REPORT ON CARCINOGENS, ELEVENTH EDITION

Introduction

The probability that a resident of the United States will develop cancer

at some point in his or her lifetime is 1 in 2 for men and 1 in 3 for

women (ACS 2004). Nearly everyone’s life has been directly or

indirectly affected by cancer. Most scientists involved in cancer research

believe that the environment in which we live and work may be a major

contributor to the development of cancer (Lichtenstein et al. 2000). In

this context, the “environment” is anything that people interact with,

including exposures resulting from lifestyle choices, such as what we eat,

drink, or smoke; natural and medical radiation, including exposure to

sunlight; workplace exposures; drugs; socioeconomic factors that affect

exposures and susceptibility; and substances in air, water, and soil (OTA

1981, IOM 2001). Other factors that play a major role in cancer

development are infectious diseases, aging, and individual susceptibility,

such as genetic predisposition (Montesano 2001). We rarely know what

environmental factors and conditions are responsible for the onset and

development of cancers; however, we have some understanding of how

some types of cancer develop, especially cancers related to certain

occupational exposures or the use of specific drugs. Many experts firmly

believe that much of the cancer associated with the environment may be

avoided (Tomatis et al. 1997). 

The people of the United States, concerned about the relationship

between their environment and cancer, have asked, through the U.S.

Congress, for information about substances that are known or appear

likely to cause cancer (i.e., to be carcinogenic). Section 301(b)(4) of

the Public Health Service Act, as amended, provides that the Secretary

of the Department of Health and Human Services (DHHS) shall

publish a biennial report that contains the following information:

A) A list of all substances (1) which either are known to be

human carcinogens or may reasonably be anticipated to be

human carcinogens and (2) to which a significant number

of persons residing in the United States are exposed.

B) Information concerning the nature of such exposure and the

estimated number of persons exposed to such substances.

C) A statement identifying (1) each substance contained in

this list for which no effluent, ambient, or exposure

standard has been established by a Federal agency and (2)

for each effluent, ambient, or exposure standard established

by a Federal agency with respect to a substance contained

in this list, the extent to which such standard decreases the

risk to public health from exposure to the substance.

D) A description of (1) each request received during the year to

conduct research into, or testing for, the carcinogenicity of a

substance and (2) how the Secretary and other responsible

entities responded to each request. 

The Report on Carcinogens (RoC) is an informational scientific and

public health document that identifies and discusses agents, substances,

mixtures, or exposure circumstances that may pose a hazard to human

health by virtue of their carcinogenicity. It serves as a meaningful and

useful compilation of data on (1) the carcinogenicity (ability to cause

cancer), genotoxicity (ability to damage genes), and biologic

mechanisms (modes of action in the body) of the listed substances in

humans and/or in animals, (2) the potential for human exposure to

these substances, and (3) Federal regulations to limit exposures. The

RoC does not present quantitative assessments of the risks of cancer

associated with these substances. Thus listing of substances in the RoC

only indicates a potential hazard and does not establish the exposure

conditions that would pose cancer risks to individuals in their daily lives.

Such formal risk assessments are the responsibility of the appropriate

federal, state, and local health regulatory and research agencies. 

The substances listed in the RoC are either known or reasonably

anticipated to cause cancer in humans in certain situations. With many

listed substances, cancer may develop only after prolonged exposure. For

example, smoking tobacco is known to cause cancer in humans, but not

all people who smoke develop smoking-related cancer. With some

substances or exposure circumstances, however, cancer may develop

after even brief exposure. Examples include certain occupational

exposures to asbestos or bis(chloromethyl) ether. The cancer hazard that

listed substances pose to any one person depends on many factors.

Among these are the intrinsic carcinogenicity of the substance, the

amount and duration of exposure, and an individual’s susceptibility to

the carcinogenic action of the substance. Because of these

considerations, the RoC does not attempt to rank substances according

to the relative cancer hazards they pose. 

Potential Beneficial Effects of Listed Carcinogens

As stated above, the purpose of the RoC is to identify hazards to

human health posed by carcinogenic substances; therefore, it is not

within the scope of this report to address potential benefits of exposure

to certain carcinogenic substances in special situations. For example,

numerous drugs typically used to treat cancer or other medical

conditions have been shown to increase the frequency of primary or

secondary cancers in patients undergoing treatment for specific

diseases. In these cases, the benefits of using the drug to treat or prevent

a specific disease outweigh the added cancer risks associated with its

use. Personal decisions concerning voluntary exposure to carcinogenic

substances should be based on information that is beyond the scope of

the RoC. Individuals should not make decisions concerning the use of

a given drug, or any other listed substance, based solely on the

information contained in the RoC. Such decisions should be made

only after consultation with a physician or other appropriate specialist.

Identification of Carcinogens

For many years, government research agencies (including the National

Toxicology Program), industries, academia, and other research

organizations have studied various substances to identify those that may

cause cancer. Much of this information on specific chemicals or

occupational exposures has been published in the scientific literature or

in publicly available and peer-reviewed technical reports. This literature

is a primary source of information for identifying and evaluating

substances for listing in the RoC. Many of the listed substances also

have been reviewed and evaluated by other organizations, including the

International Agency for Research on Cancer (IARC) in Lyon, France,

the Environmental Protection Agency of the State of California, and

other U.S. Federal and international agencies.

Both human and laboratory animal studies are used to evaluate

whether substances are possible human carcinogens. The strongest

evidence for establishing a relationship between exposure to any given

substance and cancer in humans comes from epidemiological studies—

studies of the occurrence of a disease in a defined population and the

factors that affect its occurrence (Bradford 1971). Epidemiological studies

of human exposure and cancer are difficult (Rothman 1986). They must

rely on natural, not experimental, human exposures and must therefore

consider many factors that may affect cancer prevalence besides the

exposure under study. One such factor is the latency period for cancer

development. The exposure to a carcinogen often occurs many years

(sometimes 20 to 30 years or more) before the first sign of cancer appears.

Another valuable method for identifying substances as potential human

carcinogens is the long-term animal bioassay. These studies provide

accurate information about dose and duration of exposure and they are

less affected than epidemiology studies by possible interaction of the test

substance with other chemicals or modifying factors (Huff 1999). In these

studies, the substance is given to one or (usually) two species of laboratory

rodents over a range of doses for nearly the animals’ entire lives. 

Experimental cancer research is based on the scientific assumption

that substances causing cancer in animals will have similar effects in

humans. It is not possible to predict with complete certainty from
INTRODUCTION

REPORT ON CARCINOGENS, ELEVENTH EDITION

animal studies alone which substances will be carcinogenic in humans.

However, known human carcinogens that have been tested adequately

in laboratory animals also cause cancer in laboratory animals (Fung et

al. 1995). In many cases, a substance first was found to cause cancer in

animals and later confirmed to cause cancer in humans (Huff 1993).

How laboratory animals respond to substances, including developing

cancer and other illnesses, does not always strictly correspond to how

people will respond. Nevertheless, laboratory animal studies remain

the best tool for detecting potential human health hazards of all kinds,

including cancer (OTA 1981, Tomatis et al. 1997). 

Listing Criteria

The criteria for listing an agent, substance, mixture, or exposure

circumstance in the RoC are as follows:

Known To Be Human Carcinogen:

There is sufficient evidence of carcinogenicity from studies

in humans*, which indicates a causal relationship between

exposure to the agent, substance, or mixture, and human

cancer.

Reasonably Anticipated To Be Human Carcinogen:

There is limited evidence of carcinogenicity from studies

in humans*, which indicates that causal interpretation is

credible, but that alternative explanations, such as chance,

bias, or confounding factors, could not adequately be

excluded, 

or

there is sufficient evidence of carcinogenicity from studies

in experimental animals, which indicates there is an

increased incidence of malignant and/or a combination of

malignant and benign tumors (1) in multiple species or at

multiple tissue sites, or (2) by multiple routes of exposure,

or (3) to an unusual degree with regard to incidence, site,

or type of tumor, or age at onset, 

or

there is less than sufficient evidence of carcinogenicity in

humans or laboratory animals; however, the agent,

substance, or mixture belongs to a well-defined, structurally

related class of substances whose members are listed in a

previous Report on Carcinogens as either known to be a

human carcinogen or reasonably anticipated to be a human

carcinogen, or there is convincing relevant information that

the agent acts through mechanisms indicating it would

likely cause cancer in humans. 

Conclusions regarding carcinogenicity in humans or experimental

animals are based on scientific judgment, with consideration given

to all relevant information. Relevant information includes, but is

not limited to, dose response, route of exposure, chemical structure,

metabolism, pharmacokinetics, sensitive sub-populations, genetic

effects, or other data relating to mechanism of action or factors that

may be unique to a given substance. For example, there may be

substances for which there is evidence of carcinogenicity in

laboratory animals, but there are compelling data indicating that

the agent acts through mechanisms which do not operate in

humans and would therefore not reasonably be anticipated to cause

cancer in humans.

*This evidence can include traditional cancer epidemiology studies, data from clinical

studies, and/or data derived from the study of tissues or cells from humans

exposed to the substance in question that can be useful for evaluating whether a

relevant cancer mechanism is operating in people.

The listing criteria presented here were first adopted for use in the

Eighth Report on Carcinogens, which was published in 1998. The

clarification noted above was issued in a Federal Register notice dated

April 2, 1999 (see 64FR15983-15984, see also Federal Register notice

dated April 19, 1999: 64FR 19188-19189). Listing criteria for

substances listed in earlier editions of the RoC are outlined in the

introductions to those editions.

Preparation of the RoC

Within the DHHS, the Secretary has delegated the responsibility for

preparing the RoC to the National Toxicology Program (NTP). The

process used to prepare the RoC involves several levels of review of the

nominations considered for listing in or delisting (removal) from the

report. Opportunities for public comment and participation are an

integral part of the review process. 

Nominations for listing in or delisting from the RoC are received

from a number of sources. Periodic requests for nominations from the

public are published in the Federal Register, the NTP Update

newsletter, and other appropriate publications. The NTP actively

solicits nominations from member agencies of the NTP Executive

Committee.1 Nominations for the RoC also come from reviews of the

literature performed by the NTP. Potential nominations are identified

from such sources as the NTP Technical Reports, the IARC

Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to

Humans, the California Environmental Protection Agency’s

Carcinogen List, and other similar sources.

Two Federal scientific review groups and one non-governmental

scientific peer-review body (a standing subcommittee of the NTP

Board of Scientific Counselors) evaluate the nominations for listing in

or delisting from the RoC. Each group reviews the relevant data on

the carcinogenicity of the substances nominated and the exposure of

U.S. residents to the substances. The members of these three review

groups may be found in Appendix D, List of Participants.

The nominations for listing in the Eleventh Report on Carcinogens

initially were evaluated by a Report on Carcinogens Review Committee

(RG1), composed of scientists from the National Institute of

Environmental Health Sciences. For each nomination, the RG1

determined whether the information available was sufficient for

applying the criteria for listing and whether the nomination warranted

formal consideration by the NTP. This committee received the

information submitted with each nomination and any relevant

supplemental materials identified by RoC staff. For each nomination

the committee reviewed this information and made a formal

recommendation to the Director, NTP, either to continue with the

formal review for listing or delisting or not to pursue the nomination at

that time. The criterion for not pursuing a nomination was the lack of

sufficient information for applying the listing criteria. Those

nominations not accepted for review were returned to the original

nominator who was invited to resubmit the nomination with additional

justification, such as new cancer data or exposure information. The

NTP Executive Committee and the NTP Board of Scientific

Counselors were informed of all nominations not accepted for review. 

Upon approval of the nominations by the Director, the NTP

announced its intent to review the nominations for the Eleventh

Report on Carcinogens and solicited public comment on all

nominations through announcements in the Federal Register and NTP

publications. The NTP then initiated an independent search and

1Agencies represented on the NTP Executive Committee include: Agency for Toxic

Substances and Disease Registry (ATSDR), Consumer Product Safety Commission

(CPSC), Environmental Protection Agency (EPA), Food and Drug Administration

(FDA), National Center for Environmental Health (NCEH/CDC), National Institute for

Occupational Safety and Health (NIOSH), Occupational Safety and Health

Administration (OSHA), Department of Health and Human Services (DHHS),

National Institutes of Health (NIH), National Cancer Institute (NCI), and National

Institute of Environmental Health Sciences/NTP (NIEHS/NTP).
INTRODUCTION

review of the scientific literature and prepared a background

document for each nomination under consideration. The comments

received in response to the public announcement were used to help

identify issues that should be addressed in the background documents.

Whenever possible, the background documents were prepared with

the assistance of a consultant or a panel of consultants with recognized

expertise on the nomination. 

The RG1 then conducted the initial scientific review of a

nomination for listing in the Eleventh Report on Carcinogens. The RG1

first reviewed the background document prepared for each nomination

and determined whether it was adequate for use in reviewing the

nomination and applying the criteria for listing in the RoC. After

acceptance of the background document the RG1 then proceeded with

scientific review of the nomination. It considered the information in the

background document and all public comments received in response to

the announcement of the nomination, and made a formal

recommendation to the NTP Director for its listing in the RoC. Upon

acceptance of the background document by the RG1, it was considered

the final document of record and was placed on the NTP RoC web site

with a notice published on the NTP list-serv and the NTP home web

site announcing its availability. 

The NTP Executive Committee’s Interagency Working Group for

the Report on Carcinogens (RG2), a governmental interagency

scientific review group, conducted a second review of the nominations.

For each nomination, the RG2 assessed whether relevant information

was available and sufficient for its listing in the RoC. The RG2

considered the original nomination, the background document, and all

public comments received in response to announcements of the

nominations. Upon completion of its review, the RG2 made its formal

recommendations to the NTP Director for listing the nominations in

the RoC. 

The third review of the nominations was an independent external

scientific peer review by a standing subcommittee of the NTP Board

of Scientific Counselors (the RoC Subcommittee). The RoC

Subcommittee assessed whether the relevant information available for

each nomination was sufficient for its listing in the RoC. This review

was conducted in an open public meeting. A notice of the review

announcing the meeting and the availability of the background

documents, and soliciting public comment on the nominations was

published in the Federal Register and NTP publications. The notice

invited interested groups or individuals to submit written comments

and/or address the RoC Subcommittee during the public meeting.

Upon completion of its review, the RoC Subcommittee made its

formal recommendations to the NTP Director for listing the

nominations in the RoC. 

Following completion of the reviews by the RG1, RG2 and RoC

Subcommittee, the NTP published the nominations and the review

groups’ recommendations for each nomination in the Federal Register,

and solicited the third and final round of public comment and input

on the nominations.

The recommendations of the RG1, RG2, and RoC Subcommittee

and all public comments received were presented to the NTP Executive

Committee for review and comment. The NTP Executive Committee

reviewed the information on each nomination and provided to the

NTP Director a recommendation on its listing in the RoC.

The NTP Director received the independent recommendations of

the RG1, RG2 and RoC Subcommittee, the opinion of the NTP

Executive Committee, and all public comments concerning the

nominations. The NTP Director evaluated this input and any other

relevant information on the nominations and developed

recommendations to the Secretary, DHHS regarding whether to list

or not to list the nominations in the RoC. 

The NTP prepared the final draft of the RoC based on the NTP

Director’s recommendations and submitted it to the Secretary, DHHS,

for review and approval. Upon approval of the RoC, the Secretary

submitted it to the U. S. Congress as a final document. Submittal of

the RoC to Congress constituted publication of the report, and it

became available to the public at that time. The NTP published a

notice of the publication and availability of the Eleventh Edition of the

RoC, indicating all newly listed agents, substances, mixtures or

exposure circumstances in the Federal Register and NTP publications. 

Estimation of Exposure

The RoC is required to list only substances to which a significant

number of people living in the United States are exposed; therefore,

substances to which very few people are exposed are generally not

listed. Some substances that have been banned or restricted in use

(e.g., safrole, arsenical pesticides, and mirex) are listed either because

people who were previously exposed remain potentially at risk or

because these substances still are present in the environment. 

The RoC also is required to provide information about the nature

of exposures and the estimated numbers of people exposed to listed

substances. Four of the agencies participating with the NTP in

preparation of the Eleventh Report on Carcinogens—the Consumer

Product Safety Commission (CPSC), U.S. Environmental Protection

Agency (EPA), Food and Drug Administration (FDA), and

Occupational Safety and Health Administration (OSHA)—are

responsible for regulating hazardous substances and limiting the

exposure to and use of such substances. Information on use,

production, and exposure in each entry of the RoC was reviewed by

staff members from these four regulatory agencies. Because little

information typically is available, estimating the number of people

who could be exposed, and the route, intensity, and duration of

exposure for each substance is a very difficult task. This RoC attempts

to respond to these questions, and adequate answers that could be

obtained are included in the individual profiles for each listing.

The National Institute for Occupational Safety and Health

(NIOSH) has conducted two occupational exposure surveys: the

National Occupational Hazard Survey (NOHS), conducted from

1972 to 1974, and the National Occupational Exposure Survey

(NOES), conducted from 1981 to 1983. These surveys yielded data

on potential exposure to many listed substances. Although dated,

NOES estimates are provided in the profiles of the listings when

available, and NOHS figures are given in some profiles if no other

exposure data were available.

Regulations and Guidelines

The RoC is required to identify each listed substance for which no

standard for exposure or release into the environment has been

established by a Federal Agency. The Eleventh Report on Carcinogens

addresses this requirement by providing in each profile a summary of

the regulations and guidelines that are likely to decrease exposure to that

substance. Some of these regulations and guidelines have been enacted

for reasons other than the substance’s carcinogenicity (for example, to

prevent adverse health effects other than cancer or to prevent accidental

poisoning of children). These regulations are included in the profiles,

because reduction of exposure to a carcinogen will likely reduce the risk

for cancer. In earlier editions of the RoC, each profile contained a

summary of relevant regulations with a cumulative list of the Code of

Federal Regulations and Federal Register citations for each listing

published in a separate volume. All regulations have been researched

and presented in the Eleventh Report on Carcinogens using a new format.

Starting with this edition, the regulations for a listing are organized by

regulatory agencies and major acts, and are provided at the end of the

profile rather than in a separate volume.

The majority of the regulations cited in the RoC were enacted by

the following federal agencies: CPSC, the U.S. Department of

Transportation, the EPA, the FDA, and OSHA. The guidelines cited

REPORT ON CARCINOGENS, ELEVENTH EDITION
INTRODUCTION

REPORT ON CARCINOGENS, ELEVENTH EDITION

in the RoC are primarily those published by NIOSH and the

American Conference of Governmental Industrial Hygienists.

Additionally, regulations and guidelines enacted by other

governmental agencies not listed above are cited if their likely

outcome is to reduce exposure to the substance. It is beyond the scope

of this report to provide detailed information or interpretation

concerning the implementation of each regulatory act, and no attempt

is made to do so. Some commonly used regulatory terms are defined

in the glossary (Appendix F), and links to the websites for the Code of

Federal Regulations and for each of the major regulatory agencies are

provided in the reference section of this Introduction for those

wishing to obtain additional information on these agencies and their

regulations.

Two regulations were identified that apply to all substances listed

in the RoC: 

1. OSHA’s Hazard Communication Standard

This regulation is intended to communicate the hazards of

chemicals and appropriate protective measures to protect

employees. The program includes maintenance of a list of

hazardous chemicals, labeling of containers in the workplace,

and preparation and distribution of material safety data

sheets to employees. The rule states that chemicals shall be

considered “hazardous” if they have been listed as a

carcinogen or potential carcinogen in (1) the NTP’s RoC

(latest edition) or (2) the IARC Monographs (latest editions)

or (3) OSHA’s Occupational Safety and Health Standards,

Subpart Z – Toxic and Hazardous Substances. 

2. EPA’s Criteria for the Evaluation of Permit Applications for

Ocean Dumping of Materials under the Toxic Substances

Control Act (TSCA)

This regulation prohibits ocean dumping of materials

containing “known carcinogens, mutagens, or teratogens

or materials suspected to be carcinogens, mutagens, or

teratogens by responsible scientific opinion” as other than

trace contaminants. 

Because both of these regulations apply to all substances listed in

the RoC, they are not identified individually in the listing profiles.

However, the reader should be aware that these regulations pertain to

all substances listed in the RoC, and that their likely outcome is to

reduce exposure to listed substances. 

Two OSHA regulations identified in some of the listing profiles

require clarification: 

1. Specific substances are listed as having “comprehensive

standards” if, in addition to the permissible exposure limit

(PEL), OSHA has regulations for the substance that include

provisions for: exposure monitoring, engineering and work

practice controls, use of respirators and protective garments

and equipment, hygiene facilities, information and training,

labeling of substance containers and worker areas in which

the substance is used, and health screening programs.

2. The OSHA PEL identified in the profiles for glass wool

(respirable size), ceramic fibers (respirable size), and wood

dust are based on the standard for Particulates Not

Otherwise Regulated (PNOR). This standard sets limits

applicable to all inert or nuisance dusts, whether mineral,

inorganic, or organic, not identified specifically by

substance name. OSHA recommended that the profiles for

these three substances include the PEL established by the

PNOR standard. 

Estimation of Risk Reduction

For each effluent, ambient, or exposure standard established by a

Federal agency for a listed substance, the RoC is required to state the

extent to which, on the basis of available medical, scientific, or other

data, the implementation of that standard decreases the public’s risk

for cancer. This statement requires quantitative information on how

much protection from cancer the public is afforded by established

Federal standards. 

Estimating the extent to which listing a substance in the RoC

protects public health is perhaps the most difficult task in preparing

the RoC. The carcinogenic risk (i.e., the probability of developing

cancer) depends on many things, including the intensity, route, and

duration of exposure to a carcinogen. People may respond differently

to similar exposures, depending on their age, sex, nutritional status,

overall health, genetics, and many other factors. Only in a few

instances can risk for cancer be estimated with complete confidence,

and these estimations require studies of long-term human exposures

and cancer incidence in restricted environments, which rarely

are available. 

One possible way to provide quantitative estimates of risk reduction

might be to assume that the cancer risk is directly proportional to

exposure. This approach also presumes that data exists on past and

present exposure levels, or that all workplace conditions comply with

regulations. It is rare that one has information supporting these

assumptions. Despite these limitations, it is reasonable and prudent to

accept that reducing exposure, for any reason, particularly to substances

shown to be carcinogenic in experimental animals, will decrease the

incidence of cancer in people (Tomatis et al. 1997, Montesano et al.

2001). This relationship is the basis of current regulatory policies that

aim to lower human exposure to cancer-causing substances, and

thereby, improve public health.

Major environmental pollution prevention acts, such as the EPA’s

Resource Conservation and Recovery Act, Clean Water Act and Clean

Air Act, were passed in the early 1970s. These laws have lead to the

reduction in exposure to a number of substances listed in the RoC.

Although one can not draw a direct cause and effect relationship

between pollution reduction and cancer incidence, recent data from

the Surveillance, Epidemiology, and End Results (SEER) Program of

the National Cancer Institute show decreasing cancer trends for many

cancers, although others are increasing (SEER 2003). The “Annual

Report to the Nation on the Status of Cancer, 1975-2000” (Wier

et al. 2003) is based in part on the most recent SEER data and

provides an update on cancer mortality (death rates), incidence rates

(new cases), and trends in the United States. The report is issued

annually by the Centers for Disease Control and Prevention (CDC),

the American Cancer Society (ACS), the National Cancer Institute

(NCI) of the National Institutes of Health, and the North American

Association of Central Cancer Registries (NAACCR). This report

indicates that overall, cancer death rates (for men and women

combined) were stable from 1998 through 2000 - that is, rates neither

increased nor decreased. Before this time, death rates increased

through 1990, stabilized through 1994, and declined from 1994

through 1998. Throughout the late 1990s, trends for women

stabilized, while death rates for men continued to decline. Lung,

colorectal, breast and prostate cancers have the highest prevalence in

the United States and account for more than half of all cancer cases: 

• Lung cancer is the leading cause of death from cancer in men and

women in the United States. Lung cancer death rates among white

and black men declined throughout the 1990s, while the rate of

increase in deaths among women slowed during the same period,

reflecting reductions in tobacco smoking. It is interesting to note

that recently published studies have shown a rise in lung cancer and

cardiopulmonary disease due to air pollution (Montesano et al.

2001).

• Colorectal cancer death rates have been declining for both white

and black men and women beginning in the 1970s, with steeper

declines beginning in the mid-1980s. This decline is attributed to

better screening and treatment methods for this cancer. 
INTRODUCTION

• Breast cancer death rates continue to fall despite a gradual, longterm increase in incidence rates. Decreasing rates in deaths from

breast cancer and increasing incidence rates during the 1990s have

been attributed, in part, to increased use of mammography

screening and the availability of improved therapies. 

• Prostrate cancer death rates have been declining since 1994, while

incidence rates have been rising since 1995, with a 3.0 percent per

year increase in incidence in white men and a 2.3 percent per year

increase in black men. No currently recognized risk factors account

for the decline in prostate cancer mortality, although the decrease

might reflect improvements in treatment combined with improved

detection using a blood test for prostate specific antigen (PSA). 

Cancer sites without significant improvement in survival rates in

the past 25 years include the uterine corpus, cervix, larynx, liver, lung,

pancreas, stomach, and esophagus (Jemal et al. 2004).

Cancer incidence rates for all types of cancer combined increased

from the mid-1970s through 1992, declined from 1992 through

1995, and then stabilized (a non-significant increase) from 1995

through 2000. Increases in incidence rates in breast cancer and

prostate cancer offset long-term decreases in lung cancer in men (Wier

et al. 2003). The SEER data also indicate that the incidences of liver,

thyroid, melonoma of the skin and kidney cancers increased over the

time interval between 1992 ad 2000 (SEER 2003).

Listing Substances in the Eleventh Report on Carcinogens

The Eleventh Report on Carcinogens contains 246 entries, 17 of which

have not appeared in earlier editions of the RoC. 

The Eleventh Report on Carcinogens lists lead and lead compounds

as reasonably anticipated to be human carcinogens. This listing of lead

and lead compounds supersedes the listings of individual lead

compounds (including lead acetate and lead phosphate) in previous

editions of the RoC and applies to lead and all lead compounds. 

The heterocyclic amines 2-amino-3,4-dimethylimidazo[4,5-

f ]quinoline (MeIQ), 2-amino-3,8-dimethylimazo[4,5-f ]quinoxaline

(MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

(PhIP), are listed for the first time in the Eleventh Report on

Carcinogens as reasonably anticipated to be human carcinogens. Another

heterocyclic amine, 2-amino-3-methylimidazo [4,5-f ]quinoline (IQ)

was listed in the Tenth Report on Carcinogens, also as reasonably

anticipated to be a human carcinogen. These four listings have been

grouped together as a family under the title “Selected Heterocyclic

Amines.” The listing first gives evidence for the carcinogenicity for

each heterocyclic amine separately, and then presents a combined

section that discusses other information relevant to carcinogenicity,

properties, use, production, exposure and regulations. 

Three types of ionizing radiation (X-radiation, gamma radiation,

and neutrons) are listed as known to be human carcinogens for the first

time in the Eleventh Report on Carcinogens. The radioactive compound

thorium dioxide, which decays by emission of alpha particles, was first

listed in the Second Annual Report on Carcinogens (1981). Radon and

its most common isotopic forms (radon-220 and radon-222), which

also emit primarily alpha particles, were first listed in the Seventh

Annual Report on Carcinogens (1994). The profiles for these sources of

ionizing radiation have been placed together as a family of profiles

under the title “Ionizing Radiation.” 

Diethanolamine was nominated for possible listing in the Eleventh

Report on Carcinogens, but after a formal scientific review of all

relevant information pertaining to its possible carcinogenicity, was not

recommended for listing. The basis for the recommendation not to

list diethanolamine is summarized in Appendix C of the Eleventh

Report on Carcinogens. 

Section II lists the names of all the agents, substances, mixtures, or

exposure circumstances listed in the Eleventh Report on Carcinogens. It

has two parts: Section II.A identifies 58 substances as known to be

human carcinogens, and Section II.B identifies 188 substances as

reasonably anticipated to be human carcinogens. 

Section III, Substance Profiles, contains a brief description of each

substance with a summary of the evidence for its carcinogenicity;

relevant information on properties, use, production and exposure; and a

summary of the regulations and guidelines that are likely to decrease the

exposure to the substance. These profiles are in alphabetical order and

include references to scientific literature used to support the listings. 

The substances listed in the Eleventh Report on Carcinogens may

constitute only a fraction of actual human carcinogens. The RoC lists

only those nominated agents, substances, mixtures or exposure

circumstances for which relevant data exist and have been reviewed

and found to meet the listing criteria defined above. As additional

substances are nominated, they will be considered and reviewed for

possible listing in future editions of the RoC. 

Certain manufacturing processes, occupations, and exposure

circumstances have been considered by IARC and are classified by that

agency as known to be carcinogenic to humans because of associated

increased incidences of cancer among workers in these settings.

However, certain aspects of occupational exposures may differ in

different parts of the world or may have changed over time; therefore,

the manufacturing processes and occupations reviewed by IARC may

not be applicable to past or current occupational exposures in the

United States. The NTP has not yet reviewed the data supporting the

listing of these occupational situations as posing a cancer hazard. In the

interest of public health and for completeness, these occupational

exposures are identified in Appendix A of the RoC with the

corresponding IARC references.

Other Information Provided in this RoC

Section IV provides tables listing requests to the DHHS for research,

testing, and other information relating to carcinogenicity, either from

other Federal agencies or from within the DHHS, and how the DHHS

responded to the requests. Section V details the listing and delisting

procedures for the RoC. 

The Eleventh Report on Carcinogens also includes seven appendices

and an index: 

• Appendix A lists manufacturing processes, occupations, and

exposure circumstances classified by IARC as known to be

carcinogenic to humans. 

• Appendix B lists the agents, substances, mixtures, or exposure

circumstances that have been delisted from the RoC. 

• Appendix C lists the agents, substances, mixtures, or exposure

circumstances that have been reviewed but not recommended for

listing in the RoC. 

• Appendix D lists participants who collaborated in preparing the

Eleventh Report on Carcinogens. 

• Appendices E, F, and G are, respectively, a glossary of terms, a list

of acronyms and abbreviations, and a list of units of measurement

used frequently in the RoC. 

• The index (a feature introduced in the Eleventh Report on

Carcinogens) allows the user to search for listings by commonly

used synonyms or abbreviations included in the profiles or by

CAS Registry Numbers of chemical substances discussed in

the profiles. 

The eleventh edition of the RoC was prepared following

procedures that maximized the quality, objectivity, utility and integrity

of the information contained in the report. Although not anticipated,

factual errors or omissions in this report may be identified after its

distribution. If this should happen, these errors or omissions will be

addressed by the NTP. Where appropriate, corrections will initially be

posted on the RoC web site at http://ntp-server.niehs.nih.gov/

NewHomeRoc/AboutRoC.html and then made in the next edition of

REPORT ON CARCINOGENS, ELEVENTH EDITION
INTRODUCTION

REPORT ON CARCINOGENS, ELEVENTH EDITION

the RoC. For more information on the Eleventh Edition of the RoC,

including how to order a printed copy or access it on the Internet, visit

the NTP RoC web site at the address above or contact Dr. C. W.

Jameson, Head, Report on Carcinogens, National Toxicology

Program, MD EC-14, P.O. Box 12233, Research Triangle Park, NC

27709; telephone (919) 541-4096; fax (919) 541-0144; e-mail

jameson@niehs.nih.gov. 

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Huff, J.E. 1993. Chemicals and Cancer in Humans: First evidence in experimental animals. Environ. Health

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Huff, J.E. 1999. Value, validity, and historical development of carcinogenesis studies for predicting and

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WEBSITES

Consumer Product Safety Commission http://www.cpsc.gov/ 

Department of Transportation http://www.dot.gov/ 

Environmental Protection Agency http://www.epa.gov/ 

Food and Drug Administration http://www.fda.gov/ 

Occupational Safety and Health Administration http://www.osha.gov/ 

American Conference of Governmental Industrial Hygienists http://www.acgih.org/home.htm 

National Institute for Occupational Safety and Health: Pocket Guide to Chemical Hazards

http://www.cdc.gov/niosh/homepage.html 

Code of Federal Regulations (CFR): http://www.gpoaccess.gov/cfr/index.html