What Is a Carcinogen? Cancer is caused by abnormalities in a cell’s DNA (its genetic "blueprint"). These may be inherited from parents, or they may be caused by outside exposures to the body such as chemicals, radiation, or even infectious agents. Substances that can cause changes that can lead to cancer are called carcinogens. Some

Contents: How Do We Determine if Something Is a Carcinogen? How Are Carcinogens Classified? Some Important Points About These Lists? Known Human Carcinogens Probable Carcinogens Additional Resources References

Carcinogens do not cause cancer in every case, all the time. Substances classified as carcinogens may have different levels of cancer-causing potential. Some may cause cancer only after prolonged, high levels of exposure. And for any particular person, the risk of developing cancer depends on many factors, including the length and intensity of exposure to the carcinogen and the person’s genetic makeup.

How Do We Determine if Something Is a Carcinogen?

Scientists get much of their data about whether something might cause cancer from laboratory (cell culture and animal) studies. Although it isn’t possible to predict with certainty which substances will cause cancer in humans based on animal studies alone, virtually all known human carcinogens that have been adequately tested produce cancer in lab animals. In many cases, carcinogens are first found to cause cancer in lab animals and are later found to cause cancer in people. Because there are far too many substances (natural and manmade) to test each one in lab animals, scientists use knowledge about chemical structure, other types of lab tests, and information about the extent of human exposure to select chemicals for testing.

Most studies of potential carcinogens expose the lab animals to doses that are higher than common human exposures. This is so that cancer risk can be detected in relatively small groups of animals. For most carcinogens, it is assumed that those that cause cancer at larger doses in animals will also cause cancer in people. Although it isn’t always possible to know the relationship between exposure dose and risk, it is reasonable for public health purposes to assume that lowering human exposure will reduce risk.

Another important way to identify carcinogens is through epidemiologic studies, which look at human populations to determine which factors might be linked to cancer. While these studies also provide useful information, they also have their limitations. Humans do not live in a controlled environment. People are exposed to numerous substances at any one time, including those they encounter at work, school, or home; in the food they eat; and the air they breathe. And it is usually many years (often decades) between exposure to a carcinogen and the development of cancer. Therefore, it can be very hard to single out any particular exposure as having a definite link to cancer.

By combining data from both types of studies, scientists are able to make an educated assessment of a substance’s cancer-causing ability. When the available evidence is compelling but not felt to be conclusive, the substance may be considered to be a probable carcinogen.

How Are Carcinogens Classified?

International Agency for Research on Cancer (IARC)

The most widely used system for classifying carcinogens comes from the IARC, which is part if the World Health Organization (WHO). In the past 30 years, the IARC has evaluated the cancer-causing potential of about 900 likely candidates, placing them into one of the following groups:

• Group 1: Carcinogenic to humans
• Group 2A: Probably carcinogenic to humans
• Group 2B: Possibly carcinogenic to humans
• Group 3: Unclassifiable as to carcinogenicity in humans
• Group 4: Probably not carcinogenic to humans

Perhaps not surprisingly, most of the agents are of probable, possible, or unknown risk. Only about 90 are classified as "carcinogenic to humans."

National Toxicology Program (NTP)

In the United States, the NTP releases the Report on Carcinogens about every 2 years. The NTP is formed from parts of several different government agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA).

The Report on Carcinogens (RoC) identifies 2 groups of agents:

• "Known to be human carcinogens"
• "Reasonably anticipated to be human carcinogens"

Unlike the IARC’s list, the RoC does not list substances that have been studied and found not to be carcinogens. Below are the lists of known and probable human carcinogens from both groups.

Some Important Points About These Lists

• The IARC and NTP act independently but have studied many of the same agents; therefore many known or suspected carcinogens appear on both lists. But because an agent appears on one and not on the other does not necessarily mean there is a controversy, as one agency may not have evaluated it.

• These lists include only those agents that have been evaluated by the agencies. There are likely many others that have not been fully studied yet.

• Most of the agents on the list are connected only with certain kinds of cancer, not all types. For more detailed information, refer to the specific monographs or reports published by the agencies (available on their respective Web sites).

• The lists themselves say nothing about how likely the agents are to cause cancer. Carcinogens do not cause cancer at all times, under all circumstances. Some may only be carcinogenic if a person is exposed in a certain way (for example, ingesting it as opposed to touching it). Some of these agents may lead to cancer after only a very small exposure, while others might require intense exposure over many years. Again, you should refer to the agencies’ reports for specifics.

• Not all carcinogens are to be avoided at all costs. The lists include many commonly used medicines, particularly some hormones and drugs used to treat cancer. Tamoxifen, for example, increases the risk of certain kinds of uterine cancer but lowers the risk of recurrence (return) of breast cancer, which may be more important for some women. If you have questions about a medicine you are taking that appears on one of these lists, be sure to ask your doctor.

Known Human Carcinogens

International Agency for Research on Cancer (IARC)
"Carcinogenic to Humans" (Group 1)

Agents and Groups of Agents

• Aflatoxins (naturally occurring mixtures of)
• 4-Aminobiphenyl
• Arsenic and arsenic compounds (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
• Asbestos
• Azathioprine
• Benzene
• Benzidine
• Beryllium and beryllium compounds
• N,N-Bis(2-chloroethyl)-2-naphthylamine (Chlornaphazine)
• Bis(chloromethyl)ether and chloromethyl methyl ether (technical-grade)
• 1,4-Butanediol dimethanesulfonate (Busulphan; Myleran)
• Cadmium and cadmium compounds
• Chlorambucil
• 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Methyl-CCNU; Semustine)
• Chromium [VI] compounds
• Cyclophosphamide
• Cyclosporin (ciclosporin)
• Diethylstilbestrol (DES)
• Epstein-Barr virus
• Erionite
• Estrogen therapy, postmenopausal
• Estrogens, nonsteroidal (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
• Estrogens, steroidal (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
• Ethylene oxide
• Etoposide in combination with cisplatin and bleomycin
• Formaldehyde
• Gallium arsenide
• Gamma radiation
• Helicobacter pylori (infection with)
• Hepatitis B virus (chronic infection with)
• Hepatitis C virus (chronic infection with)
• Herbal remedies containing plant species of the genus Aristolochia
• Human immunodeficiency virus type 1 (infection with)
• Human papillomavirus type 16
• Human papillomavirus type 18
• Human T-cell lymphotropic virus type I
• Melphalan
• 8-Methoxypsoralen (Methoxsalen) plus ultraviolet A radiation
• MOPP and other combined chemotherapy including alkylating agents
• Mustard gas (Sulfur mustard)
• 2-Naphthylamine
• Neutrons
• Nickel compounds
• Opisthorchis viverrini (infection with)
• Oral contraceptives, combined (Note: There is also conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium)
• Oral contraceptives, sequential
• Phosphorus-32, as phosphate
• Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes), as aerosols
• Radioiodines, short-lived isotopes, including iodine-131, from atomic reactor accidents and nuclear weapons detonation (exposure during childhood)
• Radionuclides, alpha-particle-emitting, internally deposited (Note: Specific radionuclides for which there is sufficient evidence for carcinogenicity to humans are also listed individually as Group 1 agents)
• Radionuclides, beta-particle-emitting, internally deposited (Note: Specific radionuclides for which there is sufficient evidence for carcinogenicity to humans are also listed individually as Group 1 agents)
• Radium-224 and its decay products
• Radium-226 and its decay products
• Radium-228 and its decay products
• Radon-222 and its decay products
• Schistosoma haematobium (infection with)
• Silica, crystalline (inhaled in the form of quartz or cristobalite from occupational sources)
• Solar radiation
• Talc containing asbestiform fibers
• Tamoxifen (Note: There is also conclusive evidence that this agent (tamoxifen) reduces the risk of contralateral breast cancer)
• 2,3,7,8-Tetrachlorodibenzo-para-dioxin
• Thiotepa
• Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium-232 dioxide
• Treosulfan
• Vinyl chloride
• X- and Gamma radiation

Mixtures

• Alcoholic beverages
• Analgesic mixtures containing phenacetin
• Areca nut
• Betel quid with tobacco
• Betel quid without tobacco
• Coal-tar pitches
• Coal-tars
• Mineral oils, untreated and mildly treated
• Salted fish (Chinese-style)
• Shale-oils
• Soots
• Tobacco products, oral tobacco products
• Wood dust

Exposure Circumstances

• Aluminum production
• Arsenic in drinking water
• Auramine, manufacture of
• Boot and shoe manufacture and repair
• Coal gasification
• Coke production
• Furniture and cabinet making
• Hematite mining (underground) with exposure to radon
• Involuntary smoking
• Iron and steel founding
• Isopropanol manufacture (strong-acid process)
• Magenta, manufacture of
• Painter (occupational exposure as a)
• Rubber industry
• Strong inorganic acid mists containing sulfuric acid (occupational exposure to)
• Tobacco smoking

National Toxicology Program (NTP) 11th Report on Carcinogens

"Known to Be Human Carcinogens"

• Aflatoxins
• Alcoholic Beverage Consumption
• 4-Aminobiphenyl
• Analgesic Mixtures Containing Phenacetin
• Arsenic Compounds, Inorganic
• Asbestos
• Azathioprine
• Benzene
• Benzidine
• Beryllium and Beryllium Compounds
• 1,3-Butadiene
• 1,4-Butanediol Dimethylsulfonate (busulfan, Myleran ®)
• Cadmium and Cadmium Compounds
• Chlorambucil
• 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU)
• bis(Chloromethyl) Ether and Technical-Grade Chloromethyl Methyl Ether
• Chromium Hexavalent Compounds
• Coal Tar Pitches
• Coal Tars
• Coke Oven Emissions
• Cyclophosphamide
• Cyclosporin A (Ciclosporin)
• Diethylstilbestrol (DES)
• Dyes Metabolized to Benzidine
• Environmental Tobacco Smoke
• Erionite
• Estrogens, Steroidal
• Ethylene Oxide
• Hepatitis B Virus
• Hepatitis C Virus
• Human Papilloma Viruses: Some Genital-Mucosal Types
• Melphalan
• Methoxsalen with Ultraviolet A Therapy (PUVA)
• Mineral Oils (Untreated and Mildly Treated)
• Mustard Gas
• 2-Naphthylamine
• Neutrons
• Nickel Compounds
• Oral Tobacco Products
• Radon
• Silica, Crystalline (Respirable Size)
• Solar Radiation
• Soots
• Strong Inorganic Acid Mists Containing Sulfuric Acid
• Sunlamps or Sunbeds, Exposure to
• Tamoxifen
• 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); "Dioxin"
• Thiotepa
• Thorium Dioxide
• Tobacco Smoking
• Vinyl Chloride
• Ultraviolet Radiation, Broad Spectrum UV Radiation
• Wood Dust
• X-Radiation and Gamma Radiation

Probable Carcinogens

International Agency for Research on Cancer (IARC)
"Probably Carcinogenic to Humans" (Group 2A)

Agents and Groups of Agents

• Acrylamide
• Adriamycin
• Androgenic (anabolic) steroids
• Aristolochic acids (naturally occurring mixtures of)
• Azacitidine
• Benz[a]anthracene
• Benzidine-based dyes
• Benzo[a]pyrene
• Bischloroethyl nitrosourea (BCNU)
• 1,3-Butadiene
• Captafol
• Chloramphenicol
• a-Chlorinated toluenes (benzal chloride, benzotrichloride, benzyl chloride) and benzoyl chloride (combined exposures)
• 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)
• 4-Chloro-ortho-toluidine
• Chlorozotocin
• Cisplatin
• Clonorchis sinensis (infection with)
• Dibenz[a,h]anthracene
• Diethyl sulfate
• Dimethylcarbamoyl chloride
• 1,2-Dimethylhydrazine
• Dimethyl sulfate
• Epichlorohydrin
• Ethylene dibromide
• N-Ethyl-N-nitrosourea
• Etoposide
• Glycidol
• Human papillomavirus type 31
• Human papillomavirus type 33
• Indium phosphide
• IQ (2-Amino-3-methylimidazo[4,5-f]quinoline)
• Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV-8)
• Lead compounds, inorganic
• 5-Methoxypsoralen
• 4,4´-Methylene bis(2-chloroaniline) (MOCA)
• Methyl methanesulfonate
• N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)
• N-Methyl-N-nitrosourea
• Nitrogen mustard
• N-Nitrosodiethylamine
• N-Nitrosodimethylamine
• Phenacetin
• Procarbazine hydrochloride
• Styrene-7,8-oxide
• Teniposide
• Tetrachloroethylene
• ortho-Toluidine
• Trichloroethylene
• 1,2,3-Trichloropropane
• Tris(2,3-dibromopropyl) phosphate
• Ultraviolet radiation A
• Ultraviolet radiation B
• Ultraviolet radiation C
• Vinyl bromide
• Vinyl fluoride

Mixtures

• Creosotes (from coal-tars)
• Diesel engine exhaust
• Hot mate
• Non-arsenical insecticides (occupational exposures in spraying and application of)
• Polychlorinated biphenyls

Exposure Circumstances

• Art glass, glass containers and pressed ware (manufacture of)
• Cobalt metal with tungsten carbide
• Hairdresser or barber (occupational exposure as a)
• Petroleum refining (occupational exposures in)
• Sunlamps and sunbeds (use of)

National Toxicology Program (NTP) 11th Report on Carcinogens
"Reasonably Anticipated to Be Human Carcinogens"