Tobacco Documents Online

I I I I I I I I I I I I I I I I I I THORIUM DIOXIDE ntakers. Potential exposure may also occur during the formulation, packaging, preparation, or administration of the compound as a pharmaceutical. OSHA estimated that 128,500 workers were potentially exposed to the compound during its production and use. Approximately 50,000 patients worldwide were exposed to thorium dioxide when it was administered by injection for X-ray imaging purposes from 1930 to 1964 (Wegener, 1979). The injection dosages ranged from 2 to 70 mL of Thororrast solution, depending on the area to be X-rayed (Saragoca et al., 1972). Because concentrations of thorium in air, drinking water, and foods are very low, very few studies have been conducted to assess the daily human intake (ATSDR, I990-K028). The Toxic Chemical Release Inventory (EPA) listed two industrial facilities that produced, processed, or otherwise used thorium dioxide in 1988 (TRI, 1990). In compliance with the Community-Right-to-Know Program, the facilities reported releases of thorium dioxide to the environment which were estimated to total 1,330 lb. , Regulations EPA regulates thorium dioxide under the Superfund Amendmenrs and Reauthorization Act (SARA), identifying it as a toxic chemical and subjecting it to reporting requirements. Under the Food, Drug, and Cosmetic Act (FD&CA), FDA has approved thorium dioxide for use as a radiopaque medium for X-ray imaging in cases where there is limited life expectancy. In March of 1980, the Nuclear Regulatory• Commission withdrew authorizations for use and transfer of thorium dioxide for internal or external medicinal use in humans. Authorizations were issued, however, for research, development, educational, commercial, or operational purposes under conditions specified by the Commission; the use and transfer of the material for these purposes may not exceed 15 lb at any one time or a total of 150 lb in any one calendar year. FDA has recently determined that thorium dioxide for drug use is a new drug and therefore subjects it to thc requirements of a new drug application for marketing. OSHA regulates rhorium dioxide under the Hazard Communication Standard and as a chemical hazard in laboratories. Regulations are suntmarized in Volume II, Table A-41. Tobacco Smoking* First listed in the Ninth Report on Carcinogens Carcinogenicity Tobacco smoking is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans which indicate a causal relationship between tobacco smoking and human ._tncer (reviewed in IARC V.38, 1986; Burns et al., 1997a). Tobacco smoking has been determined ro cause cancer of the lunG, urinary bladder, renal pelvis, oral cavity, pharynx, larynx, esophagus, lip, and pancreas in humans. Lung cancer deaths are associated with certain tobacco smoking patterns, increasing with increasing consumption of tobacco products and decreasing in certain "roups as the amount smoked declines. Smoking cessation is associated with a decreased risk of developing cancer. The carcinogenic effects of tobacco smoke are increased in individuals with certain predisposing genetic polymorphisms. Additional Information Relevant to Carcinogenesis or Possible Mechanisms of Carcinogenesis Ta~bacco smoke has been detnonstrated to be carcinogenic in several species of experimental animals. The evidence is most clearly established for the larynx in the hamster following inhalation of zobzcco smoke, and for the skin of mice receiving dermal applications KNOWN TO BE A HUMAN CARCINOGEN of tobacco smoke condensates. Tumors of the respiratory tract have also been reported in rats exposed to cigarette smoke. Individual chemical components of tobacco smoke have been shown to be carcinogenic to humans and/or experimental animals. Tobacco smoke or tobacco smoke condensares cause cell transformation and mutations or other genetic alterations in a variety of in vitro and in viva assays, The urine of smokers has been found to be mutagenic and there is evidence o€more chromosomal damage in the somatic cells of smokers than in notumokers. Properties Nearly 4000 chemicals have been found in tobacco smoke (Vineis and Caporaso, 1995; Hoffmann and Hoffmann, 1995; IARC V.38, 1986), including acrolein, aromatic amines, benzene, formaldehyde, nitrosamines, polycyclic aromatic hydrocarbons, urethan (ethyl carbonate), radioactive elements (radium-226, radium-228, thorium- 228, polonium-210), arsenic, nickel, chromium, and cadmium. Use Currently, the primary source for tobacco smoking is cigarettes, the others being the use of pipes and cigars. The use of pipes and cigars was more prevalent in the IS`i' and 19`h centuries, but there was a shift from these products to cigarettes after 1910, following mass marketing campaigns for cigarettes (IARC V.38, 1986; Burns er. al., 1997a). Per capita consumption of cigarettes in the United States rose from 54 in 1900 (U.S. DHHS, 1989; cited by Burns et al., 1997a,b) to a peak of 4,345 in 1963 (Burns et al., 1997b). The use of tobacco products varies among racial, gender, and age groups. Currently, males have a higher prevalence of smoking than females (U.S. DHHS, 1980; cited by Burns et al., 1997b). Advertising campaigns began targeting the male population many years before targeting females, which may explain why men began smoking earlier in the cenmry than women (U.S. DHHS, 1980; cited by Burns er al., 1997b). Smoking prevalence and cessation also vary with educational attainment (U.S. DHHS, 1989; Pierce ec al., 1989; both cited by Burns et al., 1997b). Production Tobacco has been an important economic agricultural crop since the 1600s. North and Central America produced the highest quantity, with 1,158,506 tons harvested in 1982 (IARC V.38, 1986). Nicotiana tabacum is the most common species of tobacco used in cigarettes, but N rustica is also used in some areas (Garner, 1951; Wynder and Hoffmann, 1963; Tso, 1972; Akehurst, 1981; all cited by IARC V.38, 1986). For smoking tobacco, the tobacco leaf material is manipulated by physical and chemical methods during the manufacturing process, some of which are intended to reduce the yields of toxic agents and tars in smoke. The tobacco is fine cut and wmpped in paper for consumption. Generally, cigarettes are a blend of different flue-cured grades, burley, Maryland, and oriental tobaccos (IARC V.38, 1986). Regulations Applicable regulations are given in derail in the Regulations table. Federal regulations related to tobacco products that concern taxation, customs duties, the potential for hand-to-mouth transfer of toxic substances when using tobacco in the workplace, warnings that smoking will exacerbate noncancer risks of certain drugs, and environmental tobacco smoke are not addressed in this section. The U.S. Food and Drug Administration (FDA) regulates nicotine-containing cigarettes and smokeless tobacco products as nicotine-delivery medical devices under 21 CFR Part 897 "to reduce the number of children and adolescents who use these products and to reduce the life-thn-atening consequences associated with tobacco use." flEPQR7 ON CAROlN06ENS, N1tNFN EDIT7PN 1 ;3-60 2073777280

XNOWN To 8E A HUMAN CARCINOGEN %leasures to reduce the appeal of and access to cigarettes and >ntokeless tobacco products include numerous restrictions on nlvertising, including promotional items and event sponsorship. 'fobacco-product-dispensing vending machines and self-service displays are prohibited except in adult establishments that do not sllow children on the premises at any time. Retailers must request that persons up to the age of 27 present phorogmphic identification bcaring their birth date. Free distribution of tobacco products is pruhibited. Each package and advertisement must bear the label "Nicotine-Delivery Device for Persons 18 or Older." Cigarettes may not be sold in packages of kwer than 20. Attalyses of FDA jurisdiction over tobacco products (cigarettes and smokeless tobacco products) have been published in the Federal Register, including 60 FR 41453-41787, August 11, 1995, with a correction at 60 FR 65349-65350; 61 FR 44615 fE, August 28, 1996; and 61 FR 45219-45222, August 28, 1996. FDA published Children and Tobacco Executive Summaries (U.S. FDA, 1996 a,b), which are .reailabie free on the internet and by mail. The Federal Trade Commission (FTC) of the Department of Commerce administers the Federal Cigarette Labeling and Advertising Act, Public Law 89-92 as amended through Public Law 98-474 (15 U.S. 1331) (FTC, 1998). Provisions include the ban of cigarette advertisements on radio and television, submission of annual reports m Congress on current practices and methods of cigarette advertising and promotion and recommendations for appropriate legislation, and requirement of rotation of four warning statements placed conspicuously on cigarette packages and advertisements. One of the md*i` warning statements is 'SURGEON GENERAL'S WARNING: tg thaak Smoking Causes Lung Cancer, Heart Disease, Emphysema, and May ` " Th 1 f d b d l 7 e~' m rcate Pregnancy. e ast our wor s may e omttte t.omp un billboards. The Federal Communications Commission (FCC) shares IF responsibility with FTC for the ban of advertisements of cigarettes s etal ., au f and smokeless tobacco on radio and television (FTC, 1998). te~ The Department of Health and Human Services (DHHS) also ~ Itas responsibilities under the Federal Cigarette Labeling and ulatess tcc ,ndtE > use. 1 0/ 17R Advertising Act, 15 U.S.C. Section 1341, Smoking, Research, Education, and Information. DHHS was given mandates to establish and carry out a program to inform the public of any human health dangers of cigarette smoking. All activities, including educational and research programs within DHHS shall be coordinated with similar activities of other Federal and private agencies via the Interagency Committee on Smoking and Health. DHHS shall collect, analyze, >utd disseminate information, studies, and other data associated with cigarette smoking that is relevant to human health. DHHS shall develop standards, criteria, and methodologies for improved information programs related to smoking and health. DHHS is to compile State and local laws relating to cigarette use and consumption. From January 1, 1986, and biennially thereafter, the Secretary of HHS shall transmit a report to Congress that contains an uverview and assessment of educational efforts by Federal agencies and the extent of public knowledge regarding health consequences of smoking, a description of DHHS and Interagency Committee activities, and a description of private sector activities in response to dze effects of smoking and health. Regulations were not identified that corresponded to all of these mandates. However, CDC publications such as the Surgeon General's reports and the National Cancer Institute's monographs in the Smoking and Tobacco Control series appear to fulfill several of these mandates. The Centers for Disease Control and Prevention's (CDC) Office on Smoking and Health (OSH) is the delegated authority to implement major components of the DHHS's tobacco and health Program, which comprises programs of information, education, and researclL CDC's authority includes collection of tobacco ingredients REpORT ON CARCINOGENS, NINTH EOITfON VINYL CHLORIDE information to facilitate HHS's overall goal of reducing death and disability from use of tobacco products (CDC, 1997)• HHS, under 45 CFR Part 96-Subpart L-Substance Abuse Prevention and Treatment Block Grant, requires that to be eligible for Block Grants to support substance abuse prevention and treatment services, each State must have in effect and strictly enforce a law that prohibits sale or distribution of tobacco products to persons under age 18 by manufacturers, distributors, or retailers. Federal agencies have issued regulations to implement Public Law 104-52, the Prohibition of Cigarette Sales to Minors in Federal Buildings and Lands. The General Services Administration (41 CFR), the Treasury Department (31 CFR), and the Railroad Retirement Board (20 CFR) prohibit the vending and free distribution of tobacco products on property under their jurisdictions. Under 32 CFR 85.6, health promotion efforts in each military service should include smoking prevention and cessation programs. Health care providers are encouraged to take the opportunity at routine medical and dental examinations to apprise service personnel of tobacco use risks (including smokeless tobacco) and how to get help to quit. Regulations are summarized in Volume IT, Table A-42. *There is no separate CAS registry number assigned to tobacco smoking. Vinyl Chloride CAS No. 75-01-4 First Listed in the FirstAnnual Report on Careinogens CHa,,, CH rCl Carcinogenicity Vinyl chloride is known to be a human carcinogen based on sufficient evidence of carcinogenicity in human (IARC S,7, 1987). Vinyl chloride has been associated with tumors of the liver, brain, lung, and hematolymphopoietic system. A large number of epidemiological studies and case reports have substantiated the causal association between vinyl chloride and angiosarcoma of the liver. Several studies also confirm that exposure to vinyl chloride causes other forms of cancer, i.e., hepatocellular carcinoma, brain tumors, lung rumors, and malignancies of the lymphatic and hematopoietic system. Exposure to poly(vinyl chloride) dust was associated with an increased incidence of lung tumors in one study; the authors suggested that trapped vinyl chloride monomer was responsible. Melanoma occurred in excess in one study but has not been mentioned in others. Slightly elevated risks for gastric and gastrointestinal cancer (other than liver cancer) were indicated in some studies, but these were not confirmed in others. An IARC Working Group reported that there is sufficient evidence of carcinogenicity of vinyl chloride in experimental animals (IARC V.19, 1979; IARC 5.4, 1982; IARC S.7, 1987). When administered by inhalation, vinyl chloride induced pulmonary ade¢omas and adenocarcinomas, mammary adenocarcinomas, liver angiosarcomas, and angiosarcomas and adenocardnomas at other sites in mice of both sexes. Inhalation of vinyl chloride induced Zymbal gland carcinomas, nephroblastomas, and liver angiosarcomas in rats of both sexes and mammary tumors and hepatocellular carcinomas in female rats. When administered by inhalation, vinyl chloride induced skin tumors in male hamsters and angiosarcomas (liver, spleen, or skin), ntammary carcinomas, skin carcinomas, and stomach adenomas in female hamsters. Newborn rats developed angiosarcomas and hepatomas when exposed to vinyl chloride by inhalation. A III-6l