The hazard symbol for carcinogenic chemicals in the Globally Harmonized System.
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise in both natural and synthetic substances.[1]
Cancer is any disease in which normal cells are damaged and do not undergo programmed cell death as fast as they divide via mitosis. Carcinogens may increase the risk of cancer by altering cellular metabolism or damaging DNA directly in cells, which interferes with biological processes, and induces the uncontrolled, malignant division, ultimately leading to the formation of tumors. Usually, severe DNA damage leads to apoptosis, but if the programmed cell death pathway is damaged, then the cell cannot prevent itself from becoming a cancer cell.
There are many natural carcinogens. Aflatoxin B1, which is produced by the fungus Aspergillus flavus growing on stored grains, nuts and peanut butter, is an example of a potent, naturally occurring microbial carcinogen. Certain viruses such as Hepatitis B and human papilloma virus have been found to cause cancer in humans. The first one shown to cause cancer in animals is Rous sarcoma virus, discovered in 1910 by Peyton Rous.
Dioxins and dioxin-like compounds, benzene, kepone, EDB, and asbestos have all been classified as carcinogenic.[2] As far back as the 1930s, industrial smoke and tobacco smoke were identified as sources of dozens of carcinogens, including benzo[a]pyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde—which is also a hazard in embalming and making plastics. Vinyl chloride, from which PVC is manufactured, is a carcinogen and thus a hazard in PVC production.
Co-carcinogens are chemicals that do not necessarily cause cancer on their own, but promote the activity of other carcinogens in causing cancer.
After the carcinogen enters the body, the body makes an attempt to eliminate it through a process called biotransformation. The purpose of these reactions is to make the carcinogen more water-soluble so that it can be removed from the body. But these reactions can also convert a less toxic carcinogen into a more toxic carcinogen.
DNA is nucleophilic, therefore soluble carbon electrophiles are carcinogenic, because DNA attacks them. For example, some alkenes are toxicated by human enzymes to produce an electrophilic epoxide. DNA attacks the epoxide, and is bound permanently to it. This is the mechanism behind the carcinogenicity of benzo[a]pyrene in tobacco smoke, other aromatics, aflatoxin and mustard gas.
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Contents
- 1 Radiation
- 2 Carcinogens in prepared food
- 3 Carcinogens in cigarettes
- 4 Circadian disruption
- 5 Mechanisms of carcinogenicity
- 6 Classification of carcinogens
- 6.1 International Agency for Research on Cancer
- 6.2 Globally Harmonized System
- 6.3 U.S. National Toxicology Program
- 6.4 American Conference of Governmental Industrial Hygienists
- 6.5 European Union
- 6.6 Safe Work Australia
- 7 Procarcinogen
- 8 Common carcinogens
- 8.1 Occupational carcinogens
- 8.2 Others
- 9 See also
- 10 Notes
- 11 External links
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Radiation
Main article: radiation-induced cancer
CERCLA identifies all radionuclides as carcinogens, although the nature of the emitted radiation (alpha, beta, gamma, or neutron and the radioactive strength), its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenicity of radiation depends of the type of radiation, type of exposure, and penetration. For example, alpha radiation has low penetration and is not a hazard outside the body, but emitters are carcinogenic when inhaled or ingested.
For example, Thorotrast, a (incidentally radioactive) suspension previously used as a contrast medium in x-ray diagnostics, is a potent human carcinogen known because of its retention within various organs and persistent emission of alpha particles.
Not all types of electromagnetic radiation are in fact carcinogenic. Low-energy waves on the electromagnetic spectrum are thought not to be including radio waves, microwave radiation, infrared radiation and visible light. There are many many documented cases of radar technicians experiencing prolonged exposure and a higher incidence of cancer. http://www.ncbi.nlm.nih.gov/pubmed/10926722 Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, generally is carcinogenic, if received in sufficient doses.
Low level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and cancer.[3][4][5]
Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic.[citation needed] In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can produce secondary radiation through nuclear transmutation.
Carcinogens in prepared food
See also: Cooking#Cooking and carcinogens and Raw foodism
Cooking food at high temperatures, for example grilling or barbecuing meats, can lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzo[a]pyrene).[6] Charring of food resembles coking and tobacco pyrolysis, and produces similar carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human enzymes into epoxides, which attach permanently to DNA. Pre-cooking meats in a microwave oven for 2–3 minutes before grilling shortens the time on the hot pan, and removes heterocyclic amine (HCA) precursors, which can help minimize the formation of these carcinogens.[7]
Reports from the Food Standards Agency have found that the known animal carcinogen acrylamide is generated in fried or overheated carbohydrate foods (such as french fries and potato chips).[8] Studies are underway at the FDA and European regulatory agencies to assess its potential risk to humans.
Carcinogens in cigarettes
Main article: Tobacco and health
Circadian disruption
"Shiftwork that involves circadian disruption" was listed, in 2007, as a probable carcinogen by the World Health Organization's International Agency for Research on Cancer. (IARC Press release No. 180).[9] Multiple studies have documented a link between night shift work and the increased incidence of breast cancer.[10][11][12][13][14][15] Circadian disruption by exposure to light at night suppresses the production of the hormone melatonin which leads to reduction in cellular immune defense and surveillance necessary for protection from development of cancers. Melatonin also seems to have a direct protective effect against cancer, possibly in part because of its strong antioxidant properties.[16]
Mechanisms of carcinogenicity
Carcinogens can be classified as genotoxic or nongenotoxic. Genotoxins cause irreversible genetic damage or mutations by binding to DNA. Genotoxins include chemical agents like N-nitroso-N-methylurea (NMU) or non-chemical agents such as ultraviolet light and ionizing radiation. Certain viruses can also act as carcinogens by interacting with DNA.
Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds.[17]
Classification of carcinogens
Approximate equivalences
between classification schemes
| IARC |
GHS |
NTP |
ACGIH |
EU |
| Group 1 |
Cat. 1A |
Known |
A1 |
Cat. 1 |
| Group 2A |
Cat. 1B |
Reasonably
suspected |
A2 |
Cat. 2 |
| Group 2B |
| Cat. 2 |
|
A3 |
Cat. 3 |
| Group 3 |
| |
A4 |
|
| Group 4 |
A5 |
International Agency for Research on Cancer
For more details on this topic, see International Agency for Research on Cancer.
The International Agency for Research on Cancer (IARC) is an intergovernmental agency established in 1965, which forms part of the World Health Organization of the United Nations. It is based in Lyon, France. Since 1971 it has published a series of Monographs on the Evaluation of Carcinogenic Risks to Humans[18] that have been highly influential in the classification of possible carcinogens.
- Group 1: the agent (mixture) is definitely carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
- Group 2A: the agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
- Group 2B: the agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
- Group 3: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
- Group 4: the agent (mixture) is probably not carcinogenic to humans.
Globally Harmonized System
The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a United Nations initiative to attempt to harmonize the different systems of assessing chemical risk which currently exist (as of March 2009) around the world. It classifies carcinogens into two categories, of which the first may be divided again into subcategories if so desired by the competent regulatory authority:
- Category 1: known or presumed to have carcinogenic potential for humans
- Category 1A: the assessment is based primarily on human evidence
- Category 1B: the assessment is based primarily on animal evidence
- Category 2: suspected human carcinogens
U.S. National Toxicology Program
The National Toxicology Program of the U.S. Department of Health and Human Services is mandated to produce a biennial Report on Carcinogens.[19] As of June 2011, the latest edition was the 12th report (2011).[2] It classifies carcinogens into two groups:
- Known to be a human carcinogen
- Reasonably anticipated to be a human carcinogen
American Conference of Governmental Industrial Hygienists
The American Conference of Governmental Industrial Hygienists (ACGIH) is a private organization best known for its publication of threshold limit values (TLVs) for occupational exposure and monographs on workplace chemical hazards. It assesses carcinogenicity as part of wider assessment of the occupational hazards of chemicals.
- Group A1: Confirmed human carcinogen
- Group A2: Suspected human carcinogen
- Group A3: Confirmed animal carcinogen with unknown relevance to humans
- Group A4: Not classifiable as a human carcinogen
- Group A5: Not suspected as a human carcinogen
European Union
The European Union classification of carcinogens is contained in the Dangerous Substances Directive and the Dangerous Preparations Directive. It consists of three categories:
- Category 1: Substances known to be carcinogenic to humans.
- Category 2: Substances which should be regarded as if they are carcinogenic to humans.
- Category 3: Substances which cause concern for humans, owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment.
This assessment scheme is being phased out in favor of the GHS scheme (see above), to which it is very close in category definitions.
Safe Work Australia
Under a previous name, the NOHSC, in 1999 Safe Work Australia published the Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(1999)].[20] Section 4.76 of this document outlines the criteria for classifying carcinogens as approved by the Australian government. This classification consists of three categories:
- Category 1: Substances known to be carcinogenic to humans.
- Category 2: Substances that should be regarded as if they were carcinogenic to humans.
- Category 3: Substances that have possible carcinogenic effects in humans but about which there is insufficient information to make an assessment.
Procarcinogen
A procarcinogen is a precursor to a carcinogen. One example is nitrites when taken in by the diet. They are not carcinogenic themselves, but turn into nitrosamines in the body, which are carcinogenic.[21]
Common carcinogens
Occupational carcinogens
Occupational carcinogens are agents that pose a risk of cancer in several specific work-locations:
| Carcinogen |
Associated cancer sites or types |
Occupational uses or sources |
| Arsenic and its compounds |
- Lung
- Skin
- Hemangiosarcoma
|
- Smelting byproduct
- Component of:
-
- Alloys
- Electrical and semiconductor devices
- Medications (e.g. melarsoprol)
- Herbicides
- Fungicides
- Animal dips
- Drinking water from contaminated aquifers.
|
| Asbestos |
- Lungs
- Asbestosis
- Gastrointestinal tract
- Pleural Mesothelioma
- Peritoneal Mesothelioma
|
Not in widespread use, but found in:
-
- Roofing papers
- Floor tiles
- Fire-resistant textiles
- Friction linings (only outside Europe)
-
- Replacement friction linings for automobiles still may contain asbestos
|
| Benzene |
- Leukemia
- Hodgkin lymphoma
|
- Light fuel oil
- Former use as solvent and fumigant
- Printing
- Lithography
- Paint
- Rubber
- Dry cleaning
- Adhesives
- Coatings
- Detergents
|
| Beryllium and its compounds |
|
- Missile fuel
- Lightweight alloys
-
- Aerospace applications
- Nuclear reactors
|
| Cadmium and its compounds |
|
- Yellow pigments
- Phosphors
- Solders
- Batteries
- Metal paintings and coatings
|
| Hexavalent chromium(VI) compounds |
|
- Paints
- Pigments
- Preservatives
|
| Diesel exhaust |
|
- Exhaust gas from Diesel engines
|
| Ethylene oxide |
|
- Ripening agent for fruits and nuts
- Rocket propellant
- Fumigant for foodstuffs and textiles
- Sterilant for hospital equipment
|
| Nickel |
|
- Nickel plating
- Ferrous alloys
- Ceramics
- Batteries
- Stainless-steel welding byproduct
|
| Radon and its decay products |
|
-
- Quarries and mines
- Cellars and poorly ventilated places
|
| Vinyl chloride |
|
- Refrigerant
- Production of polyvinyl chloride
- Adhesive for plastics
- Former use in pressurized containers
|
| Shift work that involves
circadian disruption[9]
|
|
|
| Involuntary smoking (Passive smoking)[23] |
|
|
Radium-226, Radium-224,
Plutonium-238, Plutonium-239[24]
and other alpha particle
emitters with high atomic weight |
- Bone (they are bone seekers
- Liver
|
- Nuclear fuel processing
- Radium dial manufacturing
|
| Unless else specified in boxes, then ref is:[25] |
Others
- Gasoline (contains aromatics)
- Lead and its compounds
- Alkylating antineoplastic agents (e.g. mechlorethamine)
- Other alkylating agents (e.g. dimethyl sulfate)
- Ultraviolet radiation from the sun and UV lamps
- Alcohol (causing head and neck cancers)
- Other ionizing radiation (X-rays, gamma rays, etc.)
See also
- Acrylamide
- Asian Dust
- Carcinogenesis
- History of cancer
- Industrial Union Department v. American Petroleum Institute
- International Agency for Research on Cancer
- Mutagen
- Possible carcinogen
- Safe handling of carcinogens
- Teratogen
- Warburg hypothesis
Notes
- ^ Ames, Bruce N; Gold, Lois Swirsky (2000). "Paracelsus to parascience: The environmental cancer distraction". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 447: 3. doi:10.1016/S0027-5107(99)00194-3.
- ^ a b Report on Carcinogens, Eleventh Edition; U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program (2011).
- ^ Acharya, PVN; The Effect of Ionizing Radiation on the Formation of Age-Correlated Oligo Deoxyribo Nucleo Phospheryl Peptides in Mammalian Cells; 10th International Congress of Gerontology, Jerusalem. Abstract No. 1; January 1975. Work done while employed by Dept. of Pathology, University of Wisconsin, Madison.
- ^ Acharya, PVN; Implicatons of The Action of Low Level Ionizing Radiation on the Inducement of Irreparable DNA Damage Leading to Mammalian Aging and Chemical Carcinogenesis.; 10th International Congress of Biochemistry, Hamburg, Germany. Abstract No. 01-1-079; July 1976. Work done while employed by Dept. of Pathology, University of Wisconsin, Madison.
- ^ Acharya, PV Narasimh; Irreparable DNA-Damage by Industrial Pollutants in Pre-mature Aging, Chemical Carcinogenesis and Cardiac Hypertrophy: Experiments and Theory; 1st International Meeting of Heads of Clinical Biochemistry Laboratories, Jerusalem, Israel. April 1977. Work conducted at Industrial Safety Institute and Behavioral Cybernetics Laboratory, University of Wisconsin, Madison.
- ^ Wei Zheng, Deborah R Gustafson, Rashmi Sinha, James R Cerhan, et al. "Well-done meat intake and the risk of breast cancer." Journal of the National Cancer Institute. Oxford: Nov 18, 1998.Vol. 90, Iss. 22; pg. 1724, 6 pgs.
- ^ "National Cancer Institute, 2004 analysis and recommendations". Cancer.gov. 2004-09-15. Retrieved 2010-09-22.
- ^ "Acrylamide".
- ^ a b "IARC Monographs Programme finds cancer hazards associated with shiftwork, painting and firefighting, International Agency for Research on Cancer". Retrieved 2011-07-01
- ^ Schernhammer E, Schulmeister K. Melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels? Br J Cancer 2004;90:941–943.
- ^ Hansen J. Increased breast cancer risk among women who work predominantly at night. Epidemiology 2001; 12:74–77.
- ^ Hansen J. Light at night, shiftwork, and breast cancer risk.J Natl Cancer Inst 2001; 93:1513–1515.
- ^ Schernhammer E, Laden F, Speizer FE et al. Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. J Natl Cancer Inst 2001; 93:1563–1568.
- ^ Scott Davis, Dana K. Mirick, Richard G. Stevens (2001). "Night Shift Work, Light at Night, and Risk of Breast Cancer". Journal of the National Cancer Institute 93 (20): 1557–1562. doi:10.1093/jnci/93.20.1557. PMID 11604479.
- ^ Eva S. Schernhammer, Francine Laden, Frank E. Speizer, Walter C. Willett, David J. Hunter, Ichiro Kawachi, Graham A. Colditz (2001). "Rotating Night Shifts and Risk of Breast Cancer in Women Participating in the Nurses' Health Study". Journal of the National Cancer Institute 93 (20): 1563–1568. doi:10.1093/jnci/93.20.1563. PMID 11604480.
- ^ Navara KJ, Nelson RJ (2007) The dark side of light light at night: physiological, epidemiological, and ecological consequences. J. Pineal Res. 2007; 43:215–224
- ^ "The Gale Encyclopedia of Cancer: A guide to Cancer and its Treatments, Second Edition. Page no. 137".
- ^ "IARC Monographs". Monographs.iarc.fr. Retrieved 2010-09-22.
- ^ Section 301(b)(4) of the Public Health Service Act, as amended by Section 262, Pub. L. 95–622.
- ^ Safe Work Australia , NOHSC. (1999). Approved criteria for classifying hazardous substances [NOHSC:1008(1999)] §4.76. Accessed 21/05/2011
- ^ "Web definitions for Procarcinogen". Lactospore.com. Retrieved 2010-09-22.
- ^ a b "IARC: DIESEL ENGINE EXHAUST CARCINOGENIC" (Press release). International Agency for Research on Cancer (IARC). Retrieved June 12, 2012. "June 12, 2012 ‐‐ After a week-long meeting of international experts, the International Agency for Research on Cancer (IARC), which is part of the World Health Organization (WHO), today classified diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer"
- ^ Tobacco Smoke and Involuntary Smoking, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 83 (2004).
- ^ Survival, causes of death, and estimated tissue doses in a group of human beings injected with plutonium, 751053, R. E. Rowland and Patricia W. Durbin, 1975.
- ^ Table 6-2 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
External links
- U.S. National Toxicology Program's Report on Carcinogens
- Recognized Carcinogens
- American Cancer Society
- Database of Rodent Carcinogens
- Comparing Possible Cancer Hazards from Human Exposures to Rodent Carcinogens
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Carcinogen—Cancer causing materials and agents
|
|
| Main articles |
|
|
| Major suspected carcinogens |
- PFOA
- Tobacco smoke
- Xenoestrogen
- Bisphenol A
- Ionizing radiation
- DDT
- 1,3-Butadiene
- List of breast carcinogenic substances
- PAH
|
|
| IARC |
- International Agency for Research on Cancer / IARC agent lists: Group 1
- Group 2A
- Group 2B
- Group 3
- Group 4 (Caprolactam)
|
|
- See also
- Neoplasm
- Oncology
|
|
|
Pathology: Tumor, Neoplasm, Cancer, and Oncology (C00–D48, 140–239)
|
|
| Conditions |
| Benign tumors |
- Hyperplasia
- Cyst
- Pseudocyst
- Hamartoma
|
|
| Malignant progression |
- Dysplasia
- Carcinoma in situ
- Cancer
- Metastasis
|
|
| Topography |
- Head/Neck (Oral, Nasopharyngeal)
- Digestive system
- Respiratory system
- Bone
- Skin
- Blood
- Urogenital
- Nervous system
- Endocrine system
|
|
| Histology |
- Carcinoma
- Sarcoma
- Blastoma
- Papilloma
- Adenoma
|
|
| Other |
- Precancerous condition
- Paraneoplastic syndrome
|
|
|
| Staging/grading |
- TNM
- Ann Arbor
- Prostate cancer staging
- Gleason Grading System
- Dukes classification
|
|
| Carcinogenesis |
- Cancer cell
- Carcinogen
- Tumor suppressor genes/oncogenes
- Clonally transmissible cancer
- Oncovirus
- Cancer bacteria
|
|
| Misc. |
- Research
- List of oncology-related terms
- History
- Cancer pain
|
|
|
|
|
|
Toxicology
|
|
- History of poison
- Toxinology
|
|
| Fields |
- Aquatic toxicology
- Ecotoxicology
- Entomotoxicology
- Environmental toxicology
- Forensic toxicology
- Medical toxicology
- In vitro toxicology
- Toxicogenomics
|
|
| Concepts |
- Acceptable daily intake
- Acute toxicity
- Bioaccumulation
- Biomagnification
- Fixed Dose Procedure
- Lethal dose
- Median lethal dose (LD50)
- Poison
- Toxic capacity
- Toxicant
- Toxicity Class
- Venom
|
|
| Treatments |
- Activated carbon
- Antidote
- Cathartic
- Chelation therapy
- Gastric lavage
- Hemodialysis
- Hemoperfusion
- Whole bowel irrigation
|
|
| Incidents |
- 1858 Bradford sweets poisoning
- 2007 pet food recalls
- Bhopal disaster
- Minamata disease
- Niigata Minamata disease
- Poisoning of Alexander Litvinenko
- Seveso disaster
- List of poisonings
|
|
| Related topics |
- Biological warfare
- Carcinogen
- Food safety
- Hazard symbol
- List of extremely hazardous substances
- Mutagen
|
|
|
|
|
|
Genotoxicity
|
|
| Agent |
- Mutagen
- Clastogen
- Aneugen
- Carcinogen
|
|
| Assays |
|
|
