Cancer is a leading cause of death worldwide and diet is thought to play a substantial role in cancer etiology. The salutatory and detrimental effects of different foods, food components, and food contaminants have been widely studied in the laboratory and in epidemiologic studies. The importance of food contaminants in the link between diet and cancer has been widely studied and formal risk assessments are routinely completed by several governmental and international agencies.
Risk assessments for human hazards typically consist of two components; first, a hazard assessment to determine if a particular exposure can have adverse consequences and second, an exposure assessment to determine if the range of exposures puts an individual or population at risk of adverse consequences. In some instances, a particular exposure will be found to be carcinogenic but the exposure will be so minimal that it is of little concern to the general population. The hazard assessment may be partially based on animal studies. Human epidemiologic studies combine both parts of the typical risk assessment process into a single study by assessing the degree of exposure and the association with the risk of cancer in a single study. These studies are often limited by methods of assessing exposure, a limited range of exposure in any single population under study, confounding by other simultaneous exposures, and the need for confirmation in independent epidemiologic studies, which are often complex and expensive to perform. Both forms of data are useful in the determination of whether specific food contaminants pose a carcinogenic risk to humans.
Two important complementary programs exist that classify whether exposures pose a carcinogenic risk to humans. First, the US National Toxicology Program produces the Report on Carcinogens 1 currently in its 11th edition. This biennial report has four primary objectives:
- 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.
- Information concerning the nature of such exposure and the estimated number of persons exposed to such substances.
- 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.
- 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.
Second, the International Agency for Research on Cancer (IARC) produces IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (http://monographs.iarc.fr/) The stated objective of the IARC Monographs is as follows: “The Monographs represent the first step in carcinogenic risk assessment, which involves examination of all relevant information in order to assess the strength of the available evidence that certain exposures could alter the incidence of cancer in humans. The second step is quantitative risk estimation. Detailed, quantitative evaluations of epidemiological data may be made in the Monographs, but without extrapolation beyond the range of the data available. Quantitative extrapolation from experimental data to the human situation is not undertaken.” Unlike the Report on Carcinogens, the IARC Monographs have a worldwide perspective and may address exposures only relevant to communities outside the US. Both programs primary goal is to provide information useful to appropriate regulatory agencies without proposing specific regulations themselves. This is left to the appropriate regulatory bodies of different governmental entities.
The National Toxicology Program (http://ntp-server.niehs.nih.gov/) also completes primary research that investigates carcinogenicity of different exposures while the IARC Monograph series synthesizes extant information. Both programs rely on published research reports from public and private institutions. Both programs actively search for topics that have sufficient information to draw conclusions.
There are other important independent programs that also assess the human carcinogenicity of substances, such as the one run by the state of California. In 1986, proposition 65 required that the Governor of California to publish, at least annually, a list of chemicals known to the state to cause cancer or reproductive toxicity. The California Office of Environmental Health Hazard Assessment (http://www.oehha.ca.gov/) has been tasked with assisting the Governor of California in this and has listed 475 chemicals as carcinogens. Numerous national programs in other countries also provide valuable information regarding the carcinogenicity of different agents in humans, much of which is used in the IARC and NTP evaluations. For the purposes of this review I have included items exclusively covered by either IARC or the NTP.
Carcinogen classifications from NTP and IARC monographs
The National Toxicology Program and the IARC monographs use different categorizations in their conclusions about the human carcinogenicity of substances depending on the quality of the evidence available. The Report on Carcinogens classifies substances as “Known to be human carcinogens” or “Reasonably anticipated to be a human carcinogen.” IARC uses a more complex classification scheme which includes substances that have been reviewed but are found not classifiable as possibly carcinogenic to humans: Group1, carcinogenic to humans; Group 2A, probably carcinogenic to humans; Group 2B, possibly carcinogenic to humans; Group 3, not classifiable as to carcinogenicity in humans; Group 4, probably not carcinogenic.
Types of food contaminants
There are four primary types of potentially carcinogenic compounds that have been examined to determine if they act as carcinogens in humans. The first are natural products that may be present in food and are unavoidable. For example, the process of creating salted fish produces carcinogens which can not be easily avoided. Second, are natural products that might be avoided such as the contamination of grain with the carcinogenic fungal metabolite aflatoxin, which can be reduced or eliminated using best practices for grain storage. Third, anthropogenic chemicals may be present in food. For instance, 2,3,7,8-tetracholordibenzo-p-dioxin has been inadvertently produced during the manufacture of chlorinated hydrocarbons, but it contaminates the environment, resists degradation, and accumulates in certain foodstuffs. A fourth category of concern is anthropogenic chemicals intentionally added to foods, such as saccharin or food coloring, but these are not addressed in this review because they are not contaminants because they are added intentionally.