Today the Department of Health and Human Services released the Report on Carcinogens 9th edition. Prepared by the National Toxicology Program, which is headquartered at the National Institute of Environmental Health Sciences, the Report identifies substances -- such as metals, pesticides, drugs, and natural and synthetic chemicals -- and mixtures or exposure circumstances that are "known" or are "reasonably anticipated" to cause cancer, and to which a significant number of Americans are exposed. The Report is published every two years.
The Report is a scientific and public health document first ordered by Congress in 1978 to educate both the public and health professionals in the recognition that many cancers are apparently induced by chemicals in the home, workplace, general environment and from the use of certain drugs. It is important to understand that the Report identifies potential cancer hazards. A listing in the Report does not by itself establish that a substance presents a cancer risk to an individual in daily life. It is also important to note that the Report does not address or attempt to balance potential benefits of exposures to certain carcinogenic substances in special situations. For example, numerous drugs used to treat cancer have been shown to increase the occurrence of secondary cancers. In these instances, the benefits of exposure to the drugs for treatment or prevention of a specific disease have been determined by the FDA to outweigh the additional cancer risks associated with their use. People should not make decisions concerning the use of a given drug, or any other listed agent, based solely on the information contained in the Report. Decisions of this type should be made only after consulting with a physician or other appropriate specialist about both risks and benefits.
An agent, substance, mixture or exposure circumstance can be listed in the Report either as "known to be a human carcinogen" or as "reasonably anticipated to be a human carcinogen."
The "known" category is reserved for those substances for which there is sufficient evidence of carcinogenicity from studies in humans that indicates a cause and effect relationship between the exposure and human cancer.
The "reasonably anticipated" category includes those substances for which there is limited evidence of carcinogenicity in humans and/or sufficient evidence of carcinogenicity in experimental animals.
Conclusions regarding carcinogenicity in humans or experimental animals are based on expert, scientific judgment, with consideration given to all relevant information.
The 9th edition of the Report contains 218 entries. Fourteen of the listings are new. Eight of the new entries are listed as "known to be human carcinogens" and the other six entries as "reasonably anticipated to be human carcinogens." This Report also reclassifies six current listings from "reasonably anticipated" to "known to be human carcinogens".
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been proposed for upgrade to the "known to be a human carcinogen" category. The proposed listing is currently in litigation. Depending on the outcome of the litigation, an addendum may be published following the court's ruling. Two additional substances have been removed or delisted from the Report: saccharin and ethyl acrylate.
The new listings in the 9th edition include some agents and substances to which large numbers of people are exposed including environmental tobacco smoke, tobacco smoking, oral use of smokeless tobacco products, alcoholic beverage consumption, diesel exhaust particulates, UV solar radiation, and use of sun lamps and sun beds. The Report's findings are based on three years of study that included three scientific reviews and public comment from scientists, consumers and other interested parties.
The listing of a substance in the Report is not a regulatory action, but listing may prompt regulatory agencies to consider limiting exposures or uses of a substance. In addition, the U.S. Congress, Federal and State Agencies, businesses, unions and the general public all use the Report to ensure that reasonable precautions or regulations are in place.
The following briefly describes the additions and/or changes made to the 9th edition of the Report:
- Saccharin - Saccharin has been removed from the 9th edition. The Calorie Control Council nominated saccharin for delisting, which led to a new review of the carcinogenicity data for saccharin. Saccharin had been listed in the Report as "reasonably anticipated to be a human carcinogen" since 1981. The basis for this listing was sufficient evidence of carcinogenicity in experimental animals. Saccharin was removed from the Report after this extensive review determined that the rodent cancer data are not sufficient to meet the current criteria to list this chemical in the Report as a "reasonably anticipated human carcinogen." This is based on the determination that the observed bladder tumors in rats arose from a mechanism that is not relevant to humans.
Dr. Kenneth Olden, Director of the National Institute of Environmental Health Sciences and the National Toxicology Program, said, "Two decades ago, when saccharin was shown to produce bladder tumors in rats, it was a prudent, protective step to consider the sweetener to be a likely human carcinogen. However, our understanding of the science has advanced and allows us to make finer distinctions today. Studies now indicate that the rat bladder tumors arise from mechanisms that are not relevant to the human situation. In addition, we have decades more data from observations of humans using saccharin that adds to our confidence. In other words, with better science we can now make a better call."
- Ethyl acrylate - Ethyl acrylate, a substance used in making latex paints and textiles, which had been listed since 1989 as "reasonably anticipated to be a human carcinogen," was also delisted. The Basic Acrylic Monomer Manufacturers, Inc. (BAMM) had nominated ethyl acrylate for delisting, which led to a new review of the carcinogenicity data for ethyl acrylate. The review found that tumors induced in animal studies were seen only when the chemical was given by an oral route at high concentrations, resulting in persistent and severe gastric tissue injury. Because significant chronic human oral exposure to high concentrations of ethyl acrylate is unlikely, it was concluded that ethyl acrylate should not be considered "reasonably anticipated to be a human carcinogen."
The delistings of saccharin and ethyl acrylate are the first since a formal process for delisting substances from the Report was established in 1996.
Added as "known human carcinogens" or upgraded to that category in the 9th Report:
- Environmental tobacco smoke - Environmental tobacco smoke, generated from sidestream and exhaled mainstream smoke of cigarettes, pipes, and cigars is listed as a "known human carcinogen." The Report indicates this listing is based on the observed causal relationship between passive exposure to tobacco smoke and human lung cancer. The listing states that there are conclusive published studies that indicate increased risk of lung cancer in nonsmoking women living with smoking husbands or working with smoking co-workers.
- Tobacco smoking - Tobacco smoking (i.e. directly inhaled tobacco smoke) is listed as a "known human carcinogen." Cigarette smoking has been known to cause cancer in humans for many years, and is now considered to be the leading preventable cause of cancer in developed countries. Separate chemicals identified in tobacco smoke were already listed as carcinogens in the Report. The new listing of tobacco smoking is the result of the 1996 revision in the review process that allows for the review and listing of exposure circumstances in the Report.
- Smokeless tobacco - Smokeless tobacco (chewing tobacco and snuff) forms a third group of tobacco-related substances listed as "known human carcinogens." The Report states that cancers of the oral cavity (i.e. mouth, lip, tongue) have been associated with the use of chewing tobacco as well as snuff, which are the two main forms of smokeless tobacco used in the United States. Studies indicate that the tumors often arise at the site of placement of the tobacco.
- Consumption of alcoholic beverages - Consumption of alcoholic beverages is listed as a "known human carcinogen." The Report states that consumption of alcoholic beverages is causally related to cancers of the mouth, pharynx, larynx, and esophagus, and goes on to say that studies indicate that the risk is most pronounced among smokers and at the highest levels of consumption. The Report reports that the effect of a given level of alcoholic beverage intake on cancers of the head and neck is influenced by other factors, especially smoking, but that smoking does not explain the increased cancer hazard associated with alcoholic beverage consumption. The Report also states that there is evidence that suggests a link between alcoholic beverage consumption and cancer of the liver and breast.
- Solar UV radiation and exposure to sunlamps and sunbeds - Exposure to solar ultraviolet radiation, sunlamps, or sunbeds is listed as a "known human carcinogen." The Report cites data that indicate a causal relationship between exposure to solar radiation and melanoma and other skin cancers in humans, and that exposure to sunlamps or sunbeds is associated with melanoma. The Report also indicates that skin cancers are observed with increasing duration of exposure, and the effects are especially pronounced in individuals under 30 and for those who experience sunburn.
- Crystalline silica (respirable size) - Crystalline silica (respirable size), which is primarily quartz dust occurring in industrial and occupational settings in the form of fine, breathable particles, was also upgraded to a "known human carcinogen." Respirable crystalline silica results from mining and grinding coal. Comments were received expressing concern that this listing would lead to confusion among the public over the possibility that sand at the beach is carcinogenic. However, the Report makes clear that the listing is based on increased lung cancer rates in workers exposed to respirable-size (breathable) crystalline silica, primarily quartz and crystabolite, that are generated during sandblasting and similar activities in an occupational setting.
- Strong inorganic acid mists containing sulfuric acid - Strong inorganic acid mists containing sulfuric acid are listed as "known human carcinogens." The Report states that studies indicate occupational exposures to strong inorganic acid mists containing sulfuric acid are specifically associated with laryngeal and lung cancer in humans. Industrial processes in which occupational exposure to sulfuric acid mist has been examined include manufacture of isopropyl alcohol, lead batteries, phosphate fertilizers, soap and detergents, synthetic ethanol, and pickling and other acid treatments of metals.
- Dyes metabolized to benzidine - Dyes metabolized to benzidine are listed in the 9th Report as "known human carcinogens." These dyes are used mainly for dyeing textiles and paper. This listing is based on the fact that benzidine, which has been listed in the Report since 1980, is a known human carcinogen and once absorbed, these benzidine-based dyes are converted to free benzidine in humans. Benzidine was one of the first chemicals for which an association of occupational exposure and increased incidence of urinary bladder cancer in humans was reported.
- 1,3-Butadiene - 1,3-Butadiene was upgraded from "reasonably anticipated" to a "known human carcinogen" in the 9th Report. This chemical is used in the manufacture of synthetic rubber. The upgrading to a "known human carcinogen" was based on findings from studies in humans that provided evidence of a causal relationship between occupational exposure to 1,3-butadiene and excess mortality from hematopoietic cancers.
- Cadmium and cadmium compounds - Cadmium and cadmium compounds were upgraded from "reasonably anticipated" to "known human carcinogens" in the 9th Report. These materials are used in batteries, coating and plating, plastic and synthetic products and alloys, and had been listed as "reasonably anticipated to be a human carcinogen" since 1980. The Report identifies findings of increased risk of lung cancers in workers exposed to cadmium and cadmium compounds.
- Ethylene oxide - Ethylene oxide was upgraded from "reasonably anticipated" to a "known human carcinogen" in the 9th Report. This chemical is used to make other chemicals and is also widely used in the health care industry to sterilize medical devices. It had been listed in the Report as "reasonably anticipated to be a human carcinogen" since 1985. The Report cites findings of increased risk for leukemia and non-Hodgkin's lymphoma in workers exposed to ethylene oxide. This information coupled with data on its genotoxic and biochemical interactions with human DNA led to the upgrading to a "known human carcinogen."
- Tamoxifen - Tamoxifen is listed in the 9th Report as a "known human carcinogen" based on evidence from studies in humans that indicate tamoxifen increases the risk of uterine cancer in women. While there is clear evidence that tamoxifen causes uterine cancer in women, there is also conclusive evidence that tamoxifen therapy reduces the risk of cancer in the opposite breast in women with a previous diagnosis of breast cancer, and reduces the incidence of breast cancer in women at increased risk for this disease.
Tamoxifen has been approved by the FDA for treatment of breast cancer, for reducing the incidence of contralateral breast cancer in women with a previous diagnosis of breast cancer, and for decreasing the risk of breast cancer in women who have a high risk of getting breast cancer. At the time of this drug's approval for reducing the risk of breast cancer, it was known that women who take tamoxifen have an increased risk of getting uterine cancer. FDA approved tamoxifen for use in women with a high risk of breast cancer because the benefit of decreasing the risk of breast cancer outweighed the risks of taking tamoxifen, including the risk of getting uterine cancer.
There has been concern expressed that the listing of tamoxifen in the 9th Report could raise concerns among patients regarding its use for cancer treatment or prevention. It is, therefore, important to again note that these listings do not address potential benefits of exposures to certain carcinogenic substances. In this instance, the benefits of exposure to the substance have been determined by the FDA to outweigh the risks entailed. Personal decisions concerning voluntary exposures to carcinogenic agents need to be based on additional information that is beyond the scope of the 9th Report. It is very important that the public and physicians be aware of potential risks so that they have the necessary knowledge to weigh the benefits versus risks of using tamoxifen.
Added as "reasonably anticipated to be human carcinogens" in the 9th Report:
- Diesel exhaust particulates - Diesel exhaust particulates are listed in the 9th Report as "reasonably anticipated to be a human carcinogen." These particulates are generated in diesel exhaust, which is a complex mixture of combustion products of diesel fuel, with the exact composition depending on the type of engine, the speed and load at which it is run, and the composition of the fuel used. The Report states the listing is based on limited findings of elevated lung cancer rates in occupational groups exposed to diesel exhaust. These groups include railroad workers, mine workers, bus garage workers, and trucking company workers.
- Isoprene - Isoprene is listed in the 9th Report as "reasonably anticipated to be a human carcinogen." Isoprene is one of the major components that makes up natural rubber and is used to make synthetic rubbers. It is also emitted from plants and trees, has been detected in tobacco smoke and automobile exhaust, and was identified as a major endogenous hydrocarbon in human breath. The Report states the listing is based on findings from laboratory animal studies of isoprene where cancer was observed in multiple organ sites following long-term inhalation exposures.
- Chloroprene - Chloroprene is listed in the 9th Report as "reasonably anticipated to be a human carcinogen." It is primarily used in the production of the elastomer polychloroprene (neoprene). The Report states the listing is based on findings from laboratory animal studies of chloroprene in which cancer was observed in multiple organs of multiple species following long-term inhalation exposures.
- Phenolphthalein - Phenolphthalein is listed in the 9th Report as "reasonably anticipated to be a human carcinogen." It is used as a laboratory reagent and acid-base indicator and has been used in over-the-counter laxative preparations. The listing is based on findings from feeding studies of phenolphthalein that caused cancer in multiple organs in multiple species of experimental animals.
- Tetrafluoroethylene - Tetrafluoroethylene is listed in the 9th Report as "reasonably anticipated to be a human carcinogen." It is used in the production of polytetrafluoroethylene and other polymers. The RoC states the listing is based on findings from laboratory animal studies of
tetrafluoroethylene in which cancer was observed in multiple organs of multiple species following long-term inhalation exposures.
- Trichloroethylene - Trichloroethylene is listed in the 9th Report as "reasonably anticipated to be a human carcinogen." It is used mainly as a degreaser for metal parts and at one time was used to decaffeinate coffee. The Report states the listing is based on limited findings of elevated liver and biliary tract cancer rates in occupational groups exposed to trichloroethylene and sufficient evidence of cancer formation in experimental animal studies.
Questions regarding the 9th RoC should be directed to the NTP Liaison & Scientific Review Office at: t (919) 541-0503, f (919) 541-0295, e-mail: liaison@starbase.niehs.nih.gov
The 9th edition of the R0C is available on the NTP RoC Homepage http://ntp-server.niehs.nih.gov/NewHomeRoC/AboutRoC.html or by contacting the NTP-RoC, MD EC-14, P.O.Box 12233, Research Triangle Park, NC 27709. Phone (919) 541-4096; e-mail jameson@niehs.nih.gov