000chemicals; today, more than 80,000 chemicals

are in use, and 1,000–2,000 new chemicals arecreated and introduced into the environmenteach year. 102 Yet TSCA does not include atrue proof-of-safety provision. 103 At this time,neither industry nor government con rmthe safety of existing or new chemicalsprior to their sale and use. In fact, becausecompanies are required by TSCA section 8eto report information about known healthhazards caused by any of their products, to



avoid litigation or the costly ban or restricteduse of a product, chemical companiesgenerally do not conduct toxicity tests.Under TSCA, EPA can only require testingif it can verify that the chemical poses ahealth risk to the public. 104,105 Since TSCAwas passed, EPA has required testing of lessthan 1 percent of the chemicals in commerceand has issued regulations to control only

ve existing chemicals. Companies arerequired to provide health and safety datafor new chemicals and to periodicallyrenew approvals for the use of pesticides,but historically, chemical manufacturershave successfully claimed that much of therequested submissions are con dential,proprietary information. As a result, it

is almost impossible for scientists andenvironmentalists to challenge the release ofnew chemicals. 106

In 1989, EPA issued a ban on asbestosbased on 45,000 pages of documentationon its risks. However, TSCA stipulates thatchemicals should be restricted using theleast burdensome regulations available.In 1991, the Fifth Circuit Court of Appeals

nulli ed EPA’s ban, ruling that EPA hadfailed to show that asbestos posed anunreasonable risk, as de ned by TSCA,that was best addressed by banningit.107 Because of TSCA’s constraints andweakness, EPA also has been unable tosubstantially restrict or eliminate the use ofother known carcinogens such as mercuryand formaldehyde, and has not attempted toban any chemical since the 1991 court ruling.

By contrast, in 1976 the EU prohibitedthe use of approximately 1,100 chemicalsin cosmetics. 108 Atrazine, a widely usedherbicide believed to have endocrine-disrupting and possible carcinogenicproperties, was banned by the EU inOctober 2003 because of its ubiquitousand unpreventable water contamination. 109 The same month, the EPA approved thecontinued use of atrazine in the U.S. Mostrecently, the EU banned dichloromethane,an ingredient commonly used in paintstrippers that has been classi ed an EUCategory 3 carcinogen (possibly carcinogenicto humans). 110

Moreover, U.S. analyses of the small fractionof all chemicals and other substances incommerce were conducted on a chemical-by-chemical basis. It is not possible either toaddress the backlog of untested chemicalswith this approach, or keep up with theintroduction of new chemicals. Further,analyzing each chemical separately failsto address the potential hazards of beingexposed to combinations of chemicalsand other contaminants that may havesynergistic deleterious effects.

In January 2009, GAO added TSCA to its listof government programs at “high risk” offailure, because the law does not provide theagency with enough authority to effectively

We need to t ink a out c emical use as a cancer issueand concern ourselves wit production and use of

c emicals across our economy from fuel ef ciencyof ve icles and energy production to use of EDCs

[endocrine-disrupting c emicals] in toys, wrinkle-freeclot ing, food processing, and computers, [and] protectionof our water supplies from wastes. We need a systematic

program t at re uires ealt assessment of synt eticc emicals, old and new, as a prere uisite for t eir use.

JULIA BRODySILENT SPRING INSTITUTE



regulate chemicals. 111 Momentum isgrowing to reform TSCA, however, and theEPA Administrator has made chemicalsassessment and management a toppriority.112 In February 2009, a Congressionalhearing was convened to discuss TSCAreform; elements of such reform have beenproposed. 104 A reform bill, initially calledthe Kid Safe Chemicals Act of 2008, 113 maybe reintroduced in the 111th Congress andis expected to re ect the Administration’sintention to overhaul regulation ofchemicals in consumer products and theworkplace, requiring more testing andproviding greater authority to restrict toxicsubstances. 114 In addition, under the existingTSCA legislation, a number of chemicals,

including lead, mercury, formaldehyde, andpolychlorinated biphenyls (PCBs), recentlyhave been identi ed for revised rulemakingto strengthen control of these substances.According to EPA, BPA, phthalates, andseveral other chemical groups also havebeen targeted for action to label, restrict,or ban them under the authority of TSCAsection 6. 114

Industry In uence on EnvironmentalContaminant Regulation

Like many other industries, the U.S.chemical, manufacturing, mining, oil,agriculture, transportation/shipping, andrelated industries are substantial politicalcontributors and actively lobby legislatorsand policymakers on issues that affecttheir operations and revenue. For example,corporations aggressively block proposedchemical manufacturing, use, and disposalregulation, both through lobbying activitiesand in some cases, by manipulatingknowledge about their products (e.g.,industry-funded research). 115,116 Althoughthe Doll and Peto assessment of attributablefractions of the national cancer burdenrelated to speci c causes has been largelyabandoned by the scienti c community, itremains the basis of many existing chemicalregulations and policy. The chemicalsindustry in particular likewise continues

to use the notion of attributable fractionsto justify its claims that speci c productspose little or no cancer risk. As a result ofregulatory weaknesses and a powerful lobby,the chemicals industry operates virtuallyunfettered by regulation or accountability forharm its products may cause.

T ere’s a knee-jerk reaction on t e part of any usinesst at any regulation is a ad idea, at least in pu lic.

DAVID KRIEBELUNIVERSITy OF MASSACHUSETTS

...we know enoug now to act in ways t at weave not done, and t at s ould e our focus on

environmental and occupational cancer preventionin t e coming years—act on w at we know.

RICHARD CLAPPBOSTON UNIVERSITy

State-level Regulator EffortsSome states have taken action to ll

the regulatory void left by weak Federalregulation of environmental chemicalsand other contaminants. California haslong been a leader in this regard, but otherstates likewise are stepping up occupationaland environmental protection efforts. Forexample, the Massachusetts Toxics UseReduction Act,117 enacted in 1989 andamended most recently in 2006, requirescompanies in the state that use largequantities of speci c chemicals to evaluate,plan for, and implement (to the extentpractical) pollution prevention opportunities.Companies are required to evaluate theirefforts and update their toxics use reductionplans every 2 years.

In 2008, both Maine118 and Washingtonpassed legislation to reduce children’sexposure to toxic chemicals. TheWashington Children’s Safe ProductsAct119 focuses speci cally on eliminatinglead, cadmium, and hormone-disruptingphthalates in children’s toys. Other states(e.g., OR, MN) also have enacted or proposedtoy safety legislation.



The reality of this unequal burden is not just a health issue, but an issue of environmental justice. Further, studies by the U.S. Centers for Disease Control and Prevention (CDC) showthat while all Americans carry many foreign chemicals in their bodies, women have higherlevels of many of these chemicals than do men. 123 Some of these chemicals are found inmaternal blood, placental tissue, and breast milk samples from pregnant women and motherswho recently gave birth. 124–126 These ndings indicate that chemical contaminants are beingpassed on to the next generation, both prenatally and during breastfeeding. Some chemicalsindirectly increase cancer risk by contributing to immune and endocrine dysfunction that canin uence the effect of carcinogens.

This section includes chapters that describe major sources of cancer-associatedcontaminants, including industry and manufacturing, agriculture, and exposures related tomodern lifestyles. Additional chapters focus on potentially harmful exposures stemmingfrom medical care, military activities, and natural sources. It is crucial to bear in mind thatexposure to potential carcinogens most often occurs in mixtures that may have additive orsynergistic effects.

Appendix F provides additional information on known and suspected environmentalcarcinogens. Appendix G provides basic information about electromagnetic energy thatis relevant to discussions in Chapters 1 and 3 through 6; readers may wish to refer to thisinformation in conjunction with the material in those chapters. In addition, a table listing unitsof measure across the electromagnetic spectrum is provided in Appendix H.



the environment because they are used inhuge quantities and break down extremelyslowly, if at all. Other compounds areconverted to other forms in reaction toor combination with other environmentalelements, but the resulting compoundsare highly toxic. In still other cases,toxic compounds enter the environmentbecause they are integral components ofor ingredients in manufactured consumer

products. Examples of these types ofmanufacturing and industrial contaminants,their occupational and environmentalimpacts, and emerging contaminants ofconcern are described below.

We are not all e posed to a single agent, a single radiationor a single type of radiation, and we’re not e posed

at a single point in time. It’s a cumulative effect...

WILLIAM SUKNATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

Common Industrial andManufacturing ContaminantsT at Are Persistent int e EnvironmentNumerous chemicals and other substancesassociated with industrial and manufacturingoperations have become ubiquitousand persistent in the environment. Theparagraphs below provide several examplesdiscussed at the Panel’s meetings.

Pol halogenated Biphen lsThis large group of man-made organicchemicals includes numerous compoundssuch as polybrominated biphenyls (PBB) andpolychlorinated biphenyls (PCB). The highestserum PBB levels are associated withsigni cantly higher rates of breast cancer,non-Hodgkin lymphoma, and digestivesystem cancers (esophagus, stomach, liver,pancreas). 127 The many PCB compoundsvary in their toxicity.128 These chemicals arelinked to liver and biliary cancers and aresuspected carcinogens for breast cancer, 129

prostate cancer, 130 melanoma, 131 and non-Hodgkin lymphoma. 132 PCBs accumulate inadipose tissue. They also can induce fat celldifferentiation and in ammatory responses,which may contribute to obesity. 133 Inaddition to increased cancer risk, EPA alsoindicates that PCBs are hormone disruptorswith effects on the immune, reproductive,nervous, and endocrine systems. 134

PCBs were banned in the United Statesin the late 1970s, but still are present inthe bodies of people exposed to them andin the environment. Workers in electricalindustries were exposed to PCBs, whichwere used as coolants and lubricantsin transformers, capacitors, and otherelectrical equipment. PCBs also were usedin oils for motors and hydraulic systems,adhesives and tapes, thermal insulationmaterials, oil-based paint, dyes, caulking,carbonless copy paper, and many otherproducts.

These chemicals can still be released intothe environment from poorly maintainedhazardous waste sites containing PCBs,improper dumping of PCB wastes in land llsnot designed to handle hazardous waste, and

incinerating PCB-containing items.128

PCBspersist in the environment because many ofthese compounds degrade very slowly andcycle between air, water, and soil. They alsobioconcentrate signi cantly in the aquaticfood chain and the above-ground parts offood crops and other plants. 128 As a result,humans continue to be exposed to PCBsthrough multiple routes.

In 2009, EPA recommended that owners ofbuildings, including schools, constructed

or renovated between 1950 and 1978, testmasonry and window caulking for highPCB levels.135 The chemicals were mixedinto caulking to make it rubbery whenapplied to interior and exterior buildingsurfaces. As the caulking ages, however,it can disintegrate into PCB-containingparticles and vapors that can fall to theground or other surfaces and in ltratebuilding ventilation systems. In addition,



MercurElemental mercury occurs naturally and alsois released into the air through industrialpollution, contaminating food and watersources. It is a suspected carcinogen forbrain and central nervous system (CNS)cancers. U.S. coal- red power plants emitmore than 48 tons of mercury into the aireach year. 163 In 2008, a U.S. court of appeals

ruled 164 that EPA violated provisions of theClean Air Act when it promulgated the2005 Clean Air Mercury Rule that exemptedpower plants from existing strict toxiccontrol regulations intended to eliminateup to 90 percent of power plant mercuryemissions by 2008. EPA was given 2 years todevelop new emission standards for existingpower plants. Proposed new power plants

would be required to indicate how mercury

emissions would be controlled. A recentreport 165 by the General Accountability Of ce(GAO) found that it is technologically possibleand affordable for coal- red power plantsto install state-of-the-art pollution controlequipment that reduces mercury emissionsby as much as 90 percent. Industry has longclaimed that mercury controls would be tooexpensive, but the GAO report, based on astudy of 25 boilers at 14 plants with advancedmercury control technology, found thatthe average cost of equipment installation($3.6 million) translated into pennies permonth on consumers’ electric bills.

In addition to workers at coal- red powerplants, those in factories that producechlorine gas and caustic soda for use insome industrial processes may be exposedto mercury. Workers can be exposed tomercury in various forms when it is usedto produce batteries, thermometers, andskin creams and ointments. Cement kilnsare a major producer of mercury thatcontaminates both air and water in the U.S.These kilns also release hydrocarbons,particulate matter, sulfur dioxide, andsulfuric acid.

Unlike some pollutants, mercury emissionscreate toxic “hot spots” where environmentalexposures can be especially severe. 166 Thisis believed to result from complex processesthat move atmospherically released mercurythrough the environment; in addition, somesites (e.g., wetlands, forested areas) areparticularly sensitive to mercury input. 167 Inappropriate disposal of batteries and othermercury-containing products add to mercurycontamination of soil and water.

When exposed to microorganisms in waterand soil, elemental mercury becomesmethylmercury, a known neurotoxinthat IARC classi es as a possible humancarcinogen. 168 According to EPA statistics,more than 600,000 children born eachyear test positive for unhealthy levels ofmethylmercury, 169 exposures that may putthem at risk for brain damage and futurelearning disabilities. A tragic exposure

We are e posed to many pollutants, many at t esame time or in se uences t at [cause t em to]interact wit one anot er. And yet our policies

and most of our researc … for t e most part[address] one pollutant, one e posure at a time.

WINIFRED HAMILTONBAyLOR COLLEGE OF MEDICINE



vacate or ventilate well any indoor spaceswith new formaldehyde-containing products,and to try to select products with lowformaldehyde emissions. The health effectsof formaldehyde exposure gained nationalmedia attention when it was reported thatGulf Coast families who occupied newtrailers provided by the Federal EmergencyManagement Agency (FEMA) as temporaryhousing following Hurricane Katrina weredeveloping respiratory and other illnesses.EPA considers 0.1 parts per million to bean elevated level that can cause illness.Testing conducted by the Sierra Club foundformaldehyde concentrations as high as 0.34parts per million in the FEMA trailers. 177

Endocrine Disrupting Chemicals(EDCs)EDCs are natural or synthetic chemicalsthat can interfere with normal animal andhuman hormonal systems. These chemicalshave been developed and are used for a widevariety of industrial purposes. Recognitionthat these chemicals alter hormone action,and the possible implications of their effects,has developed slowly over the past severaldecades. 178 EDCs were rst recognizedby Congress as a public health concernwhen the Food Quality Protection Act 179 andamendments to the Safe Drinking Water

Act180 were passed. These laws mandatedthat EPA develop a screening program toidentify EDCs to which humans may beexposed. However, after more than 10 years,EPA has yet to nalize a pro le of tests toidentify potential EDCs in the environment.

The endocrinology community has expressedconcern that recent research ndings maynot be re ected in the nal EPA screeningprogram. 178 For example, it now is clearthat EDCs affect hormone systems otherthan through thyroid and steroid receptormechanisms, and that EDCs, which havebeen found in amniotic uid, 181 may havein utero and multigenerational effects.Further, current EDC policy relies ontoxicologic studies that examine high-doseeffects, when many EDC effects may occurat low doses, even when high-dose effectsare not apparent. In fact, higher doses of ahormone or hormone-mimicking chemicalcan depress a measurable low-dose effectby overwhelming or down-regulating the

endocrine system’s ability to respond. Thispattern of effect has long been recognized byendocrinologists. 178 Thus, an effect seen atlow exposure levels would not be observed athigh exposure levels 178,41 in a typical high-dose oriented assay.

The knowledge base on EDCs is growing,but many questions remain. Some in vitro studies 182,183 have shown that EDCs cancause proliferation of human breast cells inculture. Animal studies 184 show that EDCs

can cause mammary cancer, other tumors,and serious reproductive effects. However,most human studies of breast and othercancers due to EDC exposure have beeninconclusive. Nonetheless, because of thelong latency period of many cancers, theavailable evidence argues for a precautionaryapproach to these diverse chemicals, whichinclude persistent organochlorides suchas DDT/DDE, polychlorinated biphenyls,pesticides, polycyclic aromatic hydrocarbons,tobacco smoke, bisphenol A, some metals,phthalates, parabens, and growth promotersused in food production. 13 At this time,the majority of suspected EDCs arenot classi ed by either IARC or NTP ascarcinogens, and they are not regulated byany U.S. Federal agency.

Of the many known and suspected EDCs,bisphenol A (BPA) has received perhaps themost public attention in recent years (see

…I ope t at especially wit ormonally dependentcancers we really start to look at endocrine disrupters

in t e environment as important c emicals t at maycontri ute to ot t e rising incidence, as well as

t e mortality from t ese cancers. I ope we can getpast t is concept of low-dose effects ecause t ey’re

not really low doses if you’re an endocrinologist.

TyRONE HAyESUNIVERSITy OF CALIFORNIA, BERKELEy



also Part I, p. 18). BPA is used in numerousproducts, including baby bottles and foodand beverage can liners. It disrupts theendocrine system because it acts as a weakestrogen. Extensive research has linkedBPA to breast cancer, obesity, diabetes, andother serious medical problems. 88,92 TheCenter for the Evaluation of Risks to HumanReproduction concluded in 2008 that thereis “...some concern for effects on the brain,behavior, and prostate gland in fetuses,infants, and children at current humanexposures to bisphenol A.” 185 Yet in 2008, theFDA ruled that BPA is safe even for infants(letter from Stephen R. Mason, FDA, to Rep.John D. Dingell, Chair, Chairman, HouseCommittee on Energy and Commerce, 2008

February 25), based on selected studies,some of which were industry-sponsored, andwhat is alleged to have been undue in uenceby industry lobbyists. 186 FDA’s safetyassessment was rejected by a March 2009consortium of international experts fromacademia, government, and industry asincomplete and unreliable because it failedto consider all of the scienti c work relatingto BPA.187 In January 2010, FDA completed

a re-evaluation of scienti c evidence onBPA, but concluded that neither a ban onthe chemical or labeling of BPA-containingproducts was warranted. 95 In early 2009,NIEHS released a Request for Proposals forresearch on BPA effects on human health.The research will be supported for 2 yearswith $5 million of American Recovery andReinvestment Act stimulus funds. 188

...it seems to me t at t e indication of arm is our triggerfor action ut ow muc arm and ow muc weig t ofevidence do you want efore you make a decision I t inkis t e interesting uestion, and surely t e answer isdifferent depending on ow many people are e posed.

SANDRA STEINGRABERITHACA COLLEGE

Like BPA, phthalates disrupt normalhormone function by mimicking estrogen.This group of chemicals is used to makeplastics soft and pliable. They are found in awide array of consumer products, includingplastic bottles, IV tubing, toys (including softteething toys for babies), cosmetics, hairconditioners, and fragrances. Phthalatesinhibit normal binding to estrogen receptors



and suppress male androgens. In girls,phthalates may cause early puberty andhigher breast cancer risk later in life. 189 Malefetuses in the rst trimester of pregnancyappear to be particularly vulnerable todamage by phthalates, which may causeundescended testicles, hypospadias, andpossibly higher testicular cancer risk. Inhumans, phthalates have been linked toproblems with sperm count and spermquality, and like other EDCs, phthalates are asuspected breast carcinogen.

... [ reast cancer] incidence as sta ili ed in t e U.S.,ut it’s sta ili ed at one of t e ig est rates in t e

world, and as women move from lower risk regions

of t e world to t e U.S., t eir incidence goes up andcontinues to rise over a couple of generations. So weknow t at t at’s not genes and t ere’s somet ing a out

industrial society t at’s playing an important role.

JULIA BRODySILENT SPRING INSTITUTE

Emerging Industrial andManufacturing ContaminantsIn the ongoing quest for more effective andef cient ways of making industrial andconsumer products, improving processes,and achieving other desired outcomes, newchemicals and other substances are beingcreated continually. In addition, existingsubstances are being put to new uses.Unanticipated environmental hazards mayemerge from this push for progress.

Nanotechnolog

Nanomaterials are an important example ofan emerging environmental hazard born ofnew technology. Engineered nanomaterials(ENMs) are structures and systems as smallas atoms and molecules that are enablingsigni cant breakthroughs in material designand development for industry, consumerproducts, and medicine. 190 ENMs now areused in hundreds of consumer products,including cosmetics, sunscreens, other

personal care products, stain-resistantclothing, food storage containers, computers,and other electronics. Anticipatedapplications may provide new ways to cleanup pollution, increase fuel cell ef ciency,and provide drug delivery systems for cancerand other diseases. According to NIEHS,global demand for nanomaterials andnano-enabled devices is expected to exceed$1 trillion by 2015.191

However, nanomaterials can be extremelytoxic, and despite their promise, concernis growing about their potential healthand environmental risks. Most ENMsare engineered at dimensions of 1 to 100nanometers (nm), or 1 to 100 billionth ofa meter. The width of a human hair is80,000 nm.190 Because of their structure andsmall size, they can be inhaled, ingested,and absorbed through the skin, entering theblood stream, penetrating cells throughoutthe body (including the brain), and perhapsinterfering with DNA processes. 190 InAugust 2009, seven young Chinese womensuffered permanent lung damage and two ofthem died after working for months withoutadequate protection in a paint factory usingnanoparticles. 192 Once inhaled, nanoparticles

that penetrate pulmonary epithelial cells oraggregate around red blood cell membranescannot be removed. 193

ENMs that have been shed from industrialprocesses, personal care products, andother sources also can build up in theenvironment and interfere with ecologicsystems. For example, some researchsuggests that titanium dioxide nanoparticlesfrom sunscreens may be toxic to algae andwater eas that are a vital part of marineecosystems. 194,195

ENM safety research and regulation islagging behind their creation, and accordingto one report, 196 few have been adequatelytested. NIEHS is funding research 191 on thehealth and safety effects of nanomaterialsand also has, in collaboration with nationaland international partners, established anonline searchable Nanoparticle Information



Library (NIL). The goal of the NIL is tohelp occupational health professionals,industrial users, worker groups, andresearchers organize and share informationon nanomaterials, including their healthand safety-associated properties. 197 InSeptember 2009, EPA announced newrisk management actions on a number ofchemicals and other substances, 114 includingtwo carbon nanotubes (P-08-177 andP-08-328). The new regulations will requireprotective measures to limit exposure orotherwise mitigate potential health riskspresented by the carbon nanotube chemicalstructures.

Ethanol Production andCombustionEthanol fuel production is increasing inthe U.S.,198 in part due to its potential (inconcert with other alternative fuel strategies)to reduce U.S. dependence on foreignoil. Though it can be produced from plantmatter such as switchgrass and cellulose,ethanol fuel is made primarily from corn. 199 Another factor encouraging ethanol fueluse is the ability to produce and re nethe renewable raw material domestically.Ethanol production expansion also has beendriven by favorable revisions to renewablefuels standards and tax credits. 200 However,its primary bene t is its purported ability toreduce air pollution. 201 Because it contains

35 percent oxygen, ethanol already is usedas a fuel additive to help gasoline burn morecompletely, thereby reducing levels of carbonmonoxide and carcinogenic benzene andbutadiene pollution typically resulting fromgasoline combustion. As a fuel additive,ethanol is blended at 10 percent withgasoline, a mixture referred to as E10.

Though available data are limited, a review 200 of evidence regarding the environmentaleffects of fuel blends with 15 percent (E15)or greater ethanol content indicate that theircombustion increases levels of formaldehydeand acetaldehyde, which EPA classi es asprobable human carcinogens. 202 Moreover,production and combustion of E15 or higherethanol-gasoline blends have been foundto contribute to increased levels of other

air pollutants including nitrogen oxides,volatile organic compounds, ozone, andparticulate matter. 200 As the review authornotes, increased ethanol fuel use maysimply substitute one set of air pollutantsfor another.

…we don’t t ink enoug a out engineering and a outw at drives industry and w at drives ow t ey maket ings and ow we can interact wit t at kind of processengineering mentality to ave a meeting of t e mindsw ere to icity, ef uent, and limitation of e posure are as

important as t e pro t and aren’t counted in t e pro t.JEANNE MAGER STELLMANSUNy-DOWNSTATE MEDICAL CENTER



C H A P T E R2

Exposure to ContaminantsFrom Agricultural SourcesThe entire U.S. population is exposed ona daily basis to numerous agriculturalchemicals. Many of these chemicalsare known or suspected of having eithercarcinogenic or endocrine-disruptingproperties. The following sectionsdescribe the agricultural workforce, thepopulation group most heavily exposed tothese chemicals, and hazards associatedwith speci c agricultural chemicals andveterinary pharmaceuticals.

T e Agricultural Workforce

Migrant workers and contract workers...are

dif cult to identify; it’s certainly ard to track t em,ut t ey ave t e potential and often t e realityof ig er e posures and less monitoring.


In 2007, approximately 1.75 million full-time workers were employed in agriculturalproduction. 203 Unlike nearly all otherindustries in the U.S., families typicallyshare in agricultural work; half of all farm-based children under age 20 perform farmwork and an additional 307,000 children andadolescents are hired to work on farms.

In addition, between three and ve millionindividuals and their families work asmigrant or seasonal workers. 204 Due toworking and housing conditions, includinglack of child care that forces parents totake their children with them into the

elds, these workers and their familiesoften have disproportionate exposuresto pesticides and other agricultural

chemicals. 205 Many migrant workers arenot provided with protective clothing orequipment. Further, migrants often havelimited access to health care and mayexperience poor communication with healthcare providers due to language differences.Undocumented workers are likely to avoidseeking health care even if they become ill.These factors, combined with the mobility ofthe migrant population, have made it dif cultto assess the magnitude of health problems

migrants suffer as a result of their exposureto agricultural chemicals.

As with industrial chemicals and otherenvironmental exposures, children are athigher risk for cancer and other adversehealth effects from pesticide exposures.Risks for childhood cancers are linkedwith parental pesticide exposure prior

to conception, in utero exposures, anddirect exposures throughout childhood. 206 Chemical exposure levels of agricultural



exposures compared with those using publicwater supplies. Nitrate levels also can behigh in streams and rivers due to runoff ofnitrogen fertilizer from agricultural elds.Almost all public water supplies, however,have nitrate levels below the EPA MaximumContaminant Level (MCL) of 10 mg/L.

Ingesting contaminated drinking water isthe primary route of human exposure tonitrate from nitrogen fertilizers. 239 Nitratesin drinking water are important because themost likely known mechanism for humancancer related to nitrate is the body’sformation of N-nitroso compounds (NOC),which have been shown to cause tumors atmultiple organ sites in every animal speciestested, including neurological systemcancers following transplacental exposure. 240 Nitrite, the reduced form of nitrate, reactsin the acidic stomach to form nitrosatingagents that then react with certaincompounds from protein or other sourcessuch as medications to form NOCs. NOCformation is inhibited by dietary antioxidantsfound in vegetables and fruits, which mayaccount in part for the observed protectiveeffect of fruits and vegetables againstmany cancers. 239

In humans, nitrosamines and NOCs aresuspected brain and CNS carcinogens.In addition, a cohort study of older womenin Iowa241 found that those whose drinkingwater had higher long-term average nitratelevels had an increased risk of bladderand ovarian cancers. Other studies havehad mixed results or shown no associationwith nitrate intake. Small numbers ofepidemiologic studies of any one cancer

site have been conducted; such research is

needed to identify other potential nitrate-related cancer risks. 239 Limited mechanisticstudies suggest that nitrate at levels belowthe MCL could be carcinogenic. 242 Furtherresearch into this question is warranted,particularly because nitrate levels continueto rise in groundwater as use of nitrogenfertilizers increases. With greater productionof corn for fuel, nitrate levels in drinkingwater are likely to continue their upwardtrend.

Some research indicates that crop rotationand/or the use of cover crops (i.e., grassor legumes planted on a eld betweenproduction seasons) can reduce or negatethe need for nitrogen fertilizers withoutsacri cing crop yields. 243,244 Legume covercrops can x (capture) nitrogen, whichpreserves it for the next growing season andprevents nitrogen in the soil from leachinginto groundwater.

Agricultural policy in t is country as also encouragedt e e tensive use of fertili ers and t at as resultedin t e pro lems t at we’ve seen wit contaminationof water supplies, w ic in addition to t e concerns

a out uman ingestion of nitrates, as large ecologiceffects related to eutrop ication [overgrowt

of plant life and loss of o ygen in water].

MARy WARDNATIONAL CANCER INSTITUTE



Phosphate Fertilizers

Phosphate fertilizers are often contaminatedwith cadmium and are responsible forsigni cant cadmium soil and watercontamination. Fertilized soils have been

found to have two to six times the cadmiumconcentration of nearby unfertilized land. 245

In the food supply, cadmium is most highlyconcentrated in grains and seafood. Fordecades, residents of Southern Louisianahave had pancreatic cancer rates markedlyhigher than the national average. 246 Research has demonstrated an associationof rural residence, dietary factors (highconsumption of rice, seafood, and pork), andcigarette smoking with higher pancreaticcancer risk, particularly among personsof Acadian (Cajun) ancestry. 247 Cadmiumappears to be the common factor in all ofthese variables. Rice elds in the area aretreated with cadmium-containing phosphatefertilizers, which is taken up into the rice, thepredominant starch in Acadian diets. Afterthe rice harvest, the elds are again ooded,and craw sh, a staple seafood in the localdiet, are farmed in the previously fertilized

elds. Urinary cadmium excretion levels in

studied Louisiana pancreatic cancer patientshave been found to be more than four-foldhigher than control subjects. 247

Industrially, cadmium is used inmanufacturing processes such aselectroplating, production of polyvinylchloride (PVC) products, and nickel-cadmiumbatteries. An estimated half-millionmanufacturing workers are exposed tocadmium. 248

Phosphate fertilizers also acceleratethe leaching of arsenic from soilsinto groundwater. 249 The arsenic soilcontamination is often the result of previousfertilization with arsenic-containingpesticides. Further, the addition ofphosphates to soil has been found toincrease arsenic accumulation in wheat. 250

Veterinary P armaceuticalsExcept for animals raised on organic farms,most livestock in feed lots and poultry farmsare given antibiotics, growth hormones, andfeed that may consist in part of animal tissuethat itself may be contaminated by thesedrugs. When excreted, these medicationsbecome part of the toxic run-off fromagricultural operations. The impact of thiscontamination on human cancer is unknownat this time, but there is speculation thatthe growth hormones may contribute toendocrine disruption in humans.

...agricultural e posures are very comple .We ave talked a lot a out pesticides ut t ere aremany ot er e posures t at are agricultural as well andt ey are agricultural in an occupational setting ut t eye pand into t e general environment, and people aree posed t roug contaminated water. T ey are e posedt roug food, as well as t e occupational e posures.

LAURA BEANE FREEMANNATIONAL CANCER INSTITUTE



C H A P T E R3

Environmental ExposuresRelated to Modern LifestylesConveniences of modern life—automobileand airplane travel, dry cleaning, potabletap water, electricity, and cellularcommunications, to name a few—have madedaily life easier for virtually all Americans.Many of these conveniences, however,have come at a considerable price to theenvironment. Some of the environmentaleffects of modern life are known orsuspected of harming human health.

Air PollutionIn June 2009, the Environmental ProtectionAgency (EPA) released the results of its mostrecent National-Scale Air Toxics Assessment(NATA), which is conducted every 3 years toestimate concentrations of air pollutantsacross the country, population exposures,and the potential public health risk due to airtoxics inhalation. 80 Using the most currentavailable air emission inventory (2002) and

census data, NATA characterized cancerand non-cancer effects from inhaling the124 air toxics on which chronic exposurehealth data exist. Of the toxics assessed,80 are carcinogens.

NATA estimated that the average increasedcancer risk in 2002 due to inhalation ofoutdoor air toxics was 36 per million; thatis, an additional 36 people per million

(approximately 11,000 Americans basedon current population estimates) couldbe expected to develop cancer as a resultof breathing air toxics compared to thosenot exposed. The estimate assumes thatindividuals would be exposed at 2002 levelsover the course of their lifetime. 251

Figure 5 shows the distribution of theestimated 2 million Americans ( <1 percentof the total U.S. population) with a cancer

risk greater than 100 per million. Someof the areas shown are “hotspots” createdby local industrial emissions. Examples ofthese emissions include tetrachloroethylenefrom dry cleaning operations and methylenechloride, a commonly used industrial solvent.NATA results indicate that local industryemissions account for about 25 percent ofthe average overall cancer risk due to airtoxics.251 EPA is preparing a NATA updateusing 2005 data that is expected to bereleased in late 2009 or early 2010.

Mobile Sources of Air PollutionAccording to the 2002 NATA results,emissions from personal cars, power boats,off-road vehicles, and other on-road vehicles,excluding particulate matter from dieselexhaust, account for about 30 percent ofthe overall cancer risk from air pollutants.The majority of this risk is from benzene,



As of July 2009, 17,059 municipalitieswere covered by a smoke-free provision (inworkplaces and/or restaurants and/or bars)that collectively cover almost 71 percentof the U.S. population. 263 A substantialnumber of workers, however, continue to beexposed to tobacco smoke on the job. Barand restaurant workers continue to haveamong the highest exposure rates. All of theissues related to tobacco-related cancers inthe workplace also apply to tobacco use andtobacco smoke exposures in the home andaround children.

Drinking WaterContaminationAmericans’ drinking water comes fromgroundwater and rain that lls streams,reservoirs, rivers, lakes, and ultimately, theoceans. Chemicals improperly stored anddisposed of by industry and individuals alikesoak into the soil and eventually leach intogroundwater. As clouds and rain, waterabsorbs chemicals in the air. As a result,the water we drink is steeped in varyingmixtures of chemicals and other substances.Some of these contaminants are not harmfulto human health in trace or extremely smallamounts, while others can causeor contribute to numerous diseases,including cancer.

Assessing health hazards due to drinkingwater contamination is dif cult, since ittypically is challenging to estimate the levelsand timing of exposures and the speci cchemicals involved. It also can be dif cult tode ne exposed populations clearly and selectthe most appropriate disease endpoints orintermediate biologic markers for study.Further, it often is not possible to identify thecause of observed health effects when thereare multiple exposures or to link speci chealth effects with individual chemicals thatoccur in mixtures.

Public water ltration and treatment plantsremove some contaminants, but currenttechnologies cannot remove them all.

Water treatment systems vary signi cantlyacross the country since they are tailored(to the extent practicable) to treat the watercontaminants that are found in each vicinity.Arsenic, microbes, nitrates, radium, uranium,selenium, antimony, sulfate, magnesium,calcium, iron, manganese, potassium,phosphorous, and other metals are among

the substances commonly removed fromdrinking water supplies. 264 Because ofconcerns about water pollution, some peopleuse home ltration systems to further treatwater from public supplies or wells and/oruse bottled water for drinking and cooking.

…in a country w ere I work ard and I vote, I feellike I ave een involuntarily e posed to t ingst at could ave made me sick and I can’t makeinformed decisions w en t at’s t e situation.

KATRINA COOKEBREAST CANCER SURVIVOR, INDIANA

Water Supplies

Public Systems

Most Americans rely on public systems forthe water they use for drinking, cooking,irrigating crops (including feed crops) andornamental plants, and watering livestock.As Table 4 shows, the U.S. population isserved by more than 52,000 communitywater systems. The quality of drinkingwater is regulated by the Safe DrinkingWater Act (SDWA) of 1974, but enforcementtakes place at the state level. 180 Thelegislation authorizes EPA to establishstandards (Maximum Contaminant Levels,

or MCLs) to protect tap water and requiresthat owners and operators of public watersystems comply with these standards.Regulated chemicals in drinking waterinclude 53 organic chemicals (e.g., atrazine,benzene), 16 inorganic chemicals (e.g.,arsenic, nitrate), 7 disinfection by-products(e.g., trihalomethanes), 6 microorganisms(e.g., cryptosporidium ), and 4 radionuclides(e.g., alpha particles from radon, radium).



changing, with a rising proportion of peopleusing headsets or using the phone primarilyto send and receive text messages. Usinga cell phone in these ways dramaticallyreduces the time during which the phone isheld against the head, and therefore, reducesindividuals’ cranial exposure to RF.

Considerable disagreement exists withinthe scienti c community regarding potentialharm due to RF exposure from cellularphones and other wireless devices, and manyof the available studies have been interpretedquite differently by researchers on both sidesof the issue. As one speaker noted, data onthe long-term use of newer equipment stillare relatively sparse, and it may be severalyears before enough data accumulate toreach informed conclusions about the harmcell phones, cell phone towers, and otherwireless devices/networks may cause.

Limited evidence suggests that risk of abrain tumor (speci cally, glioma) on thesame side of the head where the usertypically holds the phone may be increasedamong long-term cell phone users, 275,276 but other studies 277,278 show no association.A 2009 meta-analysis 279 of 23 case-controlstudies involving almost 38,000 people foundno connection between cell phone use andcancerous or benign tumors, but a subsetanalysis of the eight studies considered mostrigorous methodologically showed that long-term cell phone users had a 10–30 percentincreased risk of tumors compared withpeople who seldom or never used a cellphone. All but one of these eight studieswere conducted by the same researcher

in Sweden, which has raised questions280

about whether speci c characteristics of theSwedish population could have in uencedthe results. For example, a high proportionof Swedes live in rural areas, and more RFenergy usually is needed to operate cellphones in rural areas; higher RF exposuresin this population could be a factor in thestronger cell phone-tumor association.

…t e most urgent issue t at we need to address…is w et er c ildren or adolescents using cell

p ones are at increased risk. Studies on ioni ingradiation ave s own t at c ildren are most sensitive

among all mem ers of populations in terms ofcarcinogenic e posure to ioni ing radiation.

MARTHA LINETNATIONAL CANCER INSTITUTE

Brain cancer incidence trends by age from1973–2005 show that incidence rates have

not increased apace with the explosive risein cell phone use in the United States since1992.281 Studies also have assessed andfailed to show an increased risk of cancerof the parotid gland, acoustic neuroma,meningioma, or uveal melanoma, evenamong longer-term (5–10 years) and heavierusers. 282–285

In addition, it was noted that ndings fromavailable case-control, questionnaire-based studies may be confounded by recallbias, 286 selection bias, or other questionnairelimitations. Cohort studies may avoidsome of these methodologic limitations. 287 Epidemiologic study results have beenlimited regarding the relative importanceof different RF sources. These studies alsohave been able to assess only short lagperiods and have focused on a small numberof cancer types. 288 Thus, while considerableresearch has been conducted on cancer



risk due to RF from cell phones, cell phonetowers, and other wireless devices, theavailable data are neither consistent norconclusive, and a mechanism of RF-relatedcancer has yet to be identi ed. Forthcomingresults from the INTERPHONE combinedstudies 289 from 13 populations are expectedto provide the most stable risk estimates yeton glioma, meningioma, acoustic neuroma,and parotid gland tumors. However, themethodology and partial industry funding ofsome of the INTERPHONE studies have beencriticized.

Speakers emphasized that continuedresearch is needed to resolve key questions,including:

Are cancer risks increased among•long-duration cell phone users ofcontemporary equipment?

Do heavy users experience elevated•cancer risks?

Do children or adolescents using cell•phones face increased cancer risk?

Until these questions are answered withsome degree of con dence, cell phone userscan reduce their exposure to radiofrequency

energy by making fewer calls, reducingthe length of calls, sending text messagesinstead of calling, using cell phones onlywhen landline phones are unavailable, usinga wired “hands-free” device so that thephone need not be held against the head,and refraining from keeping an active phoneclipped to the belt or in a pocket.

In the face of uncertainty about RF energyand cell phone-related cancer risks, someresearchers, 290 several countries (Germany,France, Austria, United Kingdom, Russia),and the European Environment Agency havetaken a precautionary stance regarding cellphone use, particularly by children. 291 Unlikeadults—even longer-term cell phone users—children have ahead of them a lifetime of RFand other radiation exposures and, therefore,special caution is prudent. At this time, nolong-term epidemiologic studies of cancerrisk related to cell phone use by children

or adolescents are available. Large cohortstudies of children’s cell phone use andsubsequent cancer risk are underway inDenmark and Norway, and a case-controlstudy of cell phone use during childhood isongoing in Denmark, Norway, Sweden, andSwitzerland. 292

Electric Power Lines and OtherSources of Extremel LowFrequenc (ELF) RadiationAs with RF radiation, current and potentialharm from ELF is sharply disputed withinthe scienti c community. To an even greaterdegree than is the case with cell phones,determination of potential harm has to datebeen hampered by the great dif culty inisolating and quantifying multiple exposures,



C H A P T E R4

Exposure to Hazards fromMedical SourcesIn the past two decades, signi cant strideshave been made in our ability to diagnoseand treat human disease, including cancer.Many of these advances, particularlyin diagnosis, have been made possibleby improved imaging technologies andnuclear medicine examinations. Othertreatment advances have been accomplishedthrough new pharmaceutical interventionsfor numerous diseases. It is becoming

increasingly clear, however, that some ofthese same drugs and technologies thathave contributed so greatly to health statusand longevity also carry risks. This chapterdescribes issues of signi cant concernregarding medical radiation and unintendedexposure to pharmaceuticals.

Medical RadiationMedical imaging and nuclear medicine

tests have become invaluable tools forcancer and other disease screening,diagnosis, minimally invasive surgicalprocedures, treatment, and treatmentmonitoring. Speakers described trendsin the use of these technologies, specialconsiderations when imaging vulnerablepopulations, and training and safety issuesrelated to imaging equipment and imagingtechnologists. Table 6 provides de nitions of

terms commonly used to describe medicalradiation exposures.

Trends in Medical Imaging andNuclear MedicineFigure 7 indicates the contribution of varioussources of radiation exposure to the totalcollective effective dose (see Table 6 forde nitions of medical radiation dose terms)

in the United States, as recently reassessedby the National Council on RadiationProtection and Measurements (NCRP). 307 NCRP is a non-pro t body chartered by theU.S. Congress to make recommendationson protecting people from excess radiationexposure and on metrics for exposureassessment.

While ionizing radiation exposures fromradon, occupational, and other sources haveremained essentially stable over the past30 years, Americans now are estimated toreceive nearly half (48 percent) of their totalradiation exposure from medical imagingand other medical sources, comparedwith only 15 percent in the early 1980s(Figure 8 ).308

As Figure 8 shows, computed tomography(CT) and nuclear medicine tests alonecontributed 36 percent of the total radiation



Figure 7All E posure CategoriesCollective Effective Dose (percent), 2006

Total collective effective dose (1,870,000 person-sieverts [Sv]) and total effective dose per individual in the U.S. population (6.2 millisieverts [mSv]).Percent values rounded to the nearest 1%, except for those <1%.

Source: National Council on Radiation Protection and Measurement. Ionizing Radiation Exposure of the Population of the United States.Report No. 160, Figure 1-1. Bethesda, MD: NCRP; 2009.

Figure 8NCRP Report No. 160, Ioni ing Radiation E posureof t e Population of t e United States

Source: National Council on Radiation Protection and Measurements, Report No. 160, Figure 4-12; 2009 March 3.



sample radiation doses for common medicalimaging and nuclear medicine procedures.

CT produces a larger radiation dose thanother imaging tests that require radiation.As Table 7 shows, an average chestCT delivers an effective radiation dose(~7.0 mSv) equivalent to as much as 350chest x-rays (posterior/anterior, 0.02 mSv).Moreover, many individuals who receive a CTscan will have more than one scan related toa single medical condition. According to onestudy, 313 30 percent of patients who have CTscans have at least three scans, 7 percentof patients who have CT scans have at least

ve scans, and 4 percent of patients willreceive at least nine scans. Trauma patientsreceive a mean of three scans in their initialevaluation. 314 Taking into account machinevariability, usage variability, mean multiplescans, and other factors that can easilyvary dose by a factor of two, the relevantorgan dose range for CT is 5–100 mSv. 315

As Figure 10 shows, survivors of the atomicbomb attack on Hiroshima who were 2,000–3,000 yards from ground zero received aneffective dose in the same 5–100 mSv range.

Figure 9 Num er of CT Procedures in U.S.

N U M B E R O F S C A N S

( M I L L I O N S

)

YEAR

‘93 ‘94 ‘95 ‘96 ‘97 ‘98 ‘99 ‘00 ‘01 ‘02 ‘03 ‘04 ‘05 ‘06 ‘07

18.3 19.521.0

22.6

25.1 26.3

30.6

34.9

39.6

45.4

50.1

53.9

57.6

62.0

68.7

0

10

20

30

40

50

60

70

80

Source: IMV Benchmark Report on CT, 2008.



Table 7Adult Effective Radiation Doses for Various Radiology,Interventional Radiology, Computed Tomograp y,

and Nuclear Medicine E aminations

SOURCE AVERAGE EFFECTIVEDOSE (mSv)

VALUES REPORTED INLITERATURE (mSv)

x-ray

Chest X-ray (posterior/anterior) 0.02 0.05–0.24

Abdominal X-ray 0.07 0.04–1.1

Mammography 0.4 0.10–0.6

Cervical spine X-ray 0.2 0.07–0.3

Panoramic dental X-ray 0.01 0.007–0.09

Barium enema (includes uoroscopy) 8.0 2.0–18.0

Computed Tomograp y (CT)

Head CT 2.0 0.9–4.0Chest CT 7.0 4.0–18.0

Abdominal CT 8.0 3.5–25.0

Pelvis CT 6.0 3.3–10.0

Three-phase liver CT 15.0 --

Coronary angiography CT 16.0 5.0–32.0

Virtual colonoscopy CT 10.0 4.0–13.2

PET CT 45.0 --

Interventional Radiograp y (IR)

Coronary angiography (diagnostic) IR 7.0 2.0–15.8

Nuclear Medicine (NM)

Brain NM with FDG 14.1 --

Cardiac stress-rest test with thallium 201chloride

40.7 --

Renal NM 1.8–3.3(depending on

radiopharmaceuticalused)

--

Bone 6.3 --

Tumor NM with18

F-FDG 14.1 ----: Data not available; PET: positron emission tomography scan; FDG: uorodeoxyglucose; 18F: uorine 18

Sources:Mettler FA Jr, Huda W, Yoshizumi TT, Mahesh M. Effective doses in radiology and diagnostic nuclear medicine: a catalog. Radiology. 2008; 248(1):254-63.

Mettler FA Jr, White Paper and Presentation, President’s Cancer Panel Meeting, 2009 January 27.

Most estimates of radiation-related cancerrisk are based on studies of atomic bombsurvivors. 316 The Life Span Study (LSS),317 a 40-year study of nearly 28,000 atomicbomb survivors exposed to this dose,

showed a small but statistically signi cantradiation-associated increase in solid tumorrisk. A recent large-scale study of 400,000radiation workers in the nuclear industry 318 who were exposed to an average cumulative



estimates for many tests are made usingadult-sized acrylic models (“phantoms”) andcomputational models; models are neededfor estimating dose using phantoms thatmore appropriately consider the size, shape,and composition of children’s anatomies. 341

Further, compared with adults, children havemany more years of life ahead, time duringwhich a radiation-induced tumor can grow,possibly potentiated by other environmentalexposures. Most solid tumors take decades

to develop to a point at which they can bedetected or cause symptoms. As Figure 11illustrates, the potential for radiation-induced lifetime cancer risk increases theyounger the child is at the time the dose isreceived, even when the dose is the same.According to one estimate, a 1-year-old is10–15 times more likely than a 50-year-oldto develop a malignancy from the same doseof radiation. 343 Thus, avoiding unnecessary

radiation risks in this sensitive populationis crucial. 344 As many as one-third of CTscurrently performed in children may beunnecessary. 345

Figure 11Estimated Radiation-Induced Lifetime Cancer Riskas a Function of Age at E posure

0

1000

2000

3000

4000

5000

Source: BEIR-VII, 2006.

Pediatric CT usage is increasing very rapidly inc ildren and generally speaking, c ildren aremore sensitive to radiation t an adults…

DAVID BRENNERCOLUMBIA UNIVERSITy MEDICAL CENTER

The Image GentlySM

campaign346

is a newinitiative of the Alliance for RadiationSafety in Pediatric Imaging, which beganas a committee of the Society for PediatricRadiology in late 2006. The campaign waslaunched in January 2008. Its goal is tochange medical practice by increasingawareness of the opportunities to lowerradiation dose in the imaging of children.The campaign provides educational



materials to community radiologists,pediatricians, radiologic technologists,medical physicists, and parents. Fourways to decrease radiation to children areemphasized: 347

Reduce or “child size” the amount of•radiation used. Reduce dose as low asreasonably achievable (ALARA) to producea quality image.

Scan only when necessary.•

Scan only the indicated region.•

Scan once; multiphase scanning usually•is not necessary in children.

As of May 2009, 29 organizations dedicatedto reducing the radiation doses childrenreceive from medical imaging examinationshave endorsed the Image Gently campaign. 341

It is reasonable to anticipate that such broadsupport will speed information disseminationand practice change in imaging and nuclearmedicine studies in children. In addition,the Society for Pediatric Radiology and theNational Cancer Institute (NCI) collaboratedto develop and circulate a pamphlet 348 forhealth care providers on pediatric CT andradiation risks.

...in many, many places it's clear t at w ile doses couldave een reduced y a factor of alf from regularx-rays [to digital systems], t ey've actually gone

up y a factor of 50 percent for t e same study.

FRED METTLER, JR.UNIVERSITy OF NEW MEXICO

NEW MEXICO VA HEALTHCARE SySTEM

Medical Radiation Technologists,Radiologists, and HealthProfessionalsProtecting radiation technologists andother medical staff from excessive radiationexposure has been a concern for many years,with dose limits and lifelong monitoringprocedures established in most countries. 349 The dose limit recommended by theInternational Commission on RadiologicalProtection (ICRP) and adopted by all buta few countries is 20 mSv annually, or100 mSv over 5 years. 350 Nearly 98 percentof those who work with ionizing radiationin any aspect of medical practice receive aradiation dose lower than the typical annualdose from all natural sources (e.g., radon,



cosmic radiation, radiation from soil andfood)—about 3 mSv. Only one-half percent ofmedical workers reach or exceed this doselimit.349 It should be noted, however, thatthe U.S. is one of the countries that doesnot adhere to the ICRP recommended doselimits. The Occupational Safety and HealthAdministration regulations stipulate a doselimit for whole body radiation of 50 mSv peryear and, under certain conditions, up to120 mSv per year. 351

Since 1982, the U.S. has conducted acollaborative cohort study of more than146,000 radiation technologists certi edfor two or more years from 1926–1982. 352 This cohort has been followed since 1983to estimate the annual and cumulativeradiation doses of each technologist, withthe goal of assessing occupational radiation-related dose-response patterns. Althoughfollow-up continues, to date, cancer riskselevated to a statistically signi cant levelhave been found only among technologistsworking before 1950. Historically, patientexposures have been of less concern sinceit was assumed that they would undergoexaminations involving ionizing radiation onlyrarely and that any risk was offset by the

expected diagnostic bene t of the test.

Radiation Equipment andTechnologist Licensure andRegulationRadiation exposure from the same test variesconsiderably depending on the age of theequipment and the skill and knowledge ofthe technician. Newer equipment assessesthe shape of the individual being scanned

and determines the minimum amount ofradiation needed to produce an acceptableimage. This approach typically lowers totalradiation dose, and therefore cancer risk. 353 In addition, newer machines used for cardiacangiography shut off while the heart is inmotion during heart beats, emitting radiationonly between beats; this approach alsoreduces radiation dose substantially. 354

Licensure of imaging and radiation therapytechnologists varies from state to statedepending on the type of test performed bythe technologist. Some states have onlypartial regulation, and six states and theDistrict of Columbia have no licensure orregulatory provisions of any kind ( Figure 12).It is estimated that of approximately 50,000radiologic technologists who perform CTscans, only about 23,000 are certi ed in CT. 341

…a t ird of all CT scans practically could e replaced yot er approac es or don’t ave to e performed at all. butit’s going to e really ard to target t is one-t ird ecauset ere are so many pressures on p ysicians to do CT scans.

DAVID BRENNERCOLUMBIA UNIVERSITy MEDICAL CENTER

The public is largely unaware of the radiationdoses delivered by CT, positron emissiontesting, and other examinations that involveionizing radiation, or of potential lifetimemedical radiation doses and associatedcancer risk. Speakers suggested that ifpatients were more aware of radiationexposure due to speci c tests and the cancerrisk that can accrue with cumulative medicalradiation exposure, they might be more likely

to raise this issue with their physicians.Doctors then may suggest alternatives thatdo not involve radiation (e.g., blood tests,magnetic resonance imaging, ultrasound)but still yield suf cient diagnosticinformation. A recently initiated internationalproject would facilitate such doctor-patientdiscussions; efforts are underway to develop“smart cards” on which all radiation dosesreceived by an individual are recorded. 349 This information, when shared by thepatient, also could prevent unnecessaryrepeat scans and would overcome data gapsrelated to patient recall. Though not usingreadable card technology, a number of othermedical centers in the U.S. record and/orprovide patients with dose information for allprocedures that require radiation exposure.The number of institutions adopting thispractice appears to be growing; amongthem, the Clinical Center at the National



ages and a growing percentage of peopleare prescribed medications to treatacute and chronic health conditions. TheNational Health and Nutrition ExaminationSurvey, a national sample of the U.S.civilian population, found that duringthe period 2001–2004, 46.7 percent ofthe surveyed population reported takingat least one prescription drug in theprevious month; 20.2 percent reportedtaking three or more prescription drugsin the prior month. 356 Among the humanmedications found in water supplies areantidepressants, medications for high bloodpressure and diabetes, anticonvulsants,steroid medications, oral contraceptives,hormone replacement therapy medications,codeine, non-prescription pain relievers,chemotherapy drugs, heart medications, andantibiotics. 357,358

In addition, because unneeded or expiredprescription drugs cannot by law be returnedto the pharmacy, people have few optionsfor disposing of them. Legislation 359 hasbeen introduced in the 111th Congress thatwould amend the Controlled Substances

Act360 to facilitate the safe disposal oflegally prescribed controlled substances byauthorized facilities. If passed, it would helplimit the disposal of these medications intothe water supply and prevent their diversioninto illegal sales.

The Federal government has not establishedlimits on the amounts of pharmaceuticalsin drinking water and does not requirewater testing to determine the amountspresent. 361 Scant research has been doneon the long-term or synergistic effects ofmultiple drug exposures of this kind. Sincemedications are intended to have speci ceffects at very low doses, environmentalscientists and others are urging increasedresearch to identify both human andenvironmental risks and greater attentionby the U.S. Environmental ProtectionAgency to this issue. One in vitro studyshowed that exposure to a complex mixtureof medications at environmental levelscan inhibit human embryonic kidney cellgrowth.362 The possible cancer-relatedeffects of pharmaceuticals in drinking waterare as yet unknown.



C H A P T E R5

Exposure to Contaminants and OtherHazards from Military SourcesThe military is a major source of toxicoccupational and environmental exposuresthat can increase cancer risk. Information isavailable about some military activities thathave directly or indirectly exposed militaryand civilian personnel to carcinogens andcontaminated soil and water in numerouslocations in the United States and abroad.However, we may never know the full extentof environmental contamination from militarysources. This chapter provides examplesof chemical and radiation contaminationrelated to military operations.

C emical ContaminationAs noted in Part I , Superfund sites are areasthat have been designated as among theworst areas of toxic contamination in theUnited States. Nearly 900 Superfund sitesare abandoned military facilities or facilitiesthat produced materials and products foror otherwise supported military needs. 363 In some cases, Superfund sites and theareas surrounding them became heavilycontaminated due to improper storage anddisposal of substances such as solvents,machining oils, metalworking uids, andmetals. Many of these substances areknown or suspected carcinogens. Insome cases, these contaminants have

spread far beyond their points of originbecause they have been transportedby wind currents or have leached intodrinking water supplies. Perchlorate andthe solvents trichloroethylene (TCE) andperchloroethylene (PCE/perc) are examplesof this type of contamination.

PerchloratePerchlorate is a rocket fuel component andby-product of rocket and missile testing. Ithas spread from numerous manufacturingsites into drinking water systems; it alsocan accumulate in leafy food crops andfruit irrigated by perchlorate-contaminatedwater. 364 Now ubiquitous in the environment,perchlorate has been detected in the urineof people in all parts of the United States. 365 Perchlorate accumulates in the thyroidgland and can block iodide transfer intothe thyroid, resulting in iodine de ciency.

Adequate iodide is crucial for neurologicaldevelopment. A recent study found that alltypes of powdered baby formula (e.g., milk,soy) are contaminated with perchlorate. 365 If perchlorate also is in tap water used tomix the formula, babies may be doublydosed with the chemical. Long-termexposure to perchlorate has been shownto induce thyroid cancer in rats and mice,



recognized by the VA as associated withexposure to Agent Orange and otherherbicides are chronic lymphocytic leukemia,Hodgkin lymphoma, multiple myeloma, non-Hodgkin lymphoma, prostate cancer, andsome soft tissue sarcomas. 375

ChromiumAccording to recent reports, 376,377 defensecontractor employees assigned in 2003 torebuild a water pumping facility in Iraq andNational Guardsmen from several statesresponsible for their security were exposedvia inhalation and skin contact to a chemicalcontaining hexavalent chromium that wasleft at the site. The chemical originally

was used to remove and prevent corrosionin the water pipes; it later may have beenused by Baathists during the U.S. invasionin an attempt to destroy or sabotage theplant. While on site, many of the exposedindividuals suffered skin sores, nose bleeds,nausea, stomach pain, and respiratoryproblems, including coughing up blood.Some still have residual respiratory andother ailments. As of September 2008, onesoldier who served at the facility had diedfrom lung cancer and another had beendiagnosed with cancer of the sinus cavity.While chromium exposure has not beenproven to be the cause of disease in thesecases, both are consistent with evidence forchromium-induced cancers.

Radioactive ContaminationHundreds of thousands of military personneland civilians in the United States receivedsigni cant radiation doses as a result of theirparticipation in nuclear weapons testingand supporting occupations and industries,including nuclear fuel and weaponsproduction, and uranium mining, milling,and ore transport. Hundreds of thousandsmore were irradiated at levels suf cient tocause cancer and other diseases. Thesepopulations include the families of militaryand civilian workers, and people—knownas “downwinders”—living or working in

communities surrounding or downstreamfrom testing and related activities, and inrelatively distant areas to which nuclearfallout or other radioactive material spread.As speakers at the Panel’s meetingsdetailed and as summarized below, Federalresponses to the plight of affected individualshave been unsatisfactory.

Radiation Exposures Due toNuclear Weapons TestingExposure to ionizing radiation relatedto nuclear weapons testing is anunderappreciated worldwide issue.Longstanding denial by many governmentsas to the type and magnitude of cancer

and other radiation-related health risksfrom nuclear weapons testing exposureshas kept many of those affected fromreceiving needed care. In recent years,some countries have begun to acknowledgeradiation exposures resulting from theirnuclear weapons testing programs. Forexample, the government of France hasagreed to monetary settlements withpersons exposed during its nuclear weaponstests in Algeria and French Polynesia. 378



Most of those affected, both in theUnited States and elsewhere, lackknowledge about the extent of their exposureor potential health problems they mayface. Similarly, most health care providersare not aware of cancer and other latentradiation effects and therefore are unlikely toadequately monitor patients for these healthconditions.

An estimated 210,000 people, mostly servicemembers, took part in atmospheric nuclearweapons tests between 1945 and 1962 in theU.S. and in the Paci c and Atlantic oceans.The Department of Veterans Affairs (VA)estimates that the average radiation dosereceived by these individuals was about0.6 rem (6 mSv). In addition, an estimated195,000 service members participated in thepost-World War II occupation of Hiroshimaand Nagasaki, Japan, or were prisonersof war in Japan; the estimated averageradiation dose sustained by these individualswas < 0.1 rem (<1 mSv).379,380 Since 1978,the Defense Threat Reduction Agency’sNuclear Test Personnel Review program hasmaintained a database of U.S. atmosphericnuclear test activity participants andindividuals who served with the occupation

forces or were prisoners of war in Japan. 381

Nuclear Weapons PlantsThe Hanford nuclear weapons facility (alsocalled the Hanford Nuclear Reservation) insouth-central Washington is one of dozensof nuclear weapons and weapons fuelproduction sites in the U.S.; others includefacilities at Oak Ridge, Tennessee andSavannah River, Georgia. Many Hanford fuelproduction workers have developed cancersthey maintain were caused by radiation

exposures they experienced during theiremployment. In addition, a recent study 382 offormer Hanford construction workers foundthey were three times more likely to developmultiple myeloma, a relatively rare bloodsystem cancer, than the general population.

Higher incidence of multiple myeloma alsohas been documented at other DOE weaponsproduction sites. The construction workersalso were found to be 11 times more likelyto develop mesothelioma, probably due toasbestos exposures at the site.

In its 2002 report, 383 the Panel describedradiation exposures and health problems,including cancer, experienced by theYakima Nation and other Northwest NativeAmericans who live in close proximity to the

Hanford nuclear weapons production plant.In addition to numerous gaseous emissionsof radioactive iodine (I-131) during its nearly30 years of operation, the Hanford site, whichcovers nearly 600 square miles, dischargedover 400 billion gallons of radioactive wasteinto the surrounding soil and the ColumbiaRiver.384 The plant ceased operations in1972, but it now is the largest nuclear wastestorage site in the country.

T e testing was almost all done a ove ground....and t eyield was e ual to 7,200 hiros ima om s....T at’s like

e ploding 1.6 hiros ima om s per day for 12 years in t eMars all Islands. T at’s ow muc radiation t ere was.

NEAL PALAFOXUNIVERSITy OF HAWAI’I



Nuclear waste at Hanford has an estimated195 million curies of radioactivity. 385 Nearly5 tons of plutonium and over 53 milliongallons of radioactive plutonium wasteare stored in hundreds of undergroundtanks. 386 Many of the storage tanks havea capacity of one million gallons. DOEacknowledges that approximately 60 of thetanks have leaked, and others are suspectedof leaking.387 As of 2008, only seven of theleaking tanks had been emptied. 388 Anestimated one million gallons of high-levelnuclear and chemical waste have leaked intothe soil, contaminating 200 square milesof land under the Hanford facility. Thisradioactive waste continues to leach into thegroundwater that empties into the Columbia

River, the principal site of salmon spawningin the region and main water source foragriculture and recreation in most ofsouthern Washington and northern Oregon.The river also supplies drinking water fornearly a million people.

The Hanford cleanup program is perhapsone of the most complex, technicallychallenging, and costly hazard remediationprojects ever attempted. 388 Its annual budgetis greater than that of hundreds of other

Superfund cleanups combined. The cleanupwas initiated in 1989 with an expectation thatthe job would be completed in 30 years. In2009, the job was less than half completed,and the current Department of Energy (DOE)budget allows for emptying only one storagetank per year.

Uranium Miners, Mill Workers,and Ore Transporters

Uranium mining and milling were essentialunderpinnings of the U.S. nuclear weaponsprogram. Military and civilian personnel,including Native Americans, receivedsubstantial radiation doses in the courseof their employment and are eligible forcompensation for lung and renal cancersand certain other medical conditions (seebelow). Much of the uranium mined in theU.S. was located in or near Navajo tribal

lands in New Mexico. The Navajo banneduranium mining and milling in 2005. Morethan 1,000 uranium mines and mill sitesexist in the region, and most have notbeen sealed or cleaned up 389 since miningdeclined following the Cold War years; someare designated Superfund sites. Many ofthe miners and mill workers were Navajowho worked without respirators or otherprotection and still live with their familiesnear the work sites, where they continuallybreathe uranium dust and drink uranium-contaminated water. Both the Navajo andLaguna tribes have experienced markedlyhigher than average rates of lung cancer,as well as kidney disease, birth defects, andother health problems.

…a w ole group of kids e posed as c ildrenave een ignored completely. (referring

to hanford and Nevada Test Site)

TRISHA THOMPSON PRITIKINHANFORD DOWNWINDER

Of late, global warming and uctuating oilprices have brought a renewed interest innuclear power, which in turn has causeda resurgence of interest in uranium mining,

primarily in New Mexico. Several companieshave applied for mining licenses; 390,391 these actions are of great concern to theNavajo Nation.

Downwinders and OtherCommunities Near NuclearTest Sites, Nuclear Power andWeapons Plants, and UraniumMines and Mills

It may never be known how many hundredsof thousands—or millions—of people livingnear and downwind and/or downstreamfrom nuclear weapons testing sites, nuclearpower and weapons plants, uranium minesand mills, and nuclear waste storage siteshave been exposed to signi cant radioactivecontamination. This contamination occurreddue to nuclear weapons tests, radioactivegaseous emissions, radioactive waste



square miles. A wind change caused thefallout cloud to drift over four other atollsinhabited by more than 600 people. Thesepeople received acute radiation dosesestimated at 2,000 mSv. 398 Although theywere evacuated from these islands forseveral years following the blast, they werereturned there for a period of years while theislands still were contaminated before beingrescued by Greenpeace, an environmentalprotection advocacy organization. As aresult, prolonged radiation doses followedthe acute exposures. Some of the affectedislands remain uninhabitable. Other islandsand atolls were affected to varying degrees.

In addition to the Marshallese, many workersfrom U.S.-associated Micronesia werebrought to the Marshall Islands to cleanup after the blast; their level of exposure isunknown. NCI’s 2004 report 399 estimatedthat 530 excess cancers would be expectedin the people living in the Marshall Islandsduring the testing period, and that due tothe latency period of cancer, about half ofthese malignancies had yet to be detected.The increase in all cancers resultingfrom fallout exposure was estimated at9 percent, but radiation-related cancer

estimates varied considerably by cancertype and atoll of residence at the time ofthe blast. The population of the Rongelapand Ailinginae atolls received the highestradiation exposure. In that population,98 percent of projected thyroid cancers and76 percent of projected stomach cancerswere estimated to be radiation-related.Since publication of the 2004 report, workhas been underway to develop more re nedestimates of radiation exposure among theMarshallese, using additional collected dataand more contemporary environmentalradiation measurements. Eight manuscriptshave been prepared and submitted for peerreview and publication before the end of2009.400 One speaker stated that health carestandards for the Marshallese affected by thenuclear testing program are lower than thosefor peoples affected by ionizing radiationfrom the Nevada Test Site or Hanford nuclearweapons site, but emphasized strongly that

they should be fully commensurate withU.S. standards for prevention, screening,diagnosis, and treatment. In addition, it wasnoted that there has been no considerationof the stress and related illness sufferedby the Marshallese due to the irreparabledisruption of their culture and loss of theirhomeland.

Federal Compensation andRelated Programs for PersonsExposed to Radiation fromNuclear SourcesPeople exposed to radiation from nuclearsources, and the families of exposedindividuals, have sought appropriate medicalcare and monetary compensation for healthproblems, disabilities, and prematuredeath resulting from radiation exposures.Claimants, however, have encounteredsigni cant barriers to accessing bene tsthrough Federal programs created toprovide such health care and compensation.As detailed below, the principal barriershave been dif culties claimants face indocumenting radiation exposures andproving that their injuries or disease resulted

from those exposures.

...t e medical system in t e Mars all Islands and a lot ofMicronesia can’t andle t is. We’re talking a out cancersand radiation oncology, and in all of t e U.S.-associatedPaci c t ere is one oncologist; t at person is in Guam.

NEAL PALAFOXUNIVERSITy OF HAWAI’I

The Radiation Exposure Compensation Act(RECA)

In 1990, the Federal government passedthe Radiation Exposure Compensation Act(RECA),401,402 to provide for compassionatepayments to individuals who developedcertain cancers and other serious diseasesas a result of their exposure to radiationreleased during above-ground nuclearweapons tests, due to radiation exposureduring employment in underground uraniummines, and as a result of living or working



The Marshall Islands Special Medical CareProgram 408 is a separate medical careprogram established to provide care forindividuals directly or indirectly sufferingradiation-related injury, illness, or otherconditions as a result of the Castle Bravonuclear bomb test. There has beendisagreement, however, as to who should becovered under this program, with individualsfrom Micronesia and Guam maintaining thatthey too were affected by fallout from theblast. According to one speaker, authoritygoverning the program has been unclear,and funding for the program has beengrossly inadequate.

Funding issues are exacerbated by thelimited health resources available in theMarshall Islands and elsewhere in thePaci c Islands to treat affected individualswho seek care through the Section 177 andSpecial Medical Care programs.

Marshall Islands Nuclear Claims Tribunal

In June 1983, a formal agreement wasestablished between the U.S. Governmentand the RMI in which the U.S. recognizedthe contributions and sacri ces of theMarshallese with regard to the U.S. nucleartesting program. Under the Section 177

Agreement, a Nuclear Claims Tribunal wasestablished with jurisdiction to “render

nal determination upon all claims past,present and future, of the Government,citizens and nationals of the MarshallIslands...in any way related to the NuclearTesting Program.” 409 The U.S. provided$150 million for compensation for damagescaused by the testing program. In 2000,following the release of previously classi edindividual records and other documentsdescribing effects of the testing program,the RMI submitted a Petition of ChangedCircumstances, requesting additionalcompensation for injuries and damages. 410 As of June 2007, $45.75 million has beenpaid toward the $83 million in claims forpersonal injury awarded by the Tribunal. In2007, the Tribunal awarded over $1 billionin property damage awards in a class actionsuit led by residents of two of the mosthighly affected islands. This award hasnot been paid. Other medical and propertydamage claims continue to be led.

MARShALL ISLANDS

Energy Employees Occupational IllnessCompensation Program 411

In July 2001, Congress passed theEnergy Employees Occupational IllnessCompensation Program Act in recognition



personnel who participated in atmosphericnuclear weapons tests at the Trinity Site inNew Mexico, the NTS, and in the Paci c,or who were stationed or prisoners of warin Japan after the atomic bombs weredetonated. Following the recommendationof a 2003 National Academy of Sciencesreport 413 on the Dose ReconstructionProgram, the Veterans’ Bene ts Act of2003414 provided for the establishment of anindependent advisory board—the VBDR—tooversee the dose reconstruction and claimssettlement programs.

Advisory Committee on Energy-RelatedEpidemiologic Research (ACERER)

Created in 1992, ACERER was charged tohelp the U.S. Department of Health andHuman Services (HHS) ensure that itsresearch into the potential health effectsof nuclear production and testing wasscienti cally sound and that questionsfrom downwinders about health riskswere answered. ACERER was critical ofa 2002 CDC study415 on radiation-relateddisease that found little or no cancer risk.The study was revised in January 2007,but the cancer-related ndings wereessentially unchanged. 416 Based on the2002 study, ACERER recommended thatthe government notify Americans known tohave received high radiation doses. Theserecommendations were at odds with HHSpolicy at the time. 393 ACERER’s commissionwas allowed to expire in February 2002,without notice either to members orstakeholders. According to one speaker,ACERER was the only avenue for communityinput on radiation-related disease dueto government nuclear production andweapons testing.

Legislation Introduced Since the Panel’sMeetings

The Charlie Wolf Nuclear Compensation Act(S.757/H.R.1828), introduced in Congress inApril 2009, would make it easier for formerRocky Flats, Tennessee nuclear weapons

plant workers to seek compensation forillnesses contracted due to exposure toradiation and toxins at the plant. Theplant itself was closed in 1992; most of itsbuildings were removed by 2005 and workerrecords are no longer available or no longerexist.417 Importantly, should this or a similarbill become law, it would for the rst timeshift the burden of proof from the workersand their families to the federal government.

The Atomic Veterans Relief Act (H.R.2573)was introduced in Congress in 2009; thebill would revise the eligibility criteriafor presumption of service-connection ofcertain diseases and disabilities for veteransexposed to ionizing radiation during militaryservice. The bill also would require thegovernment to follow speci c procedures forthe mathematical calculation of the level ofexposure sustained by the veteran.

Depleted UraniumAs the sections above detail, thousands ofmilitary and civilian workers were exposedto ionizing radiation during World War IIand throughout the Cold War era in dosesthat are acknowledged to be cancer-

causing. More recently, many participantsin the Balkan con ict and in the wars inAfghanistan and Iraq have been exposedto depleted uranium (DU), a by-product ofuranium enrichment. DU has some civilianapplications, but in the military it is usedto make DU “penetrator” ammunition andmilitary armor. 418 Individuals in the vicinityof exploded DU penetrator ammunitionor damaged military armor can beexposed to DU by ingesting food and watercontaminated by DU particles or uraniumfrom corroding DU penetrators, inhalingairborne DU particles, and if wounded,by shrapnel. Little is known about theDU exposure of munitions and militaryequipment manufacturing workers. In vitro and rodent studies suggest that chronic DUexposure may be linked to leukemia andhave genetic, reproductive, and neurologicaleffects. 419



cancers arise from exposures below thatlevel.440 As with other types of potentiallyhazardous exposures, vigorous debateexists regarding the relative safety of low-dose exposures. Speakers at the PCPmeetings questioned whether EPA’s actionlevel for radon should be lowered. An EPArepresentative emphasized that the currentaction level does not imply that levels below4 pCi/L are safe; signi cant risk exists belowthe action level and, in fact, no safe exposurelevel has been identi ed. 441 In 2009, theWorld Health Organization (WHO) revised itsrecommendation for a maximum acceptableradon concentration in a residential dwellingto 2.7 pCi/L.442

Radon and its decay products account for37 percent of the overall population radiationdose from natural sources. 308 As Figure 14shows, radon levels vary considerably acrossthe United States. EPA emphasizes thatelevated radon levels can be found in homesin all three zones, and that all homes shouldbe tested for radon. 443

It’s important to know t at radon is naturallyoccurring, ut in t e ome it’s not naturallyoccurring; it’s en anced. We can uild omesradon resistant. We just c oose not to do so.

WILLIAM FIELDUNIVERSITy OF IOWA

Figure 14EPA Map of Radon zones

Source: U.S. Environmental Protection Agency, April, 2009 [Internet]. [cited 2009 May 20] Available from: http://www.epa.gov/radon/zonemap.html.

While the public may know that radonexists, relatively few people are aware of thelevels at which radon concentration shouldcause signi cant concern. As a result ofconcerted efforts by EPA pursuant to theIndoor Air Abatement Act, most states nowhave radon reduction programs, yet as ofDecember 2008, none require mandatoryradon testing prior to a home sale. 444 More

than half of states have residential realestate disclosure laws, 441 meaning that ifthe radon level of a home is known, it mustbe disclosed. If a home’s radon level is notknown, it is up to the prospective buyer toarrange for a radon test. In most states,

Guam

Zone 1 (red) counties have a predicted average indoor radonscreening level greater than 4 pCi/L (picocuries per liter)

Zone 2 (orange) counties have a predicted average indoor radonscreening level between 2 and 4 pCi/L

Zone 3 (yellow) have a predicted average indoor radon screeninglevel less than 2 pCi/L



of the Inspector General at EPA, mostradon testing devices on the market requirereevaluation to determine their accuracy. 445 Approximately 20 states have enactedlegislation requiring professional certi cationor licensure of both testers and/or radonmitigation vendors, 444 but implementationvaries widely.

Well-established methods are available toreduce radon concentrations to below theEPA action level in homes with elevatedradon concentrations. 448–451 According toone speaker at a Panel meeting, radonventing for new home construction costsapproximately $300–500. It is required insome states (WA, MN, MI, NJ, ME); onlythree states (CT, NJ, RI) require radoncontrol in new school construction. 441 Retro tting existing homes that have highradon concentrations with mitigation ventingcosts approximately $1,200; in one study,mitigation reduced average residentialradon levels from more than 10 pCi/Lto 1.2 pCi/L.451 EPA recommends thathomeowners consider mitigation if radonlevels are at 2–4 pCi/L. 441

ArsenicInorganic arsenic, a potent toxin, is found inbedrock at varying levels worldwide. Mostinorganic arsenic in drinking water is fromnatural sources, but human activities suchas mining, ore processing, use of arsenic-containing pesticides, and burning of fossilfuels are major contributors to waterbornearsenic in the U.S. 267 Both the EPA MaximumContaminant Level (MCL)452 and WHO453 recommendations for inorganic arsenic

limits in drinking water are 10 micrograms/liter. Organic arsenic compounds (thosecontaining carbon) are found mainly inaquatic organisms, and are far less toxicthan inorganic arsenic.

Ecologic, cohort, and case-control studiesof highly exposed populations have linkedinorganic arsenic in drinking water withskin, lung, bladder, and kidney cancer inboth sexes and with prostate cancer inmen. 267 Both EPA and the InternationalAgency for Research on Cancer classifyingested inorganic arsenic as a knownhuman carcinogen. 77,454 Inorganic arsenicalso is associated with numerous non-cancer conditions, including gastrointestinal,vascular, neurologic, blood system,endocrine, respiratory, skin, reproductive,and developmental effects. 267,454

Cancer risk related to low-level inorganicarsenic exposure has been estimated byextrapolation from high-exposure studies.Exposure is determined by the presenceof arsenic and arsenic metabolites inurine. A large, NCI-led, collaborative case-control study underway in northern NewEngland is assessing the carcinogenicityof arsenic exposure at lower doses. Otherresearchers are attempting to understandvariations in individual susceptibility tocarcinogenic effects of ingested arsenic.Some evidence suggests that diets de cientin micronutrients such as vitamins B-2,

B-6, B-12, and folic acid may increasesusceptibility to arsenic-induced cancers. 267



Just as there are many opportunities forharmful environmental exposures, ampleopportunities also exist for intervention,change, and prevention to protect the healthof current and future generations and reducethe national burden of cancer. The Panelconcludes that:

We Need to Determine t eFull E tent of EnvironmentalIn uences on Cancer.At this time, we do not know how muchenvironmental exposures in uence cancerrisk and related immune and endocrine

dysfunction. Environmental contaminationvaries greatly by type and magnitudeacross the nation, and the lifetime effectsof exposure to combinations of chemicalsand other agents are largely unstudied.Similarly, the cancer impact of exposuresduring key “windows of vulnerability” suchas the prenatal period, early life, and pubertyare not well understood. Nonetheless, whilethese diverse effects often are dif cult toquantify with existing technologies andresearch methods, in a great many instances,we know enough to act.

T e Nation Needsa Compre ensive,Co esive Policy Agenda

Regarding EnvironmentalContaminants and Protectionof human healt .Environmental health, including cancerrisk, has been largely excluded from overallnational policy on protecting and improvingthe health of Americans. It is more effectiveto prevent disease than to treat it, but cancerprevention efforts have focused narrowlyon smoking, other lifestyle behaviors, and

chemopreventive interventions. Scienti cevidence on individual and multipleenvironmental exposure effects on diseaseinitiation and outcomes, and consequenthealth system and societal costs are notbeing adequately integrated into nationalpolicy decisions and strategies for diseaseprevention, health care access, and healthsystem reform.



C ildren Are at SpecialRisk for Cancer Due toEnvironmental Contaminantsand S ould be Protected.Opportunities for eliminating or minimizingcancer-causing and cancer-promotingenvironmental exposures must be actedupon to protect all Americans, but especiallychildren. They are at special risk due totheir smaller body mass and rapid physicaldevelopment, both of which magnifytheir vulnerability to known or suspectedcarcinogens, including radiation. Numerousenvironmental contaminants can cross theplacental barrier; to a disturbing extent,

babies are born “pre-polluted.” Childrenalso can be harmed by genetic or otherdamage sustained by the mother (and insome cases, the father). There is a criticallack of knowledge and appreciation ofenvironmental threats to children’s healthand a severe shortage of researchersand clinicians trained in children’senvironmental health.

Continued Epidemiologicand Ot er EnvironmentalCancer Researc Is Needed.Available evidence on the level of potentialharm and increased cancer risk from manyenvironmental exposures is insuf cientor equivocal. The Panel is particularlyconcerned that the impact, mechanismsof action, and potential interaction of someknown and suspected carcinogens arepoorly de ned.

Meaningful measurement and•assessment of the cancer risk associatedwith many environmental exposuresis hampered by a lack of accuratemeasurement tools and methodologies.This is particularly true regarding

cumulative exposure to speci cestablished or possible carcinogens(e.g., radon, low-dose radiofrequencyand electromagnetic energy, endocrinedisrupting chemicals), gene-environmentinteractions, emerging technologies (e.g.,nanoparticles), and the effects of multipleagent exposures.

Single-agent toxicity testing and reliance•on animal testing are inadequateto address the backlog of untestedchemicals already in use and the plethoraof new chemicals introduced every year.Some high-throughput screening (HTS)technologies are available to enabletesting of many chemicals and othercontaminants simultaneously, but manyremain to be developed to meet chemicaltesting needs. Support also is neededto develop methods for interpreting thewealth of data that HTS technologiesgenerate. At this time, incentives toencourage development of this researchare nearly non-existent.

Support for large, longitudinal studies•to clarify the nature and magnitude ofcancer risk attributable to environmentalcontaminants must continue. The

capacity to collect biologic samples atthe inception of studies is essential;even if current technologies do not allowthese samples to be fully utilized at thistime, it must be assumed that suchtechnologies will evolve and enable use ofcollected biosamples to provide essentialstudy baseline data. Personal healthdata privacy issues that currently limitresearch access to data and biosampleswill need to be addressed.

Cancer risk assessment also is hampered• by lack of access to existing exposuredata, especially for occupational/industrial exposures, and regardinglevels of radon, asbestos, and othercontaminants in schools and day carecenters.



An Environmental healtParadigm for Long-LatencyDisease Is Needed.Recognizing that results of laboratoryand animal studies do not always predicthuman responses, an environmental healthparadigm for long-latency diseases isneeded to enable regulatory action basedon compelling animal and in vitro evidencebefore cause and effect in humans hasbeen proven.

E isting Regulations forEnvironmental ContaminantsNeed to be Enforcedand Updated; StrongerRegulation is Needed.Weak laws and regulations, inef cientenforcement, regulatory complexity, andfragmented authority allow avoidableexposures to known or suspected cancer-causing and cancer-promoting agents tocontinue and proliferate in the workplaceand the community. Existing regulations,and the exposure assessments on whichthey are based, are outdated in most cases,and many known or suspected carcinogensare completely unregulated. Enforcement ofmost existing regulations is poor. In virtuallyall cases, regulations fail to take multipleexposures and exposure interactionsinto account. In addition, regulationsfor workplace environments are focusedmore on safety than on health. Industryhas exploited regulatory weaknesses,

such as government’s reactionary(rather than precautionary) approach toregulation. Likewise, industry has exploitedgovernment’s use of the awed and grosslyoutdated Doll and Peto methodology forassessing “attributable fractions” of thecancer burden due to speci c environmentalexposures. This methodology has been usedeffectively by industry to justify introducinguntested chemicals into the environment.

Radiation E posurefrom Medical SourcesIs Underappreciated.The use of computed tomography (CT) andother radiation-emitting tests is growingrapidly. Many physicians, other healthcare providers, and the public are unawareof the radiation dose delivered by speci cimaging and nuclear medicine studiesand the signi cant variation in radiationdose that can occur due to differences inequipment, technologist skill, applicationof dose-reduction strategies, and patientsize, age, and gender. Moreover, many donot recognize that radiation exposure is

cumulative, and that a single large doseand numerous low doses equal to the singlelarge dose have much the same effect onthe body over time. At least one initiativeis underway to improve and disseminateradiation reduction strategies and educatephysicians, device manufacturers, theirtraining staff, and others about radiationdoses associated with speci c tests.Additional efforts are needed to eliminateunnecessary testing and improve bothequipment capability and operator skill to

ensure that radiation doses are as low asreasonably achievable without sacri cingimage or test data quality. No mechanismexists to enable individuals to estimatetheir personal cumulative radiationexposure, which would help patients andphysicians weigh the bene ts and potentialharm of contemplated imaging and nuclearmedicine tests.



Medical Professionals Needto Consider Occupational andEnvironmental Factors W enDiagnosing Patient Illness.Physicians and other medical professionalsask infrequently about patient workplace andhome environments when taking a medicalhistory. Such information can be invaluablein discovering underlying causes of disease.Moreover, gathering this information wouldcontribute substantially to the body ofknowledge on environmental cancer risk.

Workers, Ot er Populationswit Known E posures,and t e General Pu licRe uire Full Disclosureof Knowledge a outEnvironmental Cancer Risks.Individuals and communities are notbeing provided all available informationabout environmental exposures they haveexperienced, the cumulative effects of such

exposures, and how to minimize harmfulexposures. The disproportionate burden ofexposure to known or suspected carcinogensexperienced by speci c populations (e.g.,agricultural and chemical workers andtheir families, radiation-exposed groupssuch as uranium mine workers, nuclearindustry workers, nuclear test site workersand “downwinders,” residents of cancer “hotspots” or other contaminated areas) has notbeen fully acknowledged.

T e Military Needs toAggressively Addresst e To ic EnvironmentalE posures It has Caused.Toxic materials produced for and used by themilitary have caused widespread air, soil,and water pollution across the United Statesand beyond our borders, including chemicaland radiation contamination in and aroundcurrent and former military installations,materiel production facilities, and mines.These contaminants, many of which mayhave serious long-term and latent effectsincluding cancer, are a danger both tomilitary personnel and civilians. Overall,

the military has not responded adequatelyto health problems associated with itsoperations absent substantial pressurefrom those affected, advocacy groups, orthe media. Of special concern, the U.S.has not met its obligation to provide forongoing health needs of the people of theRepublic of the Marshall Islands resultingfrom radiation exposures they receivedduring U.S. nuclear weapons testing in thePaci c from 1946–1958.

Safer Alternatives to ManyCurrently Used C emicalsAre Urgently Needed.The requisite knowledge and technologiesexist to develop alternatives to manycurrently used chemical agents known orbelieved to cause or promote cancer. Manychemists require additional training tounderstand environmental hazards andreformulate products. Importantly, “greenchemistry” alternative products themselvesrequire longitudinal study to ensure that theydo not pose unexpected health hazards.





2. A thorough new assessment of workplace chemicaland other exposures is needed to quantify currenthealth risks. Previous estimates of occupationalcancer risk are outdated and should no longer be usedby government or industry.

Congress

National Academy of Science/Institute of MedicineNational Science Foundation (NSF)

General Accountability Of ceOther multidisciplinary groupappointed for this taskHHS/National Institute forOccupational Safety and Health(NIOSH)DOL:

OSHA•Mine Safety and Health•

Administration (MSHA)

3. In large measure, adequate environmental healthregulatory agencies and infrastructures alreadyexist, but agencies responsible for promulgatingand enforcing regulations related to environmentalexposures are failing to carry out their responsibilities.The following are needed:

A more integrated, coordinated, and transparent•system for promulgating and enforcingenvironmental contaminant policy and regulations,driven by science and free of political or industryin uence, must be developed to protect public

health.

EPAHHS/FDA

USDADOL:

OSHA•MSHA•

Better concordance of exposure measures and•standards is needed to facilitate interagency andinternational regulatory policy and enforcement andto identify research needs.

HHS/National Institute ofEnvironmental Health Services(NIEHS)EPADOL/OSHA

The United States should carefully consider the•potential impact on consumers and commerce ofthe Globally Harmonized System for classifyingcarcinogens.

President/AdministrationCongress





Information sharing among the public, researchers,•regulatory agencies, industry, and otherstakeholders must be a bedrock component of theenvironmental health regulatory system mission.

EPA

DOL:OSHA•MSHA•

HHS:FDA•Center for Disease Control and•Prevention (CDC)

USDADepartment of Defense (DoD)

Department of Energy (DOE)Environmental and cancer researchcommunities

IndustryMedia

Environmental and public health advocates should•be included in developing the environmental cancerresearch and policy agendas and in informationdissemination.

Advocates

EPAHHS:

FDA•CDC•

DOE

4. Epidemiologic and hazard assessment researchmust be continued and strengthened in areas in

which the evidence is unclear, especially researchon workplace exposures, the impact of in utero andchildhood exposures, and exposures that appear tohave multigenerational effects. Current funding forfederally supported occupational and environmentalepidemiologic cancer research is inadequate.

CongressEPA

HHS:National Cancer Institute (NCI)•NIEHS•National Institute for Child Health•and Human DevelopmentNIOSH•

EPANSF

Nongovernmental research funders





5. Measurement tool development and exposureassessment research, including the developmentof new research models and endpoints, shouldbe accelerated to enable better quanti cation ofexposures at individual, occupational, and populationlevels.

High-throughput screening technologies and•related data interpretation models should bedeveloped and used to evaluate multiple exposuressimultaneously. It may be possible to screenapparently similar suspect chemicals together andregulate these as a group as indicated by ndings.

HHSNIEHS•NIOSH•

NSFDoD/Applied Research ProjectsAgencyIndustry

Methods for long-term monitoring and• quanti cation of electromagnetic energy exposuresrelated to cell phones and wireless technologies areurgently needed given the escalating use of thesedevices by larger and younger segments of thepopulation and the higher radiofrequencies newerdevices produce.

DOEHHS/NIOSH

EPANational Council on RadiationProtection and Measurements(NCRP)

6. The cancer risk attributable to residential radonexposure has been clearly demonstrated and must bebetter addressed. The following are needed:

The Environmental Protection Agency (EPA) should•consider lowering its current action level (4 pCi/L)

for radon exposure, taking into account data onradon-related cancer risk developed since theexisting action level was established.

EPA

Public and health care provider education should•be developed and broadly disseminated to raiseawareness of radon-related cancer risk.

HHS

Health care provider professionalorganizationsMedia

Improved testing methods for residential radon•exposure and better methods for assessingcumulative exposure should be developed. Taxdeductions or other incentives should beimplemented to encourage radon mitigation

retro tting of existing housing. Building codechanges should be made to require radon reductionventing in new construction.

Industry

CongressInternal Revenue Service


All schools, day care centers, and workplaces•should be tested at regular intervals for radon.Radon level data must be made available to thepublic. Buildings found to have levels in excess ofthe EPA action level should be mitigated.






7. Actions must be taken to minimize radiation exposurefrom medical sources. Speci cally:

Health care providers, radiology technicians, and•the public must be informed about the extentof radiation exposure from commonly usedimaging and nuclear medicine examinations andthe potential health risks of these procedures.Referring physicians are responsible for discussingwith the patient the balance of bene t and riskassociated with each imaging or nuclear medicineprocedure being recommended. An educational/decision-making tool that considers each patient’scumulative lifetime radiation exposure shouldbe developed to facilitate these provider-patientcommunications.

Physicians and other health careprovidersHealth professional organizationsAdvocates

MediaHHS:

Agency for Healthcare Research•and QualityNCI•

The estimated effective radiation dose of all imaging•and nuclear medicine tests performed should be arequired element in patient records and should bea core data element in all electronic health recordssystems. In addition, patients should be assistedto reconstruct an estimate of the total medicalradiation dose they have received.

Joint Commission for Accreditation ofHealthcare Organizations (JCAHO)

HHS:FDA•Centers for Medicare and•Medicaid Services (CMS)CDC•Health Resources and Services•Administration (HRSA)Indian Health Service (IHS)•Of ce of the National Coordinator•for Health Information Technology(ONCHIT)

Department of Veterans Affairs (VA)DoD


Radiation dose-lowering techniques must be•implemented consistently and to the maximumextent feasible.


Inspection of radiation-emitting medical equipment•and pharmaceuticals must become more stringent,and uniform credentialing of technicians whoadminister scans is needed.

JCAHO

Radiation technologist professionalorganizations

HHS/FDA





8. The unequal burden of exposure to known andsuspected carcinogens must be addressed.

Individuals exposed to nuclear fallout and other•nuclear contamination by biologically importantradionuclides must be provided all availableinformation on these exposures. A system mustbe developed to enable affected individuals toreconstruct and add radiation doses received sothat they can adequately assess their cumulativeexposure and potential health risks, includingcancer.

DoDDOE

Nuclear Regulatory CommissionHHS/NCIVA

NCRP

The Advisory Committee on Energy-related•Epidemiologic Research (ACERER) should berechartered, or a similar body convened, to enableindividuals exposed to nuclear testing fallout andother nuclear exposures to participate in policymaking and other decisions that will affect theiraccess to health care and compensation related tothose exposures.

DOE

Geographic areas and vulnerable populations•(including but not limited to children, migrant andother farm workers, and residents of high-povertyareas and cancer "hot spots") should be studiedto determine environmental in uences on cancerrisk; identi ed risks must be remediated to themaximum extent possible.

EPA

HHS/NIEHSDoD

USDA

The U.S. Government should honor and make•payments according to the judgment of theMarshall Islands Tribunal.

President/Administration

Congress





9. Physicians and other medical personnel shouldroutinely query patients about their previous andcurrent workplace and home environments as partof the standard medical history. This information willincrease the likelihood that environmental factors incancer and other illnesses are considered and willstrengthen the body of information on environmentalexposures and disease. Data on workplace and homeenvironmental history should be incorporated intoexisting and developing automated medical recordssystems.


HHS:ONCHIT•NCI: Surveillance, Epidemiology,•and End Results ProgramCDC: National Program of Cancer•RegistriesCMS•HRSA•IHS•

DoD: TRICARE

VA: Veterans Health InformationSystem and Technology Architecture

Private insurer patient databases

10. “Green chemistry” initiatives and research, includingprocess redesign, should be pursued and supportedmore aggressively, but new products must be well-studied prior to and following their introduction intothe environment and stringently regulated to ensuretheir short- and long-term safety.

HHS/NIEHSEPA

NSF

11. Public health messages should be developed anddisseminated to raise awareness of environmentalcancer risks and encourage people to reduce oreliminate exposures whenever possible.

HHS:FDA•CDC•HRSA•

CMS•USDADOE

Federal CommunicationsCommissionAdvocates

Media

* The Panel recognizes that entities other than those listed may have a vital role or interest in implementation of the recommendations.



What Individuals Can Do:RecommendationsMuch remains to be learned about the effects of environmental exposures on cancer risk.Based on what is known, however, there is much that government and industry can do now toaddress environmental cancer risk. The Panel’s recommendations in this regard are detailedabove. At the same time, individuals can take important steps in their own lives to reducetheir exposure to environmental elements that increase risk for cancer and other diseases.And collectively, individual small actions can drastically reduce the number and levels ofenvironmental contaminants.

ChILDREN

1. It is vitally important to recognize that children are far more susceptible to damage fromenvironmental carcinogens and endocrine-disrupting compounds than adults. To the extentpossible, parents and child care providers should choose foods, house and garden products,play spaces, toys, medicines, and medical tests that will minimize children’s exposure to toxics.Ideally, both mothers and fathers should avoid exposure to endocrine-disrupting chemicals andknown or suspected carcinogens prior to a child’s conception and throughout pregnancy andearly life, when risk of damage is greatest.

ChEMICAL ExPOSURES

2. Individuals and families have many opportunities to reduce or eliminate chemical exposures. Forexample:

Family exposure to numerous occupational chemicals can be reduced by removing shoes•

before entering the home and washing work clothes separately from the other family laundry.Filtering home tap or well water can decrease exposure to numerous known or suspected•carcinogens and endocrine-disrupting chemicals. Unless the home water source is knownto be contaminated, it is preferable to use ltered tap water instead of commercially bottledwater.

Storing and carrying water in stainless steel, glass, or BPA- and phthalate-free containers•will reduce exposure to endocrine-disrupting and other chemicals that may leach into waterfrom plastics. This action also will decrease the need for plastic bottles, the manufactureof which produces toxic by-products, and reduce the need to dispose of and recycle plasticbottles. Similarly, microwaving food and beverages in ceramic or glass instead of plasticcontainers will reduce exposure to endocrine-disrupting chemicals that may leach into foodwhen containers are heated.



Exposure to pesticides can be decreased by choosing, to the extent possible, food grown•without pesticides or chemical fertilizers and washing conventionally grown produce toremove residues. Similarly, exposure to antibiotics, growth hormones, and toxic run-offfrom livestock feed lots can be minimized by eating free-range meat raised without thesemedications if it is available. Avoiding or minimizing consumption of processed, charred, andwell-done meats will reduce exposure to carcinogenic heterocyclic amines and polyaromatic

hydrocarbons.Individuals can consult information sources such as the Household Products Database to help•them make informed decisions about the products they buy and use.

Properly disposing of pharmaceuticals, household chemicals, paints, and other materials will•minimize drinking water and soil contamination. Individuals also can choose products madewith non-toxic substances or environmentally safe chemicals. Similarly, reducing or ceasinglandscaping pesticide and fertilizer use will help keep these chemicals from contaminatingdrinking water supplies.

Turning off lights and electrical devices when not in use reduces exposure to petroleum•combustion by-products because doing so reduces the need for electricity, much of which isgenerated using fossil fuels. Driving a fuel-ef cient car, biking or walking when possible, orusing public transportation also cuts the amount of toxic auto exhaust in the air.

Individuals can reduce or eliminate exposure to secondhand tobacco smoke in the home, auto,•and public places. Most counseling and medications to help smokers quit are covered byhealth insurance or available at little or no cost.

RADIATION

3. Adults and children can reduce their exposure to electromagnetic energy by wearing a headsetwhen using a cell phone, texting instead of calling, and keeping calls brief.

4. It is advisable to periodically check home radon levels. Home buyers should conduct a radon testin any home they are considering purchasing.

5. To reduce exposure to radiation from medical sources, patients should discuss with their healthcare providers the need for medical tests or procedures that involve radiation exposure. Keyconsiderations include personal history of radiation exposure, the expected bene t of the test,and alternative ways of obtaining the same information. In addition, to help limit cumulativemedical radiation exposure, individuals can create a record of all imaging or nuclear medicinetests received and, if known, the estimated radiation dose for each test.

6. Adults and children can avoid overexposure to ultraviolet light by wearing protective clothing andsunscreens when outdoors and avoiding exposure when the sunlight is most intense.

SELF-ADVOCACY

7. Each person can become an active voice in his or her community. To a greater extent than manyrealize, individuals have the power to affect public policy by letting policymakers know thatthey strongly support environmental cancer research and measures that will reduce or removefrom the environment toxics that are known or suspected carcinogens or endocrine-disruptingchemicals. Individuals also can in uence industry by selecting non-toxic products and, wherethese do not exist, communicating with manufacturers and trade organizations about their desirefor safer products.



1 American Cancer Society. Cancer facts & gures 2009. Atlanta: ACS; 2009.

2 Horner JM, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N, et al., editors. SEERCancer Statistics Review, 1975-2006 [Internet]. Bethesda (MD): National Cancer Institute;based on November 2008 SEER data submission, posted to the SEER Web site, 2009 [cited

2009 Jul 19]. Available from: http://seer.cancer.gov/csr/1975_2006/.3 National Heart, Lung, and Blood Institute. Fact book: scal year 2008 [Internet]. Bethesda

(MD): National Institutes of Health; 2009. [cited 2009 Dec 4]. Available from:http://www.nhlbi.nih.gov/about/factpdf.htm.

4 Willet WC. Balancing life-style and genomics research for disease prevention. Science.2002;296:695-8.

5 Fleming J, Huang T, Toland A. The role of parental and grandparental epigeneticalterations in familial cancer risk. Perspect Cancer Res. 2008;68(22):9116-21.

6 Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer inthe United States today. JNCI. 1981;66:1191-308.

7 Harvard Center for Cancer Prevention, Harvard School of Public Health. Harvard Reporton Cancer Prevention. Vol. 1: Human causes of cancer [Internet]. Cancer Causes Control.1996;7 (Suppl 1):S3-S4 [cited 2009 Jul 2]. Available from: http://www.hsph.harvard.edu/cancer/resources_materials/reports.index.htm.

8 Doll R. Epidemiological evidence of the effects of behavior and the environment on the riskof human cancer. Recent Results Cancer Res. 1998;154:3-21.

9 Weinberg RA. The biology of cancer. New York (NY): Garland Science; 2007.

10 Arnold SF, McLachlan JA. Synergistic signals in the environment [Internet]. EnvironHealth Perspect. 1996 Oct;104(10):1020-3 [cited 2009 Nov 12]. Available from:http://www.ehponline.org/members/1996/104-10/arnold.html.

11 Rajapakse N, Silva E, Kortenkamp A. Combining xenoestrogens at levels below individualno-observed-effect concentrations dramatically enhances steroid hormone action. EnvironHealth Perspect. 2002 Sep;110(9):917-21.

12 Kelsey J, Gammon M, John E. Reproductive factors and breast cancer. Epidemiol Rev.1993;15(1):36-47.



13 Gray J, Evans N, Taylor B, Rizzo J, Walker M. State of the evidence: the connectionbetween breast cancer and the environment. Int J Occup Environ Health. 2009;15:43-78.

14 Rudel RA, Perovich LJ. Endocrine disrupting chemicals in indoor and outdoor air. AtmosEnviron. 2009;43:170-81.

15

Diaminti-Kandarakis ED, Bourguignon J-P, Guidice LC, Hauser R, Prins GS, Soto AM, etal. Endocrine-disrupting chemicals: an Endocrine Society scienti c statement. Endocr Rev.2009;30:293-42.

16 International Agency for Research on Cancer. Special report: policy—a review ofhuman carcinogens Part C: metals, arsenic, dusts, and bres [Internet]. Lancet Oncol.2009;10:453-4 [cited 2009 May 19]. Available from: http://www.thelancet.com/oncology.

17 Bird A. Perceptions of epigenetics. Nature. 2007;447:396-8.

18 Jablonka E, Raz G. Transgenerational epigenetic inheritance: prevalence, mechanisms,and implications for the study of heredity and evolution. Q Rev Biol. 2009 Jun;84(2):131-76.

19 Centers for Disease Control and Prevention. About DES: DES history [Internet]. Atlanta(GA): CDC; 2009 [cited 2009 Sep 15]. Available from: http://www.cdc.gov/DES/consumers/about/history.html.

20 Centers for Disease Control and Prevention. About DES: known health effects for DESdaughters [Internet]. Atlanta (GA): CDC; 2009 [cited 2009 Jul 24]. Available from:http://www.cdc.gov/DES/consumers/about/effects_daughters.html.

21 Blatt J, Van Le L, Weiner T, Sailer S. Ovarian carcinoma in an adolescent withtransgenerational exposure to diethylstilbestrol. J Pediatr Hematol Oncol. 2003Aug;25(8):635-6.

22 Titus-Ernstoff L, Troisi R, Hatch EE, Hyer M, Wise LA, Palmer JR, et al. Offspring ofwomen exposed in utero to diethylstilbestrol (DES): a preliminary report of benign andmalignant pathology in the third generation. Epidemiology. 2008 Mar;19(2):251-7.

23 National Cancer Institute. Connecting the nation’s cancer community: an annual planand budget proposal scal year 2010. NIH Publication No. 08-6363. Bethesda (MD):National Institutes of Health; 2008 Jan.

24 World Health Organization. The health of children and adolescents: report by theSecretariat. Executive Board EB109/10 109th session. Geneva (Switzerland): WHO;2001 Dec 12.

25

U.S. Environmental Protection Agency. Child-speci c exposure factors handbook ( nalreport) 2008 [Internet]. EPA/600/R-06/096F. Washington (DC): EPA; 2008 [cited 2009 Dec 4].Available from: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=199243.

26 Environmental Working Group. Body burden—the pollution in newborns [Internet].Washington (DC): EWG; 2005 Jul 14 [cited 2009 Jul 6]. Available from:http://www.ewg.org/reports_content/bodyburden2/pdf/bodyburden2_ nal-r2.pdf.

27 National Academy of Sciences, National Research Council, Commission on Life Sciences,Committee on Pesticides in the Diets of Infants and Children. Pesticides in the diets ofinfants and children. Washington (DC): National Academies Press; 1993.



42 International Commission on Radiological Protection. Report of the task group onreference man [Internet]. Ann ICRP. 1975;23:1-480 [cited 2009 Dec 4]. Available from:http://www.sciencedirect.com/science/journal/00742740.

43 National Research Council, Committee on the Biological Effects of Ionizing Radiation.Health effects of exposures to low levels of ionizing radiation: BEIR V [Internet].Washington (DC): National Academies Press; 1990. Available from: http://www.nap.edu/openbook.php?isbn=0309039959.

44 Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation,National Research Council. Health risks from exposure to low levels of ionizing radiation:BEIR VII—Phase 2 [Internet]. Washington (DC): National Academies Press; 2006. Availablefrom: http://www.nap.edu/catalog.php?record_id=11340.

45 Makhijani A. The use of reference man in radiation protection standards and guidancewith recommendations for change [Internet]. Takoma Park (MD): Institute for Energyand Environmental Research [updated 2009 Apr; cited 2010 Mar 16]. Available from:http://www.ieer.org/reports/referenceman.pdf.

46 DeSimone LA. Quality of water from domestic wells in principal aquifers of the UnitedStates, 1991-2004. U.S. Geological Survey Scienti c Investigations Report 2008-5227[Internet]. Reston (VA): USGS; 2009. Available from: http://pubs.usgs.gov/sir/2008/5227.

47 American Conference of Governmental Industrial Hygienists. History of ACGIH [Internet].Cincinnati (OH): ACGIH; 2007 May 15 [cited 2009 Sep 4]. Available from: http://www.acgih.org/About/history.htm.

48 American Conference of Governmental Industrial Hygienists. TLV/BEI resources: ACGIHguidelines for industrial hygienists [Internet]. Cincinnati (OH): ACGIH; 2008 Jan 30 [cited2009 Sep 4]. Available from: http://www.acgih.org/tlv/.

49 Centers for Disease Control and Prevention. About NIOSH [Internet]. Atlanta (GA): CDC;2009 Jun 26 [cited 2009 Sep 4]. Available from: http://www.cdc.gov/niosh/about.html.

50 U.S. Department of Labor. Compliance assistance by law—the Occupational Safety andHealth Act [Internet]. Washington (DC): DOL; 2006 Oct 5 [cited 2009 Sep 4]. Available from:http://www.dol.gov/compliance/laws/comp-osha.htm.

51 U.S. Department of Labor. OSHA standards development [Internet]. Washington (DC):DOL [cited 2009 Sep 20]. Available from: http://www.osha.gov/OCIS/stand_dev.html.

52 LaDou J. Current occupational & environmental medicine. New York (NY): McGraw Hill;2007.

53 Michaels D, Monforton C. Manufacturing uncertainty: contested science and the protectionof the public’s health and environment. Am J Public Health. 2005 Jul; 95(S1):S39-S48.

54 U.S. Department of Labor. 13 carcinogens (4-Nitrobiphenyl, etc.)—1910.1003 [Internet].Washington (DC): DOL; 2008 Dec 12 [cited 2009 Sep 8]. Available from: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10007.

55 Brandys RC, Brandys GM. Global occupational exposure limits for over 6,000 speci cchemicals. Hinsdale (IL): OEHCS, Inc.; 2008.



56 Zahm SH, Blair A. Occupational cancer among women: where have we been and whereare we going? Am J Ind Med. 2003;44:565-75.

57 Frank AL. Approach to the patient with an occupational or environmental illness. OccEnviron Med. 2000 Dec;27(4):877-93.

58

Wartenberg D. Environmental factors in cancer: trichloroethylene and related solvents:science, regulation, and cancer prevention. Presented at the President’s Cancer Panelmeeting; 2008 Sep 16; East Brunswick, NJ.

59 Centers for Disease Control and Prevention. The National Environmental Public HealthTracking Network [Internet]. Atlanta (GA): CDC; 2009 [cited 2009 Jul 23]. Available from:http://ephtracking.cdc.gov/showHome.action.

60 Ward EM, Schulte PA, Bayard S, Blair A, Brandt-Rauf P, Butler MA, et al. Priorities fordevelopment of research methods in occupational cancer. Environ Health Perspect.2003;111(1):1-12.

61 National Institutes of Health, Centers for Disease Control and Prevention, U.S.Environmental Protection Agency. The National Children’s Study [Internet]. [updated 2009Apr 17; cited 2009 Jul 11]. Available from: http://www.nationalchildrensstudy.gov/about/Pages/default.aspx.

62 U.S. Congress (106th). Children’s Health Act of 2000, P.L. 106-310.

63 Brown RC, Dwyer T, Kasten C, Krotoski D, Li Z, Linet MS, et al. Cohort pro le: theInternational Childhood Cancer Cohort Consortium (I4C). Int J Epidemiol. 2007;36(4):724-30.

64 Landrigan PJ. Childhood cancer and the environment. Presented at the President’s CancerPanel meeting; 2008 Sep 16; East Brunswick, NJ.

65 Soffritti M, Belpoggi F, Esposti DD, Falcioni L, Bua L. Consequences of exposureto carcinogens beginning during developmental life. Basic Clin Pharmacol Toxicol.2008;102:118-24.

66 Conolly RB, Beck BD, Goodman JI. Stimulating research to improve the scienti c basis ofrisk assessment. Toxicol Sci. 1999;49:1-4.

67 Abbott A. Toxicity testing gets a makeover. Nature. 2009 Sep 10;461:158.

68 National Academy of Sciences, Board on Environmental Studies and Toxicology. Toxicitytesting in the 21st century: a vision and a strategy. Washington (DC): National Academies

Press; 2007.69 Collins FS, Gray GM, Bucher JR. Transforming environmental health protection. Science.

2008;319:906-7.

70 Austin C, Kavlock R, Tice R. Tox21: putting a lens on the vision of toxicity testing inthe 21st century [Internet]. [updated 2008 Aug 19; cited 2009 Sep 20]. Available from:http://www.alttox.org/ttrc/overarching-challenges/way-forward/austin-kavlock-tice/.



85 Science & Environmental Health Network. Wingspread conference on the precautionaryprinciple [Internet]. Ames (IA): SEHN; 1998 Jan 26 [cited 2009 Jul 6]. Available from:http://www.sehn.org/wing.html.

86 Kriebel D. Cancer prevention through a precautionary approach to environmentalchemicals. Presented at the President’s Cancer Panel meeting; 2008 Sep 16;East Brunswick, NJ.

87 Ozonoff D. On being careful what we wish for: some dif culties with operationalizing theprecautionary principle. Int J Occup Med Environ Health. 2004;17(1):35-41.

88 vom Saal FS, Akingbemi BT, Belcher SM, Birnbaum LS, Crain DA, Eriksen M, et al.Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms,effects in animals and potential to impact human health at current levels of exposure.Reprod Toxicol. 2007 Aug-Sep;24(2):131-8.

89 Centers for Disease Control and Prevention. Spotlight on bisphenol A [Internet].Atlanta (GA): CDC; 2009 Jul [cited 2009 Aug 20]. Available from: http://www.cdc.gov/

exposurereport/pdf/factsheet_bisphenol.pdf.90 Calafat AM, Ye X, Wong L-Y, Reidy JA, Needham LL. Exposure of the U.S. population

to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect. 2009Jan;116(1):39-44.

91 vom Saal FS, Welshons WV. Large effects from small exposures. II. The importance ofpositive controls in low-dose research on bisphenol A. Environ Res. 2006;100:50-76.

92 Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, et al. Association ofurinary bisphenol A concentration with medical disorders and laboratory abnormalities inadults. JAMA. 2008;300(11):1303-10.

93 LaPensee EW, Tuttle TR, Fox SR, Ben-Jonothan N. Bisphenol A at low nanomolar dosesconfers chemoresistance in estrogen receptor-alpha-positive and -negative breast cancercells. Environ Health Perspect. 2009 Feb;117(2):175-80.

94 Wetherill YB, Petre CE, Monk KR, Puga A, Knudsen KE. The xenoestrogen bisphenolA induces inappropriate androgen receptor activation and mitogenesis in prostaticadenocarcinoma cells. Mol Cancer Ther. 2002 May;1(7):515-24.

95 U.S. Food and Drug Administration. Update on bisphenol A for use in food contactapplications: January 2010 [Internet]. Washington (DC): FDA; 2010 15 Jan [cited 2009 Jan31]. Available from: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm197739.htm.

96 Environment Directorate General, European Commission. REACH in brief [Internet].Brussels (Belgium): EC; 2007 Oct [cited 2009 May 19]. Available from: http://ec.europa.eu/environment/chemicals/reach/pdf/2007_02_reach_in_brief.pdf.

97 European Commission. What is REACH? [Internet] Brussels (Belgium): EC[cited 2009 May 19]. Available from: http://ec.europa.eu/environment/chemicals/reach/reach_intro.htm.

98 Avril T. Obama plan would tighten rules on toxic chemicals. The Philadelphia Enquirer.2009 Sep 30:A1.



99 U.S. Government Accountability Of ce. EPA-state enforcement partnership has improved,but EPA’s oversight needs further enhancement. GAO-07-883[Internet]. Washington (DC):GAO; 2007 Jul [cited 2009 Dec 4]. Available from: http://www.gao.gov/new.items/d07883.pdf.

100 Subcommittee on Science and Technology. FDA science and mission at risk: report ofthe Subcommittee on Science and Technology [Internet]. Washington (DC): FDA ScienceBoard; 2007 Nov [cited 2009 Nov 12]. Available from: http://www.fda.gov/ohrms/dockets/ac/07/brie ng/2007-4329b_02_01_FDA%20Report%20on%20Science%20and%20Technology.pdf.

101 U.S. Congress (99th). The Toxic Substances Control Act of 1976, P.L. 99-469, 15 USCSection 2601-92.

102 Kennedy D. Toxic dilemmas. Science. 2007;318:1217.

103 Vandenberg LN, Maf ni MV, Sonnenschein C, Rubin BS, Soto AM. Bisphenol-A and thegreat divide: a review of controversies in the eld of endocrine disruption. Endocr Rev.

2009;30(1):75-95.104 U.S. Environmental Protection Agency. TSCA statute, regulations, and enforcement

[Internet]. Washington (DC): EPA [updated 2009 Jan 2; cited 2009 Jun 30].Available from: http://www.epa.gov/compliance/civil/tsca/tscaenfstatreq.html.

105 Denison RA. Ten essential elements in TSCA reform. Environmental Law Reporter.2009;39:10020-8.

106 Service RF. A new wave of chemical regulations just ahead? Science. 2009 Aug 7;235:692-3.

107 Corrosion Proof Fittings v. EPA, 947 F.2d 1201 (5th Cir. 1991) [Internet]. [cited 2010 Jan 27].Available from: http://scholar.google.com/scholar_case?q=corrosion+proof+ ttings+vs+epa&hl=en&as_sdt=2002&case=6165892895625819539.

108 Council of the European Communities. Council Directive 76/768/EEC of 27 July 1976 on theapproximation of the laws of the Member States relating to cosmetic products [Internet].OJEU. 1976 Sep 27;L262:169-200 [cited 2009 Dec 4]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31976L0768:EN:HTML.

109 Sass JB, Colangelo A. European Union bans atrazine, while the United States negotiatescontinued use. Int J Occup Environ Health. 2006;12:260-7.

110 European Parliament. Dichloromethane to be banned in paint-strippers [Internet].

[updated 2009 Jan 14; cited 2009 Aug 31]. Available from: http://www.europarl.europa.eu/sides/getDoc.do?language=EN&type=IM-PRESS&reference=20090113IPR46095.

111 Pegg JR. Congress considers reform of U.S. chemicals control law [Internet].Environment News Service; 2009 Feb 26 [cited 2009 Jun 20]. Available from:http://www.ens-newswire.com/ens/feb2009/2009-02-26-10.asp.

112 Stokstad E. Putting chemicals on a path to better risk assessment. Science. 2009 Aug 7;325:694-5.

113 U.S. Congress (110th). Kid Safe Chemicals Act of 2008, H.R. 6100/S. 3040.



114 U.S. Environmental Protection Agency. Enhancing EPA’s chemical management program[Internet]. Washington (DC): EPA; 2009 Sep 29 [cited 2009 Nov 7]. Available from: http://www.epa.gov/oppt/existingchemicals/pubs/enhanchems.html.

115 Clapp R, Hoppin P, Kriebel D. Erosion of the integrity of public health science in the USA.Occup Environ Med. 2006;63:367-8.

116 Michaels D. Doubt is their product: industry groups are ghting government regulation byfomenting scienti c uncertainty. Scienti c American. 2005;29:96-101.

117 Massachusetts Department of Environmental Protection. Toxics Use Reduction Act(TURA) overview [Internet]. Boston (MA): MassDEP [cited 2009 Sep 2]. Available from:http://www.mass.gov/dep/toxics/tura/turaover.htm.

118 Maine State Legislature. An Act to Protect Children’s Health and the Environment fromToxic Chemicals in Toys and Children’s Products. Public Law, Chapter 643, 123rd MaineState Legislature [Internet]. Augusta (ME): Maine State Legislature; 2008 Apr 17 [cited2009 Sep 2]. Available from: http://www.chemicalspolicy.org/legislationdocs/Maine/

ME_1691.pdf.119 Stif er L, McGann C. Gregoire signs toughest toy law in U.S. [Internet]. seattlepi.com;

2008 Apr 2 [cited 2009 Sep 2]. Available from: http://www.seattlepi.com/local/357287_toys02.html.

120 Kogevinas M, Pearce N, Susser M, Boffetta P, editors. Social inequalities and cancer. IARCScienti c Publication No.138. Lyon (France): International Agency for Research on Cancer;1997.

121 Ash M, Boyce JK, Chang G, Pastor M, Scoggins J, Tran J. Justice in the air: trackingtoxic pollution from America’s industries and companies to our states, cities, andneighborhoods. San Francisco (CA): Creative Commons; 2009 Apr.

122 Ledford H. Prevention by numbers. Nature. 2009;459:792-3.

123 Centers for Disease Control and Prevention. Third national report on human exposure toenvironmental chemicals. Atlanta (GA): CDC; 2005.

124 Shen H, Main KM, Virtanen HE, Damggard IN, Haavisto AM, Boisen KA, et al. From motherto child: investigation of prenatal and postnatal exposure to persistent bioaccumulatingtoxicants using breast milk and placenta biomonitoring. Chemosphere. 2006;65:1667-77.

125 Anderson HA, Wolff MS. Environmental contaminants in human milk. J Expo Anal EnvironEpidemiol. 2000;10(II Suppl):755-60.

126 Van der Ven K, Van der Ven H, Thibold A, Bauer O, Kaisi M, Mbura J, et al. Chlorinatedhydrocarbon content of fetal and maternal body tissues and uids in full term pregnantwomen: a comparison of Germany and Tanzania. Hum Reprod. 1992;(Suppl 1):95-100.

127 Davis DL. Presented at the President’s Cancer Panel meeting; 2008 Sep 16;East Brunswick, NJ.

128 U.S. Environmental Protection Agency. Polychlorinated biphenyls [Internet]. Washington(DC): EPA [updated 2009 Jun 25; cited 2009 Jul 23]. Available from: http://www.epa.gov/osw/hazard/tsd/pcbs/index.htm.



156 U.S. Environmental Protection Agency. National-scale Air Toxics Assessment for 2002:frequent questions [Internet]. Washington (DC): EPA; 2009 Jun [cited 2009 Jul 28].Available from: http://www.epa.gov/ttn/atw/nata2002/natafaq.html.

157 International Agency for Research on Cancer. IARC monographs on the evaluation ofcarcinogenic risks to humans. Vol. 46: diesel and engine exhausts and some nitroarenes[Internet]. Lyon (France): IARC; 1989. Available from: http://monographs.iarc.fr/ENG/Monographs/vol46/volume46.pdf.

158 Garshick E, Laden F, Hart J, Rosner B, Davis ME, Eisen EA, et al. Lung cancer and vehicleexhaust in trucking industry workers. Environ Health Perspect. 2008 Oct;116:1327-32.

159 Scott J, Sinnamon H. Protecting American health from global shipping pollution:establishing an emission control area in U.S. waters. New York (NY): EnvironmentalDefense Fund; 2009.

160 Control of emissions from new marine compression-ignition engines at or above 30 litersper cylinder; proposed rule (2007 Dec 7). 72 Federal Register. 2007;69522:69545-69546.

161 Bureau of Automotive Repair, Engineering and Research Branch, State of California.Methodology for calculating vehicle miles traveled (VMT). Report 2000–06 [Internet].Sacramento (CA): the Bureau; 2000 Sep 30 [cited 2009 Dec 4]. Available from:http://www.epa.gov/otaq/regs/im/vmt.pdf.

162 U.S. Environmental Protection Agency. Regulatory announcement: proposal of EmissionControl Area designation for geographic control of emissions from ships. EPA-420-F-09-015 [Internet]. Washington (DC): EPA; 2009 Mar [updated 2009 Apr 24; cited 2009Sep 7]. Available from: http://www.epa.gov/oms/regs/nonroad/marine/ci/420f09015.htm.

163 U.S. Environmental Protection Agency. Control of mercury emissions from coal- redelectric utility boilers: interim report including errata [Internet]. Research Triangle Park(NC): EPA; 2002 [cited 2009 Jul 23]. Available from: http://www.epa.gov/ttnatw01/utility/hgwhitepaper nal.pdf.

164 U.S. Circuit Court of Appeals for the District of Columbia. State of New Jersey, et al.v. Environmental Protection Agency, Utility Air Regulatory Group, et al. No. 05-1097[Internet]. 2008 Feb 8 [cited 2009 Jul 23]. Available from: http://pacer.cadc.uscourts.gov/docs/common/opinions/200802/05-1097a.pdf.

165 General Accountability Of ce. Preliminary observations on the effectiveness and costs ofmercury control technologies at coal- red power plants. Testimony by Stephenson JB,2009 Jul 9.

166 American Public Health Association. EPA’s mercury pollution plan broke Clean Air Act,court rules. The Nation’s Health. 2008 Apr;39:6.

167 American Institute of Biological Sciences. Hotspots of mercury contamination: harmfullevels of neurotoxin in sh and birds [Internet]. Science Daily. Washington (DC): theInstitute; 2007 Jan 3 [cited 2009 Sep 6]. Available from: http://www.sciencedaily.com/releases/2007/01/070103110132.htm.



182 Soto AM, Justicia H, Wray JW, Sonnenschein C. p-Nonylphenol: an estrogenic xenobioticreleased from “modi ed” polystyrene. Environ Health Perspect. 1991;92:167-73.

183 Zava DT, Blen M, Duwe G. Estrogenic activity of natural and synthetic estrogens in humanbreast cancer cells in culture. Environ Health Perspect. 1997 Apr;105(Suppl 3):637-45.

184

Rudel RA, Att eld KR, Schifano JN, Brody JG. Chemicals causing mammary gland tumorsin animals signal new directions for epidemiology, chemicals testing, and risk assessmentfor breast cancer prevention. Cancer. 2007;109(Suppl 12):2635-66.

185 National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction.NTP-CERHR monograph on the potential human reproductive and developmental effectsof bisphenol-A. NIH Pub. No. 08-5994. Research Triangle Park (NC): National Institute ofEnvironmental Health Sciences; 2008 Sep.

186 Rust S, Kissinger M. FDA relied heavily on BPA lobby [Internet]. Milwaukee Journal-Sentinel. 2009 May 16 [cited 2009 Jul 25]. Available from: http://www.jsonline.com/watchdog/watchdogreports/45228647.html.

187 Kissinger M, Rust S. Consortium rejects FDA claim of BPA’s safety [Internet]. MilwaukeeJournal-Sentinel. 2008 Apr 11 [cited 2009 Jul 25]. Available from: http://www.jsonline.com/watchdog/watchdogreports/42858807.html.

188 National Institute of Environmental Health Sciences. Request for proposals:bisphenol A: research to impact human health [Internet]. Research Triangle Park (NC):National Institutes of Health [cited 2010 Jan 22]. Available from: http://www.niehs.nih.gov/recovery/bpa.cfm.

189 Rizzo J. State of the evidence: the connection between breast cancer and the environment.Policy and research recommendations for moving forward. Presented at the President’sCancer Panel meeting; 2008 Sep 16; East Brunswick, NJ.

190 Nudelman J, Taylor B, Evans N, Rizzo R, Gray J, Engel C, Walker M. Policy and researchrecommendations emerging from the scienti c evidence connecting environmental factorsand breast cancer. Int J Occup Environ Health. 2009;15:79-101.

191 National Institute of Environmental Health Sciences. Grand Opportunity grant programin engineered nanomaterial environmental health and safety (RC-2) [Internet]. ResearchTriangle Park (NC): National Institutes of Health [cited 2009 Nov 8]. Available from:http://www.niehs.nih.gov/recovery/nanomaterial-go.cfm.

192 Lyn TE. Deaths, lung damage linked to nanoparticles in China [Internet]. News Daily. 2009Aug 19 [cited 2009 Nov 7]. Available from: http://www.newsdaily.com/sotries/tre57ily7-us-china-nanoparticles/.

193 Song Y, Li X, Du X. Exposure to nanoparticles is related to pleural effusion, pulmonarybrosis, and granuloma. Eur Resp J. 2009;34(3):559-67.

194 Hund-Rinke K, Simon M. Ecotoxic effect of photocatalytic active nanoparticles (TiO2) onalgae and daphnids. Environ Sci Pollut Res Int. 2006 Jul;13(4):225-32.

195 Warheit DB, Hoke RA, Finlay C, Donner EM, Reed KL, Sayes CM. Development of a baseset of toxicity tests using ultra ne TiO2 particles as a component of nanoparticle riskmanagement. Toxic Ltr. 2007 Jul;171(3):99-110.



196 Friends of the Earth, International Center for Technology Assessment, Consumers Union.Manufactured nanomaterials and sunscreens: top reasons for precaution [Internet].Washington (DC): Friends of the Earth; 2009 Aug 19 [cited 2009 Nov 7]. Available from:http://www.foe.org/sites/default/ les/SunscreensReport.pdf.

197 National Institute for Occupational Safety and Health. The nanotechnology information

library (NIL) [Internet]. Atlanta (GA): Centers for Disease Control and Prevention [updated2009 Aug 28; cited 2009 Nov 7]. Available from: http://www.cdc.gov/niosh/topics/nanotech/NIL.html.

198 Energy Information Administration, U.S. Department of Energy. Annual U.S. oxygenateplant production of fuel ethanol [Internet]. Petroleum Navigator. Washington (DC): DOE;2008 [cited 2009 Nov 8]. Available from: http://tonto.eia.doe.gov/dnav/pet/hist/m_epooxe_yop_nus_1A.htm.

199 Biello D. Want to reduce air pollution? Don’t rely on ethanol necessarily [Internet].Scienti c American. 2007 Apr 18 [cited 2009 Nov 7]. Available from: http://www.scienti camerican.com/article.cfm?id=reduce-air-pollution-do-not-rely-on-ethanol.

200 Naidenko OV. Ethanol-gasoline fuel blends may cause human health risks and engineissues [Internet]. Washington (DC): Environmental Working Group; 2009 May 18 [cited 2009Nov 7]. Available from: http://www.ewg.org/ les/2009/ethanol-gasoline-white-paper.pdf.

201 Renewable Fuels Association. Policy positions: ethanol’s positive impact on theenvironment & air quality [Internet]. Washington (DC): RFA [cited 2009 Nov 7]. Availablefrom: http://www.ethanolrfa.org/policy/positions/environment/.

202 U.S. Environmental Protection Agency. Health effects notebook for hazardous airpollutants [Internet]. Washington (DC): EPA [updated 2007 Nov 6; cited 2009 Nov 8].Available from: http://www.epa.gov/ttn/atw/hlthef/hapindex.html.

203 National Institute for Occupational Safety and Health. NIOSH Safety and health topic:agricultural safety [Internet]. Atlanta (GA): Centers for Disease Control and Prevention[updated 2009 Jun 3; cited 2009 Jul 26]. Available from: http://www.cdc.gov/niosh/topics/aginjury/.

204 National Center for Farmworker Health. About America’s farm workers: introduction[Internet]. Buda (TX): NCFH; 2002 [cited 2009 Jul 26]. Available from: http://www.ncfh.org/?pid=4&page=1.

205 Blair A, Zahm SH. Agricultural exposures and cancer. Environ Health Perspect.1995;103(Suppl 8):205-8.

206 Zahm SH, Ward MH. Pesticides and childhood cancer. Environ Health Perspect.1998;106(Suppl 3):893-908.

207 Lewis RG, Fortmann RC, Camann DE. Evaluation of methods for monitoring the potentialexposure of small children to pesticides in the residential environment. Arch EnvironContam Toxicol. 1994;26(1):37-46.

208 Curwin BD, Hein MJ, Sanderson WT, Nishioka MG, Reynolds SJ, Ward EM, Alavanja MC.Pesticide contamination inside farm and nonfarm homes. J Occup Environ Hyg. 2005Jul;2(7):357-67.



209 Monge P, Wesseling C, Guardado J, Lundberg I, Ahlbom A, Cantor KP, et al. Parentaloccupational exposure to pesticides and the risk of childhood leukemia in Costa Rica.Scand J Work Environ Health. 2007;33(4):293-303.

210 Menegaux F, Baruchel A, Bertrand Y, Lescoeur B, Leverger G, Nelken B, et al. Householdexposure to pesticides and risk of childhood acute leukaemia. Occup Environ Med.2006;63:131-4.

211 Meinert R, Schüz J, Kaletsch U, Kaatsch P, Michaelis J. Leukemia and non-Hodgkin’slymphoma in childhood and exposure to pesticides: results of a register-based case-control study in Germany. Am J Epidemiol. 2000 Apr 1;151(7):639-46.

212 The National Cancer Institute. The Agricultural Health Study [Internet]. Bethesda (MD):National Institutes of Health [updated 2009 Dec; cited 2010 Mar 16]. Available from:http://aghealth.nci.nih.gov/.

213 Alavanja MCR, Sandler DP, Lynch DF, Knott C, Lubin JH, Tarone R, et al. Cancer incidencein the Agricultural Health Study. Scand J Work Environ Health. 2005;31(S1):39-45.

214 U.S. Environmental Protection Agency. Pesticide product information system (PPIS)[Internet]. Washington (DC): EPA [updated 2010 Feb 8; cited 2010 Feb 14].Available from: http://www.epa.gov/opppmsd1/PPISdata/.

215 National Cancer Institute, National Institute of Environmental Health Sciences. Cancerand the environment: what you need to know, what you can do. NIH Pub. No. 03-2039.Bethesda (MD): National Institutes of Health; 2003 Aug.

216 International Agency for Research on Cancer. IARC monographs on the evaluationof carcinogenic risks to humans: overall evaluations of carcinogenicity to humans,Group 2A Probably Carcinogenic to Humans [Internet]. Lyon (France): IARC [updated2009 Mar 28; cited 2009 Nov 8]. Available from: http://monographs.iarc.fr/ENG/Classi cation/crthgr02a.php.

217 International Agency for Research on Cancer. IARC monographs on the evaluation ofcarcinogenic risks to humans: overall evaluations of carcinogenicity to humans, Group 1Carcinogenic to Humans [Internet]. Lyon (France): IARC [updated 2009 Jan 16; cited 2009Nov 8]. Available from: http://monographs.iarc.fr/ENG/Classi cation/crthgr01.php.

218 International Agency for Research on Cancer. IARC monographs on the evaluation ofcarcinogenic risks to humans: overall evaluations of carcinogenicity to humans, Group 2BPossibly Carcinogenic to Humans [Internet]. Lyon (France): IARC [updated 2009 Mar 28;cited 2009 Nov 8]. Available from: http://monographs.iarc.fr/ENG/Classi cation/crthgr02b.php.

219 Purdue Research Foundation. National pesticide information retrieval system: chemicalingredients [Internet]. West Lafayette (IN): PRF [cited 2009 Nov 8]. Available from:http://ppis.ceris.purdue.edu/htbin/epachem.com.

220 U.S. Environmental Protection Agency. Prevention, pesticides and toxic substances.Of ce of Pesticide Programs biennial report for FY 1998 and 1999. Washington (DC):EPA; 1999 Dec.



221 U.S. Congress (98th). The Federal Insecticide, Fungicide and Rodenticide Act, P.L. 98-201,7 U.S.C., Section 136.

222 U.S. Environmental Protection Agency. Response to Freedom of Information Act request0104-97 from Sandra Marquardt. Washington (DC): EPA;1998 Feb 18.

223

Jacobs M, Clapp D. Agriculture and cancer: a need for action. Bolinas (CA): Collaborativeon Health and the Environment; 2008 Oct.

224 U.S. Department of Agriculture. Pesticide Data Program [Internet]. Washington (DC):USDA [updated 2008 Dec 18; cited 2009 Jul 26]. Available from: http://www.ams.usda.gov/AMSv1.0/ams.fetchTemplateData.do?template=TemplateC&navID=PesticideDataProgram&rightNav1=PesticideDataProgram&topNav=&leftNav=&page=PesticideDataProgram&resultType=&acct=pestcddataprg.

225 U.S. Environmental Protection Agency. Atrazine interim reregistration eligibility decision(IRED) Q&A’s—January 2003 [Internet]. Washington (DC): EPA [updated 2008 Aug 23; cited2009 Aug 24]. Available from: http://www.epa.gov/opp00001/factsheets/atrazine.htm.

226 Ackerman F. The economics of atrazine. Int J Occup Environ Health. 2007;13:437-45.

227 Fenton SE. Endocrine disrupting compounds and mammary gland development:early exposure and later life consequences. Endocrinology. 2006;147(Suppl):S18-S24.

228 Rayner JL, Enoch RR, Fenton SE. Adverse effects of prenatal exposure to atrazine during acritical period of mammary gland growth. Toxicol Sci. 2005;87:255-66.

229 Stoker TE, Robinette CL, Cooper RL. Maternal exposure to atrazine during lactationsuppresses suckling-induced prolactin release and results in prostatitis in the adultoffspring. Toxicol Sci. 1999;52:68-79.

230 Alavanja MCR, Bonner MR. Pesticides and human cancers. Cancer Invest. 2005;23:700-11.231 International Agency for Research on Cancer. IARC monographs on the evaluation of

carcinogenic risks to humans. Vol. 73 [Internet]. Lyon (France): IARC; 1999. Available from:http://monographs.iarc.fr/ENG/monographs/vol73/mono73-8.pdf.

232 U.S. Environmental Protection Agency. Atrazine updates [Internet]. Washington (DC): EPA[updated 2009 Oct 23; cited 2009 Nov 7]. Available from: http://monographs.iarc.fr/ENG/monographs/vol73/mono73-8.pdf.

233 Zheng T, Holford T, Mayne S, Ward B, Carter D, Owens PH, et al. DDE and DDT in breastadipose tissue and risk of female breast cancer. Am J Epidemiol. 1999;150:453-8.

234 Shen H, Main KM, Virtanen HE, Damggard IN, Haavisto AM, Kaleva M, et al. Frommother to child: investigation of prenatal and postnatal exposure to persistentbioaccumulating toxicants using breast milk and placenta biomonitoring. Chemosphere.2007;67:S236-S262.

235 Cohn BA, Wolff MS, Cirillo PM, Sholtz RI. DDT and breast cancer in young women: newdata on the signi cance of age at exposure. Environ Health Perspect. 2007;115:1406-14.



236 McGlynn KA, Quraishi SM, Graubard BI, Weber JP, Rubertone MV, Erickson RL. Persistentorganochlorine pesticides and risk of testicular germ cell tumors. JNCI. 2008 May 7;100(9):663-71.

237 Vitousek PM, Aber JD, Howarth RW, Likens GE, Matson PA, Schindler DW, et al.Human alteration of the global nitrogen cycle: sources and consequences. Ecol App.1997;7(3):737-50.

238 Nolan BT, Stoner JD. Nutrients in groundwaters of the conterminous United States,1992-1995. Environ Sci Technol. 2000;34:1156-65.

239 Ward MH. Too much of a good thing? Nitrate from nitrogen fertilizers and cancer.Presented at the President’s Cancer Panel meeting; 2008 Oct 21; Indianapolis, IN.

240 Lijinsky W. The signi cance of N-nitroso compounds as environmental carcinogens.J Environ Sci Health. 1986;C4(1):1-45.

241 Weyer PJ, Cerhan JR, Kross BC, Hallberg GR, Kantamneni J, Breuer G, et al. Municipaldrinking water nitrate level and cancer risk in older women: the Iowa Women’s HealthStudy. Epidemiology. 2001;12(3):327-38.

242 Ward MH, deKok TM, Levallois P, Brender J, Gulis G, Nolan BT, et al. Workgroup report:drinking water nitrate and health—recent ndings and research needs. Environ HealthPerspect. 2005 Nov;113(11):1607-14.

243 Marsh M, Longer D, Skinner V. The effect of Austrian winter-pea cover crop and cow-peacompanion crop on corn yield. Discovery: the Student Journal of the Dale BumpersCollege of Agricultural, Food and Life Sciences. 2008 Fall;9:57-63.

244 Riedell WE, Pikul JL Jr, Jaradat AA, Shumacher TE. Nitrogen fertilizer and long-term croprotation effects on soil fertility, corn yield, and seed composition. In: Coombes S, editor.2008 Annual Report. Brookings (SD): Eastern South Dakota Soil and Water Research Farm;2009 Mar 18.

245 International Agency for Research on Cancer. Evaluation of carcinogenic risk, someinorganic and organometallic compounds. Vol. 2 [Internet]. Lyon (France): IARC; 1973:74-99. Available from: http://monographs.iarc.fr/ENG/Monographs/vol87/mono87-5.pdf.

246 Mason TJ, McKay FW, Hoover R, Blot WJ, Fraumeni JF Jr. Atlas of cancer mortality forUS counties 1950-1969. Department of Health, Education and Welfare Publication No.(Nf )75-780. Washington (DC): U.S. Government Printing Of ce; 1975.

247 Falk RT, Pickle LW, Fontham ET, Correa P, Fraumeni JF Jr. Lifestyle risk factors for

pancreatic cancer in Louisiana: a case-control study. Am J Epidemiol. 1988;128:324-36.248 Finkel AM, Ryan PB. Risk in the workplace: where analysis began and problems remain

unresolved. In: Robson MG, Toscano WA, editors. Risk assessment for environmentalhealth. Hoboken (NJ): John Wiley and Sons, Inc.; 2007:187-237.

249 Davenport JR, Peryea FJ. Phosphate fertilizers in uence leaching of lead and arsenic in asoil contaminated with lead arsenate. Water Air Soil Pollut. 1991 Aug;57-58(1):101-10.



264 U.S. Environmental Protection Agency. Removing multiple contaminants from drinkingwater: issues to consider [Internet]. Washington (DC): EPA; 2007 Dec [cited 2009 Nov10]. Available from: http://www.epa.gov/ogwdw000/treatment/pdfs/poster_treatment_technologies.pdf.

265 Environmental Working Group. A national assessment of tap water quality [Internet].Washington (DC): EWG; 2005 Dec 20 [cited 2009 Sep 18]. Available from: http://www.ewg.org/tapwater/ ndings.php.

266 Naidenko O, Leiba N, Sharp R, Houlihan J. Bottled water quality investigation: 10 majorbrands, 38 pollutants [Internet]. Washington (DC): Environmental Working Group; 2008Oct 15 [cited 2009 Jul 21]. Available from: http://www.ewg.org/book/export/html/27010.

267 Cantor KP. Carcinogens in drinking water: the epidemiologic evidence. Presented at thePresident’s Cancer Panel meeting; 2008 Dec 4; Charleston, SC.

268 U.S. Environmental Protection Agency. National primary drinking water regulations;disinfectants and disinfection byproducts. Federal Register. 1998;63(241):69389-476.

269 Bove GE Jr, Rogerson PA, Vena JE. Case control study of the geographic variabilityof exposure to disinfectant by-products and risk for rectal cancer. Int J Health Geogr.2007;6:18.

270 Villanueva CM, Cantor KP, Cordier S, Jaakkola JJ, King WD, Lynch CF, et al. Disinfectionbyproducts and bladder cancer: a pooled analysis. Epidemiology. 2004;15:357-67.

271 Boorman GA, Dellarco V, Dunnick JK, Chapin RE, Hunter S, Hauchman F, et al. Drinkingwater disinfection byproducts: review and approach to toxicity evaluation. Environ HealthPerspect. 1999 Feb;107(Suppl 1):207-17.

272 Cantor KP, Lynch CF, Hildesheim ME, Dosemeci M, Lubin J, Alavanja M, et al. Drinkingwater source and chlorination byproducts in Iowa. III. Risk of brain cancer. Am J Epidemiol.1999 Sep 15;150(6):552-60.

273 Miller GT. Biodiversity: sustaining soils and producing food. In: Sustaining the earth. 6th ed.Paci c Grove, CA: Thompson Learning, Inc.; 2004:211-6.

274 Cellular Telecommunications and Internet Association. CTIA—The Wireless Association ® announces semi-annual wireless industry survey results [Internet]. Washington (DC): CTIA;2009 Apr 1 [cited 2009 Sep 16]. Available from: http://www.ctia.org/media/press/body.cfm/prid/1811.

275 Khurana VG, Teo C, Kundi M, Hardell L, Carlberg M. Cell phones and brain tumors: a

review including the long-term epidemiologic data. Surg Neurol. 2009;72(3):205-14;discussion 214-5.

276 Hardell L, Carlberg M, Söderqvist F, Hansson Mild K. Meta-analysis of long-term mobilephone use and the association with brain tumours. Int J Oncol. 2008 May;32(5):1097-103.

277 Shoemaker MJ, Swerdlow AJ. Risk of pituitary tumors in cellular phone users: a case-control study. Epidemiology. 2009 May;20(3):348-54.



278 Hours M, Bernard M, Montestrucq L, Arslan M, Bergeret A, Deltour I, et al. Cell phonesand risk of brain and acoustic nerve tumours: the French INTERPHONE case-controlstudy. Rev Epidemiol Sante Publique. 2007 Oct;55(5):321-32.

279 Myung SK, Ju W, McDonnell DD, Lee YJ, Kazinets G, Cheng CT, et al. Mobile phone useand risk of tumors: a meta-analysis. J Clin Oncol. 2009;27(33):5565-72.

280 Roan S. Analysis links cellphone use to tumor risk; a scienti c look at eight of the mostcareful studies points to a connection. Some questions remain [Internet]. Los AngelesTimes. 2009 Oct 14:A16.

281 Ries LAG, Melbert D, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, et al., editors.SEER cancer statistics review—1975-2005 [Internet]. Bethesda (MD): National CancerInstitute; based on November 2007 SEER data submission, posted to the SEER Web site2008 [cited 2009 Jun 22]. Available from:http://seer.cancer.gov/csr/1975_2005.

282 Lahkola A, Tokola K, Auvinen A. Meta-analysis of mobile phone use and intracranial

tumors. Scand J Work Environ Health. 2006;32(3):171-7.283 Lahkola A, Salminen T, Raitanan J, Heinävaara S, Schoemaker MJ, Christensen HC, et al.

Meningioma and mobile phone use—a collaborative case-control study in ve NorthernEuropean countries. Int J Epidemiol. 2008;37(6):1304-13.

284 Schüz J, Jacobsen R, Olsen JH, Boice JD Jr, McLaughlin JK, Johansen C. Cellulartelephone use and cancer risk: update of a nationwide Danish cohort. JNCI.2006;98(23):1707-13.

285 Stang A, Schmidt-Pokrzywniak A, Lash TL, Kommatzsch PK, Taubert G, Bornfeld N, etal. Mobile phone use and risk of uveal melanoma: results of the risk factors for uvealmelanoma case-control study. JNCI. 2009;101:120-123.

286 Vrijheid M, Armstrong BK, Bédard D, Brown J, Deltour I, Iavarone I, et al. Recall bias in theassessment of exposure to mobile phones. J Expo Sci Environ Epidemiol. 2009;19:369-81.

287 Bonita R, Beaglehole R, Kjellstrom T. Basic epidemiology. 2nd ed. Geneva: World HealthOrganization; 2006.

288 Ahlbom A, Green A, Kheifets L, Savitz D, Swerdlow A, International Commission for Non-Ionizing Radiation Protection, Standing Committee on Epidemiology. Epidemiology ofhealth effects of radiofrequency exposure. Environ Health Perspect. 2004;112(17):1741-54.

289 Cardis E, Richardson L, Deltour I, Armstrong B, Feychting M, Johansen C, et al.

The INTERPHONE study: design, epidemiological methods, and description of the studypopulation. Eur J Epidemiol. 2007;22:647-64.

290 Carpenter D, Sage C, editors. BioInitiative report: a rationale for a biologically-based publicexposure standard for electromagnetic elds (ELF and RF). Vol. 1. ISBN: 978-1-4276-3105-3 [Internet]. BioInitiative Working Group; 2007 Aug 31 [cited 2009 Dec 4]. Available from:http://www.bioinitiative.org/index.htm.



319 Picano E. Sustainability of medical imaging. Br Med J. 2004;328:578-80.

320 Mettler FA Jr, Huda W, Yoshizumi TT, Mahesh M. Effective doses in radiology anddiagnostic nuclear medicine: a catalog. Radiology. 2008;248(1):254-63.

321 Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation exposure.

N Engl J Med. 2007;357(22):51-8.322 International Marketing Ventures. 2007 CT Market Summary Report [Internet]. Des Plaines

(IL): IVM; 2008 [cited 2009 Dec 4]. Available from: http://www.imvinfo.com/index.aspx?sec=ct&sub=dis&itemid=20081.

323 Mettler FA Jr. Medical radiation exposure: how much, why, and so what? Presented at thePresident’s Cancer Panel meeting; 2009 Jan 27; Phoenix, AZ.

324 Brenner DJ, Elliston CD. Estimated radiation risks potentially associated with full-body CTscreening. Radiology. 2004 Sep;232(3):735-8.

325 Lee CI, Haims AH, Monico EP, Brink JA, Forman HP. Diagnostic CT scans: assessmentof patient, physician, and radiologist awareness of radiation dose and possible risks.Radiology. 2004;231:393-8.

326 Slovis TL, Berdon WE. Panel discussion. Ped Radiol. 2002;32:242-4.

327 Hall EJ, Brenner DJ. Cancer risks from diagnostic radiology. Br J Radiol. 2008 May;81(965):362-78.

328 Amis ES Jr, Butler PF, Applegate KE, Birnbaum SB, Brateman LF, Hevezi JM, et al.American College of Radiology white paper on radiation dose in medicine. J Am CollRadiol. 2007;4:272-84.

329

American College of Radiology. ACR Appropriateness Criteria ® October 2008 Version[Internet]. Reston (VA): ACR; 2009 [cited 2009 Jun 5]. Available from: http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria.aspx.

330 McCollough CH, Bruesewitz MR, Ko er JM Jr. CT dose reduction and dose managementtools: overview of available options. RadioGraphics. 2006;26:503-12.

331 Valentin J, editor. Managing patient dose in multi-detector computed tomography. AnnICRP. 2007;37(1):1-79, iii.

332 Prasad SR, Wittram C, Shepard J-A, McLoud T, Rhea J. Standard-dose and 50%-reduced-dose chest CT: comparing the effect on image quality. Am J Radiol. 2002;179:461-5.

333 Raff G, Chinnaiyan K, Abidov A, Kazerooni EA, Goraya T, Michigan Heart, et al. Markedradiation dose reduction in a statewide coronary CT quality improvement registry(abstract 4717) [Internet]. Circulation. 2008;118:S_936 [cited 2009 May 27]. Available from:http://circ.ahajournals.org/cgi/content/meeting_abstract/118/18_MeetingAbstracts/S_936.

334 Gofman JW. Preventing breast cancer: the story of a major, proven, preventable causeof this disease. 2nd ed. San Francisco (CA): CNR Book Division, Committee for NuclearResponsibility; 1996.



335 Gofman JW. Radiation from medical procedures in the pathogenesis of cancer andischemic heart disease: dose-response studies with physicians per 100,000 population.San Francisco (CA): CNR Book Division, Committee for Nuclear Responsibility; 1999.

336 Einstein AJ, Henzlova MJ, Rajogopalan S. Estimating risk of cancer associated withradiation exposure from a 64-slice computed tomography coronary angiography. JAMA.2007;298(3):317-23.

337 Hurwitz LM, Yoshizumi TT, Reiman RE, Paulson EK, Frush DP, Nguyen GT, et al.Radiation dose to the female breast from 16-MDCT body protocols. Am J Roentgenol.2006;186(6):1718-22.

338 Parker MS, Hui FK, Camacho MA, Chung JK, Broga DW, Sethi NN. Female breast radiationexposure from CT pulmonary angiography. Am J Roentgenol. 2005;185(5):1228-33.

339 American College of Radiology. Mammography accreditation program: overview [Internet].Reston (VA): ACR [revised 2008 Apr 1; cited 2009 May 30]. Available from: http://www.acr.org/accreditation/mammography/overview/overview.aspx.

340 U.S. Congress (102nd). Mammography Quality Standards Act of 1992, P.L. 102-539.

341 American College of Radiology. Alliance for Radiation Safety in Pediatric Imaging andimaging manufacturers agree to collaborate to standardize methods to measure, reportpediatric dose from CT scans [Internet]. Reston (VA): ACR [cited 2009 May 21]. Availablefrom: http://www.acr.org/MainMenuCategories/media_room/FeaturedCategories/PressReleases/Archive/AllianceVendorstoStandardizeDoseReporting.aspx.

342 Ron E. Ionising radiation and cancer risk: evidence from epidemiology. Ped Radiol.2002;32:232-7.

343 McCormack J, Towson JEC, Flower MA. Radiation protection and dosimetry in clinicalpractice. In: Murray IPC, Ell PG, editors. Nuclear medicine in clinical practice andtreatment. Oxford (United Kingdom): Churchill Livingstone;1998:1655.

344 Sadetzki S, Mandelzweig L. Childhood exposure to external ionising radiation and solidcancer risk. Br J Cancer. 2009;100:1021-5.

345 Slovis TL. The ALARA (as low as reasonably achievable) concept in pediatric CT intelligentdose reduction. Multidisciplinary conference organized by the Society of PediatricRadiology, August 18-19, 2001. Ped Radiol. 2002 Apr;32:217-317.

346 Alliance for Radiation Safety in Pediatric Imaging. Image Gently [Internet]. Cincinnati (OH):the Alliance [cited 2009 May 25]. Available from: http://www.pedrad.org/associations/5364/

ig/.347 Goske JM, Applegate KE, Boylan J, Butler PF, Callahan MJ, Coley BD, et al. The Image

Gently campaign: working together to change practice. Am J Roentgenol. 2008;190:273-4.

348 National Cancer Institute. Radiation risks and pediatric computed tomography (CT):a guide for health care providers [Internet]. Bethesda (MD): National Institutes of Health;2008 [cited 2009 Jun 9]. Available from: http://www.nci.nih.gov/cancertopics/causes/radiation-risks-pediatric-CT.



363 U.S. Environmental Protection Agency. Superfund Information System [Internet].Washington (DC): EPA [cited 2009 Nov 14]. Available from: http://cfpub.epa.gov/supercpad/cursites/srchsites.cfm.

364 Sanchez CA, Barraj LM, Blount B, Scrafford CG, Valentin-Blasini L, Smith KM, et al.Perchlorate exposure from food crops produced in the lower Colorado River region. J ExpoSci Environ Epidemiol. 2009;19(4):359-68.

365 Schier JG, Wolkin AF, Valentin-Blasini L, Martin G, Belson MG, Kieszak SM, et al.Perchlorate exposure from infant formula and comparisons with the perchlorate referencedose. J Expo Sci Environ Epidemiol. 2009 Mar 18. [Epub ahead of print].

366 Agency for Toxic Substances and Disease Registry. ToxFAQs™ for perchlorates [Internet].Atlanta (GA): Centers for Disease Control and Prevention; 2008 Sep [cited 2009 Jul 24].Available from: http://www.atsdr.cdc.gov/tfacts162.html.

367 Jones M. For 30 years, Camp Lejeune exposed troops to chemicals [Internet].MiamiHerald.com. 2009 Mar 23 [cited 2009 Jul 22]. Available from: http://www.atsdr.cdc.

gov/sites/lejeune/update.html.368 Beamish R. US does about-face on Camp Lejeune’s tap water [Internet]. Associated Press

Online. 2009 Apr 29 [cited 2009 Jul 23]. Available from: http://www.thefreelibrary.com/US+does+about-face+on+Camp+Lejeune’s+tap+water-a01611855170.

369 Levesque WR. A battle over Lejeune statistics. St. Petersburg Times. 2009 Nov 12:1A.

370 Agency for Toxic Substances & Disease Registry. Study on birth defects and childhoodcancers [Internet]. Atlanta (GA): Centers for Disease Control and Prevention [updated 2009Jul 6; cited 2009 Jul 23]. Available from: http://www.atsdr.cdc.gov/sites/lejeune/update.html.

371 Tucker ST, editor. Encyclopedia of the Vietnam War: political, social, and military history.Santa Barbara (CA): ABC-CLIO;1998.

372 National Organization on Disability. U.S. Vietnam veterans and Agent Orange:understanding the impact 40 years later [Internet]. Washington (DC):NOD; 2009 Jun 1[cited 2010 Feb 17]. Available from: http://www.nod.org/_uploads/documents/live/agent_orange.pdf.

373 U.S. Congress (102nd). Agent Orange Act, P.L. 102-4.

374 U.S. Department of Veterans Affairs. Agent Orange [Internet]. Washington (DC): VA[reviewed/updated 2009 Jul 13; cited 2009 Jul 25]. Available from: http://www.publichealth.

va.gov/exposures/agentorange/.375 U.S. Department of Veterans Affairs. Agent Orange: diseases associated with Agent

Orange exposure [Internet]. Washington (DC): VA [reviewed/updated 2009 Jul 21; cited 2009Jul 25]. Available from: http://www.publichealth.va.gov/exposures/agentorange/diseases.asp.

376 Riely K. W.Va. soldiers sue rm for chemical exposure in Iraq [Internet]. Pittsburgh Post-Gazette. 2009 Jul 12 [cited 2009 Jul 18]. Available from: http://www.post-gazette.com/pg/09193/983405-114.stm.



377 Associated Press. Guard still seeking ex-soldiers about toxic risk. New York (NY):Associated Press State & Local Wire; 2008 Sep 15.

378 Cowell A. France to pay nuclear test victims [Internet]. The New York Times. 2009Mar 25 [cited 2009 Dec 4]. Available from: http://www.nytimes.com/2009/03/25/world/europe/25france.html.

379 U.S. Department of Veterans Affairs. VA programs for veterans exposed to radiation[Internet]. Washington (DC): VA; 1999 Jan [updated 2006 Jul; cited 2009 Jun 11]. Availablefrom: http://www.research.va.gov/news/press_releases/radiation-0199.cfm.

380 U.S. Department of Veterans Affairs. VA programs for veterans exposed to radiation[Internet]. Washington (DC): VA; 2002 Sep [cited 2009 Jun 11]. Available from: http://www.cdc.gov/niosh/ocas/pdfs/misc/varadfs.pdf.

381 Defense Threat Reduction Agency. Nuclear Test Personnel Review (NTPR) Program[Internet]. Washington (DC): U.S. Department of Defense [cited 2009 Jun 11]. Availablefrom: http://www.dtra.mil/rd/programs/nuclear_personnel/NTPR_fact.cfm.

382 Dement JM, Ringen K, Welch LS, Bingham E, Quinn P. Mortality of older constructionand craft workers employed at Department of Energy nuclear sites. Am J Ind Med.2009;52:671-82.

383 Reuben, SH. Facing cancer in Indian country: the Yakima Nation and Paci c Northwesttribes. President’s Cancer Panel 2002 Annual Report. Bethesda (MD): National CancerInstitute; 2003 Dec.

384 The Hanford Downwinders Litigation Information Resource. A brief history of Hanford[Internet]. [cited 2009 Jun 6]. Available from: http://www.downwinders.com/hanford_hist.html.

385 Long ME. Half-life: the lethal legacy of America’s nuclear waste. National Geographic.2002 Jul:15-21.

386 Washington Physicians for Social Responsibility. Tank leaks at Hanford: a review of newallegations [Internet]. Seattle (WA): WPSR; 2006 Sep [cited 2009 Sep 10]. Available from:http://www.clarku.edu/mtafund/prodlib/wpsr/WPSR_Tank_Leaks_Review.pdf.

387 U.S. Department of Energy Of ce of River Protection. The accelerated retrieval, treatmentand disposal of tank waste and closure of tanks at the Hanford Site. Environmental impactstatement: a guide to understanding the issues. Richland (WA): DOE; 2003 Jan.

388 Stif er L. Troubled Hanford cleanup has state mulling lawsuit [Internet]. seattlepi.com.

[updated 2008 Mar 20; cited 2009 Sep 18]. Available from: http://www.seattlepi.com/local/355924_hanford21.html.

389 Southwest Research and Information Center data.

390 The cold war threat to the Navajo [Internet]. The New York Times. 2008 Feb 12. Availablefrom: http://www.nytimes.com/2008/02/12/opinion/12tue3.html.

391 Lydersen K. As uranium rms eye N.M., Navajos are wary; as ore’s prices rebound,Navajos are wary of return of industry with poor safety record in area. The WashingtonPost. 2008 Mar 28:A2.



420 World Health Organization. Radon and cancer. Fact sheet No. 291 [Internet]. Geneva(Switzerland): WHO [updated 2009 Sep; cited 2010 Jan 25]. Available from: http://www.who.int/mediacentre/factsheets/fs291/en/index.html.

421 Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest. 2003;123(1Suppl):21S-49S.

422

Field RW. Radon occurrence and health risks. Occupational and environmental medicinesecrets. Philadelphia (PA): Hanley and Belfus; 1999.

423 Thompson RE, Nelson DF, Popkin JH, Popkin Z. Case-control study of lung cancer riskfrom residential radon exposure in Worcester County, Massachussets. Health Phys.2008;94(3):228-41.

424 Yarmoshenko IV, Kirdin IA, Zhukovsky MV, Astrakhantseva SY. Meta-analysis oftwenty radon and lung cancer case control studies. In: McLaughlin JP, SimopoulosSE, Steinhäusler F, editors. Radioactivity in the environment (a companion series tothe Journal of Environmental Radioactivity). The Natural Radiation Environment VII.Amsterdam: Elsevier; 2005 Mar.

425 International Agency for Research on Cancer. Man-made bers and radon. IARCmonographs on the evaluation of carcinogenic risk of chemicals to humans. Vol 43.Lyon (France): IARC; 1988.

426 Krewski D, Lubin JF, Zielinski JM, Alavanja M, Catalan VS, Field RW, et al. A combinedanalysis of North American case-control studies of residential radon and lung cancer.J Toxicol Environ Health. 2006;Part A. 69(7):533-97.

427 Krewski D, Lubin JH, Zielinski JM, Alavanja M, Catalan VS, Field RW, et al. Residentialradon and risk of lung cancer: a combined analysis of 7 North American case-controlstudies. Epidemiology. 2005;16(2):137-45.

428 Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, et al. Radon inhomes and risk of lung cancer: collaborative analysis of individual data from 13 Europeancase-control studies. Br Med J. 2005;330(7485):223-7.

429 Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, et al. Residentialradon and lung cancer: detailed results of a collaborative analysis of individual dataon 7,148 subjects with lung cancer and 14,208 subjects without lung cancer from 13epidemiological studies in Europe. Scand J Work Environ Health. 2006;32(1):1-83.

430 Lubin J, Wang XY, Boice JD, Xu ZY, Blot WJ, De Wang L, et al. Risk of lung cancer andresidential radon in China: pooled results of two studies. Int J Cancer. 2004:109(1):132-7.

431 National Research Council Commission on Life Sciences. Health effects of exposure toradon: BEIR VI, Committee on Health Risks of Exposure to Radon, Board on RadiationEffects Research. Washington (DC): National Academies Press; 1999.

432 Little JB, Radford EP Jr, McCombs HI, Hunt VR, Nelson CN. Distribution of polonium-210in pulmonary tissues of cigarette smokers. N Engl J Med. 1965;273:1343-51.

433 Smith BJ, Zhang L, Field RW. Iowa radon leukemia study: a hierarchical population riskmodel. Stat Med. 2007;26(25):4619-42.



449 Brodhead B. Nationwide survey of RCP listed mitigation contractors. Proceedings of the1995 International Radon Symposium, Nashville, TN [Internet]. Fletcher (NC): AmericanAssociation of Radon Scientists and Technologists; 1995 [cited 2010 Jan 25]. Availablefrom: http://aarst.org/radon_research_papers.shtml.

450 U.S. Environmental Protection Agency. Technical support document for the 1992 Citizen’sGuide to Radon. 400-K92-011. Washington (DC): U.S. Government Printing Of ce; 2002.

451 Steck DJ. Post-mitigation radon concentrations in Minnesota homes. Proceedings ofthe American Association of Radon Scientists and Technologists 2008 InternationalSymposium, Las Vegas, NV, September 14-17, 2008 [Internet]. Fletcher (NC): AmericanAssociation of Radon Scientists and Technologists; 2008 [cited 2010 Jan 25]. Availablefrom: http://aarst.org/radon_research_papers.shtml.

452 U.S. Environmental Protection Agency. National primary drinking water regulations;arsenic and clari cations to compliance and new source contaminants monitoring:40 CFR Parts 9,141, and 142. Federal Register. 2001;66(14)6975-7066.

453

World Health Organization. Arsenic in drinking water. Fact sheet No. 210 [Internet].Geneva (Switzerland): WHO [revised 2001 May; cited 2009 Aug 24]. Available from:http://www.who.int/mediacentre/factsheets/fs210/en/.

454 International Agency for Research on Cancer. IARC monographs on the evaluationof carcinogenic risks to humans. Vol. 84: some drinking water disinfectants andcontaminants, including arsenic [Internet]. Lyon (France): IARC; 2004. Available from:http://monographs.iarc.fr/ENG/Monographs/vol84/mono84-1.pdf.


http://slidepdf.com/reader/full/reducing-cancer-risk-pcpreport0809508 184/240A–2 2008–2009 ANNUAL REPORT | PRESIDENT’S CANCER PANEL

NAME AFFILIATION

R. William Field, Ph.D. College of Public HealthUniversity of Iowa

Adam M. Finkel, Sc.D., M.P.P., C.I.H. School of Public Health

University of Medicine and Dentistry of New JerseyJoan D. Flocks, J.D., M.A. University of Florida Levin College of Law

Elizabeth T.H. Fontham, Dr.P.H., M.P.H. Louisiana State University Health Sciences Center

Marilie D. Gammon, Ph.D. University of North Carolina

Winifred J. Hamilton, Ph.D. Baylor College of Medicine

Tyrone B. Hayes, Ph.D. University of California, Berkeley

David Kriebel, Sc.D. School of Health and EnvironmentUniversity of Massachusetts Lowell

Margaret L. Kripke, Ph.D. President’s Cancer PanelThe University of Texas M.D. Anderson Cancer Center

Beverly Laird, Ph.D. National Cancer Institute

Philip J. Landrigan, M.D., M.Sc. Mount Sinai School of Medicine

LaSalle D. Leffall, Jr., M.D., F.A.C.S. President’s Cancer PanelHoward University College of Medicine

Michael Lerner, Ph.D. Commonweal

Martha S. Linet, M.D., M.P.H. National Cancer Institute

Heather Logan Canadian Cancer Society

Jay H. Lubin, Ph.D. National Cancer Institute

Mahadevappa Mahesh,M.S., Ph.D., F.A.A.P.M.

Johns Hopkins University School of MedicineAmerican College of Radiology

Fred A. Mettler, Jr., M.D., M.P.H. University of New Mexico School of MedicineNew Mexico VA Healthcare System

Frank E. Mirer, Ph.D., C.I.H. Hunter College School of Health Sciences

Marion Moses, M.D. Pesticide Education Center

Neal A. Palafox, M.D., M.P.H. John A. Burns School of MedicineUniversity of Hawai’i at Manoa

Christopher J. Portier, Ph.D. National Institute of Environmental Health Sciences

Trisha Thompson Pritikin,Esq., M.Ed., O.T.R.

Hanford Downwinder

Peggy Reynolds, Ph.D., M.P.H. Northern California Cancer Center

Jeanne Rizzo, R.N. Breast Cancer Fund



NAME AFFILIATION

Jonathan Samet, M.D., M.S. University of Southern CaliforniaNorris Comprehensive Cancer Center

Abby B. Sandler, Ph.D. President’s Cancer Panel

National Cancer InstitutePaul A. Schulte, Ph.D. National Institute for Occupational Safety and Health

Centers for Disease Control and Prevention

Sandra Steingraber, Ph.D. Ithaca College

Jeanne Mager Stellman, Ph.D. State University of New York—Downstate Medical Center

William A. Suk, Ph.D., M.P.H. National Institute of Environmental Health Sciences

John E. Vena, Ph.D. University of Georgia College of Public Health

Mary H. Ward, Ph.D. National Cancer Institute

Daniel E. Wartenberg, Ph.D. Robert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New Jersey

Richard Wiles, M.A. Environmental Working Group



A P P E N D I X

bRecommendations of NIOSh E pert Panel for

En ancing Occupational Cancer Researc Met ods

FOCUS AREA RECOMMENDATIONS

Identi cation of OccupationalCarcinogens

Improve surveillance of occupational cancer with inclusionof workplace factors in national surveillance system.

Improve workplace exposure assessment and characterizationfor prioritization of carcinogenicity testing.

Improve simulation of occupational exposurecircumstances for experimental studies.

Develop new strategies for predicting andtesting the adverse effects of mixtures.

Develop and validate experimental and

computational methods for carcinogenicity.

Epidemiologic Researcin Occupational Cancer

Improve methods to:

Characterize extent of occupational and environmental•exposures by all routes;Identify populations for study;•Estimate levels of exposure retrospectively;•

Conduct surveillance of occupationally related cancer;•Identify, validate, and utilize biological markers as surrogate•endpoints; andDetermine the relationship between maternal and paternal•occupational exposure and cancer in offspring.

Increase emphasis on:

Prospective studies with collection of biological samples and•use of archival samples;Multicenter case-control studies;•Applying advances in genetic research to better understand the•etiology of occupational cancer and the basis for inter-individualdifferences in susceptibility; andStudies of occupational cancer in women and minorities.•



U.S. NATIONAL TOxICOLOGY PROGRAM (NTP)

Known to be a humanCarcinogen

There is suf cient evidence of carcinogenicity from studies inhumans that indicates a causal relationship between exposure tothe agent, substance, or mixture and human cancer.

Reasona ly Anticipatedto be Carcinogenic

There is limited evidence of carcinogenicity from studies in humansthat indicates that causal interpretation is credible, but thatalternative explanations, such as chance, bias, or confoundingfactors, could not adequately be excluded, or

There is suf cient evidence of carcinogenicity from studies inexperimental animals that indicates there is an increased incidenceof malignant and/or a combination of malignant and benign tumors(1) in multiple species or at multiple tissue sites, or (2) by multipleroutes of exposure, or (3) to an unusual degree with regard toincidence, site, or type of tumor, or age at onset, or

There is less than suf cient evidence of carcinogenicity inhumans or laboratory animals; however, the agent, substance,

or mixture belongs to a well-de ned, structurally related class ofsubstances whose members are listed in a previous NTP Reporton Carcinogens as either known to be a human carcinogenor reasonably anticipated to be a human carcinogen, or thereis convincing relevant information that the agent acts throughmechanisms indicating it would likely cause cancer in humans.



INTERNATIONAL AGENCY FOR RESEARCh ON CANCER (IARC)

Group 1 Carcinogenic to humans: There is suf cient evidence ofcarcinogenicity in humans. However, an agent or mixture maybe placed in this category when evidence of carcinogenicity inhumans is less than suf cient but there is suf cient evidence of

carcinogenicity in experimental animals and strong evidence inexposed humans that the agent or mixture acts through a relevantmechanism of carcinogenicity.

Group 2A Probably carcinogenic to humans: There is limited evidenceof carcinogenicity in humans and suf cient evidence ofcarcinogenicity in experimental animals. In some cases, anagent or mixture may be classi ed in this category when there isinadequate evidence of carcinogenicity in humans and suf cientevidence of carcinogenicity in experimental animals and strongevidence that the carcinogenesis is mediated by a mechanismthat also operates in humans. In addition, an agent, mixture, orexposure circumstance may be classi ed in this category solely onthe basis of limited evidence of carcinogenicity in humans.

Group 2b Possibly carcinogenic to humans: There is limited evidence ofcarcinogenicity in humans and less than suf cient evidence ofcarcinogenicity in experimental animals. An agent, mixture, orexposure circumstance may be included in this category whenthere is inadequate evidence of carcinogenicity in humans but thereis suf cient evidence of carcinogenicity in experimental animals. Insome instances, an agent, mixture, or exposure circumstance forwhich there is inadequate evidence of carcinogenicity in humansbut limited evidence of carcinogenicity in experimental animalstogether with supporting evidence from other relevant data may beplaced in this group.

Group 3 Not classi able as to carcinogenicity to humans: The evidenceof carcinogenicity is inadequate in humans and inadequateor limited in experimental animals. In some cases, agents ormixtures for which the evidence of carcinogenicity is inadequate inhumans but suf cient in experimental animals may be placed inthis category when there is strong evidence that the mechanismof carcinogenicity in experimental animals does not operate inhumans. Agents, mixtures, and exposure circumstances that donot fall into any other group are also placed in this category.

Group 4 Probably not carcinogenic to humans: This category is used foragents or mixtures for which there is evidence suggesting lackof carcinogenicity in humans and in experimental animals. Insome instances, agents or mixtures for which there is inadequateevidence of carcinogenicity in humans but evidence suggestinglack of carcinogenicity in experimental animals, consistently andstrongly supported by a broad range of other relevant data, may beclassi ed in this group.



U.S. ENVIRONMENTAL PROTECTION AGENCY (EPA)

Carcinogenic to humans This descriptor indicates strong evidence of human carcinogenicity.It covers different combinations of evidence.

This descriptor is appropriate when there is convincing•epidemiologic evidence of a causal association betweenhuman exposure and cancer.Exceptionally, this descriptor may be equally appropriate with•a lesser weight of epidemiologic evidence that is strengthenedby other lines of evidence. It can be used when all of thefollowing conditions are met:

(a) There is strong evidence of an association between humanexposure and either cancer or the key precursor eventsof the agent's mode of action but not enough for a causalassociation, and

(b) There is extensive evidence of carcinogenicity in animals, and (c) The mode(s) of carcinogenic action and associated key

precursor events have been identi ed in animals, and (d) There is strong evidence that the key precursor events that

precede the cancer response in animals are anticipated tooccur in humans and progress to tumors, based on availablebiological information.

Likely to be Carcinogenicto humans

This descriptor is appropriate when the weight of the evidenceis adequate to demonstrate carcinogenic potential to humansbut does not reach the weight of evidence for the descriptor

“Carcinogenic to Humans.” Adequate evidence consistent with thisdescriptor covers a broad spectrum. As stated previously, the useof the term “likely” as a weight of evidence descriptor does notcorrespond to a quanti able probability. The examples below aremeant to represent the broad range of data combinations that arecovered by this descriptor; they are illustrative and provide neithera checklist nor a limitation for the data that might support use ofthis descriptor. Moreover, additional information (e.g., on modeof action) might change the choice of descriptor for the illustratedexamples. Supporting data for this descriptor may include:

An agent demonstrating a plausible (but not de nitively causal)•association between human exposure and cancer, in mostcases with some supporting biological, experimental evidence,though not necessarily carcinogenicity data from animalexperiments;An agent that has tested positive in animal experiments in more•than one species, sex, strain, site, or exposure route, with orwithout evidence of carcinogenicity in humans;A positive tumor study that raises additional biological concerns•beyond that of a statistically signi cant result—for example, ahigh degree of malignancy, or an early age at onset;A rare animal tumor response in a single experiment that is•assumed to be relevant to humans; or

A positive tumor study that is strengthened by other lines of•evidence—for example, either plausible (but not de nitivelycausal) association between human exposure and cancer or evidence that the agent or an important metabolite causesevents generally known to be associated with tumor formation(such as DNA reactivity or effects on cell growth control) likelyto be related to the tumor response in this case.



Suggestive Evidence ofCarcinogenic Potential

This descriptor of the database is appropriate when the weight ofevidence is suggestive of carcinogenicity; a concern for potentialcarcinogenic effects in humans is raised, but the data are judgednot suf cient for a stronger conclusion. This descriptor coversa spectrum of evidence associated with varying levels of concernfor carcinogenicity, ranging from a positive cancer result in the

only study on an agent to a single positive cancer result in anextensive database that includes negative studies in other species.Depending on the extent of the database, additional studies may ormay not provide further insights. Some examples include:

A small, and possibly not statistically signi cant, increase in•tumor incidence observed in a single animal or human studythat does not reach the weight of evidence for the descriptor"Likely to Be Carcinogenic to Humans." The study generallywould not be contradicted by other studies of equal qualityin the same population group or experimental system (seediscussions of con icting evidence and differing results , below);

A small increase in a tumor with a high background rate in that•sex and strain, when there is some but insuf cient evidence

that the observed tumors may be due to intrinsic factors thatcause background tumors and not due to the agent beingassessed. (When there is a high background rate of a speci ctumor in animals of a particular sex and strain, then there maybe biological factors operating independently of the agent beingassessed that could be responsible for the development of theobserved tumors.) In this case, the reasons for determiningthat the tumors are not due to the agent are explained;Evidence of a positive response in a study whose power, design,•or conduct limits the ability to draw a con dent conclusion(but does not make the study fatally awed), but where thecarcinogenic potential is strengthened by other lines ofevidence (such as structure-activity relationships); or

A statistically signi cant increase at one dose only, but no• signi cant response at the other doses and no overall trend.

Inade uate Informationto Assess CarcinogenicPotential

This descriptor is appropriate when available data are judgedinadequate for applying one of the other descriptors. Additionalstudies generally would be expected to provide further insights.Some examples include:

Little or no pertinent information;•

Con icting evidence—that is, some studies provide evidence of•carcinogenicity but other studies of equal quality in the samesex and strain are negative. Differing results—that is, positiveresults in some studies and negative results in one or moredifferent experimental systems—do not constitute con icting

evidence , as the term is used here. Depending on the overallweight of evidence, differing results can be considered eithersuggestive evidence or likely evidence; orNegative results that are not suf ciently robust for the•descriptor “Not Likely to Be Carcinogenic to Humans.”



Not Likely to beCarcinogenic to humans

This descriptor is appropriate when the available data areconsidered robust for deciding that there is no basis for humanhazard concern. In some instances, there can be positive resultsin experimental animals when there is strong, consistent evidencethat each mode of action in experimental animals does not operatein humans. In other cases, there can be convincing evidence in

both humans and animals that the agent is not carcinogenic. The judgment may be based on data such as:Animal evidence that demonstrates lack of carcinogenic effect•in both sexes in well-designed and well-conducted studies inat least two appropriate animal species (in the absence of otheranimal or human data suggesting a potential for cancer effects);

Convincing and extensive experimental evidence showing•that the only carcinogenic effects observed in animals are notrelevant to humans;

Convincing evidence that carcinogenic effects are not likely by a•particular exposure route; orConvincing evidence that carcinogenic effects are not likely•

below a de ned dose range.A descriptor of “not likely” applies only to the circumstancessupported by the data. For example, an agent may be “Not Likelyto Be Carcinogenic” by one route but not necessarily by another. Inthose cases that have positive animal experiment(s) but the resultsare judged to be not relevant to humans, the narrative discusseswhy the results are not relevant.



A P P E N D I X

DSelected Federal Laws Related to Environmental ha ards

FEDERAL LAWS REGARDING AIR qUALITY

Bill Year background Aut ori ations

Air PollutionControl Act(APCA)

P.L. 84-159

1955 The rst federal air pollutionlegislation.

Prompted by air inversionevents:

Air pollution cloud in•Donora, PA, 1948;lingered for 5 days,20 dead, 6,000 sick; and

“Killer Fog” in London, 1952;•3,000 dead.

Funded research for scope and sources ofair pollution.

Clean AirAct (CAA)

P.L. 88-206

1963 The rst federal legislationregarding air pollution control.

Developed a national program toaddress air pollution related toenvironmental problems.

Supports research into techniquesto minimize air pollution.

Motor VehicleAir PollutionControl Act(MVAPCA)

P.L. 89-272

1965 Amended the 1963 CAA. Developed federal emissions standardsfor new vehicles.

Air QualityAct (AQA)

P.L. 90-148

1967 Expanded federal governmentactivities.

Developed enforcement procedures forair pollution problems involving interstatetransport of pollutants.

Expanded research to prevent and controlair pollution.




CAA Extension

P.L. 91-604

1970 The rst comprehensivefederal response to addressair pollution.

A major shift in the federalgovernment’s role in airpollution control.

Established National Ambient Air QualityStandards (NAAQS).

Established requirements for State

Implementation Plans to achieve NAAQS.Established New Source PerformanceStandards for new and modi edstationary sources.

Established National Emission Standardsfor Hazardous Air Pollutants (HAPs).

Increased enforcement authority.

Developed requirements for controlof motor vehicle emissions.

CAAAmendments(CAA77)

P.L. 95-95

1977 Amended the 1963 CAA. Developed provisions related to thePrevention of Signi cant Deterioration.

Developed provisions for areas considerednon-attainment for NAAQS.

CAAAmendments(CAA90)

P.L. 101-549

1990 Amended the 1963 CAA. Developed programs for Acid DepositionControl (acid rain).

Developed a program to control 189 toxicpollutants, including those previouslyregulated by the National EmissionStandards for HAPs.

Established permit program requirements.

Expanded and modi ed provisionsconcerning the attainment of NAAQS.

Expanded and modi ed enforcementauthority to include Indian Tribes.

FEDERAL LAWS REGARDING WATER qUALITY


Federal Water

PollutionControl Act(FWPCA)

P.L. 80-845

1948 Objective: to restore and

maintain the chemical,physical, and biologicalintegrity of the nation's waters.

Amended in 1956, 1961, 1966,1970, 1972, 1977, and 1987to strengthen enforcementprovisions.

Established comprehensive programs

for eliminating or reducing the pollutionof interstate waters and tributaries andimproving the sanitary condition of surfaceand underground waters.

Provided assistance to states,municipalities, and interstate agenciesin constructing treatment plants toprevent discharges of inadequately treatedsewage and other wastes into interstatewaters or tributaries.




Safe DrinkingWater Act(SDWA)

P.L. 93-523

1974 The main federal law ensuringthe quality of Americans’drinking water.

Excludes private wells.Amended in 1986 and 1996.

Established U.S. Environmental ProtectionAgency (EPA) health-based standards fordrinking water quality to protect againstmicrobial, disinfection by-product, and

other contaminants.Required EPA protection of drinking watersources such as rivers, lakes, reservoirs,springs, and groundwater wells.

Initiated funding to state water systemsto make infrastructure or managementimprovements or to help systems assessand protect their source water.

Required EPA oversight of states,localities, and water suppliers whoimplement standards.

Required EPA conducted cost-bene tanalyses for every new standard.

Clean WaterAct (CWA)

P.L. 95-217

1977 The principal statute governingwater quality.

Goals:

To end all discharges•entirely and to restore,maintain and preservethe integrity of the nation’swaters; and

To provide water that is both• shable and swimmable.

Regulated direct and indirect pollutantdischarge into the nation’s waters.

Mandated permits for wastewater andstorm water discharges.

Regulated publicly owned treatmentworks for municipal and industrialwastewater.

Required states to establish site-speci cwater quality standards for navigablebodies of water.

Regulated other activities that affectwater quality, such as dredging and the

lling of wetlands.

Oil PollutionAct (OPA)

P.L. 101-380

1990 The principal statute governingoil spills into the nation'swaterways.

Prompted by the Exxon Valdezoil spill in March of 1989.

Amended the 1977 CWA.

Includes the Oil Terminal andOil Tanker EnvironmentalOversight and Monitoring Act.

Established liability and limitationson liability for damages resultingfrom oil pollution, and establishes afund for the payment of compensationfor such damages.

Mandated a “National Oil and HazardousSubstances Pollution Contingency Plan(NCP)” to provide the organizationalstructure and procedures for preparingfor and responding to discharges of oiland releases of hazardous substances,pollutants, and contaminants.

Required preparation of spill preventionand response plans by coastal facilities,vessels, and certain geographic regions.



FEDERAL LAWS REGARDING NUCLEAR MATERIALS, FACILITIES, AND REGULATION


Atomic EnergyAct (AEA)

P.L. 79-585

1946 Shifted nuclear powermanagement from military

to civilian control.

Established the Atomic EnergyCommission (AEC) and gave it

responsibility for the developmentand production of nuclear weaponsand for both the development and thesafety regulation of the civilian usesof nuclear materials.

AEAAmendments

P.L. 83-703

1954 The fundamental U.S. lawon use of nuclear materialsand facilities.

Amended the 1946 AEA.

Regulated the development and useof nuclear materials and facilities.

The Price-AndersonNuclearIndustriesIndemnity Act

P.L. 85-256

1957 Objective: to ensure theavailability of a large poolof funds to provide promptand orderly compensation ofmembers of the public whoincur damages from a nuclearor radiological incident despiteliability.

Provided the same protection available fora covered licensee or contractor, throughindemni cation, for persons who maybe legally liable, regardless of identity orrelationship to the licensed activity.

Later amended to require NuclearRegulatory Commission (NRC) licenseesand Department of Energy contractors toenter into agreements of indemni cationto cover personal injury and propertydamage to those harmed by a nuclear orradiological incident.

ReorganizationPlan No. 3of 1970

35 F.R. 15623

1970 Issued by President Nixon toorganize the government’senvironmentally relatedactivities rationally andsystematically.

Established the U.S. EnvironmentalProtection Agency and gave it a rolein establishing "generally applicableenvironmental standards for theprotection of the general environmentfrom radioactive material."

Established the National Oceanic andAtmospheric Administration.

EnergyReorganizationAct (ERA)

P.L. 95-601

1974 Superseded the 1954 AEA. Established the Nuclear RegulatoryCommission.

Split the functions assigned by the AEAto the Atomic Energy Commission.

Assigned to the Department of Energy•the responsibility for the developmentand production of nuclear weapons,promotion of nuclear power, and otherenergy-related work; and

Assigned to the NRC the regulatory•work, which does not includeregulation of defense nuclear facilities.




UraniumMill TailingsRadiationControl Act

P.L. 95-604

1978 Objective: to prevent orminimize, among other things,the diffusion of radon into theenvironment.

Established programs for the stabilizationand control of mill tailings at active andinactive uranium or thorium mill sites.

Gave the NRC regulatory authority overmill tailing at sites under NRC license.

ReorganizationPlan No. 1of 1980

45 F.R. 40561

1980 Issued by President Carter inresponse to a GovernmentAccountability Of ce (GAO)report stating that the NRCneeded more aggressiveleadership.

Strengthened the executive andadministrative roles of the NRCChairman, particularly in emergencies,transferring to the Chairman "all thefunctions vested in the Commissionpertaining to an emergency concerninga particular facility or materials ...regulated by the Commission."

Provided that all policy formulation,policy-related rulemaking, and ordersand adjudications would remain vestedwith the full Commission.

FEDERAL LAWS REGARDING PESTICIDES


FederalInsecticideAct (FIA)

P.L. 61-152

1910 Passed in response toconcerns from theUnited States Departmentof Agriculture (USDA) andfarm groups about the saleof fraudulent or substandardpesticide products.

Superseded by FIFRA.

Ensured the quality of pesticide chemicalspurchased by consumers.

Set standards for the manufacture ofParis Green, lead arsenate, insecticides,and fungicides.

Provided for inspections, seizure ofadulterated or misbranded products,and prosecution of violators.

Federal Food,Drug andCosmetic Act(FFDCA)

P.L. 75-717

1938 Includes various otherregulations not relatedto pesticides.

Supersedes the 1906 FederalFood and Drug Act, which didnot address pesticides.

Authorized the Food and DrugAdministration (FDA) to oversee safetyof food, drugs, and cosmetics.

Required coloring for certain pesticidesto prevent their use as our.

FederalInsecticide,Fungicide andRodenticideAct (FIFRA)

P.L. 80-104

1947 The basic system of pesticideregulation to protectapplicators, consumersand the environment.

Supersedes the 1910 FIA.

Granted pesticide regulatory authority toU.S. Department of Agriculture (USDA).




MillerAmendment

P.L. 83-518

1954 Also known as The PesticideResidues Amendment.

Amended the 1938 FFDCA.

Established EPA health-based standards(tolerances) for pesticides used in or onfoods or animal feed.

Allowed exemptions for pesticides fromthe requirement of a tolerance.

Required pesticide residue levels infoods to be monitored and enforcedby FDA (fruits, vegetables, seafood)and USDA (meat, milk, poultry, eggs,aquacultural foods).

Food AdditivesAmendment

P.L. 85-929

1958 Amended the 1938 FFDCA. Established zero tolerance for cancer-causing food additives (i.e. pesticides).

The FederalEnvironmentalPesticideControl Act

P.L. 92-516

1972 Amended the 1947 FIFRA.

Amended in 1996 by theFood Quality ProtectionAct (FQPA).

Moved pesticide regulatory authorityto EPA.

Established registration for all pesticides.

Proscribed pesticide labelingrequirements.

Required pesticide applicants to showproper pesticide use “will not generallycause unreasonable adverse effects onthe environment.”

Established a system of examination

and certi cation at the private andcommercial levels for applicators whowish to purchase and use restricteduse pesticides.

Established review processes forantimicrobials, biopesticides, andconventional pesticides.

FederalAdvisoryCommitteeAct (FACA)

P.L. 92-463

1972 The legal foundation de ninghow federal advisorycommittees operate.

Has special emphasis onopen meetings, chartering,public involvement, andreporting.

Allowed EPA to charter the EndocrineDisruptor Screening and Testing AdvisoryCommittee (EDSTAC) to advise EPA onestablishing a program to:

Develop a exible process to select and•prioritize pesticides for screening;

Develop a process for identifying new•and existing screening tests;Agree on a set of available, validated•screening tests for early application;andDevelop a process and criteria for•deciding when additional tests beyondscreening are needed and how any ofthese additional tests will be validated.




Food QualityProtectionAct (FQPA)

P.L. 104-170

1996 Represents an effort to updateand resolve the inconsistenciesbetween FIFRA and FFDCA.

Fundamentally changed theway EPA regulates pesticides.

Mandated a single, health-based standardfor all pesticides in all foods.

Provided special protections for infants

and children.Expedited approval of safer pesticides.

Created incentives for the developmentand maintenance of effective cropprotection tools for American farmers.

Required periodic reevaluation of pesticideregistrations and tolerances to ensurepesticide registrations will remain up todate with current science.

Directed EPA to develop a screeningprogram to determine whether certainsubstances may have hormonal effectsin humans.

FEDERAL LAWS REGARDING ENVIRONMENTAL POLICY


NationalEnvironmentalPolicy Act(NEPA)

P.L. 91-190

1970 The basic national charterfor the protection of theenvironment.

Objective: to “encourageproductive and enjoyable

harmony between man andthe environment; to promoteefforts which will preventor eliminate damage to theenvironment and biosphereand stimulate the healthand welfare of man; and toenrich the understanding ofthe ecological systems andnatural resources importantto the Nation.”

Trustees have integratedOil Pollution Act restoration

planning with the NEPAprocess.

Required the government to considerthe consequences of major federalactions on human and natural aspectsof the environment in order to minimize,where possible, adverse impacts.

Established the EnvironmentalAssessment (EA) process of environmentalreview and public noti cation for federalplanning and decision making.

EnvironmentalJustice

ExecutiveOrder 12898

1994 Issued by President Clinton toaddress environmental justicein minority and low-incomepopulations.

Required each federal agency toidentify and address, as appropriate,disproportionately high and adversehuman health or environmental effectsof its programs, policies and activitieson minority and low income populations.



FEDERAL LAWS REGARDING COMPENSATION OF SPECIAL COhORTS


The Radiation-Exposed

VeteransCompensationAct (REVCA)

P.L. 100-321

1988 Objective: to providecompassionate compensation

for service-based radiationexposure.

Applies to World War II veteranswho served in Hiroshimaor Nagasaki, were prisonersof war in Japan, or whoparticipated in tests of nucleardevices and who developedcertain cancers.

Bypassed the requirement fordemonstration of a connection

between a veteran’s disability andthe veteran’s military service ineligible veterans.

RadiationExposureCompensationAct (RECA)

P.L. 101-426

1990 Implementing regulations wereissued by the Department ofJustice in 1992.

Revisions to the regulations in1999 served to greater assistclaimants in establishingentitlement to an award.

Provided for compassionate paymentsto individuals who contracted certaincancers and other serious diseases asa result of:

Residing or working “downwind”•of The Nevada Test Site ($50,000);

Worker participation in above-ground•nuclear weapons tests ($75,000); or

Working in uranium mines ($100,000).•

RECAAmendments

P.L. 106-245

2000 Amended the 1990 RECAto increase the number ofindividuals covered by RECAand to improve the ability

of individuals to establishentitlement to an award.

Added uranium mill workers and oretransporters to the claimant categories.

Provided additional compensableillnesses.

Lowered the radiation exposurethreshold for uranium miners.

Included above-ground miners within“uranium miner” category.

Modi ed medical documentationrequirements.

Removed certain lifestyle restrictions.

Added geographic areas to thedownwinder claimant category.




ProvidingCompensationto America’sNuclear

WeaponsWorkers

ExecutiveOrder 13179

2000 Issued by President Clintonin response to the dif cultiesexperienced by workersseeking compensation.

Built upon the framework ofEEOICPA.

Set out federal agency responsibilities to:

Provide necessary information•and help to DOE employees andits contractors to determine iftheir illnesses are associated withconditions of their nuclear weapons-related work;Provide workers and their survivors•with all pertinent and availableinformation necessary for evaluatingand processing claims; and

Ensure that this program minimizes•the administrative burden on workersand their survivors, and respects theirdignity and privacy.

21st CenturyDepartmentof JusticeAppropriationAuthorizationAct

P.L. 107-273

2002 Contained several technicalrevisions to RECA. Reinserted a previously covered areafor downwinder claimants that haderroneously been removed by the2000 Amendments.

Clari ed the requirement that lungcancer must be “primary” for allclaimant categories.

Provided uranium miners the optionof establishing exposure to 40 workinglevel months of radiation or establishingemployment in a mine for 1 year.

Eliminated the requirement for uraniumworkers diagnosed with lung cancerto submit evidence of a nonmalignantrespiratory disease.



OThER RELEVANT FEDERAL LAWS


ResourceConservation

and RecoveryAct (RCRA)

P.L. 94-580

1976 Regulates hazardous andnonhazardous wastes.

Regulates facilities thatgenerate, treat, store, ordispose of hazardous waste.

Established a system for controllinghazardous waste from the time it is

generated until its ultimate disposal.Prevented environmental problems byensuring that wastes are well managedfrom “cradle to grave”, reducing theamount of waste generated, conservingenergy and natural resources.

Required clean up of environmentalproblems caused by the mismanagementof wastes.

ToxicSubstancesControl Act(TSCA)

P.L. 94-469

1976 Addresses the production,importation, use, and disposalof speci c chemicals.

Excludes foods, drugs,cosmetics, and pesticides.

Required pre-manufacture noti cationfor “new chemical substances.”

Required testing of chemicals bymanufacturers, importers and processorswhere risks or exposures of concernare found.

Issued Signi cant New Use Rules (SNURs)when EPA identi es a “signi cant newuse” that could result in exposures to,or release of, a substance of concern.

Maintained the TSCA Inventory—aninventory that contains more than83,000 chemicals. As new chemicals

are commercially manufactured orimported, they are placed on the list.

Required those importing or exportingchemicals to comply with certi cationreporting.

Required reporting and recordkeepingby persons who manufacture, import,process, and/or distribute chemicalsubstances in commerce.

Required that any person whomanufactures, imports, processes, ordistributes in commerce a chemicalsubstance or mixture and who obtainsinformation which reasonably supportsthe conclusion that such substance ormixture presents a substantial risk ofinjury to health or the environment toimmediately inform EPA.




EmergencyPlanning andCommunityRight-to-Know

Act (EPCRA)P.L. 99-499

1986 Created under the 1986 SARA.

Designed to improvecommunity access to

information about chemicalhazards and to facilitate thedevelopment of chemicalemergency response plansby state/tribe and localgovernments.

Established four types of reportingobligations for facilities that storeor manage speci ed chemicals:

Required facilities to notify emergency•response commissions of thepresence of any “extremely hazardoussubstance” if such substance is inexcess of the substance’s thresholdplanning quantity;Required a facility to notify emergency•response commissions in the eventof a release exceeding the reportablequantity of CERCLA hazardoussubstance or an EPCRA extremelyhazardous substance (excludesproper application of pesticideproducts, as well as handling and

storage of those pesticide productsby an agricultural producer);

Required facilities at which a•hazardous chemical is present inan amount exceeding a speci edthreshold must submit material safetydata sheets and hazardous chemicalinventory forms to the state/tribeemergency planning committee, thelocal emergency planning committeeand the re department (excludeshazardous chemicals used in routineagricultural operations and fertilizersheld for resale by retailers); and

Required certain manufacturing•facilities to submit an annual toxicchemical release report if they have10 or more employees and if theymanufacture, process, or use speci edchemicals in amounts greater thanthreshold quantities.



A P P E N D I X

EFederal Agencies Involved in

Environmental Regulation or Researc

REGULATION/ENFORCEMENT

Environmental ProtectionAgency—EPA

Establishes air quality standards and regulates emissions ofhazardous air pollutants, including radioisotopes.

Establishes quality standards for surface waters and drinkingwater and regulates discharges of pollutants into water (includesstandards for radioisotopes).

Enforces cleanup of uncontrolled or abandoned hazardous-wastesites by responsible parties and cleans up orphan sites (CERCLA/Superfund).

Regulates generation, transportation, treatment, storage, anddisposal of hazardous waste.

Licenses pesticides for distribution/sale within the U.S. andestablishes and enforces tolerances for pesticide residueson foods.

Authorized to regulate production, importation, and use of“new chemicals” that may pose a threat to human health orthe environment. Speci c authority to regulate PCBs, asbestos,radon, and lead-based paint. Tobacco, certain tobacco products,nuclear materials, munitions, foods, food additives, drugs,cosmetics, and pesticides are exempt from EPA oversight.

Authorized to require producers/importers/processors to testexisting chemicals for health and environmental effects if there

is evidence of substantial exposure levels and/or unreasonablerisk to health or the environment and/or submit unpublished datarelated to health and safety of chemicals.

Establishes standards for release of radioactive material fromnuclear waste stored in deep geological repositories (waste sitesare identi ed, built, and operated by DOE and licensed by NRC).



Food and DrugAdministration—FDA(Department of Health andHuman Services—HHS)

Establishes standards for radiation-emitting electronic products(medical and nonmedical) such as lasers, X-ray systems,ultrasound equipment, microwave ovens, and color televisions.

Accredits and enforces standards for mammography facilities.

Monitors the food supply to ensure that pesticide residues do notexceed allowable levels (established by EPA).

Regulates the labeling and safety of bottled water.

Oversees food safety, including the safety of food additives, foods/ingredients developed through technology, and food contactsubstances (FDA does not regulate traditional meats and poultry,which are the purview of USDA).

Authorized to regulate the manufacture, marketing, anddistribution of tobacco products.

Nuclear Regulatory Commission Regulates civilian use and storage of nuclear materials

(e.g., nuclear power plants, research reactors, and othermedical, industrial, and academic licensees).

Regulates the manufacture and distribution of nuclearby-product materials for medical use.

Department of Energy—DOE Conducts nuclear energy research and development.

Maintains and enhances the safety, reliability, and performanceof the U.S. nuclear weapons stockpile and oversees the design,production, and testing of nuclear products for military application.

Produces and sells many stable and radioactive isotopes that arewidely used in medicine, industrial, and research applications.

Supplies radioisotope power systems to NASA.

Oversees occupational radiation protection and conduct of DOEemployees and contractors at DOE sites and enforces contractorcompliance with DOE worker and safety, nuclear, and securityrequirements.

Department of Agriculture Manages the collection, analysis, data entry, and reporting ofpesticide residues on agricultural commodities in the U.S. foodsupply, with an emphasis on those highly consumed by infantsand children.

Occupational Safety andhealt Administration—OShA(Department of Labor—DOL)

Conducts investigations and enforces standards to maintainsafe and healthful working conditions for most people employedin the U.S. (excluding miners, transportation workers, manypublic employees, and the self-employed). Standards limit workerexposure to ionizing radiation and carcinogenic chemicals,among other things.



Mine Safety and healtAdministration(DOL)

Develops and enforces safety and health standards that apply toall U.S. mines. Standards exist for asbestos, diesel particulate,and dust as well as potentially hazardous chemicals.

Federal Communications

Commission

Authorizes and licenses communications devices, transmitters,

and facilities that generate radiofrequency electromagnetic elds.

C emical Safety board Investigates causes of industrial chemical accidents and makesrecommendations to plants, industrial organizations, labor groups,OSHA, and EPA to avoid future incidents.

Consumer ProductSafety Commission

Protects consumers from products that pose re, electrical,chemical (including potential carcinogens), or mechanical hazardby developing voluntary or mandatory standards, issuing productrecalls, conducting research on potential product hazards, andinforming and educating consumers.

Does not have jurisdiction over automobiles, tires, boats, tobacco,rearms, food, drugs, cosmetics, pesticides, and medical devices.

RESEARCh/SERVICE

Agency for To ic Su stancesand Disease Registry(HHS)

Identi es sites contaminated with hazardous substances andmakes recommendations to EPA, state regulatory agencies, orprivate organizations regarding ways to prevent or reduce furtherexposure and illness.

Conducts studies in communities near Superfund sites todetermine the health effects of exposure to hazardous substances.Funds similar research by universities, state agencies, and

others. Maintains registries of people who have been exposed totrichloroethane, trichloroethylene, benzene, and dioxin.

Conducts public health assessments of legitimate hazardouswaste storage or destruction facilities at the request of EPA, states,or individuals.

Provides technical assistance to federal agencies, states, andlocal governments that respond to accidental spills or releasesof hazardous substances.

National Center forTo icological Researc(FDA, HHS)

Conducts toxicology research to inform regulatory decisionsand reduce risks associated with FDA-regulated products.

National Center forEnvironmental healt(Centers for Disease Controland Prevention—CDC, HHS)

Conducts research and surveillance to investigate effects ofthe environment on human health.

Provides information, resources, and technical assistance to otheragencies/organizations that are implementing interventions orpreparing for/responding to environmental emergencies.

Develops and optimizes laboratory tests to help measure andtreat persons exposed to toxic substances.



A P P E N D I X

FSummary of Environmental and Occupational Links wit Cancer

CATEGORY CARCINOGENICAGENT SOURCE/USES STRONG* SUSPECTED**

AromaticAmines

Benzidine,2-naphylamine,4,4’-methylenebis2-choloraniline(MOCA),Chlornaphazine,HeterocyclicAromatic Amines

Used as antioxidantsin the production ofrubber and cutting oils,as intermediates in azodye manufacturing,and as pesticides.Common contaminant inchemical and mechanicindustries and aluminumtransformation and an aircontaminant from tobaccosmoking. Used widely inthe textile industry and as

hair dyes.

Bladder(Benzidine,2-naphylamine,4,4’-methylenebis2-choloraniline(MOCA),chlornaphazine)

Prostate(heterocyclicaromaticamines)

C lorinationby-Products

Trihalomethanes Trihalomethanesinclude chloroform,bromodichloromethane,chlorodibromomethane, andbromoform. Result fromthe interaction of chlorinewith organic chemicals.Several halogenatedcompounds may form fromthese reactions, althoughtrihalomethanes are themost common. Brominated

by-products are alsoformed from the reactionof chlorinated by-productswith low levels of bromide indrinking water.

Bladder Colorectum,Esophagus

*Strong evidence of a causal link is based primaril on a Group 1 designation b the International Agenc for Research on Cancer.

**Suspected evidence of a causal link is based on the authors’ assessment that results of epidemiologic studies are mixed, et positive ndingsfrom well-designed and conducted studies, including animal studies warrant precautionar action and additional scienti c investigation.




EnvironmentalTo acco Smoke

Contains morethan 50 knowncarcinogens

Also known as passivesmoke, environmentaltobacco smoke is acombination of smokeemitted from the burningend of a cigarette, cigar,or pipe, and smoke exhaledby the smoker.

Lung, Breast

Metals Arsenic Produced commercially asa by-product of nonferrousmetal production, primarilyfrom copper production.Comprises greater than10% of dust content insome smelter operations.Inorganic arsenic is

primarily used to preservewood, but also is used as apesticide, mainly on cottonplants.

Bladder, Kidney,Lung, Skin, SoftTissue Sarcoma(angiosarcoma ofthe liver)

Brain/CentralNervousSystem,Liver/Biliary,Prostate,Soft TissueSarcoma

Beryllium Used in the nuclear, aircraft,and medical devicesindustries. Used also asan alloy or in specialtyceramics for electrical andelectronic applications.Found as a contaminant inthe combustion of coal andfuel oil.

Lung

Cadmium Occurs naturally in orestogether with zinc, lead,and copper. Used asstabilizers in polyvinylchloride products, colorpigment, several alloys,and now most commonlyin rechargeable nickel-cadmium batteries. Alsopresent as a pollutant inphosphate fertilizers.

Lung Pancreas,Kidney,Prostate

Chromium Used in steel and other alloy

production. Chromium IIIand Chromium VI are usedin chrome plating, themanufacture of dyes andpigments, leather tanning,and wood preserving.

Lung, Nasal/

Nasopharynx






Silica An inorganic particle usedin foundries, brick-making,and sandblasting.

Lung

Talc containingasbestiform bers

A mineral used in themanufacture of pottery,paper, paint, and cosmetics.

Lung Ovary

Wood Dust Used primarily in carpentry, joinery, and in furniture andcabinetry making.

Lung, Nasal/Nasopharynx

Larynx

Pesticides Herbicides,Fungicides, andInsecticides

Used for preventing,destroying, repelling, ormitigating pests. Alsoused as plant regulators,defoliants, or desiccants.

The majority of pesticidesas registered with the U.S.Environmental ProtectionAgency (EPA) are used inagricultural applications,although residentialapplication also is animportant source.

Brain/CentralNervousSystem,Breast, Colon,Hodgkin

Lymphoma,Leukemia,Lung, MultipleMyeloma,Non-HodgkinLymphoma,Ovary,Pancreas,Kidney,Soft TissueSarcoma,Stomach,Testicle






Petroc emicalsandCom ustionby-Products

PetroleumProducts, MotorVehicle Exhaust(including diesel),Polycyclic AromaticHydrocarbons(PAHs), Soot,and Dioxins

Petrochemicals arederived from natural gasor petroleum and used toproduce a variety of otherchemicals and materialsincluding pesticides,plastics, medicines, anddyes. Substances can beproduced as the buildingblocks for other products,but mainly result from theincomplete combustionof burning coal, oil, gas(diesel exhaust), householdwaste, tobacco, and otherorganic substances. Dioxinsare a class of chemical

that are the by-productsof combustion processescontaining chlorine andcarbon-based chemicalssuch as polyvinyl chlorideplastics. Dioxins alsoare created during thechlorine-bleachingprocesses for whiteningpaper and wood pulp andare a contaminant in theherbicide, Agent Orange,used in Vietnam.

Lung (PAHs,air pollutionincludingdiesel exhaust,soot, dioxin),Non-HodgkinLymphoma(dioxin), SoftTissue Sarcoma(dioxin), Skin(PAHs)

Bladder(PAHs, dieselexhaust),Breast (dioxin,PAHs),Esophagus(soot), Larynx(PAHs),MultipleMyeloma(dioxin),Prostate(dioxin, PAHs)

Radiation Ionizing Radiation Any one of several typesof particles and rays givenoff by radioactive material,high-voltage equipment,nuclear reactions, and stars.Alpha and beta particles,X-rays, and gamma raysare radiation particles ofconcern to human health.

Bladder, Bone,Brain/CentralNervous System,Breast, Colon,Leukemia,Liver/Biliary,Lung, MultipleMyeloma, Nasaland Nasopharynx,Ovary, Soft TissueSarcoma, Skin,Stomach, Thyroid

Note: Based

on combinedevidence fromA-bomb survivor,occupationaland medicalirradiationevidence.






Vinyl Chloride Used in polyvinyl resins forthe production of plasticpipes, oor coverings, and inelectrical and transportationapplications.

Liver/Biliary, SoftTissue Sarcoma(angio-sarcomaof the liver)

Solvents Benzene Used as an intermediate inthe production of plastics,resins, and some syntheticand nylon bers. Alsoused to make some typesof rubbers, lubricants,dyes, detergents, drugs,and pesticides. Also foundin crude oil, gasoline, andcigarette smoke.

Leukemia,MultipleMyeloma,Non-HodgkinLymphoma

Brain/CentralNervousSystem,Lung, Nasal/Nasopharynx

CarbonTetrachloride Used primarily in variousindustrial applications.Before being banned, wasused in the productionof refrigeration uid andpropellants for aerosol cans,as a pesticide, as a cleaning

uid and degreasing agent,in re extinguishers, and inspot removers.

Leukemia

Methylene Chloride Used primarily as a solventin industrial applicationsand as a paint stripper.

Also found in some aerosoland pesticide productsand in the production ofphotographic lm.

Brain/CentralNervousSystem, Liver/

Biliary

Styrene Used in the productionof rubber, plastic,insulation, berglass,pipes, automobile parts,food containers, and carpetbacking.

Non-HodgkinLymphoma

Toluene Used in the productionof paints, paint thinners,

ngernail polish, lacquers,adhesives, and rubber. Alsoused in some printing andleather tanning processes.

Brain/CentralNervous

System, Lung,Colorectum






Trichloroethylene(TCE)

Used mainly for degreasingmetal parts. Previouslyused as a dry cleaningagent. May be found inprinting inks, varnishes,adhesives, paints, andlacquers. Importantcontaminant in the generalenvironment as a result ofemissions and leakage fromindustrial settings.

Liver/Biliary Cervix,HodgkinLymphoma,Kidney,Leukemia,Non-HodgkinLymphoma

Tetrachloroethylene(PCE)

Used to degreasemetal parts and as asolvent in a variety ofindustrial applications.Since the 1930s, usedby an increasinglylarge percentage of U.S.dry cleaning operations.

Bladder,Cervix,Esophagus,Kidney,Non-HodgkinLymphoma

Xylene(s) Used as a cleaning agent,a thinner for paint, andin paints and varnishes.Used in printing, rubber,and leather industries, andfound in small amounts ingasoline and airplane fuel.

Brain/CentralNervousSystem,Colorectum

Ot er Creosotes Includes coal tar and coaltar pitch formed by high-

temperature treatmentof wood, coal, or fromthe resin of the creosotebush. Wood creosotehistorically was used as adisinfectant, laxative, andcough treatment. Coaltar products are used inmedicine, animal and birdrepellents, and pesticides.Coal tar creosote iswidely used as a woodpreservative. Coal tar, coaltar pitch, and coal tar pitch

volatiles are used in roo ng,road paving, aluminumsmelting, and coking.

Bladder (coaltars), Lung, Skin






EndocrineDisruptors

A number of natural andsynthetic chemicalscapable of mimicking thebody’s natural hormones.See detailed list at: http://www.ourstolenfuture.org/Basics/chemlist.htm.

Breast (DES),Cervix (DES)

Breast(bisphenol A),Prostate(bisphenol A),Testicle(chlorinatedinsecticides)

Hair Dyes Coloring products usedon hair. Hair dyes usuallyfall into one of fourcategories: temporary,semi-permanent, demi,and permanent. Chemicalagents used in dyes arespeci c to the color and thedegree of permanency.

Bladder,Brain/CentralNervousSystem,Leukemia,MultipleMyeloma,Non-HodgkinLymphoma

Nitrosaminesand N-nitrosoCompounds

Chemicals that form whenamines and nitrosatingagents chemically react.Found in the rubber, metal,and agricultural industries,and in cosmetics and foodssuch as fried bacon andcured meats.

Brain/CentralNervousSystem, Kidney

PolychlorinatedBiphenyls (PCBs)

Used as coolants andlubricants in transformers,capacitors, and otherelectrical equipment.PCBs were banned in theU.S. in 1977.

Liver/Biliary Breast,Non-HodgkinLymphoma



Updated from: Clapp RC, Jacobs M, Loechler EL. Environmental and Occupational Causes of Cancer; New Evidence 2005-2007. Reviews onEnvironmental Health. 2008;23(1):1-37.



Little question exists that intermediate andhigh doses of ionizing radiation (greaterthan 100 millisieverts, mSv), deliveredeither as an acute dose or over a prolongedperiod, result in signi cant harm to humanhealth, including cancer development. Less

certainty exists, however, regarding lowerdoses of radiation. Compared with higherdoses, low-dose radiation is likely to conferless cancer risk, but requires progressivelylarger epidemiologic studies to quantify suchrisk to a useful degree of precision.

Figure 15 Electromagnetic Spectrum

Adapted from:NASA, Regions of the Electromagnetic Spectrum. Accessed online: http://imagine.gsfc.nasa.gov/docs/science/know_l1/spectrum_chart.html.

Georgia State University, Department of Physics and Astronomy. Hyperphysics-Electricity and Magnetism. Accessed online:http://hyperphysics.phy-astr.gsu.edu/hbase/ems2.html

Sources:National Cancer Institute. Biodosimetry—Stable chromosome aberration frequencies [Web page on the Internet]. Bethesda (MD): Division of CancerEpidemiology and Genetics, Radiation Epidemiology Branch, NCI [cited 2009 Nov 28]. Available from: http://dceg.cancer.gov/reb/research/methods/7.

U.S. Department of Health and Human Services. 11th report on carcinogens. Research Triangle Park (NC): National Toxicology Program; 2005 Jan 31.[cited 2009 Dec 4 ]. Available from: http://ntp.niehs.nih.gov/?objectid=035E5806-F735-FE81-FF769DFE5509AF0A.

Evans N, Sage C, Jacobs M, Clapp R. Radiation and cancer: a need for action. Bolinas (CA): Collaborative on Health and the Environment; 2009 Jan.

Brenner DJ, Doll RD, Goodhead DT, Hall EJ, Land CD, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know.Proceedings of the National Academy of Sciences. 2003;100(24):13761-13766.



A P P E N D I X

hElectromagnetic Energy Units of Measure

SI UNIT MEASURE DEFINITION OThER COMMONUNITS CONVERSIONS

I o n i z i n g R a d i a t i o n

Becquerel (Bq) Radioactivity The rate of radiation

emission from asource.

Kilobecquerel (kBq)

Gigabecquerel (GBq)Curies (Ci)Microcurie (µCi)Picocurie (pCi)

1 Bq = 10-3 kBq

1 Bq = 10-9

GBq1 Bq = 2.7 x 10-11 Ci1 Bq = 2.7 x 10-5 µCi1 Bq = 27 pCi

Gray (Gy) Absorbed Dose The amount of energyabsorbed per unitweight of the organ ortissue.

Milligray (mGy)Rads

1 Gy = 1000 mGy1 Gy = 100 Rads

Sievert (Sv) Equivalent Dose The absorbed dose multiplied by aradiation weightingfactor, which accountsfor variability of harmin radiation type.

Millisievert (mSv)RemMillirem (mRem)

1 Sv = 1000 mSv1 Sv = 100 Rem1 Sv = 105 mRem

Effective Dose The absorbed dose multiplied by a tissueweighting factor,which accounts forvariability of harm intissue type.



CollectiveEffective Dose

The total estimatedamount of radiationto all members ofa population overa speci ed periodof time.



N o n -

I o n i z i n g

R a d i a t i o n Tesla (T) Magnetic Field The magnetic forceexerted on a moving

charged particle.Nanotesla (nT)Gauss (G) 1 T = 10

-9

nT1 T = 104 G

Hertz (Hz) Frequency The number ofenergy wave cyclesper second.

Megahertz (MHz) 1 Hz = 10-6 MHz

Sources:Units for Measuring Ionizing Radiation. In: Encyclopædia Britannica [Internet]. 2009 [cited 2009 May 14]. Available from: http://www.britannica.com/EBchecked/topic/488507/radiation/28855/Units-for-measuring-ionizing-radiation.

National Institute of Standards and Technology. The NIST Reference on Constants Units and Uncertainty [Internet]. [cited 2009 May 14]. Available from:http://physics.nist.gov/cuu/Units/units.html.

U.S. Army Corps of Engineers. H ow big is a Picocurie [Internet]. [cited 2009 May 14]. Available from: http://www.lrb.usace.army.mil/fusrap/docs/fusrap-fs-picocurie.pdf.

Canadian Centre for Occupational Health and Safety. Radiation—Quantities and Units of Ionizing Radiation [Internet]. 2007 Jun [cited 2010 Mar 15]. Available from:http://www.ccohs.ca/oshanswers/phys_agents/ionizing.html.



A P P E N D I X

IResearc Recommended y PCP Meeting Participants

Participants at the President’s Cancer Panel2008–2009 meetings on environmental

in uences on cancer identi ed several areasin which environmental cancer researchis needed, as well as speci c studiesthat would improve our understandingof environmental cancer and supportenvironmental cancer hazard assessmentand control:

Conduct new or updated assessments ofcurrent occupational and environmentalexposures:

Update exposure assessments in U.S.•workers, particularly those with bodyburdens of persistent pollutants; the mostrecent study was conducted in the 1980s.

Assess children’s exposures to•agricultural pesticides, considering drift,inadvertent parental “take-home” ofoccupational chemicals, and ingestion.

Assess cancer risks attributable to•exposures and speci c occupations wherecurrent, scienti cally sound assessments

do not exist. Such assessments shouldcorrect aws in the methodology usedby Doll and Peto and must considersynergistic effects of multiple exposures.

Improve quantitative radiation risk•estimates, including dose reconstruction,and develop new research tools.

Improve toxicity testing methods andtechnologies for new and existingchemicals:

Develop high throughput screening (HTS)•technologies to enable simultaneoustesting for molecular, biochemical, andfunctional impacts of multiple possiblecarcinogens. Speci cally, developHTS tools and assays that will supportthe National Toxicology Program’sthree-tiered testing program nowunder development. The program andsupporting technologies should re ectcurrent scienti c knowledge (e.g.,about environmental and occupationalcarcinogens, immunotoxicants, anddevelopmental toxicants).

Conduct mechanistic studies to•determine whether perturbed biologicalmechanisms that cause cancer inanimals have the same effect in humans.

Identify and validate biological markers•that can be used as surrogate endpointsfor cancer to accelerate research results.

Develop alternative methods for• assessing carcinogenicity; studiescurrently are limited to substances thatare believed to be genotoxic or mutagenic.Research is needed to improve methodsand technologies for assessing the impactof epigenetic changes, gene-environmentinteractions, and other non-genotoxicmechanisms (e.g., telomere length) oncancer risk.



Increase focus on understudied exposuremechanisms:

Assess the effects of exposure to•chemical mixtures.

Determine the effects of chronic low-dose•

exposures.Elucidate the effects of gene-environment•interactions on individual susceptibility toenvironmental cancer.

Identify determinants of susceptibility to•radiation-related cancer.

Increase research on understudiedpopulation groups:

Elucidate epigenetic and other•relationships between parental exposureand childhood cancer.

Determine why rates of childhood•leukemia, brain, and testicular cancer arerising. The National Children’s Study isa good foundation on which to build theknowledge base in this area.

Design and conduct other large•prospective studies to furtherexplore “windows of susceptibility” toenvironmental carcinogens; researchto date shows that the same exposuresat different ages may lead to differentcancers.

Conduct research on understudiedenvironmental chemical exposures:

Follow up existing leads on associations•between individual pesticides and speci ccancers. In addition, conduct studies toassess the carcinogenic potential of inertas well as active ingredients in pesticides.Inert ingredients often are consideredproprietary and do not undergotoxicological testing.

Conduct additional research on the•effects of nitrate in drinking water. Fewstudies have been conducted to determineassociations between nitrate in drinkingwater and speci c cancer sites. Inaddition, the impact of early life exposureis not well understood. Cross-sectionalbiomonitoring studies of nitrate ingestionwill enhance understanding of adverseeffects of nitrate, N-nitroso compounds,and other nitrogen compounds onvulnerable populations.

Identify cancer risk (other than bladder•cancer) associated with water disinfectionby-products. In particular, colon andrectal cancer studies to date have beeninconclusive; these potential links needfurther research.

Determine the mechanism of arsenic•carcinogenesis.

Further investigate links between•endocrine-disrupting chemicals andbreast and other cancers.

Conduct research on the carcinogenicity•of emerging air pollutants not included inthe National Air Toxics Assessment, suchas nanomaterials.

Investigate the suspected link between•

polycyclic aromatic amines and breastcancer, especially in populations that maybe genetically susceptible.



Conduct research on understudied radiationexposures:

Quantify workplace radon exposures.•

Resolve controversies regarding the•safety or harm of low doses of various

forms of radiation in adults and children.Identify circumstances under which low-dose radiation may have a hormetic effect.

Develop radiation dose and risk estimates•that better re ect the current and futureU.S. population. Existing dose and riskestimates have been based on adultmales; estimates should account forpopulation diversity, including children.In addition, develop medical radiation riskestimates that are not based on acute

doses received by atomic bomb survivors.Expand research on possible harmful•effects of cell phone use, especially inchildren. Cell phone use still is relativelyrecent, and studies to date have hadmixed ndings; most involve users ofolder equipment. Findings from cohortstudies now underway are anticipated, butlonger-term studies of individuals usingcurrent equipment are needed.

Conduct additional research on possible•

links between electromagnetic elds(EMF) and cancer; identify mechanism(s)of EMF carcinogenesis.

Monitor changing patterns of radiation•exposure.

Conduct research on toxins and endocrinedisrupting chemicals in personal careproducts and cosmetics; only 11 percent ofthe ingredients in these products have beentested for safety.

Raise the priority of and investment inresearch to develop non-toxic products andprocesses:

Increase research on sustainable•production, such as:

Green chemistry initiatives, including–new product development andredesign of products or processes toeliminate harmful substances ratherthan mechanical engineering tactics toreduce exposures;

Compostable bio-based plastics; and–

Solar, wind, and hydroelectric power.–

Develop, test, and evaluate preventioncommunication strategies and interventions,especially in high-risk occupations andpopulations.

reducing cancer risk pcp_report_08!09!508

Documents