A carcinogen is an agent, mixture, or exposure that increases the occurrence of cancer. Carcinogen identification is an activity based on the evaluation of the results of scientific research. Pertinent data for carcinogen identification include human epidemiologic studies, long-term bioassays in experimental animals, and other relevant data on toxicokinetics and cancer mechanisms. Several classification systems exist to identify the degree of carcinogenicity of agents. The most widely used system is developed by the International Agency for Research on Cancer (IARC), which is part of the World Health Organization.
Most of the existing data about whether an agent might cause cancer originate from laboratory (cell culture and animal) studies. Although it is not 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 have been found to 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 humans. For most carcinogens, it is assumed that those that cause cancer at larger doses in animals will also cause cancer in humans.
Another source of data about carcinogens comes from epidemiologic studies, which provide evidence of a carcinogenic hazard but often are not sufficiently sensitive to identify a carcinogenic hazard except when the risk is high or when it involves an unusual form of cancer. In addition, it is difficult to single out any particular exposure as having a definite link to cancer. For these reasons, laboratory studies generally provide the best means of assessing potential risks to humans.
The most widely used system for classifying carcinogens originates from IARC. This agency releases the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, which are scientific evaluations developed by international working groups of expert scientists. Agents are selected for evaluation on the basis of evidence of human exposure and some evidence or suspicion of carcinogenicity. The IARC Monographs include a critical review of the pertinent peer-reviewed scientific literature as the basis for an evaluation of the weight of the evidence that an agent may be carcinogenic to humans. Published continuously since 1972, the scope of the IARC Monographs has expanded beyond chemicals to include complex mixtures, occupational exposures, lifestyle factors, physical and biologic agents, and other potentially carcinogenic exposures. In the past 30 years, IARC has evaluated the cancer-causing potential of about 900 likely candidates. These evaluations provide the scientific support for public health measures implemented by many national and international health agencies around the world. IARC categorizes agents into the following five potential categories.
If a substance is classified as belonging to Group 1, it is labeled “carcinogenic to humans.” This category is used when there is sufficient evidence of carcinogenicity in humans. An agent may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent acts through a relevant mechanism of carcinogenicity. Only 91 agents have been characterized as “carcinogenic to humans.”
This category is used when there is limited evidence of carcinogenicity in humans but sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent may be classified in this category when there is inadequate evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and strong evidence that the carcinogenesis is mediated by a mechanism that also operates in humans. An agent, mixture, or exposure may be classified in this category solely on the basis of limited evidence of carcinogenicity in humans. Sixty-seven agents have been classified as “probably carcinogenic to humans.”
This category is used for agents, mixtures, and exposures for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture, or exposure for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group. Two hundred and forty agents have been categorized as “possibly carcinogenic to humans.”
This category is used most commonly for agents, mixtures, and exposures for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Agents for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans.
This category is used for agents or mixtures for which there is evidence suggesting a lack of carcinogenicity in humans and in experimental animals. In some instances, agents or mixtures for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting a lack of carcinogenicity in experimental animals, consistently and strongly supported by a broad range of other relevant data, may be categorized into this group.
In addition to the IARC, other programs and agencies have implemented systems for labeling the carcinogenicity of substances. For example, the National Toxicology Program, mandated in 1978 by an act of the U.S. Congress, releases its Report of Carcinogens approximately every 2 years and lists agents as either “known to be a human carcinogen” or “reasonably anticipated to be a human carcinogen.”
The U.S. Environmental Protection Agency (EPA) assesses the health hazards of chemical contaminants present in the environment. These assessments cover cancer and other adverse effects. The hazard assessments are coupled with dose-response assessments that the EPA uses in its regulatory and informational programs.
The California EPA maintains a list of “chemicals known to the state to cause cancer” under the mandate created by Proposition 65, a 1986 ballot initiative enacted to protect citizens from chemicals known to cause cancer, birth defects, or other reproductive harm and to inform citizens about exposures to such chemicals. A chemical is listed if an independent committee of scientists and health professionals finds that the chemical has been clearly shown to cause cancer, if an authoritative body has identified it as causing cancer, or if a California or U.S. government agency requires that it be labeled or identified as causing cancer.
Cancer; Environmental and Occupational Epidemiology
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